A Study to Evaluate Safety, PK and PD of FDL169 in Cystic Fibrosis Subjects

NCT ID: NCT03093714

Last Updated: 2018-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-23
• Study Completion Date: 2018-04-03

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.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

FDL 169 test formulation (Dose Level 1)

Multiple dose (Dose Level 1) FDL 169 test formulation administered as repeat doses in CF subjects

Group Type: EXPERIMENTAL

FDL169

Intervention Type: DRUG

CFTR corrector

FDL 169 test formulation (Dose Level 2)

Multiple dose (Dose Level 2) FDL 169 test formulation administered as repeat doses in CF subjects

Group Type: EXPERIMENTAL

FDL169

Intervention Type: DRUG

CFTR corrector

FDL 169 test formulation ( Dose Level 3)

Multiple dose (Dose Level 3) FDL 169 test formulation administered as repeat doses in CF subjects

Group Type: EXPERIMENTAL

FDL169

Intervention Type: DRUG

CFTR corrector

Placebo

Multiple dose placebo as repeat doses in CF subjects

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo for FDL169

Interventions

FDL169

CFTR corrector

Intervention Type: DRUG

Placebo

Placebo for FDL169

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Flatley Discovery Lab LLC

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Claudia Ordonez, MD

Role: STUDY_CHAIR

Flatley Discovery Lab

Locations

Mater Misericordiae Ltd

South Brisbane, Queenland, Australia

The Prince Charles Hospital

Chermside, Queensland, Australia

The Alfred Hospital

Melbourne, , Australia

FN v Motole, Pediatrická klinika, Centrum cystické fibrózy

Brno, , Czechia

FN v Motole, Pediatrická klinika, Centrum cystické fibrózy

Prague, , Czechia

Charité - Universitätsmedizin Berlin CVK

Berlin, , Germany

Klinik Donaustauf, Zentrum für Pneumologie

Donaustauf, , Germany

Ruhrlandklinik

Essen, , Germany

Universitätsklinikum Frankfurt

Frankfurt, , Germany

NICRN Respiratory Research Office, Belfast City Hospital

Belfast, , United Kingdom

Research Dept., Liverpool Heart and Chest Hospital

Liverpool, , United Kingdom

Royal Brompton Hospital

London, , United Kingdom

The Medicines Evaluation Unit (MEU)

Manchester, , United Kingdom

NIHR Wellcome Trust Clinical Research Facility

Southampton, , United Kingdom

Countries

Australia; Czechia; Germany; United Kingdom

References

Heneghan M, 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. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.

Reference Type: DERIVED

PMID: 37983082 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33331662 (View on PubMed)

Other Identifiers

FDL169-2015-04

Identifier Type: -

Identifier Source: org_study_id