Clinical trial NCT02724527: Study of Cavosonstat (N91115) in CF Patients Who Are Heterozygous for F508del-CFTR and a Gating Mutation and Being Treated With Ivacaftor
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
N91115
Cavosonstat
Lead sponsor: Nivalis Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2016-03-31
Enrollment: 19
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: 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).

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).

Eligibility criteria: 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

Primary outcomes:
measure: The absolute change in ppFEV1 in the N91115 treated group
timeFrame: Baseline, week 4 and 8 assessments
Secondary outcomes:
measure: The relative change from study baseline within the active treatment group in ppFEV1 values
timeFrame: Baseline, week 4 and 8 assessments
measure: Absolute change from study baseline within the active treatment group in sweat chloride
timeFrame: Baseline, week 4 and 8 assessments
measure: Changes in the respiratory domain of the Cystic Fibrosis Questionnaire - Revised, (CFQ-R)
timeFrame: Baseline, week 4 and 8 assessments
measure: Absolute change from baseline within the active treatment group in Patient Global Impression of Change
timeFrame: Baseline, week 4 and 8 assessments
measure: Safety as determined by adverse events assessment
timeFrame: Baseline to 8 weeks treatment with a 28-day follow up period
measure: Pharmacokinetic Assessment of Maximum Plasma Concentration [Cmax] for N91115 & ivacaftor
timeFrame: Weeks 1, 4 and 8
measure: Pharmacokinetic Assessment of area under the plasma concentration verse time curve [AUC] for N91115 & ivacaftor
timeFrame: Weeks 1, 4 and 8
Other outcomes:
Locations:
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Columbia University
state: New York
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: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Pittsburgh
country: United States
facility: Children's Hospital Pittsburgh
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Madison
country: United States
facility: Medical Center of Wisconsin
state: Wisconsin
Study officials:
affiliation: Rainbow Babies and Children's Hospital/ University
name: James Chmiel, MD
role: PRINCIPAL_INVESTIGATOR
References: