A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of N91115 to Evaluate Efficacy and Safety in Patients With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation Treated With Lumacaftor/Ivacaftor
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Cystic Fibrosis
- Sponsor
- Nivalis Therapeutics, Inc.
- Enrollment
- 138
- Locations
- 46
- Primary Endpoint
- Absolute change from baseline in percent predicted FEV1 (ppFEV1)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This will be a double-blind, randomized, placebo-controlled, parallel group study. The purpose of this study is to investigate the efficacy and safety of Cavosonstat (N91115) in adult patients with CF who are homozygous for the F508del-CFTR mutation and being treated with lumacaftor/ivacaftor (Orkambi™).
Detailed Description
Primary Objective: * Assess the efficacy of N91115 at 12 weeks when added to preexisting treatment with lumacaftor/ivacaftor in adult patients with CF who are homozygous for the F508del-CFTR mutation Secondary Objectives: * Assess the effect of N91115 added to lumacaftor/ivacaftor on safety * Assess the effect of lumacaftor/ivacaftor added to N91115 on the pharmacokinetics of N91115, lumacaftor, and ivacaftor
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have been treated with lumacaftor/ivacaftor for at least 8 weeks prior to Day 1 (start of dosing)
- •A history of Sweat Chloride (SC) ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT) (either before or after starting lumacaftor/ivacaftor treatment)
- •Body weight ≥ 40 kg
- •ppFEV1 40 - 85 % predicted (inclusive) at screening
- •Oxygen saturation ≥ 90% breathing ambient air at screening
Exclusion Criteria
- •Any acute infection that requires treatment or hospitalization within 2 weeks of Study Day 1
- •Colonization with organisms associated with more rapid decline in pulmonary status, such as Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus
- •Any change in the regimen for chronic therapies for CF lung disease (e.g., Pulmozyme®, hypertonic saline, Azithromycin, TOBI®, Cayston®) within 4 weeks of Study Day 1
- •Are pregnant, planning a pregnancy, or breast-feeding at screening
- •Blood hemoglobin \< 10 g/dL at screening
- •Serum albumin \< 2.5 g/dL at screening
- •Abnormal liver function defined as ≥ 3 x upper limit of normal (ULN)
- •History of abnormal renal function within 3 months of screening
- •History of ventricular tachycardia or other clinically significant ventricular arrhythmias
- •History, including the screening assessment, of prolonged QT and/or QTcF (Fridericia's correction) interval
Arms & Interventions
Placebo
Placebo Capsule
Intervention: Placebo
Cavosonstat (N91115) 200 mg
Cavosonstat (N91115) 200 mg twice daily (BID)
Intervention: Cavosonstat
Cavosonstat (N91115) 400 mg
Cavosonstat (N91115) 400 mg BID
Intervention: Cavosonstat
Outcomes
Primary Outcomes
Absolute change from baseline in percent predicted FEV1 (ppFEV1)
Time Frame: From baseline to 12 weeks
Forced Expiratory Volume in one second (FEV1) from before study (Baseline) to after 12 weeks of N91115 treatment
Secondary Outcomes
- Absolute change from baseline in Cystic Fibrosis Questionnaire -Revised CFQ-R (respiratory symptom scale)(baseline to 16 weeks)
- Absolute change from baseline in Patient Global Impression of Change (PGIC)(baseline to 12 weeks)
- Relative change from baseline in ppFEV1(baseline to 12 weeks)
- Absolute change from baseline in sweat chloride(baseline to 12 weeks)
- Absolute change from baseline in body mass index (BMI)(baseline to 12 weeks)
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])(baseline to 16 weeks)
- Pharmacokinetic Measurements of Maximum Plasma Concentration [Cmax], of N91115, lumacaftor, and ivacaftor(baseline to 12 weeks)
- Pharmacokinetic Measurements of Area Under the Curve (AUC) for N91115, Ivacaftor and lumacaftor(baseline to 12 weeks)