Cystic Fibrosis
Conditions
Keywords
Cystic Fibrosis, N91115, Cavosonstat
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
Interventions
DRUGCavosonstat
GSNOR inhibitor
DRUGPlacebo
Control sample with only capsule excipients and fillers
Sponsors
Medidata Solutions
Nivalis Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * History of solid organ or hematological transplantation * History of alcohol abuse or drug abuse * Ongoing participation in another therapeutic clinical trial * Use of continuous (24 hr/day) or nocturnal supplemental oxygen
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute change from baseline in percent predicted FEV1 (ppFEV1) | From baseline to 12 weeks | Forced Expiratory Volume in one second (FEV1) from before study (Baseline) to after 12 weeks of N91115 treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative change from baseline in ppFEV1 | baseline to 12 weeks | Forced Expiratory Volume in one second (FEV1) from before study (Baseline) to after 12 weeks of N91115 treatment |
| Absolute change from baseline in sweat chloride | baseline to 12 weeks | A sweat chloride measurement on the skin at study start and after 12 weeks of N91115 |
| Absolute change from baseline in Cystic Fibrosis Questionnaire -Revised CFQ-R (respiratory symptom scale) | baseline to 16 weeks | Comparison of the Questionnaire from study start to 16 weeks |
| Absolute change from baseline in body mass index (BMI) | baseline to 12 weeks | Assessment of change in body mass index from study start to after 12 weeks of N91115 |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]) | baseline to 16 weeks | Any adverse events assessment including clinical laboratory values, electrocardiogram (ECG), pulmonary exacerbations, or vital sign changes |
| Pharmacokinetic Measurements of Maximum Plasma Concentration [Cmax], of N91115, lumacaftor, and ivacaftor | baseline to 12 weeks | Maximum Plasma Concentration \[Cmax\] measurements of N91115, lumacaftor and ivacaftor |
| Pharmacokinetic Measurements of Area Under the Curve (AUC) for N91115, Ivacaftor and lumacaftor | baseline to 12 weeks | AUC measurements of N91115, lumacaftor and ivacaftor |
| Absolute change from baseline in Patient Global Impression of Change (PGIC) | baseline to 12 weeks | Patient reported outcome journal |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of pulmonary exacerbations | baseline to 12 weeks | Assessment of number of pulmonary exacerbations at baseline compared through 12 weeks |
Countries
United States
Outcome results
None listed