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

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: FDL169; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia, 3004
    • The Alfred Hospital
  • Queenland
    • South Brisbane, Queenland, Australia, 4101
      • Mater Misericordiae Ltd
  • Queensland
    • Chermside, Queensland, Australia, 4032
      • The Prince Charles Hospital
• Czechia
  • Brno, Czechia
    • FN v Motole, Pediatrická klinika, Centrum cystické fibrózy
  • Praha, Czechia
    • FN v Motole, Pediatrická klinika, Centrum cystické fibrózy
• Germany
  • Berlin, Germany
    • Charite - Universitatsmedizin Berlin CVK
  • Donaustauf, Germany, 93093
    • Klinik Donaustauf, Zentrum für Pneumologie
  • Essen, Germany
    • Ruhrlandklinik
  • Frankfurt, Germany
    • Universitätsklinikum Frankfurt
• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • NICRN Respiratory Research Office, Belfast City Hospital
  • Liverpool, United Kingdom, L14 3PE
    • Research Dept., Liverpool Heart and Chest Hospital
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital
  • Manchester, United Kingdom, M23 9QZ
    • The Medicines Evaluation Unit (MEU)
  • Southampton, United Kingdom, SO16 6YD
    • NIHR Wellcome Trust Clinical Research Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FDL 169 test formulation (Dose Level 1); Multiple dose (Dose Level 1) FDL 169 test formulation administered as repeat doses in CF subjects	Drug: FDL169; CFTR corrector
Experimental: FDL 169 test formulation (Dose Level 2); Multiple dose (Dose Level 2) FDL 169 test formulation administered as repeat doses in CF subjects	Drug: FDL169; CFTR corrector
Experimental: FDL 169 test formulation ( Dose Level 3); Multiple dose (Dose Level 3) FDL 169 test formulation administered as repeat doses in CF subjects	Drug: FDL169; CFTR corrector
Placebo Comparator: Placebo; Multiple dose placebo as repeat doses in CF subjects	Drug: Placebo; Placebo for FDL169

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Safety and tolerability of FDL169 as determined by the incidence of adverse events (AEs) and serious adverse events (SAEs).	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameters, Cmax	The pharmacokinetic parameters of FDL169: maximal plasma concentration (Cmax).	28 days
Pharmacokinetic parameters, Tmax	The pharmacokinetic parameters of FDL169: maximal concentration (Tmax).	28 days
Pharmacokinetic parameters, AUC	The pharmacokinetic parameters of FDL169: area under the plasma concentration curve (AUC).	28 days
Pharmacokinetic parameters, CL/F	The pharmacokinetic parameters of FDL169: clearance (CL/F).	28 days
Pharmacokinetic parameters, V/F	The pharmacokinetic parameters of FDL169: apparent volume of distribution (V/F).	28 days

Collaborators and Investigators

• Sponsor: Flatley Discovery Lab LLC
• Investigators: Study Chair: Claudia Ordonez, MD, Flatley Discovery Lab

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2017
• Primary Completion (Actual): April 3, 2018
• Study Completion (Actual): April 3, 2018

Study Registration Dates

• First Submitted: March 16, 2017
• First Submitted That Met QC Criteria: March 27, 2017
• First Posted (Actual): March 28, 2017

Study Record Updates

• Last Update Posted (Actual): April 12, 2018
• Last Update Submitted That Met QC Criteria: April 11, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Cystic Fibrosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: FDL169-2015-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No