A Two-Part Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Repeat Doses of Inhaled ETD001 in People With Cystic Fibrosis
NCT Number: NCT06478706
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Cystic Fibrosis
Interventions: DRUG: ETD001|DRUG: Placebo
Sponsor: Enterprise Therapeutics Ltd
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 40
Study Design: Allocation: RANDOMIZED|Intervention Model: CROSSOVER|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-06-26
Completion Date: 2025-07-29
Locations: Hospices Civils de Lyon, Lyon, 69495, France|CHU de Montpellier, Montpellier, 34295, France|Hôpital Cochin, Paris, 75014, France|Hôpitaux de Toulouse, Toulouse, 31059, France|Charité Universtaetsmedizin, Berlin, 13353, Germany|CF-Studienzentrum Universitätsklinikum Köln, Cologne, 50924, Germany|Westdeutsches Lungenzentrum am Universitätsklinikum, Essen, 45239, Germany|Universitätsklinikum Frankfurt, Frankfurt, 60590, Germany|IKF Pneumologie, Frankfurt, 60596, Germany|LMU Kinikum, Munich, 80336, Germany|Belfast Health and Social Care Trust, Belfast, BT9 7AB, United Kingdom|Royal Papworth Hospital, Cambridge, CB2 0AY, United Kingdom|All Wales Adult CF Centre, Cardiff, CF64 2XX, United Kingdom|Queen Elizabeth University Hospital West of Scotland CF Service, Glasgow, G51 4TR, United Kingdom|Royal Brompton Hospital, London, SW3 6LL, United Kingdom|Southampton General Hospital, Southampton, SO16 6YD, United Kingdom

Summary:
This study is the first to give ETD001 to people with CF. The study will be run in two parts. Part A will assess if ETD001 is safe to give to people with CF, and Part B will assess if ETD001 improves lung function. The study drug is taken twice a day, in Part A it is taken for 7 days and in Part B for 28 days. In Part B there will be a separate period where dummy medicine is given for 28 days so the treatments can be compared.

In Part A participants will receive 13 doses of either ETD001 or placebo, 8 people will take part. Participants will take up to 56 days to finish the study and make 5 outpatient visits.

In Part B participants will receive 55 doses of ETD001 and 55 doses of placebo, 32 people will take part. Participants will take up to 140 days to finish the study and will make 8 outpatient visits.

Study assessments include physical examinations, vital signs, heart traces, blood/urine samples, breathing tests and health questionnaires.

Primary Outcome Measures: Part A: Safety and tolerability of repeat inhaled doses of ETD001 monitored by assessment of adverse events, Incidence of treatment emergent adverse events(AE)/serious AE), withdrawals due to AE, 28 days|Part B: Effect of repeat inhaled doses of ETD001 on percent predicted forced expiratory volume in 1 second (ppFEV1), Change in ppFEV1 measured by spirometry from baseline to Day 28 (for either Treatment Period 1 or Treatment Period 2), compared to placebo, Treatment Period 1 & 2 - Day 1 (pre-dose, 1, 2 & 4 hours post dose), Day 14 (pre-dose, 1 & 2 hours post), Day 28 (at 0, 1, 2 & 4 hours post dose)
Secondary Outcome Measures: Part A: Characterisation of plasma pharmacokinetics (PK), Peak plasma concentration and time observed (Cmax \& Tmax) of ETD001 following dosing., Day 1 (pre-dose, 0.25, 0.5, 1, 2, 4 & 6 hours)|Part A: Characterisation of plasma pharmacokinetics (PK), Area under the concentration versus time curve from time 0 to last quantifiable concentration (AUC(0-t)) of ETD001 following dosing., Day 1 (pre-dose, 0.25, 0.5, 1, 2, 4 & 6 hours, Day 7 (pre-dose), Day 28 (single sample)|Part A: Characterisation of plasma pharmacokinetics (PK), Area under the concentration versus time curve within a dosing interval (AUC(0-tau)) of ETD001 following dosing., Day 1 (pre-dose, 0.25, 0.5, 1, 2, 4 & 6 hours, Day 7 (pre-dose)|Part A: Characterisation of plasma pharmacokinetics (PK), Area under the concentration versus time curve from time 0 to infinity (AUC(inf)) of ETD001 following dosing., Day 1 (pre-dose, 0.25, 0.5, 1, 2, 4 & 6 hours, Day 7 (pre-dose) Day 28 (single sample)|Part A: Characterisation of plasma pharmacokinetics (PK), Apparent terminal rate constant and apparent terminal half life (λz, T1/2) of ETD001 following dosing., Day 1 (pre-dose, 0.25, 0.5, 1, 2, 4 & 6 hours, Day 7 (pre-dose), Day 28 (single sample)|Part A: Characterisation of urine PK, Amount ETD001 excreted in urine (Ae), Day 1 (0 - 6 hours)|Part A: Characterisation of urine PK, Fraction of ETD001 dose excreted (Fe), Day 1 (0 - 6 hours)|Part A: Characterisation of urine PK, Renal clearance of ETD001 (CLr), Day 1 (0 - 6 hours)|Part B: Effect of repeat inhaled doses of ETD001 on other lung function assessments, Relative change in ppFEV1, absolute change in FVC, FEV1/FVC ratio and FEF25-75 measured by spirometry, from baseline to Day 28 (for either Treatment Period 1 or Treatment Period 2), compared to placebo, Treatment Period 1 & 2; Day 1 (pre-dose, 1, 2 & 4 hours), Day 14 (pre-dose, 1 & 2 hours), Day 28 (pre-dose, 1, 2 & 4 hours)|Part B: Safety and tolerability of repeat inhaled doses of ETD001 monitored by assessment of adverse events, Incidence of treatment emergent adverse events(AE)/serious AE), withdrawals due to AE, 105 days|Part B: Effect of repeat inhaled doses of ETD001 on the quality of life questionnaire, the Cystic Fibrosis Questionnaire (revised) (CFQ-R), Change in CFQ-R (respiratory domain) from baseline to Day 28 (for either Treatment Period 1 or Treatment Period 2), compared to placebo, Treatment Period 1 & 2; Day 1 & Day 28 (pre-dose)|Part B: Characterisation of plasma PK, Population PK characteristics and model generated individual PK parameters (Cmax \& Tmax), Treatment Period 1 & 2; Day 1 (0 & 1 hour), Day 14 (0 & 2 hours), Day 28 (0 & 4 hours), Follow up (Day 105) 1 sample|Part B: Characterisation of plasma PK, Population PK characteristics and model generated individual PK parameters (AUC(0-t)), Treatment Period 1 & 2; Day 1 (0 & 1 hour), Day 14 (0 & 2 hours), Day 28 (0 & 4 hours), Follow up (Day 105) 1 sample|Part B: Characterisation of plasma PK, Population PK characteristics and model generated individual PK parameters (AUC(0-tau)), Treatment Period 1 & 2; Day 1 (0 & 1 hour), Day 14 (0 & 2 hours), Day 28 (0 & 4 hours), Follow up (Day 105) 1 sample|Part B: Characterisation of plasma PK, Population PK characteristics and model generated individual PK parameters (AUC(0-inf)), Treatment Period 1 & 2; Day 1 (0 & 1 hour), Day 14 (0 & 2 hours), Day 28 (0 & 4 hours), Follow up (Day 105) 1 sample|Part B: Characterisation of plasma PK, Population PK characteristics and model generated individual PK parameters (λz, T1/2), Treatment Period 1 & 2; Day 1 (0 & 1 hour), Day 14 (0 & 2 hours), Day 28 (0 & 4 hours), Follow up (Day 105) 1 sample