Study of Cavosonstat (N91115) in Patients With CF Homozygous for the F508del-CFTR Mutation
- Registration Number
- NCT02589236
- Lead Sponsor
- Nivalis Therapeutics, Inc.
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 138
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cavosonstat (N91115) 400 mg Cavosonstat Cavosonstat (N91115) 400 mg BID Placebo Placebo Placebo Capsule Cavosonstat (N91115) 200 mg Cavosonstat Cavosonstat (N91115) 200 mg twice daily (BID)
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 Patient Global Impression of Change (PGIC) baseline to 12 weeks Patient reported outcome journal
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 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
Trial Locations
- Locations (46)
Yale University
🇺🇸New Haven, Connecticut, United States
Maine Medical Center
🇺🇸Portland, Maine, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Rainbow Babies and Children's Hospital - Case Medical Center
🇺🇸Cleveland, Ohio, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Cincinnati Children's Hospital
🇺🇸Cincinnati, Ohio, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Columbia University
🇺🇸New York, New York, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
Dell Children's Hospital | Austin Children's Chest Associates
🇺🇸Austin, Texas, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Banner University of Arizona Medical Center
🇺🇸Tucson, Arizona, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
University of Alabama
🇺🇸Birmingham, Alabama, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
Tampa General Hospital
🇺🇸Tampa, Florida, United States
Via Christi Research
🇺🇸Wichita, Kansas, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
University of Massachusetts Medical School
🇺🇸Worcester, Massachusetts, United States
Wayne State University-Harper
🇺🇸Detroit, Michigan, United States
St. Louis University
🇺🇸St. Louis, Missouri, United States
Spectrum Health Butterworth Hospital
🇺🇸Grand Rapids, Michigan, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Washington University
🇺🇸St. Louis, Missouri, United States
Wake Forest University School of Medicine
🇺🇸Winston-Salem, North Carolina, United States
University of North Carolina Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Medical Center of Wisconsin
🇺🇸Madison, Wisconsin, United States
ProMedica Toledo Children's Hospital
🇺🇸Toledo, Ohio, United States
Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
St. Luke's CF Center of Idaho
🇺🇸Boise, Idaho, United States
Stanford University
🇺🇸Palo Alto, California, United States
University of Iowa Children's Hospital
🇺🇸Iowa City, Iowa, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States