New ICH E6 to Place More Demands on Trials, but COVID-19 Could Help Ease Adjustments

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COVID-19 Update…2 Industry Briefs …3 Up and Coming…5 Pandemic Is Expediting Protocol Finalization Drug & Device Pipeline News…10 in COVID-19 Studies Twenty-eight drugs and devices have entered a new trial phase this week. By James Miessler weeks, says Suzanne Caruso, WCG Clinical Research Center Spotlight…12 he worldwide rush demanded by the vice president of clinical solutions. pandemic to develop and/or identify “We have a virus that basically didn’t exist T a potential treatment or vaccine five months ago, and now we have more WEBINAR has culminated in remarkable success in than 950 active trials,” Caruso said at a WCG expediting COVID-19 trials, and the lessons Clinical webinar last week. “Those are indus- Final ICH E6 (R2) Guideline learned are likely to be applied even after try-sponsored trials, those are investigator- on Good Clinical Practices the pandemic is over. initiated trials. I think [the pandemic] forced The Real Impact of The pandemic has led to a rapid speed- a speed, and speed to getting trials ongoing the Changes MAY up in the time it takes to get from protocol is going to have a lasting impact on the clini- finalization to first patient visit for COVID-19 cal trial landscape beyond COVID.” REGISTER 27 studies. Investigators normally would finalize The numbers show that non-COVID, their trial protocols in a six-month process — industry-sponsored trials have seen an perhaps three with great efficiency — and enormous deceleration in participant en- LEAD GENERATION then proceed with site selection, contracting, rollment and a massive increase in holds as Generate Leads budgeting and other tasks. Now, the majority a result of the pandemic. Prior to January, While Building of COVID trials are going from having a final seven clinical trials were put on hold per Credibility and Trust protocol to first patient first visit in just four see Pandemic Is Expediting on page 7 » Webinars White papers New ICH E6 to Place More Demands on Trials, but COVID-19 Could Help Ease Adjustments POSITION YOURSELF AS A THOUGHT LEADER By Elizabeth Tilley Hinkle The introduction in E6(R2) of risk-based ust two years after releasing a major re- management and quality tolerance limits vision of its good clinical practice (GCP) (QTLs) caused the biggest problems, Crissy J guideline, the International Council MacDonald, vice president of client delivery June 22 – July 2, 2020 on Harmonization (ICH) is planning a new at life sciences consulting firm The Avoca update that would require additional adjust- Group, said at a CenterWatch webinar last MAGI's Clinical Research ments from sponsors and sites that still may week. She noted that difficulties in these Cloud Conference 2020 be trying to catch up with the first revision. areas could, in fact, greatly affect individual 48 sessions and workshops Surprisingly, the COVID-19 pandemic could organizations’ ability to comply with the over eight days in eight tracks REGISTER end up making that task easier. upcoming E6(R3). ICH announced in November 2019 that According to a poll of 188 industry repre- it planned to again revise ICH E6 — Good sentatives attending the May 5 CenterWatch Clinical Practice, to fill gaps in areas of the webinar on the forthcoming E6(R3) guid- guideline that were not addressed in a 2016 ance, a mere 8 percent have successfully The CRC’s Guide to Coordinating revision. ICH’s announcement that it would completed adoption of the current E6(R2) The CRC’s Guide Clinical Research to Coordinating Clinical Research revise E6 again caused consternation within and 17 percent were less than halfway Stay informed and be an industry still grappling with challenges pre- through that process. Another 31 percent prepared to respond to sented by the 2016 revision, known as E6(R2). see New ICH E6 on page 8 industry changes. » FOURTH EDITION

COVID-19 Drug Research London’s Guy’s and St. Thomas’ Hos- agent and have advanced it to testing. The Roundup pital will run a trial of convalescent plasma drug is designed to disrupt interaction of Below is a roundup of research activity for treating COVID-19. The treatment uses do- the virus’ endoribonuclease with a protein on COVID-19 vaccines and treatments for nated blood plasma from patients that have necessary for its replication. the past week. To see last week’s column, recovered from the virus and transfuses it Amgen said it has plans to test its block- click here. into COVID-19 patients whose bodies are not buster psoriasis drug Otezla (apremilast) as COVID-19 Vaccines: making enough antibodies to fight the virus. a possible coronavirus treatment. The com- Pfizer and BioNTech have begun a U.S. Glenmark Pharmaceuticals has re- pany expects to begin trials of the drug in trial of COVID-19 vaccine candidates at the ceived approval from the Indian government the coming weeks and is looking to study the NYU Grossman School of Medicine and the to conduct COVID-19 trials of the antiviral drug in multiple scenarios. Amgen CEO Rob- University of Maryland School of Medicine. favipiravir, which is approved for treating ert Bradway said the drug could help prevent The phase 1/2 study will assess four mRNA influenza in Japan. The randomized study will respiratory stress in late-stage patients. vaccine hopefuls in one continuous trial have 150 mild-to-severe coronavirus patients. Incyte and Novartis plan to initiate that will involve 360 healthy subjects be- Massachusetts General Hospital will another phase 3 COVID-19 trial of their JAK tween 18 to 55 and 65 to 85 years of age. conduct a trial of Mallinckrodt’s INOmax inhibitor Jakafi (ruxolitinib). The study will Predictive Oncology is developing a (nitric oxide) for treating low blood-oxygen evaluate the drug in coronavirus patients on COVID-19 vaccine using a novel nanopar- levels in patients with severe COVID-19 mechanical ventilation and ones who have ticle vaccine platform. The company said lung complications. Mallinckrodt previously acute respiratory distress syndrome. The two its next move is to seek quotes for a phase received Canadian approval for a trial of have already launched a trial of the drug on 1 trial from CROs approved by the HHS’s high-dose inhaled nitric oxide therapy to COVID-19 patients with cytokine storm. Biomedical Advanced Research and Devel- treat COVID-19 infections and associated Researchers at Royal Oak, Mich.’s Beau- opment Authority (BARDA). lung complications. mont Hospital are enrolling patients in a Moderna is planning to begin phase Eli Lilly and Junshi Biosciences have phase 2 trial to evaluate a combination of 3 trials of its coronavirus vaccine by early teamed up to develop antibodies that can naltrexone and ketamine as a COVID-19 summer, speeding up its original timeline potentially prevent and/or treat COVID-19. treatment. The study is trying to determine that had the trials starting in the fall. The Eli Lilly and Junshi plan to begin clinically if the combination can lessen the severity of agency recently cleared a phase 2 trial for testing the lead antibody, JS016, in the symptoms by reducing inflammation. the vaccine candidate, mRNA-1273, which second quarter of this year. CSL Behring Australia said it is cur- involves approximately 600 participants. Vir Biotechnology and Alnylam Phar- rently developing an anti-coronavirus COVID-19 Treatments: maceuticals have identified an investiga- plasma product for potential use in Aus- Montefiore Health System, Albert tional therapeutic, VIR-2703, as a possible tralia. The treatment, known as COVID-19 Einstein College of Medicine and NYU COVID-19 treatment. The inhaled SARS-CoV- Immunoglobulin, is being designed for Langone have launched a clinical trial 2-targeting small-interfering RNA (siRNA) severely ill patients, particularly ones studying the effectiveness of convalescent blocks production of specific proteins and that are progressing toward being put on plasma in COVID-19 patients. The trial will could prevent or treat a coronavirus infection. ventilation. It is being developed at the enroll 300 people that have COVID-19 Anixa Biosciences and OntoChem have company’s advanced manufacturing site in respiratory symptoms, with half of them identified a potential COVID-19 therapeutic Broadmeadows, Victoria. receiving a placebo. CTI BioPharma has begun a phase 3 trial to evaluate its oral multikinase inhibitor pacritinib in patients hospital- CenterWatch Weekly ized with severe COVID-19. The trial, (ISSN 1528-5731) CenterWatch Main and Editorial Offices 300 N. Washington St., Suite 200, Falls Church, VA 22046 Beth Belton Editorial Director which is expected to enroll patients in Tel: 866.219.3440 • 617.948.5100 Stephanie Akers Production [email protected] / [email protected] both the U.S. and Europe in May, will Russell Titsch Business Development Director Permission requests can be emailed to [email protected]. compare pacritinib plus the standard of © 2020 CenterWatch. No part of this publication may be distributed care to placebo plus standard of care in or reproduced in any form or by any means without the express Advertising packages and reprints are available: written consent of the publisher. Email [email protected] or call 703.538.7651. 358 hospitalized patients.

