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A Multicenter, Multi-Outbreak, Randomized, Controlled Safety And
2018 Ebola MCM RCT Protocol Page 1 of 92 IND#: 125530 CONFIDENTIAL 4 October 2019, version 7.0 A Multicenter, Multi-Outbreak, Randomized, Controlled Safety and Efficacy Study of Investigational Therapeutics for the Treatment of Patients with Ebola Virus Disease Short Title: 2018 Ebola MCM RCT Protocol Sponsored by: Office of Clinical Research Policy and Regulatory Operations (OCRPRO) National Institute of Allergy and Infectious Diseases 5601 Fishers Lane Bethesda, MD 20892 NIH Protocol Number: 19-I-0003 Protocol IND #: 125530 ClinicalTrials.gov Number: NCT03719586 Date: 4 October 2019 Version: 7.0 CONFIDENTIAL This document is confidential. No part of it may be transmitted, reproduced, published, or used by other persons without prior written authorization from the study sponsor and principal investigator. 2018 Ebola MCM RCT Protocol Page 2 of 92 IND#: 125530 CONFIDENTIAL 4 October 2019, version 7.0 KEY ROLES DRC Principal Investigator: Jean-Jacques Muyembe-Tamfum, MD, PhD Director-General, DRC National Institute for Biomedical Research Professor of Microbiology, Kinshasa University Medical School Kinshasa Gombe Democratic Republic of the Congo Phone: +243 898949289 Email: [email protected] Other International Investigators: see Appendix E Statistical Lead: Lori Dodd, PhD Biostatistics Research Branch, DCR, NIAID 5601 Fishers Lane, Room 4C31 Rockville, MD 20852 Phone: 240-669-5247 Email: [email protected] U.S. Principal Investigator: Richard T. Davey, Jr., MD Clinical Research Section, LIR, NIAID, NIH Building 10, Room 4-1479, Bethesda, -
Ebola Hemorrhagic Fever: Properties of the Pathogen and Development of Vaccines and Chemotherapeutic Agents O
ISSN 00268933, Molecular Biology, 2015, Vol. 49, No. 4, pp. 480–493. © Pleiades Publishing, Inc., 2015. Original Russian Text © O.I. Kiselev, A.V. Vasin, M.P. Shevyryova, E.G. Deeva, K.V. Sivak, V.V. Egorov, V.B. Tsvetkov, A.Yu. Egorov, E.A. RomanovskayaRomanko, L.A. Stepanova, A.B. Komissarov, L.M. Tsybalova, G.M. Ignatjev, 2015, published in Molekulyarnaya Biologiya, 2015, Vol. 49, No. 4, pp. 541–554. REVIEWS UDC 578.2,578.76 Ebola Hemorrhagic Fever: Properties of the Pathogen and Development of Vaccines and Chemotherapeutic Agents O. I. Kiseleva, A. V. Vasina, b, M. P. Shevyryovac, E. G. Deevaa, K. V. Sivaka, V. V. Egorova, V. B. Tsvetkova, d, A. Yu. Egorova, E. A. RomanovskayaRomankoa, L. A. Stepanovaa, A. B. Komissarova, L. M. Tsybalovaa, and G. M. Ignatjeva a Institute of Influenza, Ministry of Health of the Russian Federation, St. Petersburg, 197376 Russia; email: [email protected] b St. Petersburg State Polytechnic University, St. Petersburg, 195251 Russia c Ministry of Health of the Russian Federation, Moscow, 127994 Russia d Topchiev Institute of Petrochemical Synthesis, Moscow, 119991 Russia Received December 29, 2014; in final form, January 16, 2015 Abstract—Ebola hemorrhagic fever (EHF) epidemic currently ongoing in West Africa is not the first among numerous epidemics in the continent. Yet it seems to be the worst EHF epidemic outbreak caused by Ebola virus Zaire since 1976 as regards its extremely large scale and rapid spread in the population. Experiments to study the agent have continued for more than 20 years. The EHF virus has a relatively simple genome with seven genes and additional reading frame resulting from RNA editing. -
Rabbit Anti-Marburgvirus (MARV) VLP Pab ELISA Data
4 Research Court, Suite 300 Rockville, MD 20850 877-411-2041 [email protected] Rabbit anti-Marburgvirus (MARV) VLP pAb ELISA Data: Catalog #: 04-0005 IgG IgG + IgG + Lot #: MMIG201001IBT Dilution MMARV ZEBOV 1:X Antigen Antigen Immunogen: MARV (Musoke strain) Virus-like Particles (VLPs) containing glycoprotein (GP) 1000 3.30 2.66 Nucleoprotein (NP), and viral protein (VP40). 3162 3.07 1.80 10000 2.68 0.89 Description: Protein A purified rabbit polyclonal 31623 1.87 0.37 antibody reactive to MARV VLP raised in New 100000 0.99 0.14 Zealand white rabbits. 316228 0.43 0.05 1000000 0.17 0.02 Supplied: 0.5 mg of antibody is supplied in PBS at a concentration of 5.75 mg/mL. 0.01% Sodium azide has been added. -Antigen is coated on ELISA plates overnight. -Add 200µl blocking buffer then wash wells with Clonality: Polyclonal PBST. -Antiserum is diluted semi-log. Relevance: the filovirus Marburgvirus is a -Incubate antibody for 2 hour. Category A (NIAID) and HHS select agent. -Wash unbound antibodies and add HRP- Recommended Dilutions: conjugated anti-rabbit IgG. -Wash plates and add substrate to develop color for ELISA: Assay-dependent dilution. 20 minutes. WB: Assay-dependent dilution -Read absorbance at 650nm. Amount of color is directly proportional to amount of antibodies. Storage: 2-3 weeks +4oC, -20◦C long term Western Blot Cross Reactivity: Historical data showed some cross-reactivity with Ebola Virus (EBOV) and -Antiserum recognizes Marburg musoke Sudan Virus (SUDV) VLP’s, most likely due to glycoprotein, nucleoprotein, and VP40 antibodies against Baculovirus proteins since the VLP’s were expressed in SF9-Baculovirus system. -
Refreshing the Biologic Pipeline 2020
news feature Credit: Science Lab / Alamy Stock Photo Refreshing the biologic pipeline 2020 In the absence of face-to-face meetings, FDA and industry implemented regulatory workarounds to maintain drug and biologics approvals. These could be here to stay. John Hodgson OVID-19 might have been expected since 1996) — a small miracle in itself “COVID-19 confronted us with the need to severely impair drug approvals (Fig. 1 and Table 1). to better triage sponsors’ questions,” says Cin 2020. In the event, however, To the usual crop of rare disease and Peter Marks, the director of the Center for industry and regulators delivered a small genetic-niche cancer treatments, 2020 Biologics Evaluation and Research (CBER) miracle. They found workarounds and also added a chimeric antigen receptor at the FDA. “That was perhaps the single surrogate methods of engagement. Starting (CAR)-T cell therapy with a cleaner biggest takeaway from the pandemic related in January 2020, when the outbreak veered manufacturing process and the first to product applications.” Marks says that it westward, the number of face-to face approved blockbuster indication for a became very apparent with some COVID- meetings declined rapidly; by March, small-interfering RNA (siRNA) — the 19-related files that resolving a single they were replaced by Webex and Teams. European Medicines Agency’s (EMA) issue can help a sponsor enormously and (Secure Zoom meeting are to be added registration of the RNA interference accelerate the development cycle. Before this year.) And remarkably, by 31 December, (RNAi) therapy Leqvio (inclisiran) for COVID-19, it was conceivable that a small the US Food and Drug Administration cardiovascular disease. -
Atoltivimab, Maftivimab, and Odesivimab
PATIENT & CAREGIVER EDUCATION Atoltivimab, Maftivimab, and Odesivimab This information from Lexicomp® explains what you need to know about this medication, including what it’s used for, how to take it, its side effects, and when to call your healthcare provider. What is this drug used for? It is used to treat infections caused by Ebolavirus. What do I need to tell my doctor BEFORE I take this drug? If you are allergic to this drug; any part of this drug; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had. If you are breast-feeding. Do not breast-feed while you take this drug. This drug may interact with other drugs or health problems. Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor. Atoltivimab, Maftivimab, and Odesivimab 1/5 What are some things I need to know or do while I take this drug? Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists. Talk with your doctor before getting any vaccines. Use of some vaccines with this drug may either raise the chance of an infection or make the vaccine not work as well. Tell your doctor if you are pregnant or plan on getting pregnant. -
October 2020
PharmNOTES Summary about new FDA-approved products, new indications, first-time generics, and WHAT IS IN THE PIPELINE. From: OCTOBER 2020 Date: 11/06/2020 ©2020 PharmPix. All rights reserved Table of Contents Page News 3 New FDA Approved Products 4-5 Inmazeb™ (atoltivimab, maftivimab, and odesivimab-ebgn) 4 Veklury™ (remdesivir) 5 New FDA Approved Formulations, Dosage Forms, Combination Products and Other Differences 6 New FDA Approved Indications 7 New First-Time Generic Drug Approval 8 Pipeline 9 References 10 2 NEWS ……………………………………………………………………………………………………………... Drug issue Date Details Avoid Use of NSAIDs in 10/15/2020 The FDA issued a warning to avoid the use of Non-steroidal Anti-inflammatory Drugs (NSAIDs) during pregnancy at 20 weeks or Pregnancy at 20 Weeks later. The use of NSAIDs around 20 weeks or later in pregnancy may cause serious kidney problems in the fetus, low levels of or Later amniotic fluids, and other complications. Previously NSAIDs labels warned to avoid use during the last three (3) months of pregnancy due to the risk of premature closure of the fetal ductus arteriosus. The FDA now requires changes in the prescribing information for both prescription and over the counter (OTC) NSAIDs. Recommendations for healthcare professionals: • Advise pregnant women to avoid the use of NSAIDs at 20 weeks of pregnancy or later. • If NSAIDs are necessary during 20 to 30 weeks of pregnancy, limit treatment to the lowest dose possible and for the shortest duration. Consider ultrasound monitoring of amniotic fluid if treatment extends over 48 hours. If low levels of amniotic fluid are identified, discontinue the NSAID. -
To Ebola Reston
WHO/HSE/EPR/2009.2 WHO experts consultation on Ebola Reston pathogenicity in humans Geneva, Switzerland 1 April 2009 EPIDEMIC AND PANDEMIC ALERT AND RESPONSE WHO experts consultation on Ebola Reston pathogenicity in humans Geneva, Switzerland 1 April 2009 © World Health Organization 2009 All rights reserved. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distin- guished by initial capital letters. All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either express or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. This publication contains the collective views of an international group of experts and does not necessarily represent the decisions or the policies of the World Health Organization. -
How Severe and Prevalent Are Ebola and Marburg Viruses?
