Hhps [email protected]

ECFS2021

P-042

Alastair Reid Alastair Children’s Royal years and above. and years

ClinicalTrials.gov

people with CF aged 12 12 aged CF with people – study the of phase NCT04602468 NCT04602468

Damian Downey Damian City Belfast We present the baseline data from the first first the from data baseline the present We

CONTACT INFORMATION CONTACT

Elnazir Basil Tallaght CHI

Paul McNally Paul Therapies/ClinicalTrials Biology/Physiology/New Cell - 2 CT. controlled spirometry and LCI for sites core

the ECFS Clinical Trials Network, including the the including Network, Trials Clinical ECFS the Michael Williamson Michael St Temple CHI

oxide metabolism. RECOVER is supported by by supported is RECOVER metabolism. oxide

Des Cox Des Crumlin CHI disease markers, nasal inflammation and nitric nitric and inflammation nasal markers, disease

adherence, GI symptoms and inflammation, liver liver inflammation, and symptoms GI adherence,

Jane Davies Jane Brompton Royal

Ireland and the CF Trust. Supported by ECFS by Supported Trust. CF the and Ireland CTN. - spirometry controlled CT scores, treatment treatment scores, CT controlled spirometry

for RECOVER is from the Cystic Fibrosis Foundation, CF CF Foundation, Fibrosis Cystic the from is RECOVER for

endpoints include lung clearance index (LCI), (LCI), index clearance lung include endpoints

Linnane Barry Limerick UH

study team, collaborators and staff at our clinical sites. Funding Funding sites. clinical our at staff and collaborators team, study

collected as part of normal care, key RECOVER RECOVER key care, normal of part as collected

their time, dedication and enthusiasm, the whole RECOVER RECOVER whole the enthusiasm, and dedication time, their

11. In addition to routine data data routine to addition In 11. - 6 and 12+ McKone Ed UH Vincent’s St

We want to thank all of our study participants and parents for for parents and participants study our of all thank to want We

conducted in 2 phases in line with ETI approval: approval: ETI with line in phases 2 in conducted

adults prescribed ETI. The study will be be will study The ETI. prescribed adults

ACKNOWLEDGEMENTS RECOVER SITES RECOVER AKNOWLEDGEMENTS RECOVER COLLABORATORS RECOVER

will examine important outcomes in children and and children in outcomes important examine will

clinical sites in Ireland and the UK over 2 years, years, 2 over UK the and Ireland in sites clinical

examining the impact of ETI, and conducted in 8 8 in conducted and ETI, of impact the examining

approval study study approval - post centre - multi a RECOVER,

11 year old group. old year 11 - 6 the to children

achievable from the data. data. the from achievable

active planning is underway for the recruitment of of recruitment the for underway is planning active

sputum sample collection. sample sputum seeks to broaden the scope and reach of the research insights insights research the of reach and scope the broaden to seeks METHODS

Data collection is ongoing for the 12+ cohort and and cohort 12+ the for ongoing is collection Data

The main impact on data collection was in the area of of area the in was collection data on impact main The Banking of biological samples (blood, sputum, stool, nasal lavage) lavage) nasal stool, sputum, (blood, samples biological of Banking

challenges acceptable levels of recruitment were seen. seen. were recruitment of levels acceptable challenges based around annual assessment and quarterly clinic attendance. attendance. clinic quarterly and assessment annual around based Study Progress Study

and collection of samples and test results. Despite these these Despite results. test and samples of collection and comprehensive array of outcome measures on each study participant participant study each on measures outcome of array comprehensive

aerosol generating procedures impacted on recruitment recruitment on impacted procedures generating aerosol The sampling schedule of RECOVER is designed to collect a a collect to designed is RECOVER of schedule sampling The combination CFTR modulator. CFTR combination

Enforced limitations on CF centre attendances and and attendances centre CF on limitations Enforced as the vast majority moved to ETI from a dual dual a from ETI to moved majority vast the as

setting. RECOVER Design RECOVER

ethics committees for COVID19 related projects. projects. related COVID19 for committees ethics from lower sweat chloride levels in the FF group group FF the in levels chloride sweat lower from

and health of people with CF in a real world world real a in CF with people of health and

increased priority given by clinical sites, universities and and universities sites, clinical by given priority increased

X X X Use Antibiotic participants reveals no significant differences apart apart differences significant no reveals participants

understanding of the impact of ETI in the lives lives the in ETI of impact the of understanding

X Caps Reading Caps MEMS foreshortened, and made more complex given the the given complex more made and foreshortened,

Baseline data from the currently recruited recruited currently the from data Baseline

The Aim of RECOVER is to develop a deeper deeper a develop to is RECOVER of Aim The

X X X X X X X X X Questionnaire Adherence

Europe meant that the study setup period was was period setup study the that meant Europe

X X X Pharmacy Records MPR Records Pharmacy Baseline Data Baseline

challenges to the study. Accelerated approval for ETI in in ETI for approval Accelerated study. the to challenges

X X X X R - CFQ

AIM

19 pandemic introduced a number of of number a introduced pandemic 19 - COVID The

X X X X X X Abdominal Symptom Score Symptom Abdominal = Fraction of exhaled nitric oxide. nitric exhaled of Fraction = FeNo FEV1, predicted

for F508del/minimum function mutation, ppFEV1 = percent percent = ppFEV1 mutation, function F508del/minimum for X X Blood Collection Blood