WHO Outlines Criteria for recruitment, enrollment, site visits New Transplant Guidance COVID-19 Vaccine Challenge and monitoring. PPD says it is working Recommends Endpoints, Trial Trials closely with customers to minimize Designs for CMV Drugs A working group of the World Health Orga- trial disruptions and ensure continued Sponsors of drugs to treat or prevent cyto- nization (WHO) has indicated its support access to drug supplies for patients in megalovirus (CMV) disease in organ or stem of COVID-19 vaccine challenge studies, but ongoing studies. cell transplant patients may use CMV blood made it clear that those trials must meet In March, the big CRO launched a new levels (CMV viremia) as a validated surrogate eight conditions for them to be considered. program to transfer participants in an endpoint, according to a guidance the FDA In its guidance, the WHO working group affected trial to other research sites. finalized last week. made it clear that there needs to be scien- PPD also reports it is working on 39 For trials of preventive therapies, tific justification, an assessment of potential studies related to COVID-19 treatments participants should have no detectable benefits, fully informed consent of partici- and vaccines. post-transplant CMV infection within five pants and a focus on enrolling only healthy, } In a recent report, Ironwood Pharma- days of beginning therapy. Treatment trials young adults who are considered to be at ceuticals announced it has paused should enroll organ transplant patients with low risk of serious disease. enrollment in a phase 3 trial of its re- virological evidence of CMV replication or The report noted healthcare workers and fractory gastroesophageal reflex drug, stem cell transplant recipients with clinical researchers would be appropriate partici- IW-3718. Most trial sites have stopped evidence of tissue-invasive CMV disease. pants for a COVID-19 challenge study, as in-person screening activities but Read the final guidance here: https://bit. they have a higher probability of infection continue to monitor patients already ly/2YXh0xd. and are informed about the risks associated enrolled and being treated, the com- with the virus. pany said. As a result, Ironwood will not New Research Platform Seeks To read the full WHO report, click here: have top-line data ready to report by to Improve Collaboration https://bit.ly/2A3UE2m. the second half of 2020 as planned. Across COVID-19 Trials On the other hand, the company’s The COVID-19 Collaboration Platform Pharma, CRO Fates a Mixed collaboration with Allergan on a (COVIDCP), a new initiative from universi- Bag as Pandemic Continues phase 2 trial of MD-7246, a drug to ties and clinical trial organizations across Pharma companies and CROs are expe- relieve abdominal pain resulting from the U.S., will bring together research teams riencing ups and downs in the second irritable bowel syndrome, is moving who are working on vaccines and treat- quarter of 2020, with some fighting to forward and has completed patient ments for COVID-19. keep their trials afloat amidst pandemic dosing, which will allow it to share The research teams can share trial pro- uncertainties while others are slowly get- top-line data in the second quarter of tocols and data, and aggregate and analyze ting back on track. Here’s a sampling of 2020, earlier than the planned target evidence as well as receiving support for what happened last week: of mid-2020. developing multisite trials, and free data } Amid the uncertainty surrounding } As many clinical trials continue to slow storage and anonymization. the COVID-19 pandemic, PRA Health down and some stop altogether, one Partners of the 10-member COVIDCP Sciences says it has been working to UK biotech is looking to hit the restart include the Johns Hopkins Department of mitigate the effect of the pandemic on button on enrollment of a phase 3 Biostatistics, the Harvard Data Science In- its ongoing studies by using its mobile study. NuCana has announced that stitute, the International Forum for Acute health platform and remote moni- it will recommence recruitment of Care Trialists (INFACT), Drexel University toring technology. Gathering data new patients for a study of nucleotide Dornsife School of Public Health, and remotely and supporting virtual trials analog Acelarin plus cisplatin for the the McGill Department of Epidemiology, will help the CRO limit the exposure of treatment of biliary tract cancer. The Biostatistics and Occupational Health, staff and conserve valuable resources. phase 3 trial is designed to enroll up to among others. } PPD says it also has been feeling the 828 patients across 120 sites. The first Trials posted on the COVIDCP platform pandemic pain as some of its cus- sites to reopen are located in Australia, are open for collaboration. Learn more tomers delay new studies or pause Canada, South Korea, Taiwan, Ukraine about COVIDCP here: https://bit.ly/2LcxyJk. ongoing studies or activities such as and the UK. continues on next page »

New Survey on How COVID-19 The survey also revealed that only 8 per- tion of Clinical Research Professionals (ACRP) is Affecting Clinical Trials cent of respondents have tested patients for has set up a Clinical Research Site Sustain- Shows Major Impact an active COVID-19 infection. Only 3 percent ability Fund to provide grants to sites for A new survey of investigator sites reveals tested patients for prior infection. continuing education and career develop- approximately 69 percent of respondents Respondents also suggested that deci- ment resources. said lockdown measures have impacted sions to postpone a trial or halt recruit- The fund is part of ACRP’s Partners in their ability to conduct ongoing trials and ment should be made on a region-specific Workforce Advancement initiative, which is 78 percent said COVID-19 has affected their basis, as COVID-19 is not affecting all parts working toward setting standards for work- ability to start new trials. of the world equally. To ensure they have force competencies and fostering diversity Only 11 percent of the 1,030 respondents additional financial support to employ in the clinical trials industry. said they were “extremely concerned” about study coordinators during delayed or sus- their ability to collect clinical outcomes data pended studies, sites suggested contracts ThoughtSphere Acquires during the pandemic. The global survey was should be amended for increased remote Patent for Platform That conducted by Medidata the week of April 23. monitoring work and increased overhead Quickly Intakes, Processes More than half (63 percent) of survey reimbursements. Also, sites commented Study Data respondents said they have stopped new pa- that they want sponsors and CROs to ThoughtSphere, a cloud-based clinical tient recruitment for an ongoing trial, whereas develop study-specific contingency plans data management provider, has secured 43 percent said they have delayed their study. to prevent deviations from scheduled visit a patent for a data management plat- Only 12 percent of sites that responded to the windows in case another outbreak occurs form that uses statistical and machine survey have said they cancelled studies. in the future. learning methods to map, aggregate Nearly 45 percent of respondents said The majority of respondents were from and standardize clinical trial data from they have switched study participants from the U.S. (58.3 percent), followed by Asia (23.8 disparate sources. in-clinic visits to virtual/telemedicine. Around percent), the EU/UK (8.1 percent), South/ The new data management platform one-third (33 percent) of respondents said Central America (7.1 percent) and Middle adapts to any data structure and source they have amended their study protocol, and East/Africa (2.7 percent). Respondents were — including electronic data capturing another third (32 percent) have said they mostly study coordinators (73 percent), systems, electronic medical records and have not allowed randomization of patients followed by investigators (11.2 percent), wearables — and allows for the conver- who have completed screening. directors (5.4 percent), clinical nurses (4.1 sion of these trial data to a standard- On a scale from one to five, with five percent) and “other” (6.3 percent). ized format. According to the company, representing “being extremely concerned,” To read the survey, click here: https://bit. clients who use the newly patented tool respondents were most concerned with ly/2Li3qMt. have reduced data management costs their ability to enroll (weighted mean: by 30 percent and have saved approxi- 3.73) and recruit patients (3.66). They also ACRP Launches Fund to Help mately 50 percent of time in their data reported concerns about financial implica- Sites Educate Workforce management efforts. tions for cancelled trials (3.42) and patient During COVID-19 Through the end of the year, Thought- access to the research site (3.05), among To support research teams at sites struggling Sphere is offering the platform for free to other concerns. with the impact of COVID-19, the Associa- clinical trials focused on COVID-19.

