Study of Cavosonstat (N91115) in CF Patients Who Are Heterozygous for F508del-CFTR and a Gating Mutation and Being Treated With Ivacaftor (SNO-7)

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of N91115 for Efficacy and Safety in Patients With CF Heterozygous for F508del-CFTR + Gating Mutation Being Treated With Ivacaftor

Cavosonstat (N91115) is being studied as a potential novel therapy for cystic fibrosis (CF), and this study assesses a target population of patients who are heterozygous for F508del-CFTR and a gating mutation that is approved for treatment with ivacaftor (G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R).

Study Overview

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

Detailed Description

Assess the effect of Cavosonstat (N91115) on lung function when added to preexisting treatment with ivacaftor in adult patients with CF who are heterozygous for F508del-CFTR and a gating mutation that is approved for treatment with ivacaftor (G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R).

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • Ohio
    • 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
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital Pittsburgh
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • 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:

• Confirmed diagnosis of CF, heterozygous for F508del-CFTR and a gating mutation that is approved for treatment with ivacaftor (G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R)
• Have been treated with chronic ivacaftor twice daily for at least 6 months prior to Screening (date of consent) and are currently being treated with commercially available Ivacaftor
• Negative serum pregnancy test
• Weight ≥ 40 kg at screening
• Oxygen saturation by pulse oximetry ≥ 90% breathing ambient air, at screening

Exclusion Criteria:

• Any acute infection, including acute upper or lower respiratory infections and pulmonary exacerbations that require treatment that has completed within 2 weeks of Study Day 1 or hospitalization discharge within 2 weeks of Study Day 1
• Recent infection (per investigator discretion) with organisms associated with more rapid decline in pulmonary status, for example: 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
• Blood hemoglobin < 10 g/dL at screening
• Serum albumin < 2.5 g/dL at screening
• Abnormal liver or renal function
• 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 (> 450 msec for men; > 470 msec for women)
• History of solid organ or hematological transplantation
• History of alcohol abuse or drug abuse (including cannabis, cocaine, and opioids) in the year prior to screening
• 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 Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching capsule (BID administration Q12H)	Drug: Placebo; Matched Placebo capsule; Other Names: Control
Experimental: Cavosonstat (N91115) 400 mg; Cavosonstat (N91115) at 400 mg dose (100 mg x 4 capsules) (BID administration Q12H)	Drug: Cavosonstat; CFTR modulator that stabilizes CFTR; Other Names: N91115

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The absolute change in ppFEV1 in the N91115 treated group	Forced Expiratory Volume (FEV) absolute measurements comparing baseline to after 4 and 8 weeks of N91115 treatment. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) is calculated using the Hankinson method.	Baseline, week 4 and 8 assessments

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The relative change from study baseline within the active treatment group in ppFEV1 values	Forced Expiratory Volume relative measurements comparing baseline to after 4 and 8 weeks of N91115 treatment. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) is calculated using the Hankinson method.	Baseline, week 4 and 8 assessments
Absolute change from study baseline within the active treatment group in sweat chloride	Sweat chloride concentration measured by pilocarpine iontophoresis, a standard clinical laboratory technique. Sweat collection accomplished with the Wescor Macroduct System.	Baseline, week 4 and 8 assessments
Changes in the respiratory domain of the Cystic Fibrosis Questionnaire - Revised, (CFQ-R)	Patient questionnaires will compare baseline scores on their respiratory symptoms to weeks 4 and 8	Baseline, week 4 and 8 assessments
Absolute change from baseline within the active treatment group in Patient Global Impression of Change	Patient questionnaires will compare baseline global impression of changes in health from baseline to weeks 4 and 8	Baseline, week 4 and 8 assessments
Safety as determined by adverse events assessment	Assessments of clinical laboratory values, electrocardiogram (ECG), pulmonary exacerbations, and vital signs	Baseline to 8 weeks treatment with a 28-day follow up period
Pharmacokinetic Assessment of Maximum Plasma Concentration [Cmax] for N91115 & ivacaftor	Plasma collection for assessment of N91115 and ivacaftor Cmax	Weeks 1, 4 and 8
Pharmacokinetic Assessment of area under the plasma concentration verse time curve [AUC] for N91115 & ivacaftor	Plasma collection for assessment of N91115 and ivacaftor AUC	Weeks 1, 4 and 8

Collaborators and Investigators

• Sponsor: Nivalis Therapeutics, Inc.
• Investigators: Principal Investigator: James Chmiel, MD, Rainbow Babies and Children's Hospital/ University

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Anticipated): April 1, 2017
• Study Completion (Anticipated): April 1, 2017

Study Registration Dates

• First Submitted: March 11, 2016
• First Submitted That Met QC Criteria: March 25, 2016
• First Posted (Estimate): March 31, 2016

Study Record Updates

• Last Update Posted (Estimate): November 21, 2016
• Last Update Submitted That Met QC Criteria: November 17, 2016
• Last Verified: November 1, 2016

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-06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No