Cystic Fibrosis
Conditions
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.
Interventions
DRUGETD001
Twice daily doses
DRUGPlacebo
Twice daily doses
Sponsors
Enterprise Therapeutics Ltd
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Safety and tolerability of repeat inhaled doses of ETD001 monitored by assessment of adverse events | 28 days | Incidence of treatment emergent adverse events(AE)/serious AE), withdrawals due to AE |
| Part B: Effect of repeat inhaled doses of ETD001 on percent predicted forced expiratory volume in 1 second (ppFEV1) | 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) | Change in ppFEV1 measured by spirometry from baseline to Day 28 (for either Treatment Period 1 or Treatment Period 2), compared to placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Effect of repeat inhaled doses of ETD001 on other lung function assessments | 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) | 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 |
| Part B: Safety and tolerability of repeat inhaled doses of ETD001 monitored by assessment of adverse events | 105 days | Incidence of treatment emergent adverse events(AE)/serious AE), withdrawals due to AE |
| Part A: Characterisation of plasma pharmacokinetics (PK) | Day 1 (pre-dose, 0.25, 0.5, 1, 2, 4 & 6 hours) | Peak plasma concentration and time observed (Cmax & Tmax) of ETD001 following dosing. |
| Part B: Characterisation of plasma PK | 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 | Population PK characteristics and model generated individual PK parameters (Cmax & Tmax) |
| Part B: Effect of repeat inhaled doses of ETD001 on the quality of life questionnaire, the Cystic Fibrosis Questionnaire (revised) (CFQ-R) | Treatment Period 1 & 2; Day 1 & Day 28 (pre-dose) | Change in CFQ-R (respiratory domain) from baseline to Day 28 (for either Treatment Period 1 or Treatment Period 2), compared to placebo |
| Part A: Characterisation of urine PK | Day 1 (0 - 6 hours) | Amount ETD001 excreted in urine (Ae) |
Countries
France, Germany, Italy, United Kingdom
Outcome results
None listed