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

Cystic Fibrosis Clinical Trial

— SNO-7  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02724527
• Other study ID #: N91115-2CF-06
• Status: Active, not recruiting
• Phase: Phase 2
• First received: March 11, 2016
• Last updated: November 17, 2016
• Start date: April 2016
• Est. completion date: April 2017

Study information

• Verified date: November 2016
• 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

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).

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 19
• Est. completion date: April 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 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
CFTR modulator that stabilizes CFTR
• Placebo
Matched Placebo capsule

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Boston Children's Hospital	Boston	Massachusetts
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	National Jewish Health	Denver	Colorado
United States	Medical Center of Wisconsin	Madison	Wisconsin
United States	Columbia University	New York	New York
United States	Children's Hospital Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	University of Utah	Salt Lake City	Utah
United States	Washington University	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Nivalis Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	Pharmacokinetic Assessment of Maximum Plasma Concentration [Cmax] for N91115 & ivacaftor	Plasma collection for assessment of N91115 and ivacaftor Cmax	Weeks 1, 4 and 8	No
Secondary	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	No