Real World Clinical Outcomes with Novel Modulator Therapy Combinations in people with Cystic Fibrosis (RECOVER) P. McNally 1, 2, E. McKone 3, 4, D. Cox 2, 4, B. Linnane 5, 6, M. Williamson 7, B. Elnazir 8, 9, D. Downey 10, 11, A. Reid 11, 12, A. Fleming 1, A. Jackson 13, B. Bourke 2, 4, A. Quittner 14, 15, J. Mainz 16, 17, H. Tiddens 18, F. Ratjen 19, 20, J. Davies 21, 22, on behalf of the RECOVER research team and collaborators 1Royal College of Surgeons, Ireland, Dublin, Ireland, 2Children's Health Ireland at Crumlin, Dublin 12, Ireland, 3St. Vincent's University Hospital, Dublin, Ireland, 4University College Dublin, Dublin, Ireland, 5University of Limerick, Limerick, Ireland, 6University Hospital Limerick, Limerick, Ireland, 7Children's Health Ireland at Temple Street, Dublin, Ireland, 8Children's Health Ireland at Tallaght, Dublin, Ireland, 9Trinity College Dublin, Dublin, Ireland, 10Belfast City Hospital, Belfast, United Kingdom, 11Belfast Health and Social Care Trust, Belfast, United Kingdom, 12Royal Belfast Hospital for Sick Children, Belfast, United Kingdom, 13Cystic Fibrosis Registry of Ireland, Dublin, Ireland, 14University of Miami, Miami, United States, 15Nicklaus Children's Hospital, Miami, United States, 16MHB Theodor Fontane, Brandenburg, Germany, 17Klinikum Westbrandenburg, Potsdam, Germany, 18Erasmus MC, Rotterdam, Netherlands, 19The Hospital for Sick Children (SickKids), Toronto, Canada, 20University of Toronto, Toronto, Canada, 21The Royal Brompton Hospital, London, United Kingdom, 22Imperial College London, London, United Kingdom INTRODUCTION RESULTS VISIT SCHEDULE Month 0 1 2 3 6 9 12 15 18 21 24 Group FF MF p value Sweat Chloride X X X X Recruitment (n) 70 37 NA at: Real world, post approval studies contribute Recruitment LCI X X X X X Age (SD) 19.26(1.1) 19.24(1.9) 0.99 significantly to the evidence surrounding the Spirometry-controlled CT X X X Female (%) 32(45.7) 18(48.6) 0.77 Recruitment commenced in October 2020. 113 PWCF Height / Weight / BMI X X X X X X X X X Presented impact of new treatments, including CFTR Sweat Chloride (SE) 77.7(2.4) 91.94(3.5) 0.003 have been recruited to the study to date with 6 FEV1 X X X X X X X X X modulators, but can be complex undertakings. ppFEV1 (SE) 82.9(1.9) 83.2(2.7) 0.94 withdrawals. The reason for withdrawals included Airway Sampling (Micro) X X X X X X X X X Elexacaftor-Tezacaftor-Ivacaftor (ETI) was LCI (SE) 11.96(0.71) 12.76(0.8) 0.46 removal of study consent, amended ETI dosage for Nasal Lavage X X X approved by EMA sooner than expected in FeNO (SE) 14.47(1.3) 12.97(1.7) 0.49 clinical reasons, discontinuation of ETI for medical FeNO X X X August 2020 during a global pandemic. Liver Function Testing X X X X X X BMI z score (SE) 0.14(0.10) 0.06(0.12) 0.64 reasons and pregnancy in one subject. Data on 107 Liver Ultrasound X X X Weight z score (SE) 0.1(0.11) 0.03(0.10) 0.68 PWCF is presented. Sputum Collection X X X X Height z score (SE) -0.1(0.14) -0.11(0.13) 0.96 Liver Examination X X X Table 1: Baseline characteristics of recruited participants. Stool Collection X X X X Study Challenges FF = homozygous for the F508del mutation, MF = heterozygous Blood Collection X X for F508del/minimum function mutation, ppFEV1 = percent AIM The COVID-19 pandemic introduced a number of Abdominal Symptom Score X X X X X X predicted FEV1, FeNo = Fraction of exhaled nitric oxide. challenges to the study. Accelerated approval for ETI in CFQ-R X X X X Pharmacy Records MPR X X X Baseline Data Europe meant that the study setup period was The Aim of RECOVER is to develop a deeper Adherence Questionnaire X X X X X X X X X foreshortened, and made more complex given the Baseline data from the currently recruited understanding of the impact of ETI in the lives MEMS Caps Reading X increased priority given by clinical sites, universities and Antibiotic Use X X X participants reveals no significant differences apart and health of people with CF in a real world ethics committees for COVID19 related projects. from lower sweat chloride levels in the FF group setting. RECOVER Design Enforced limitations on CF centre attendances and as the vast majority moved to ETI from a dual aerosol generating procedures impacted on recruitment The sampling schedule of RECOVER is designed to collect a combination CFTR modulator. and collection of samples and test results. Despite these comprehensive array of outcome measures on each study participant challenges acceptable levels of recruitment were seen. based around annual assessment and quarterly clinic attendance. Study Progress METHODS The main impact on data collection was in the area of Banking of biological samples (blood, sputum, stool, nasal lavage) Data collection is ongoing for the 12+ cohort and sputum sample collection. seeks to broaden the scope and reach of the research insights active planning is underway for the recruitment of achievable from the data. children to the 6-11 year old group. RECOVER, a multi-centre post-approval study examining the impact of ETI, and conducted in 8 clinical sites in Ireland and the UK over 2 years, will examine important outcomes in children and RECOVER SITES RECOVER COLLABORATORS ACKNOWLEDGEMENTSAKNOWLEDGEMENTS adults prescribed ETI. The study will be conducted in 2 phases in line with ETI approval: St Vincent’s UH Ed McKone We want to thank all of our study participants and parents for 12+ and 6-11. In addition to routine data their time, dedication and enthusiasm, the whole RECOVER collected as part of normal care, key RECOVER UH Limerick Barry Linnane study team, collaborators and staff at our clinical sites. Funding endpoints include lung clearance index (LCI), for RECOVER is from the Cystic Fibrosis Foundation, CF spirometry controlled CT scores, treatment Royal Brompton Jane Davies Ireland and the CF Trust. Supported by ECFS-CTN. adherence, GI symptoms and inflammation, liver disease markers, nasal inflammation and nitric CHI Crumlin Des Cox oxide metabolism. RECOVER is supported by the ECFS Clinical Trials Network, including the CHI Temple St Michael Williamson core sites for LCI and spirometry controlled CT. 2 - Cell Biology/Physiology/New Therapies/ClinicalTrials Paul McNally CHI Tallaght Basil Elnazir CONTACT INFORMATION We present the baseline data from the first Belfast City Damian Downey phase of the study – people with CF aged 12 ClinicalTrials.gov NCT04602468 years and above. Royal Children’s Alastair Reid [email protected] hhps://recovercf.ie P-042 ECFS2021.