Nyakarahuka et al. BMC Infectious Diseases (2016) 16:708 DOI 10.1186/s12879-016-2045-6 RESEARCHARTICLE Open Access How severe and prevalent are Ebola and Marburg viruses? A systematic review and meta-analysis of the case fatality rates and seroprevalence Luke Nyakarahuka1,2,5* , Clovice Kankya2, Randi Krontveit3, Benjamin Mayer4, Frank N. Mwiine2, Julius Lutwama5 and Eystein Skjerve1 Abstract Background: Ebola and Marburg virus diseases are said to occur at a low prevalence, but are very severe diseases with high lethalities. The fatality rates reported in different outbreaks ranged from 24–100%. In addition, sero-surveys conducted have shown different seropositivity for both Ebola and Marburg viruses. We aimed to use a meta-analysis approach to estimate the case fatality and seroprevalence rates of these filoviruses, providing vital information for epidemic response and preparedness in countries affected by these diseases. Methods: Published literature was retrieved through a search of databases. Articles were included if they reported number of deaths, cases, and seropositivity. We further cross-referenced with ministries of health, WHO and CDC databases. The effect size was proportion represented by case fatality rate (CFR) and seroprevalence. Analysis was done using the metaprop command in STATA. Results: The weighted average CFR of Ebola virus disease was estimated to be 65.0% [95% CI (54.0–76.0%), I2 = 97.98%] whereas that of Marburg virus disease was 53.8% (26.5–80.0%, I2 = 88.6%). The overall seroprevalence of Ebola virus was 8.0% (5.0%–11.0%, I2 = 98.7%), whereas that for Marburg virus was 1.2% (0.5–2.0%, I2 = 94.8%). -
A Short Overview of Ebola Virus Disease
Short Communication Journal of Volume 6:4, 2021 DOI: 10.37421/jidm.2021.6.173 Infectious Diseases and Medicine A Short Overview of Ebola Virus Disease Akshay Thiwari* Department of Virology, University of Hyderabad, Hyderabad, Telangana, India Ebola [1] is an uncommon but lethal virus that causes fever, body Treatment for Ebola aches, diarrhea, and, in some cases, internal and external bleeding. The Ebola has no known cure, though researchers are working on one. For immune system and organs are harmed as the virus spreads through the the treatment of Ebola [2], two drug therapies have been authorized. Inmazeb body. As a result, the number of blood-clotting cells decreases. As a is a compound that consists of three monoclonal antibodies (atoltivimab, consequence, there is a lot of uncontrollable bleeding. Ebola hemorrhagic maftivimab, and odesivimab-ebgn). Ebanga (ansuvimab-zykl) is a monoclonal fever was the previous name for the outbreak, but it is now known as Ebola antibody that is given as an injection. It aids in stopping the virus from reaching virus. It kills up to 90% of those who become infected. the cell receptor. Doctors treat Ebola symptoms [3] with the following How does one contract Ebola? medication. Ebola isn't as infectious as viruses like the common cold, influenza, or Electrolytes and fluids, Oxygen (O2), Medication for high blood pressure, measles. Contact with the skin or bodily fluids of an infected animal, such as Transfusions of blood, and other diseases'. a monkey, chimp, or fruit bat, transmits the disease to humans. Then it Facts on Ebola passes from one person to the next in the same manner. -
Development of an Antibody Cocktail for Treatment of Sudan Virus Infection
Development of an antibody cocktail for treatment of Sudan virus infection Andrew S. Herberta,b, Jeffery W. Froudea,1, Ramon A. Ortiza, Ana I. Kuehnea, Danielle E. Doroskya, Russell R. Bakkena, Samantha E. Zaka,b, Nicole M. Josleyna,b, Konstantin Musiychukc, R. Mark Jonesc, Brian Greenc, Stephen J. Streatfieldc, Anna Z. Wecd,2, Natasha Bohorovae, Ognian Bohorove, Do H. Kime, Michael H. Paulye, Jesus Velascoe, Kevin J. Whaleye, Spencer W. Stoniera,b,3, Zachary A. Bornholdte, Kartik Chandrand, Larry Zeitline, Darryl Sampeyf, Vidadi Yusibovc,4, and John M. Dyea,5 aVirology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702; bThe Geneva Foundation, Tacoma, WA 98402; cFraunhofer USA Center for Molecular Biotechnology, Newark, DE 19711; dDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461; eMapp Biopharmaceutical, Inc., San Diego, CA 92121; and fBioFactura, Inc., Frederick, MD 21701 Edited by Y. Kawaoka, University of Wisconsin–Madison/University of Tokyo, Madison, WI, and approved December 30, 2019 (received for review August 28, 2019) Antibody-based therapies are a promising treatment option for antibody-based immunotherapies. Subsequently, several indepen- managing ebolavirus infections. Several Ebola virus (EBOV)-specific dent groups reported the postexposure efficacy of monoclonal and, more recently, pan-ebolavirus antibody cocktails have been antibody (mAb)-based immunotherapies against EVD in ma- described. Here, we report the development and assessment of a caques when administered as mixtures of two or more mAbs (14–17). Sudan virus (SUDV)-specific antibody cocktail. We produced a panel These landmark studies demonstrated that combination mAb- of SUDV glycoprotein (GP)-specific human chimeric monoclonal based immunotherapies are a viable treatment option for EVD antibodies (mAbs) using both plant and mammalian expression and spurred therapeutic antibody development for filoviruses. -
Antibodies to Watch in 2021 Hélène Kaplona and Janice M
MABS 2021, VOL. 13, NO. 1, e1860476 (34 pages) https://doi.org/10.1080/19420862.2020.1860476 PERSPECTIVE Antibodies to watch in 2021 Hélène Kaplona and Janice M. Reichert b aInstitut De Recherches Internationales Servier, Translational Medicine Department, Suresnes, France; bThe Antibody Society, Inc., Framingham, MA, USA ABSTRACT ARTICLE HISTORY In this 12th annual installment of the Antibodies to Watch article series, we discuss key events in antibody Received 1 December 2020 therapeutics development that occurred in 2020 and forecast events that might occur in 2021. The Accepted 1 December 2020 coronavirus disease 2019 (COVID-19) pandemic posed an array of challenges and opportunities to the KEYWORDS healthcare system in 2020, and it will continue to do so in 2021. Remarkably, by late November 2020, two Antibody therapeutics; anti-SARS-CoV antibody products, bamlanivimab and the casirivimab and imdevimab cocktail, were cancer; COVID-19; Food and authorized for emergency use by the US Food and Drug Administration (FDA) and the repurposed Drug Administration; antibodies levilimab and itolizumab had been registered for emergency use as treatments for COVID-19 European Medicines Agency; in Russia and India, respectively. Despite the pandemic, 10 antibody therapeutics had been granted the immune-mediated disorders; first approval in the US or EU in 2020, as of November, and 2 more (tanezumab and margetuximab) may Sars-CoV-2 be granted approvals in December 2020.* In addition, prolgolimab and olokizumab had been granted first approvals in Russia and cetuximab saratolacan sodium was first approved in Japan. The number of approvals in 2021 may set a record, as marketing applications for 16 investigational antibody therapeutics are already undergoing regulatory review by either the FDA or the European Medicines Agency. -
Understanding Ebola
Understanding Ebola With the arrival of Ebola in the United States, it's very easy to develop fears that the outbreak that has occurred in Africa will suddenly take shape in your state and local community. It's important to remember that unless you come in direct contact with someone who is infected with the disease, you and your family will remain safe. State and government agencies have been making preparations to address isolated cases of infection and stop the spread of the disease as soon as it has been positively identified. Every day, the Centers of Disease Control and Prevention (CDC) is monitoring developments, testing for suspected cases and safeguarding our lives with updates on events and the distribution of educational resources. Learning more about Ebola and understanding how it's contracted and spread will help you put aside irrational concerns and control any fears you might have about Ebola severely impacting your life. Use the resources below to help keep yourself calm and focused during this unfortunate time. Ebola Hemorrhagic Fever Ebola hemorrhagic fever (Ebola HF) is one of numerous Viral Hemorrhagic Fevers. It is a severe, often fatal disease in humans and nonhuman primates (such as monkeys, gorillas, and chimpanzees). Ebola HF is caused by infection with a virus of the family Filoviridae, genus Ebolavirus. When infection occurs, symptoms usually begin abruptly. The first Ebolavirus species was discovered in 1976 in what is now the Democratic Republic of the Congo near the Ebola River. Since then, outbreaks have appeared sporadically. There are five identified subspecies of Ebolavirus.