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

NCT02724527 | Unknown Phase 2 DMC

• 1 other identifier: N91115-2CF-06
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 12

Brief Summary

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).

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; N91115; Cavosonstat

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• The relative change from study baseline within the active treatment group in ppFEV1 values

  Baseline, week 4 and 8 assessments

• Absolute change from study baseline within the active treatment group in sweat chloride

  Baseline, week 4 and 8 assessments

• Changes in the respiratory domain of the Cystic Fibrosis Questionnaire - Revised, (CFQ-R)

  Baseline, week 4 and 8 assessments

• Absolute change from baseline within the active treatment group in Patient Global Impression of Change

  Baseline, week 4 and 8 assessments

• Safety as determined by adverse events assessment

  Baseline to 8 weeks treatment with a 28-day follow up period

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Matching capsule (BID administration Q12H)

Drug: Placebo

Cavosonstat (N91115) 400 mg

EXPERIMENTAL

Cavosonstat (N91115) at 400 mg dose (100 mg x 4 capsules) (BID administration Q12H)

Drug: Cavosonstat

Interventions

Cavosonstat DRUG

CFTR modulator that stabilizes CFTR

Also known as: N91115

Cavosonstat (N91115) 400 mg

Placebo DRUG

Matched Placebo capsule

Also known as: Control

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nivalis Therapeutics, Inc.: lead

Study Sites (12)

National Jewish Health

Denver, Colorado, 80206, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Rainbow Babies and Children's Hospital - Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Medical Center of Wisconsin

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

cavosonstat

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• James Chmiel, MD

  Rainbow Babies and Children's Hospital/ University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2016
• First Posted: March 31, 2016
• Study Start: April 1, 2016
• Primary Completion: April 1, 2017
• Study Completion: April 1, 2017
• Last Updated: November 21, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)