Study Challenges Study

FF = homozygous for the F508del mutation, MF = heterozygous heterozygous = MF mutation, F508del the for homozygous = FF X X X X Stool Collection Stool

Table 1: Baseline characteristics of recruited participants. participants. recruited of characteristics Baseline 1: Table

X X X Liver Examination Liver

Height z score (SE) score z Height X X X X Sputum Collection Sputum 0.96 0.11(0.13) - 0.1(0.14) - PWCF is presented. is PWCF

X X X Liver Ultrasound Liver

Weight z score (SE) score z Weight 0.68 0.03(0.10) 0.1(0.11) reasons and pregnancy in one subject. Data on 107 107 on Data subject. one in pregnancy and reasons

X X X X X X Liver Function Testing Function Liver

August 2020 during a global pandemic. pandemic. global a during 2020 August BMI z score (SE) score z BMI

0.64 0.06(0.12) 0.14(0.10)

clinical reasons, discontinuation of ETI for medical medical for ETI of discontinuation reasons, clinical

X X X

FeNO

approved by EMA sooner than expected in in expected than sooner EMA by approved (SE) FeNO 0.49 12.97(1.7) 14.47(1.3)

removal of study consent, amended ETI dosage for for dosage ETI amended consent, study of removal

X X X

Nasal Lavage Nasal

LCI (SE) LCI Ivacaftor (ETI) was was (ETI) Ivacaftor - Tezacaftor - Elexacaftor 0.46 12.76(0.8) 11.96(0.71)

withdrawals. The reason for withdrawals included included withdrawals for reason The withdrawals.

X X X X X X X X X Airway Sampling (Micro) Sampling Airway

ppFEV1 (SE) ppFEV1

0.94 83.2(2.7) 82.9(1.9) modulators, but can be complex undertakings. undertakings. complex be can but modulators,

have been recruited to the study to date with 6 6 with date to study the to recruited been have

X X X X X X X X X FEV1

Sweat Chloride (SE) Chloride Sweat 0.003 91.94(3.5) 77.7(2.4)

impact of new treatments, including CFTR CFTR including treatments, new of impact

X X X X X X X X X Height / Weight / BMI / Weight / Height

Presented PWCF 113 2020. October in commenced Recruitment

Female (%) Female 0.77 18(48.6) 32(45.7)

significantly to the evidence surrounding the the surrounding evidence the to significantly X X X controlled CT controlled - Spirometry

Age (SD) Age 0.99 19.24(1.9) 19.26(1.1)

Recruitment X X X X X LCI Real world, post approval studies contribute contribute studies approval post world, Real

Recruitment (n) Recruitment

NA 37 70

X X X X Sweat Chloride Sweat

at:

p value p MF FF Group 18 15 12 9 6 3 2 1 0 24 21 Month

INTRODUCTION

RESULTS

VISIT SCHEDULE VISIT

The Royal Brompton Hospital, London, United Kingdom, United London, Hospital, Brompton Royal The Canada, Toronto, Toronto, of University Canada, Toronto, (SickKids), Children Sick Imperial College London, London, United Kingdom United London, London, College Imperial

21 20 22

MHB Theodor Fontane, Brandenburg, Germany, Brandenburg, Fontane, Theodor MHB States, United Miami, Hospital, Children's Nicklaus States, United Miami, The Hospital for for Hospital The Netherlands, Rotterdam, MC, Erasmus Germany, Potsdam, , Westbrandenburg Klinikum

16 15 19 18 17

Royal Belfast Hospital for Sick Children, Belfast, United Kingdom, United Belfast, Children, Sick for Hospital Belfast Royal Kingdom, United Belfast, Trust, Care Social and Health Belfast Kingdom, United Belfast, University of Miami, Miami, of University Ireland, Dublin, Ireland, of Registry Fibrosis Cystic

12 11 14 13

Children's Health Ireland at Temple Street, Dublin, Ireland, Dublin, Street, Temple at Ireland Health Children's Ireland, Limerick, Limerick, Hospital University Ireland, Belfast City Hospital, Hospital, City Belfast Ireland, Dublin, Dublin, College Trinity Ireland, Dublin, Tallaght, at Ireland Health Children's

7 6 10 9 8

Children's Health Ireland at Crumlin, Dublin 12, Ireland, 12, Dublin Crumlin, at Ireland Health Children's Ireland, Dublin, Ireland, Surgeons, of College Royal University of Limerick, Limerick, Limerick, Limerick, of University Ireland, Dublin, Dublin, College University Ireland, Dublin, Hospital, University Vincent's St.

2 1 5 4 3

, on behalf of the RECOVER research team and collaborators and team research RECOVER the of behalf on , Davies

22 21,

D. Downey D. , Elnazir B. , Williamson M. , Linnane B. , Cox D. , McKone E. , McNally P. J. J. , Ratjen F. , Tiddens H. , Mainz J. , Quittner A. , Bourke B. , Jackson A. , Fleming A. , Reid A. ,

9 8, 7 6 5, 4 2, 4 3, 2 1, 20 19, 18 17 16, 15 14, 4 2, 13 1 12 11, 11 10,

with Cystic Fibrosis (RECOVER) Fibrosis Cystic with Real World Clinical Outcomes with Novel Modulator Therapy Combinations in people people in Combinations Therapy Modulator Novel with Outcomes Clinical World Real