A Two-Part Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Repeat Doses of Inhaled ETD001 in People With Cystic Fibrosis

Enterprise Therapeutics Ltd57 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Cystic Fibrosis

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 Years

Medical Language ↔ Plain English

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

Locations (21)

Hospices Civils de Lyon

Lyon, France

CHU de Montpellier

Montpellier, France

Hôpital Cochin

Paris, France

Hôpitaux de Toulouse

Toulouse, France

Charité Universtaetsmedizin

Berlin, Germany

CF-Studienzentrum Universitätsklinikum Köln

Cologne, Germany

Westdeutsches Lungenzentrum am Universitätsklinikum

Essen, Germany

Universitätsklinikum Frankfurt

Frankfurt, Germany

IKF Pneumologie

Frankfurt, Germany

LMU Kinikum

Munich, Germany

...and 11 more locations

Outcomes

Primary Outcomes

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

Time frame: 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

Time frame: 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

Part A: Characterisation of plasma pharmacokinetics (PK)

Peak plasma concentration and time observed (Cmax \& Tmax) of ETD001 following dosing.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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)

Time frame: Day 1 (0 - 6 hours)

Part A: Characterisation of urine PK

Fraction of ETD001 dose excreted (Fe)

Time frame: Day 1 (0 - 6 hours)

Part A: Characterisation of urine PK

Renal clearance of ETD001 (CLr)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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)