Back to resultsStudy of Cavosonstat (N91115) in CF Patients Who Are Heterozygous for F508del-CFTR and a Gating Mutation and Being Treated With Ivacaftor (SNO-7)
Primary Purpose
Cystic Fibrosis
Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cavosonstat
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis focused on measuring Cystic Fibrosis, N91115, Cavosonstat
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
Sites / Locations
- National Jewish Health
- Johns Hopkins Hospital
- Boston Children's Hospital
- Washington University
- Columbia University
- Cincinnati Children's Hospital
- Rainbow Babies and Children's Hospital - Case Medical Center
- Nationwide Children's Hospital
- Oregon Health and Science University
- Children's Hospital Pittsburgh
- University of Utah
- Medical Center of Wisconsin
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
Cavosonstat (N91115) 400 mg
Arm Description
Matching capsule (BID administration Q12H)
Cavosonstat (N91115) at 400 mg dose (100 mg x 4 capsules) (BID administration Q12H)
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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
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
Safety as determined by adverse events assessment
Assessments of clinical laboratory values, electrocardiogram (ECG), pulmonary exacerbations, and vital signs
Pharmacokinetic Assessment of Maximum Plasma Concentration [Cmax] for N91115 & ivacaftor
Plasma collection for assessment of N91115 and ivacaftor Cmax
Pharmacokinetic Assessment of area under the plasma concentration verse time curve [AUC] for N91115 & ivacaftor
Plasma collection for assessment of N91115 and ivacaftor AUC
Full Information
NCT ID
NCT02724527
First Posted
March 11, 2016
Last Updated
November 17, 2016
Sponsor
Nivalis Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02724527
Brief Title
Study of Cavosonstat (N91115) in CF Patients Who Are Heterozygous for F508del-CFTR and a Gating Mutation and Being Treated With Ivacaftor
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2016
Overall Recruitment Status
Unknown status
Study Start Date
April 2016 (undefined)
Primary Completion Date
April 2017 (Anticipated)
Study Completion Date
April 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nivalis Therapeutics, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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).
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
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching capsule (BID administration Q12H)
Arm Title
Cavosonstat (N91115) 400 mg
Arm Type
Experimental
Arm Description
Cavosonstat (N91115) at 400 mg dose (100 mg x 4 capsules) (BID administration Q12H)
Intervention Type
Drug
Intervention Name(s)
Cavosonstat
Other Intervention Name(s)
N91115
Intervention Description
CFTR modulator that stabilizes CFTR
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Control
Intervention Description
Matched Placebo capsule
Primary Outcome Measure Information:
Title
The absolute change in ppFEV1 in the N91115 treated group
Description
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.
Time Frame
Baseline, week 4 and 8 assessments
Secondary Outcome Measure Information:
Title
The relative change from study baseline within the active treatment group in ppFEV1 values
Description
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.
Time Frame
Baseline, week 4 and 8 assessments
Title
Absolute change from study baseline within the active treatment group in sweat chloride
Description
Sweat chloride concentration measured by pilocarpine iontophoresis, a standard clinical laboratory technique. Sweat collection accomplished with the Wescor Macroduct System.
Time Frame
Baseline, week 4 and 8 assessments
Title
Changes in the respiratory domain of the Cystic Fibrosis Questionnaire - Revised, (CFQ-R)
Description
Patient questionnaires will compare baseline scores on their respiratory symptoms to weeks 4 and 8
Time Frame
Baseline, week 4 and 8 assessments
Title
Absolute change from baseline within the active treatment group in Patient Global Impression of Change
Description
Patient questionnaires will compare baseline global impression of changes in health from baseline to weeks 4 and 8
Time Frame
Baseline, week 4 and 8 assessments
Title
Safety as determined by adverse events assessment
Description
Assessments of clinical laboratory values, electrocardiogram (ECG), pulmonary exacerbations, and vital signs
Time Frame
Baseline to 8 weeks treatment with a 28-day follow up period
Title
Pharmacokinetic Assessment of Maximum Plasma Concentration [Cmax] for N91115 & ivacaftor
Description
Plasma collection for assessment of N91115 and ivacaftor Cmax
Time Frame
Weeks 1, 4 and 8
Title
Pharmacokinetic Assessment of area under the plasma concentration verse time curve [AUC] for N91115 & ivacaftor
Description
Plasma collection for assessment of N91115 and ivacaftor AUC
Time Frame
Weeks 1, 4 and 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Chmiel, MD
Organizational Affiliation
Rainbow Babies and Children's Hospital/ University
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Jewish Health
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
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
Washington University
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
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
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Children's Hospital Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
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
Plan to Share IPD
No
Learn more about this trial
Study of Cavosonstat (N91115) in CF Patients Who Are Heterozygous for F508del-CFTR and a Gating Mutation and Being Treated With Ivacaftor
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