Your leading resource for trends, analysis, September 2018 A CenterWatch Publication Volume 25, Issue 09 Start-up Costs Can Be an Uphill Slog in Need of Change compliance guidance, expert insights and more. By John W Mitchell - sponsors. When each sponsor uses their rustration about clinical trial start-up sley, CEO at IACT Health. His company own networks and devices for patient-re- costs is not unlike Sisyphus’ dilemma. ported outcomes, it adds to site workload A host of long-standing expense and and time. With original content and exclusive interviews in each issue, - “We have no ability to standardize tech- such uphill headwinds for the clinical trial ger, and there are more procedures per pa- nology,” Kingsley says “We have to do so sector. According to some sources, such tient per day. So, you’re doing loads more many trials with so many sponsors, and problems even threaten the viability of the work, but you’re only paid when you put they have their own decision-making… sector. Sites complain they incur more over- The CenterWatch Monthly is like having your own full-time research - head costs driven by regulatory documen- themselves — you put fewer patients in tri- bia (standardization between sponsors and tation, antiquated data collection and the als today.” sites).” demands of precision medicine to name a According to Kingsley, the only way to As an example, he cites the advantages of few — all without increased compensation - sites adopting electronic platforms such as team helping you understand how and why the industry is changing. from sponsors and CROs. A recent study Subscribe Todapyate in! three times as many concurrent tri- eSource. Using such a platform could save supports this concern. Researchers at the billions compared to the aggregate cost of - from an overhead standpoint to have one www.copement fotuned thrat twhe studay tstacrt-uhp ph.asce om/cwmonthly trial that places eight patients, rather than documents. Clinically, an electronic plat- three trials that place eight patients. form also prevents errors such as entering remained unchanged for the past decade. Also, at a time when technology is con- a blood pressure incorrectly or performing CONTACT SALES  [email protected] 617.948.5100 - a patient procedure out of order from the ing investments in technology are getting technology is compounding problems in test protocol. trials done faster. None of this bodes well the clinical trial sector. In each of the three “We’re trying to convince the industry for smaller, independent players.

This feature highlights changes in clinical Erlander to lead the company as its CEO. Gemini Therapeutics trial organizations’ personnel. Erlander had been Cardiff’s chief scientific Mark Uknis has stepped into the chief officer since 2013. medical officer role at Gemini Therapeutics. Acesion Pharma Uknis leaves a position as Achillion’s vice Acesion Pharma has named Anders Holst Codexis president and global nephrology develop- its chief medical officer. Holst was senior in- Codexis has hired Stefan Lutz to the role ment lead. ternational medical director at Novo Nordisk. of senior vice president of research. Most Acesion has also recruited Birgitte Vestbjerg recently, Lutz was professor and chair Goldfinch Bio to take on the role of director of clinical op- of the chemistry department at Emory Goldfinch Bio has appointed Kyle Kuva- erations. Vestbjerg was most recently director University. Karl Schoene was also tapped lanka to the role of chief financial and of clinical operations at MC2 Therapeutics. as Codexis’ senior vice president of devel- operating officer. Kuvalanka is a consul- opment and operations. Schoene comes tant at Third Rock Ventures and was chief Advarra to Codexis from Elevance Renewable Sci- operating officer at Syros Pharmaceuticals Gadi Saarony has joined Advarra as ences, where he served as president, CEO prior to this appointment. Goldfinch the consulting company’s CEO. Saarony and director. also announced the promotion of Lori comes to Advarra from PAREXEL, where Rudolph-Owen from senior vice president he served as executive vice president and DEINOVE of R&D strategy and operations to chief chief CRS officer. French biotech DEINOVE has named Alexis development officer. Rideau as its CEO. Most recently, Rideau was AiCure a strategic partnership manager and team HORAMA Ed Ikeguchi, who previously served as chief coordinator for BIOASTER. Gene therapy company HORAMA appointed medical officer and president of AiCure, has Ian Catchpole to the role of chief scientific been named CEO of the company. Emmes officer. Catchpole most recently served as Emmes has named Joe Sliman chief medi- director of research at TC BioPharm. ANI Pharmaceuticals cal officer. Sliman joins Emmes from Social ANI Pharmaceuticals has named Patrick D. and Scientific Systems, where he served as ICON Walsh interim president and CEO to fill the senior medical director. ICON has tapped Kristen Buck, former gap left by the retiring CEO, Arthur Przybyl. senior vice president and chief of clinical Walsh has served on ANI’s board of directors Endpoint Clinical development at Optum, to join the CRO as since 2018 and has extensive pharmaceuti- Christine Oliver has been appointed its chief medical officer. cal industry experience. CEO of Endpoint Clinical. Oliver most recently served as chief operating officer Immunocore Antibe Therapeutics of the company. Brian Di Donato has been named chief Antibe Therapeutics appointed Joseph financial officer and head of strategy at Im- Stauffer to the role of chief medical officer. Enteris BioPharma munocore. Previously, Di Donato was senior Stauffer previously served as chief medical Rajiv Khosla has been appointed to the role vice president and chief financial officer at officer of Inheris Biopharma. of CEO at Enteris BioPharma. Khosla joins Achillion Pharmaceuticals. Enteris from CEUTEC, a biopharmaceuti- Aurinia Pharmaceuticals cal and venture capital consulting firm he Impel NeuroPharma Joe Miller has joined Aurinia Pharmaceu- founded in 2011. Impel NeuroPharma has named Adrian ticals as its chief financial officer. Miller Adams, current chairman of the company’s was previously the chief financial officer Galecto board of directors, as its CEO. at Cerecor. Galecto has appointed Jonathan Freve to the role of chief financial officer. Freve Intellia Therapeutics Cardiff Oncology (Trovagene) most recently served as chief financial David Lebwohl has been named chief Cardiff Oncology, which recently changed its officer and treasurer of Spring Bank medical officer of Intellia Therapeutics. name from Trovagene, has appointed Mark Pharmaceuticals. continues on next page »

