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

Study Overview
=================
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.

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

Conditions
-----------------
Cystic Fibrosis

Intervention / Treatment
-----------------
* Drug: FDL169
* Drug: Placebo


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cystic Fibrosis