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

Cystic Fibrosis Clinical Trial

— SNO-6  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02589236
• Other study ID #: N91115-2CF-05
• Status: Completed
• Phase: Phase 2
• First received: October 26, 2015
• Last updated: January 6, 2017
• Start date: November 2015
• Est. completion date: December 2016

Study information

• Verified date: January 2017
• Source: Nivalis Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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™).

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 information / eligibility

• Status: Completed
• Enrollment: 138
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Cavosonstat
GSNOR inhibitor
• Placebo
Control sample with only capsule excipients and fillers

Locations

Country	Name	City	State
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Dell Children's Hospital | Austin Children's Chest Associates	Austin	Texas
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Alabama	Birmingham	Alabama
United States	St. Luke's CF Center of Idaho	Boise	Idaho
United States	Boston Children's Hospital	Boston	Massachusetts
United States	University of North Carolina Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	Rainbow Babies and Children's Hospital - Case Medical Center	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	National Jewish Health	Denver	Colorado
United States	Wayne State University-Harper	Detroit	Michigan
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Spectrum Health Butterworth Hospital	Grand Rapids	Michigan
United States	Texas Children's Hospital	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Iowa Children's Hospital	Iowa City	Iowa
United States	University of Kentucky	Lexington	Kentucky
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Medical Center of Wisconsin	Madison	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Morristown Medical Center	Morristown	New Jersey
United States	Yale University	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Stanford University	Palo Alto	California
United States	Saint Francis Medical Center	Peoria	Illinois
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Maine Medical Center	Portland	Maine
United States	Oregon Health and Science University	Portland	Oregon
United States	UC Davis Medical Center	Sacramento	California
United States	University of Utah	Salt Lake City	Utah
United States	Seattle Children's Hospital	Seattle	Washington
United States	St. Louis University	St. Louis	Missouri
United States	Washington University	St. Louis	Missouri
United States	Tampa General Hospital	Tampa	Florida
United States	ProMedica Toledo Children's Hospital	Toledo	Ohio
United States	Banner University of Arizona Medical Center	Tucson	Arizona
United States	Via Christi Research	Wichita	Kansas
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina
United States	University of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Nivalis Therapeutics, Inc.	Medidata Solutions

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of pulmonary exacerbations	Assessment of number of pulmonary exacerbations at baseline compared through 12 weeks	baseline to 12 weeks	Yes
Primary	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	Yes
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Absolute change from baseline in Patient Global Impression of Change (PGIC)	Patient reported outcome journal	baseline to 12 weeks	No
Secondary	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	Yes
Secondary	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	No
Secondary	Pharmacokinetic Measurements of Area Under the Curve (AUC) for N91115, Ivacaftor and lumacaftor	AUC measurements of N91115, lumacaftor and ivacaftor	baseline to 12 weeks	No