Lebwohl joins the company after an almost served as executive vice president of North RespireRx Pharmaceuticals two-year stint as chief medical officer of & Central America and president of Elekta. Timothy Jones has been named president Semma Therapeutics. and CEO of RespireRx Pharmaceuticals. New Jersey COVID-19 Jones was most recently the vice president Johnson & Johnson Commission of global pharmaceuticals and medical OTC Johnson and Johnson promoted Najat Merck CEO Ken Frazier has joined the at Purisys. Khan from the role of chief operating officer New Jersey COVID-19 Restart and Recovery to chief data science officer. Commission, which will focus on guiding the Rome Therapeutics state’s post-pandemic recovery strategy, as Rosana Kapelier will lead Rome Thera- Kezar Life Sciences its chairman. peutics as its CEO following the company’s Noreen Henig has been named chief recent acquisition of $50 million in series A medical officer of Kezar Life Sciences. Most Nordic Nanovector capital funding. recently, Henig was chief medical officer of Malene Brondberg, vice president of Breath Therapeutics. investor relations and corporation com- Signant Health munications at Nordic Nanovector, has Signant Health has appointed Ian Jen- LifeMax been appointed chief financial officer of nings to the role of chief commercial officer. LifeMax has appointed Michael Huang the company. Jennings was most recently an indepen- to the role of chief medical officer. Huang dent consultant for clinical and healthcare was recently the chief medical officer of Orchestra BioMed technology companies. Spruce Biosciences. Bob Laughner has been named vice president of regulatory affairs at Orches- Targovax Mirum Pharmaceuticals tra BioMed. Prior to this appointment, Victor Levitsky has assumed the role of Peter Radovich has been named chief Laughner was regulatory director of chief scientific officer at Targovax. Levitsky operating officer of Mirum Pharmaceuti- medical device and combination products was previously vice president and head of cals. Previously, Radovich was the execu- for AstraZeneca. oncology research at Molecular Partners. tive vice president of operations at Global Blood Therapeutics. PathoQuest Tessa Therapeutics Laurent Lafferrere has been named chief Tessa Therapeutics has announced the Myocardial Solutions operating officer at PathoQuest. Lafferrere appointment of Jeffrey Buchalter to CEO. Peter Gaccione has joined Myocardial So- was most recently in charge of the SEQENS Buchalter joined Tessa in 2019 as an inde- lutions as its president. Gaccione previously Lab R&D Center at SEQENS. pendent board director.

