Study of Cavosonstat (N91115) in Patients With CF Homozygous for the F508del-CFTR Mutation (SNO-6)

• ClinicalTrials.gov Identifier: NCT02589236
• Recruitment Status: Completed
• First Posted: October 28, 2015
• Last Update Posted: January 10, 2017
• Sponsor: Nivalis Therapeutics, Inc.
• Collaborator: Medidata Solutions
• Information provided by (Responsible Party): Nivalis Therapeutics, Inc.

Tracking Information

• First Submitted Date: October 26, 2015
• First Posted Date: October 28, 2015
• Last Update Posted Date: January 10, 2017
• Study Start Date: November 2015
• Actual Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 26, 2015)

Absolute change from baseline in percent predicted FEV1 (ppFEV1) [ Time Frame: From baseline to 12 weeks ]

Forced Expiratory Volume in one second (FEV1) from before study (Baseline) to after 12 weeks of N91115 treatment

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 26, 2015)

• Relative change from baseline in ppFEV1 [ Time Frame: baseline to 12 weeks ]
  Forced Expiratory Volume in one second (FEV1) from before study (Baseline) to after 12 weeks of N91115 treatment
• Absolute change from baseline in sweat chloride [ Time Frame: baseline to 12 weeks ]
  A sweat chloride measurement on the skin at study start and after 12 weeks of N91115
• Absolute change from baseline in Cystic Fibrosis Questionnaire -Revised CFQ-R (respiratory symptom scale) [ Time Frame: baseline to 16 weeks ]
  Comparison of the Questionnaire from study start to 16 weeks
• Absolute change from baseline in body mass index (BMI) [ Time Frame: baseline to 12 weeks ]
  Assessment of change in body mass index from study start to after 12 weeks of N91115
• Absolute change from baseline in Patient Global Impression of Change (PGIC) [ Time Frame: baseline to 12 weeks ]
  Patient reported outcome journal
• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]) [ Time Frame: baseline to 16 weeks ]
  Any adverse events assessment including clinical laboratory values, electrocardiogram (ECG), pulmonary exacerbations, or vital sign changes
• Pharmacokinetic Measurements of Maximum Plasma Concentration [Cmax], of N91115, lumacaftor, and ivacaftor [ Time Frame: baseline to 12 weeks ]
  Maximum Plasma Concentration [Cmax] measurements of N91115, lumacaftor and ivacaftor
• Pharmacokinetic Measurements of Area Under the Curve (AUC) for N91115, Ivacaftor and lumacaftor [ Time Frame: baseline to 12 weeks ]
  AUC measurements of N91115, lumacaftor and ivacaftor

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: October 26, 2015)

Number of pulmonary exacerbations [ Time Frame: baseline to 12 weeks ]

Assessment of number of pulmonary exacerbations at baseline compared through 12 weeks

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: 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
• 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

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Cystic Fibrosis

Intervention

• Drug: Cavosonstat
  GSNOR inhibitor
  Other Name: N91115
• Drug: Placebo
  Control sample with only capsule excipients and fillers
  Other Name: control

Study Arms

• Placebo Comparator: Placebo
  Placebo Capsule
  Intervention: Drug: Placebo
• Experimental: Cavosonstat (N91115) 200 mg
  Cavosonstat (N91115) 200 mg twice daily (BID)
  Intervention: Drug: Cavosonstat
• Experimental: Cavosonstat (N91115) 400 mg
  Cavosonstat (N91115) 400 mg BID
  Intervention: Drug: Cavosonstat

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 27, 2016): 138
• Original Estimated Enrollment (submitted: October 26, 2015): 135
• Actual Study Completion Date: December 2016
• Actual Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02589236
• Other Study ID Numbers: N91115-2CF-05
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Nivalis Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Nivalis Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Medidata Solutions

Investigators

• Principal Investigator: Scott Donaldson, MD; University of North Carolina, Chapel Hill

• PRS Account: Nivalis Therapeutics, Inc.
• Verification Date: January 2017