Study of Cavosonstat (N91115) in Patients With CF Homozygous for the F508del-CFTR Mutation (SNO-6)

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

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™).

Study Overview

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

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

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University Of Alabama
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Banner University of Arizona Medical Center
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Palo Alto, California, United States, 94304
      • Stanford University
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Idaho
    • Boise, Idaho, United States, 83712
      • St. Luke's CF Center of Idaho
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Peoria, Illinois, United States, 61637
      • Saint Francis Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Children's Hospital
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Via Christi Research
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Wayne State University-Harper
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health Butterworth Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University
    • St. Louis, Missouri, United States, 63104
      • St. Louis University
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina Chapel Hill
    • Winston-Salem, North Carolina, United States, 27103
      • Wake Forest University School of Medicine
  • Ohio
    • Akron, Ohio, United States, 44308
      • Children's Hospital Medical Center of Akron
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital
    • Cleveland, Ohio, United States, 44106
      • Rainbow Babies and Children's Hospital - Case Medical Center
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
    • Toledo, Ohio, United States, 43606
      • ProMedica Toledo Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Austin, Texas, United States, 78723
      • Dell Children's Hospital | Austin Children's Chest Associates
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Medical Center of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Placebo Capsule	Drug: Placebo; Control sample with only capsule excipients and fillers; Other Names: control
EXPERIMENTAL: Cavosonstat (N91115) 200 mg; Cavosonstat (N91115) 200 mg twice daily (BID)	Drug: Cavosonstat; GSNOR inhibitor; Other Names: N91115
EXPERIMENTAL: Cavosonstat (N91115) 400 mg; Cavosonstat (N91115) 400 mg BID	Drug: Cavosonstat; GSNOR inhibitor; Other Names: N91115

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change from baseline in percent predicted FEV1 (ppFEV1)	Forced Expiratory Volume in one second (FEV1) from before study (Baseline) to after 12 weeks of N91115 treatment	From baseline to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative change from baseline in ppFEV1	Forced Expiratory Volume in one second (FEV1) from before study (Baseline) to after 12 weeks of N91115 treatment	baseline to 12 weeks
Absolute change from baseline in sweat chloride	A sweat chloride measurement on the skin at study start and after 12 weeks of N91115	baseline to 12 weeks
Absolute change from baseline in Cystic Fibrosis Questionnaire -Revised CFQ-R (respiratory symptom scale)	Comparison of the Questionnaire from study start to 16 weeks	baseline to 16 weeks
Absolute change from baseline in body mass index (BMI)	Assessment of change in body mass index from study start to after 12 weeks of N91115	baseline to 12 weeks
Absolute change from baseline in Patient Global Impression of Change (PGIC)	Patient reported outcome journal	baseline to 12 weeks
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])	Any adverse events assessment including clinical laboratory values, electrocardiogram (ECG), pulmonary exacerbations, or vital sign changes	baseline to 16 weeks
Pharmacokinetic Measurements of Maximum Plasma Concentration [Cmax], of N91115, lumacaftor, and ivacaftor	Maximum Plasma Concentration [Cmax] measurements of N91115, lumacaftor and ivacaftor	baseline to 12 weeks
Pharmacokinetic Measurements of Area Under the Curve (AUC) for N91115, Ivacaftor and lumacaftor	AUC measurements of N91115, lumacaftor and ivacaftor	baseline to 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of pulmonary exacerbations	Assessment of number of pulmonary exacerbations at baseline compared through 12 weeks	baseline to 12 weeks

Collaborators and Investigators

• Sponsor: Nivalis Therapeutics, Inc.
• Collaborators: Medidata Solutions

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (ACTUAL): December 1, 2016
• Study Completion (ACTUAL): December 1, 2016

Study Registration Dates

• First Submitted: October 26, 2015
• First Submitted That Met QC Criteria: October 26, 2015
• First Posted (ESTIMATE): October 28, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): January 10, 2017
• Last Update Submitted That Met QC Criteria: January 6, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; N91115; Cavosonstat
• 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: N91115-2CF-05