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Pandemic Is Expediting She cited a survey taken by WCG Clinical importantly is demonstrating to study continued from page 1 that probed how long sites think it will participants as they come in to potentially month on average, according to WCG Clini- be before they open to enrollment again. participate … that we’re showing them cal’s Knowledge Base. But as the pandemic The survey, which questioned more than how seriously we are taking the precau- developed, the number of paused trials 1,250 sites, found that more than a third (37 tions we need to take to try to minimize rose sharply to 26 for March and utterly percent) of sites were uncertain, 26 percent the risk of infection,” he said. skyrocketed in April, when 129 studies anticipated four to eight weeks, and 19 To minimize the risk of infection at a site, were placed on official hold. percent believed it would take two to four sponsors should develop a “formal pan- Industry has also seen an extreme weeks. Seven percent said one to two weeks, demic SOP” that includes the use of personal slowdown in enrollment as a result of the while just two percent said it would take protective equipment (PPE), procedures for outbreak; only 11 percent of clinical research more than two months. entering the facility, testing procedures and sites across 29 different countries said that But as of last week, WCG Clinical found other measures. they were open to enrollment as of May 1, that 51 percent of sites across 29 different “At our facilities, you basically don’t get Caruso said. A little more than a month be- countries reported they will be open to through the front door, and that means fore, on March 24, 62 percent reported that enrollment and new study starts within two vendors, employees, participants in stud- they were open for enrollment — but just a to four weeks, she said. ies, without being screened in a kind of week later, that number had plummeted to Caruso said that right now, sites should sequestered area,” he said. “You’re asking 26 percent and continued to drop afterward. be supporting study coordinators as they’re containment questions: have you been Caruso noted, however, that she anticipates forced to cover more than they’re used to sick, where have you been, taking people’s the number of trials open to enrollment will during the pandemic. temperature, asking about exposure to start to rise again in the near future. “There’s going to be tremendous impact other individuals who may have had symp- Caruso referenced WCG Clinical data in the amount of resources that the study toms in the recent past.” showing that with trial starts declining, the coordinators have to cover for their new Additionally, sponsors should reduce the number of trials waiting to kick off have studies and COVID work,” she said. “There number of participants and staff in specific risen dramatically. Just in January, 629 new are going to be COVID trials for a number site areas, scheduling subjects throughout biopharma-sponsored studies were started, of months, if not years. Providing clinical the day to ensure there is no high traffic according to the data. That number declined research coordinators for a study to be able of subjects at any point in the day. Facility to 546 in February, 492 in March, and de- to do data entry, to be able to do scheduling access should be strictly limited, with staff scended sharply to 328 in April. of patients and keeping track, I think is the receiving daily screenings upon arrival, But the number of planned new trials best way to support our site colleagues, and and space should be designated to isolate skyrocketed from 223 in February to 463 in I think that’s something a lot of sponsors are symptomatic patients at a moment’s notice. March and rose a tiny margin in April to 477. looking into in addition to remote assess- And while it may seem obvious, Wardle Caruso pointed out that industry faces a ments and remote visits.” reminded sponsors that infection control collision of forces — a number of trials that Tom Wardle, CEO of CenExel Clini- and facility cleaning is an important part of are ongoing and soon to open to enrollment cal Research, who also spoke during the reducing infection risk. vs. a number of trials that are preparing to webinar, offered advice on adapting Wardle reinforced the importance of begin and will also open to enrollment. trials to the pandemic. Successfully doing remotely monitoring patients and enabling “This is going to have tremendous so requires taking a strong educational remote visits, following current Centers impact as we come out of the COVID clinical approach toward participants, he said, for Disease Control guidelines for screen- trial landscape and turn to newer studies or advising sponsors to develop and put in ing employees and participants, and using ongoing studies,” she said. “The question re- place standard operating procedures (SOP) COVID-19 polymerase chain reaction tests ally becomes, what do we do when we have for participants and employees, including at screening, outpatient visits and inpatient this collision of new trials that our sponsors testing for the virus. unit entry. Patients and staff alike should be definitely want to get ongoing and enrolling “The response needs to be a lot of regularly reminded to continue the use of well, as well as the restarts for studies that education, a lot of training, both to clinic well-publicized guidelines for the coronavi- have been delayed as a result of that pause personnel as well as training to potential rus, such as the use of PPE, social distancing, in enrollment?” study participants, and then even more hand sanitizer and other precautions.

New ICH E6 regulatory environment; it will outline how tions may also be helping regulators become continued from page 1 GCP principles should apply to increasingly more comfortable with — or at least more reported they were 75 percent to 99 percent diverse trial types and data sources. The accepting of — faster technological change. through adoption and 22 percent said they concept paper also indicates the new guid- And that is a concern to drug spon- were 50 percent to 75 percent finished. ance will encourage flexibility whenever ap- sors and researchers. According to the Top problems in adoption were identi- propriate to facilitate incorporation of useful poll taken during the May 5 CenterWatch fied as risk-based management (27 percent technological innovations and address webinar, the most significant barrier to of respondents), QTL implementation (21 specific complexities of clinical trials. implementing new technologies within percent), organizational change manage- ICH E6(R3) will come out in two phases. the clinical trial industry is uncertain regu- ment and training (19 percent), policy and The main guidance covering the overarch- latory acceptance. The expense of new procedure updates (17 percent), and vendor ing principles and objectives is expected tech and unknown risk-benefit profiles are oversight (16 percent). to come out sometime between May and also seen as challenges. “I believe that COVID-19 has really December 2021. Accompanying it will be Another driver behind the planned changed how rapidly the adoption of these Annex 1, covering traditional interventional update has been the relatively rapid issuance technologies can be completed,” MacDonald clinical trials. At that time, work on a second of guidance by multiple international regula- said. “And this can help us adapt from E6(R2) annex will begin. Annex 2 will cover non- tors on such key topics as risk-based quality to E6(R3).” The past few months of pandemic traditional clinical trials, such as pragmatic management and monitoring, and quality by conditions have given the clinical trial indus- and decentralized studies, as well as those design (QbD). The November 2019 concept try new tools, resources and confidence in incorporating real-world data (RWD). paper lists several documents ICH will con- applying them, she added. Rapid technology development over the sult as it drafts the new E6(R3), including: Technology and clinical trial design past decade, and even more so in just the } The existing ICH E6(R2); approaches have been undergoing rapid past few years, is a primary driver behind } Other ICH guidances, including E8 — changes in the past few years, and the the decision to update ICH E6 so quickly General for Clinical Trials, and ICH Q9 — industry has been working to make technol- after the latest revision, according to the ICH Guideline on Quality Risk Management, ogy part of trial execution and to increase concept paper. which includes discussion of QbD; efficiency. And the pace at which drug spon- That paper indicates that the new E6(R3) } The FDA’s 2013 guidance on risk-based sors and researchers adopted and adapted to guidance will allow more rapid and flexible monitoring; new technologies and approaches increased incorporation of new technologies into the } A 2013 EMA reflection paper on risk- exponentially when the existing site-focused clinical study and drug approval application based quality management; and system was challenged by COVID-19. process, said Steve Whittaker, senior consul- } Three documents issued by Japan’s COVID-19 has changed the risk profile tant at The Avoca Group. Pharmaceuticals and Medical Devices for many new technologies and study Historically, regulators have been reluc- Agency (PMDA) and Ministry of designs, MacDonald said. In essence, the tant to accept data generated by unfamiliar Health, Labor and Welfare (MHLW) in risk-benefit profile of some approaches has records and so the industry has been slow 2019 on GCP for drugs, quality man- undergone a “COVID shift” as industry was to adopt new technologies or study designs agement in clinical trials and risk- forced to adopt them to ensure some sort that might hinder their ability to get new based monitoring in clinical trials. of business continuity. products approved due to regulator discom- The industry can expect all of the fea- “What used to seem too much a risk, too fort with how the data was generated. tures in E6(R2) to roll over into the upcoming much unknown, is now required if you don’t A question is whether regulators — his- new revision, Whittaker said. Some of the want to stop your trial,” MacDonald said. torically precedent-driven — can effectively highlights include quality management and ICH released a concept paper that accept and incorporate novel technologies. incorporation of QbD principles; although provides an outline of what drug sponsors Whittaker suggested that the announcement the latter were originally developed for GMP and clinical investigators might expect of E6(R3) coming so soon after adoption of purposes, they are applicable to GCPs as from E6(R3). According to that paper, the E6(R2) indicates that regulators recognize well. Risk identification, evaluation and mini- guidance will be rewritten and reorganized weaknesses in the traditional approach and mization — with emphasis on those risks with the primary objective of addressing are attempting to adapt. Industry’s rapid that would affect patient safety and/or data the complexity of clinical trials in a global adaptations in the face of COVID-19 restric- integrity — will likewise remain a priority.

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Company Drug/Device Medical Condition Status Sponsor Contact COVID-19 Trials and Actions Organicell Organicell Flow moderate to severe acute IND approved by the FDA organicell.com Regenerative respiratory syndrome (SARS) due Medicine to COVID-19 infection Global Institute of mesenchymal stem Covid-19 expanded access for giostar.com Stem Cell Therapy cells compassionate use granted by and Research the FDA (GIOSTAR) Eiger peginterferon patients with mild COVID-19 first patient treated in phase eigerbio.com Biopharmaceuticals lambda 2 trial Pulmotect PUL-042 prevention of infection with approval for two phase 2 trials pulmotect.com SARS-CoV-2 and the prevention granted by the FDA of disease progression in patients with early COVID-19 disease Athersys MultiStem cell COVID-19 Induced Acute enrollment of first patients in athersys.com therapy Respiratory Distress Syndrome phase 2/3 trial (ARDS) Mesoblast remestemcel-L COVID-19-infected patients with first patients dosed in phase mesoblast.com moderate to severe ARDS on 2/3 trial ventilator support Aridis AR-301 S. aureus induced pneumonia in enrollment of first patient in aridispharma.com Pharmaceuticals COVID-19 patients on mechanical phase 3 trial ventilators Gilead remdesivir COVID-19 Emergency Use Authorization gilead.com (EUA) granted by the FDA EUROIMMUN Anti-SARS-CoV-2 detection of COVID-19 antibodies EUA granted by the FDA perkinelmer.com (a PerkinElmer ELISA (IgG) serology company) test Rheonix Rheonix COVID-19 detection of SARS-CoV-2 EUA granted by the FDA rheonix.com MDx Assay Roche Elecsys Anti-SARS- detection of COVID-19 antibodies approved by the FDA roche.com CoV-2 antibody test Other Trials and Actions Bicycle Therapeutics BT5528 in advanced solid tumors in first patient dosed in phase 1 bicycletherapeutics.com combination with indications associated with EphA2 trial nivolumab expression Scholar Rock SRK-181 locally advanced or metastatic first patients dosed in phase scholarrock.com solid tumors 1 trial Viriom VM1500A HIV-infected patients initiation of phase 2a trial viriom.com Kubota Vision emixustat macular atrophy secondary to completion of patient kubotavision.com hydrochloride Stargardt disease enrollment in phase 3 trial Spero Therapeutics tebipenem HBr complicated urinary completion of patient sperotherapeutics.com tract infection and acute enrollment in phase 3 trial pyelonephritis continues on next page »

Company Drug/Device Medical Condition Status Sponsor Contact Alume Biosciences ALM-488 peptide-dye conjugate for IND approved by the FDA alumebiosciences.com fluorescence highlighting of nerves during head and neck surgery Green Valley GV-971 Alzheimer’s disease IND approved by the FDA greenvalleypharma.com Pharmaceutical Lipocine LPCN 1148 liver cirrhosis in adult male IND approved by the FDA lipocine.com cirrhotic patients Nanobiotix NBTXR3 patients with locally advanced IND approved by the FDA nanobiotix.com or borderline resectable cases of pancreatic ductal adenocarcinoma GeneTx GTX-102 Angelman syndrome Fast Track designation granted genetxbio.com Biotherapeutics by the FDA

Ultragenyx ultragenyx.com Pharmaceuticals Ascentage Pharma HQP1351 chronic myeloid leukemia Orphan Drug designation ascentagepharma.com granted by the FDA Seelos Therapeutics SLS-005 Sanfilippo syndrome Orphan Drug designation seelostherapeutics.com granted by the FDA AstraZeneca Farxiga adults with New York Heart approved by the FDA for new astrazeneca.com (dapagliflozin) Association's functional class indication II-IV heart failure with reduced ejection fraction Galderma Research Restylane Kysse lip augmentation and the approved by the FDA galderma.com correction of wrinkles around upper lips in adults over the age of 21 Halozyme DARZALEX FASPRO multiple myeloma approved by the FDA halozyme.com Therapeutics (daratumumab hyaluronidase Janssen Biotech human- fihj) janssen.com Novartis Tabrecta NSCLC tumors that have an approved by the FDA novartis.com (capmatinib) abnormal mesenchymal- epithelial transition gene that leads to MET exon 14 skipping Tolmar FENSOLVI pediatric patients two years of age approved by the FDA tolmar.com Pharmaceuticals (leuprolide acetate) and older with central precocious puberty

This new edition of The PI’s Guide is packed with information regarding your The PI’s Guide to responsibilities including practical and Conducting Clinical Research ethical study conduct, site and financial management, and responsibilities Conduct better, safer and more imposed by ICH E6(R2). efficient clinical trials ORDER TODAY

Research Center Spotlight is a monthly selection of clinical research centers who have Research Center Profile pages posted on CenterWatch.com. Included in their annual subscriptions, company profiles are randomly selected to appear in this section, providing added exposure for their expertise and services in conducting and managing clinical studies. To learn more about becoming a Research Center Profile page subscriber, contact Sales at 617.948.5100 or [email protected].

Center for Neurosciences MDFirst Research Tucson, AZ Lancaster, SC 520.320.2147 704.491.1102 [email protected] [email protected]

CNS is primarily involved with sponsored phase 2-4 clinical trials, but MDFirst is committed to helping sponsors exceed their recruitment, several of our investigators have developed and conducted investiga- quality assurance and data integrity goals. The center comprises of a tor-initiated studies and compassionate use trials. The clinic currently network of physicians with extensive experience in conducting phase has a database of more than 67,000 active patients. 2-4 trials of medications as well as devices. Direct Helpers Research Center Oklahoma Heart Hospital Research Foundation Hialeah, FL Oklahoma City, OK 305.828.3555 405.608.1281 [email protected] [email protected]

Direct Helpers Research Center is a dedicated medical institute that OHHRF and its for-profit subsidiary, Oklahoma Cardiovascular combines a network of committed and experienced personnel to Research Group, provide cardiovascular trial management services to conduct an array of clinical research trials in phases 1-4. pharma, medical device and biotech companies.

eStudySite Parker Jewish Institute Chula Vista, CA New Hyde Park, NY 877.500.3788 718.289.2102 [email protected] [email protected]

Through comprehensive research services agreements with partner A 527-bed institution located on the border of Long Island and New hospitals, eStudySite is able to conduct a broad range of in-patient York City, Parker offers unique inpatient medical, subacute, nursing and out-patient protocols spanning first-in-human/first-in-patient and rehabilitation programs complemented by an array of highly through pivotal trials and postmarket support. regarded community services. IMIC Renstar Medical Research Palmetto Bay, FL Ocala, FL 786.310.7477 352.629.5800 [email protected] [email protected]

The center was established in 2012 as a continuation of successful Renstar’s research staff works with local physicians completion of more than 63 trials in previous research clinics. The in private practice and community hospital set- research site is conveniently located in Palmetto Bay, an area easily tings to provide a multidisciplinary team focused on meeting enroll- accessible from South Miami and North Miami. ment goals while ensuring strict regulatory and protocol compliance. J. Lewis Research The NIH Clinical Center Salt Lake City, UT Bethesda, MD 801.487.2072 800.411.1222 [email protected] [email protected]

J. Lewis is a unique research company with more The NIH Clinical Center is part of the than 28 years of experience conducting clinical trials National Institutes of Health (NIH) in Bethesda, MD. It is the world’s for the pharmaceutical industry, specializing in phase largest biomedical research hospital and ambulatory care facility. 2-4 trials.