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

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cavosonstat
Placebo
Sponsored by
Nivalis Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring Cystic Fibrosis, N91115, Cavosonstat

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama
  • Banner University of Arizona Medical Center
  • Children's Hospital Los Angeles
  • Stanford University
  • UC Davis Medical Center
  • Children's Hospital Colorado
  • National Jewish Health
  • Yale University
  • Tampa General Hospital
  • St. Luke's CF Center of Idaho
  • Northwestern University
  • Saint Francis Medical Center
  • Indiana University
  • University of Iowa Children's Hospital
  • Via Christi Research
  • University of Kentucky
  • Maine Medical Center
  • Johns Hopkins Hospital
  • Boston Children's Hospital
  • University of Massachusetts Medical School
  • Wayne State University-Harper
  • Spectrum Health Butterworth Hospital
  • University of Minnesota
  • St. Louis University
  • Washington University
  • University of Nebraska Medical Center
  • Morristown Medical Center
  • Columbia University
  • University of North Carolina Chapel Hill
  • Wake Forest University School of Medicine
  • Children's Hospital Medical Center of Akron
  • Cincinnati Children's Hospital
  • Rainbow Babies and Children's Hospital - Case Medical Center
  • Nationwide Children's Hospital
  • ProMedica Toledo Children's Hospital
  • Oregon Health and Science University
  • Children's Hospital of Philadelphia
  • Children's Hospital of Pittsburgh of UPMC
  • Medical University of South Carolina
  • Dell Children's Hospital | Austin Children's Chest Associates
  • University of Texas Southwestern Medical Center
  • Cook Children's Medical Center
  • Texas Children's Hospital
  • University of Utah
  • Seattle Children's Hospital
  • Medical Center of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Placebo

Cavosonstat (N91115) 200 mg

Cavosonstat (N91115) 400 mg

Arm Description

Placebo Capsule

Cavosonstat (N91115) 200 mg twice daily (BID)

Cavosonstat (N91115) 400 mg BID

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Relative change from baseline in ppFEV1
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
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)
Comparison of the Questionnaire from study start to 16 weeks
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
Absolute change from baseline in Patient Global Impression of Change (PGIC)
Patient reported outcome journal
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
Pharmacokinetic Measurements of Maximum Plasma Concentration [Cmax], of N91115, lumacaftor, and ivacaftor
Maximum Plasma Concentration [Cmax] measurements of N91115, lumacaftor and ivacaftor
Pharmacokinetic Measurements of Area Under the Curve (AUC) for N91115, Ivacaftor and lumacaftor
AUC measurements of N91115, lumacaftor and ivacaftor

Full Information

First Posted
October 26, 2015
Last Updated
January 6, 2017
Sponsor
Nivalis Therapeutics, Inc.
Collaborators
Medidata Solutions
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1. Study Identification

Unique Protocol Identification Number
NCT02589236
Brief Title
Study of Cavosonstat (N91115) in Patients With CF Homozygous for the F508del-CFTR Mutation
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
November 2015 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nivalis Therapeutics, Inc.
Collaborators
Medidata Solutions

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
Cystic Fibrosis, N91115, Cavosonstat

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
138 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo Capsule
Arm Title
Cavosonstat (N91115) 200 mg
Arm Type
Experimental
Arm Description
Cavosonstat (N91115) 200 mg twice daily (BID)
Arm Title
Cavosonstat (N91115) 400 mg
Arm Type
Experimental
Arm Description
Cavosonstat (N91115) 400 mg BID
Intervention Type
Drug
Intervention Name(s)
Cavosonstat
Other Intervention Name(s)
N91115
Intervention Description
GSNOR inhibitor
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
control
Intervention Description
Control sample with only capsule excipients and fillers
Primary Outcome Measure Information:
Title
Absolute change from baseline in percent predicted FEV1 (ppFEV1)
Description
Forced Expiratory Volume in one second (FEV1) from before study (Baseline) to after 12 weeks of N91115 treatment
Time Frame
From baseline to 12 weeks
Secondary Outcome Measure Information:
Title
Relative change from baseline in ppFEV1
Description
Forced Expiratory Volume in one second (FEV1) from before study (Baseline) to after 12 weeks of N91115 treatment
Time Frame
baseline to 12 weeks
Title
Absolute change from baseline in sweat chloride
Description
A sweat chloride measurement on the skin at study start and after 12 weeks of N91115
Time Frame
baseline to 12 weeks
Title
Absolute change from baseline in Cystic Fibrosis Questionnaire -Revised CFQ-R (respiratory symptom scale)
Description
Comparison of the Questionnaire from study start to 16 weeks
Time Frame
baseline to 16 weeks
Title
Absolute change from baseline in body mass index (BMI)
Description
Assessment of change in body mass index from study start to after 12 weeks of N91115
Time Frame
baseline to 12 weeks
Title
Absolute change from baseline in Patient Global Impression of Change (PGIC)
Description
Patient reported outcome journal
Time Frame
baseline to 12 weeks
Title
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])
Description
Any adverse events assessment including clinical laboratory values, electrocardiogram (ECG), pulmonary exacerbations, or vital sign changes
Time Frame
baseline to 16 weeks
Title
Pharmacokinetic Measurements of Maximum Plasma Concentration [Cmax], of N91115, lumacaftor, and ivacaftor
Description
Maximum Plasma Concentration [Cmax] measurements of N91115, lumacaftor and ivacaftor
Time Frame
baseline to 12 weeks
Title
Pharmacokinetic Measurements of Area Under the Curve (AUC) for N91115, Ivacaftor and lumacaftor
Description
AUC measurements of N91115, lumacaftor and ivacaftor
Time Frame
baseline to 12 weeks
Other Pre-specified Outcome Measures:
Title
Number of pulmonary exacerbations
Description
Assessment of number of pulmonary exacerbations at baseline compared through 12 weeks
Time Frame
baseline to 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott Donaldson, MD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Banner University of Arizona Medical Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
UC Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
National Jewish Health
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Tampa General Hospital
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
St. Luke's CF Center of Idaho
City
Boise
State/Province
Idaho
ZIP/Postal Code
83712
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Saint Francis Medical Center
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61637
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Iowa Children's Hospital
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Via Christi Research
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Maine Medical Center
City
Portland
State/Province
Maine
ZIP/Postal Code
04102
Country
United States
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Massachusetts Medical School
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Wayne State University-Harper
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Spectrum Health Butterworth Hospital
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
St. Louis University
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
Washington University
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Morristown Medical Center
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07960
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of North Carolina Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Wake Forest University School of Medicine
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
Facility Name
Children's Hospital Medical Center of Akron
City
Akron
State/Province
Ohio
ZIP/Postal Code
44308
Country
United States
Facility Name
Cincinnati Children's Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Rainbow Babies and Children's Hospital - Case Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
ProMedica Toledo Children's Hospital
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43606
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Children's Hospital of Pittsburgh of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Dell Children's Hospital | Austin Children's Chest Associates
City
Austin
State/Province
Texas
ZIP/Postal Code
78723
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Cook Children's Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Medical Center of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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