Clinical trial NCT02589236: Study of Cavosonstat (N91115) in Patients With CF Homozygous for the F508del-CFTR Mutation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
N91115
Cavosonstat
Lead sponsor: Nivalis Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Medidata Solutions
First posted: 2015-10-28
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Absolute change from baseline in percent predicted FEV1 (ppFEV1)
timeFrame: From baseline to 12 weeks
Secondary outcomes:
measure: Relative change from baseline in ppFEV1
timeFrame: baseline to 12 weeks
measure: Absolute change from baseline in sweat chloride
timeFrame: baseline to 12 weeks
measure: Absolute change from baseline in Cystic Fibrosis Questionnaire -Revised CFQ-R (respiratory symptom scale)
timeFrame: baseline to 16 weeks
measure: Absolute change from baseline in body mass index (BMI)
timeFrame: baseline to 12 weeks
measure: Absolute change from baseline in Patient Global Impression of Change (PGIC)
timeFrame: baseline to 12 weeks
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])
timeFrame: baseline to 16 weeks
measure: Pharmacokinetic Measurements of Maximum Plasma Concentration [Cmax], of N91115, lumacaftor, and ivacaftor
timeFrame: baseline to 12 weeks
measure: Pharmacokinetic Measurements of Area Under the Curve (AUC) for N91115, Ivacaftor and lumacaftor
timeFrame: baseline to 12 weeks
Other outcomes:
measure: Number of pulmonary exacerbations
timeFrame: baseline to 12 weeks
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Tucson
country: United States
facility: Banner University of Arizona Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Boise
country: United States
facility: St. Luke's CF Center of Idaho
state: Idaho
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Peoria
country: United States
facility: Saint Francis Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Children's Hospital
state: Iowa
city: Wichita
country: United States
facility: Via Christi Research
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University-Harper
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Butterworth Hospital
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: St. Louis
country: United States
facility: St. Louis University
state: Missouri
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Chapel Hill
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Akron
country: United States
facility: Children's Hospital Medical Center of Akron
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital - Case Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Toledo
country: United States
facility: ProMedica Toledo Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Austin
country: United States
facility: Dell Children's Hospital | Austin Children's Chest Associates
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Madison
country: United States
facility: Medical Center of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Scott Donaldson, MD
role: PRINCIPAL_INVESTIGATOR
References: