Clinical trial NCT03093714: A Study to Evaluate Safety, PK and PD of FDL169 in Cystic Fibrosis Subjects
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Study to Evaluate Safety, Pharmacokinetics (PK) and Pharmacodynamics(PD) of FDL169 in Cystic Fibrosis (CF) Subjects Homozygous for the F508del-CFTR Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
Lead sponsor: Flatley Discovery Lab LLC
Sponsor class: OTHER
First posted: 2017-03-28
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, randomized, placebo-controlled, dose-escalation study. Enrollment is planned to occur at approximately 14 global sites. Approximately 24 subjects with CF.

Detailed description: This is a multicenter, randomized double-blind, placebo-controlled dose-escalation and parallel-arm, dose-ranging study. Enrollment is planned to occur at approximately 14 global sites. Approximately 24 subjects with CF who are homozygous for the F508del-CFTR mutation will be enrolled in two cohorts.

Eligibility criteria: Inclusion Criteria:

* Male or female subjects with a confirmed diagnosis of CF defined as a sweat chloride value ≥60 mmol/L by quantitative pilocarpine iontophoresis or two CF-causing mutations,documented in the subject's medical record or confirmed at screening.
* Age 18 and above on the date of informed consent.
* Weight ≥40 kg.
* Homozygous for the F508del-CFTR mutation. Genotyping to be confirmed at screening.
* Ability to perform a valid, reproducible spirometry test with demonstration of a forced expiratory volume in 1 sec (FEV1) \>40% of predicted normal for age, sex and height.
* Screening laboratory tests with no clinically significant abnormalities that would interfere with the study assessments (as judged by the Investigator).
* Subjects who are sexually active must agree to follow the study's contraception requirements.

Exclusion Criteria:

* An acute upper or lower respiratory tract infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks prior to Day 1.
* Major complications of lung disease (including massive hemoptysis, pneumothorax, or pleural effusion) within 8 weeks prior to screening.
* Impaired renal function or known portal hypertension.
* History of prolonged QT and/or QTcF (Fridericia's correction) interval (\>450 msec) or QTcF \>450 msec at Screening.
* History of solid organ or hematological transplantation.
* History of alcohol abuse or drug addiction (including cannabis, cocaine and opiates) during the past year, (as judged by the Investigator).
* Use of ivacaftor or lumacaftor, within 4 weeks of Day 1
* Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or re-initiation) in a chronic treatment/prophylaxis regimen for CF or for CF-related conditions within 4 weeks prior to Day 1.
* Ongoing immunosuppressive therapy (including systemic corticosteroids).
* Hemoglobin \<10 g/dL.
* Abnormal liver function, at screening.
* Abnormal renal function at screening.
* Ongoing participation in another clinical study or prior participation without appropriate washout (minimum of 10 half- lives or 30 days, whichever is longer) prior to Screening visit.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 28 days
Secondary outcomes:
measure: Pharmacokinetic parameters, Cmax
timeFrame: 28 days
measure: Pharmacokinetic parameters, Tmax
timeFrame: 28 days
measure: Pharmacokinetic parameters, AUC
timeFrame: 28 days
measure: Pharmacokinetic parameters, CL/F
timeFrame: 28 days
measure: Pharmacokinetic parameters, V/F
timeFrame: 28 days
Other outcomes:
Locations:
city: South Brisbane
country: Australia
facility: Mater Misericordiae Ltd
state: Queenland
city: Chermside
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Brno
country: Czechia
facility: FN v Motole, Pediatrická klinika, Centrum cystické fibrózy
city: Praha
country: Czechia
facility: FN v Motole, Pediatrická klinika, Centrum cystické fibrózy
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin CVK
city: Donaustauf
country: Germany
facility: Klinik Donaustauf, Zentrum für Pneumologie
city: Essen
country: Germany
facility: Ruhrlandklinik
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Belfast
country: United Kingdom
facility: NICRN Respiratory Research Office, Belfast City Hospital
city: Liverpool
country: United Kingdom
facility: Research Dept., Liverpool Heart and Chest Hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: Manchester
country: United Kingdom
facility: The Medicines Evaluation Unit (MEU)
city: Southampton
country: United Kingdom
facility: NIHR Wellcome Trust Clinical Research Facility
Study officials:
affiliation: Flatley Discovery Lab
name: Claudia Ordonez, MD
role: STUDY_CHAIR
References:
citation: Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.