Clinical trial NCT06478706: A Two-Part Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Repeat Doses of Inhaled ETD001 in People With Cystic Fibrosis
Official title: A Randomised, Double-Blind, Placebo Controlled, Two-Part Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Repeat Dose of Inhaled ETD001 in People With Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Enterprise Therapeutics Ltd
Sponsor class: INDUSTRY
First posted: 2024-06-27
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria:

* Male \& female ≥ 18 years of age, who fit one of the following criteria:

Women of childbearing potential using permitted contraception a minimum of 28 days before dosing until completion of the final follow up visit; Women of non-childbearing potential; Men using contraception from the time of the first dose, until completion of the final follow up visit;

* Confirmed diagnosis of CF
* FEV1 ≥ 40% and ≤ 90% of predicted normal for age, gender, and height
* Able to reproducibly perform spirometry manoeuvres
* Clinically stable CF lung disease
* Routine CF therapy has not changed within 28 days prior to screening.
* Provided written informed consent.
* Body mass index (BMI) \> 16 and \< 30 kg/m2

Exclusion Criteria:

* Abnormal liver function
* Abnormal renal function
* History of solid organ transplant
* Chest x-ray within the past 12 months with abnormalities suggesting unstable pulmonary disease other than CF
* Received CFTR modulator therapy in the 60 days before screening
* Changes in bronchodilator, corticosteroid or other anti-inflammatory medications 14 days before screening
* Unable to withhold use of long-acting bronchodilators 24 hours or short-acting bronchodilators 6 hours before spirometry assessments
* Unable to withhold use of anti-cholinergics within 24 hours of spirometry
* Started dornase alfa, hypertonic saline, or other airway clearing therapy less than 28 days before screening
* Using inhaled antibiotics for less than 2 complete cycles and unable to complete the entire study during the off or on cycle.
* Changes in inhaled or oral antibiotic use within 14 days of screening
* Taking oral corticosteroids in excess of 10 mg/day or 20 mg every other day within 14 days of screening
* Use of diuretics, or renin-angiotensin aldosterone system antihypertensive drugs , drospirenone, or trimethoprim in the 28 days before screening
* Presence of co-morbidities and medical history in the opinion of the investigator, may pose additional risk by participating in the study, or may confound the results of the study

Primary outcomes:
measure: Part A: Safety and tolerability of repeat inhaled doses of ETD001 monitored by assessment of adverse events
timeFrame: 28 days
measure: Part B: Effect of repeat inhaled doses of ETD001 on percent predicted forced expiratory volume in 1 second (ppFEV1)
timeFrame: 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 outcomes:
measure: Part A: Characterisation of plasma pharmacokinetics (PK)
timeFrame: Day 1 (pre-dose, 0.25, 0.5, 1, 2, 4 & 6 hours)
measure: Part A: Characterisation of plasma pharmacokinetics (PK)
timeFrame: Day 1 (pre-dose, 0.25, 0.5, 1, 2, 4 & 6 hours, Day 7 (pre-dose), Day 28 (single sample)
measure: Part A: Characterisation of plasma pharmacokinetics (PK)
timeFrame: Day 1 (pre-dose, 0.25, 0.5, 1, 2, 4 & 6 hours, Day 7 (pre-dose)
measure: Part A: Characterisation of plasma pharmacokinetics (PK)
timeFrame: Day 1 (pre-dose, 0.25, 0.5, 1, 2, 4 & 6 hours, Day 7 (pre-dose) Day 28 (single sample)
measure: Part A: Characterisation of plasma pharmacokinetics (PK)
timeFrame: Day 1 (pre-dose, 0.25, 0.5, 1, 2, 4 & 6 hours, Day 7 (pre-dose), Day 28 (single sample)
measure: Part A: Characterisation of urine PK
timeFrame: Day 1 (0 - 6 hours)
measure: Part A: Characterisation of urine PK
timeFrame: Day 1 (0 - 6 hours)
measure: Part A: Characterisation of urine PK
timeFrame: Day 1 (0 - 6 hours)
measure: Part B: Effect of repeat inhaled doses of ETD001 on other lung function assessments
timeFrame: 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)
measure: Part B: Safety and tolerability of repeat inhaled doses of ETD001 monitored by assessment of adverse events
timeFrame: 105 days
measure: Part B: Effect of repeat inhaled doses of ETD001 on the quality of life questionnaire, the Cystic Fibrosis Questionnaire (revised) (CFQ-R)
timeFrame: Treatment Period 1 & 2; Day 1 & Day 28 (pre-dose)
measure: Part B: Characterisation of plasma PK
timeFrame: 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
measure: Part B: Characterisation of plasma PK
timeFrame: 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
measure: Part B: Characterisation of plasma PK
timeFrame: 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
measure: Part B: Characterisation of plasma PK
timeFrame: 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
measure: Part B: Characterisation of plasma PK
timeFrame: 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
Other outcomes:
Locations:
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Montpellier
country: France
facility: CHU de Montpellier
city: Paris
country: France
facility: Hôpital Cochin
city: Toulouse
country: France
facility: Hôpitaux de Toulouse
city: Berlin
country: Germany
facility: Charité Universtaetsmedizin
city: Cologne
country: Germany
facility: CF-Studienzentrum Universitätsklinikum Köln
city: Essen
country: Germany
facility: Westdeutsches Lungenzentrum am Universitätsklinikum
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Frankfurt
country: Germany
facility: IKF Pneumologie
city: Munich
country: Germany
facility: LMU Kinikum
city: Florence
country: Italy
facility: Azienda Ospedaliera Universitaria Meyer
city: Genova
country: Italy
facility: IRCCS Istituto Giannina Gaslini
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda- Ospedale Maggiore Policlinico
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona
city: Belfast
country: United Kingdom
facility: Belfast Health and Social Care Trust
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital
city: Cardiff
country: United Kingdom
facility: All Wales Adult CF Centre
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital West of Scotland CF Service
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Enterprise Therapeutics
name: Renu Gupta, MD
role: STUDY_DIRECTOR
References: