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Safety and Pharmacokinetic Study of N6022 in Subjects With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation (SNO-1)

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
N6022
Normal saline
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, F508del-CFTR, N6022, S-Nitrosoglutathione

Eligibility Criteria

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

Inclusion Criteria:

  • Homozygous for F508del-CFTR gene
  • Sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis
  • Body weight ≥ 40 kg
  • FEV1 ≥ 40% predicted
  • Oxygen saturation ≥ 90% breathing ambient air
  • Hematology and clinical chemistry of blood and urine results with no clinically significant abnormalities that would interfere with the study assessments
  • Negative pregnancy test for women of child bearing potential
  • Sexually active subjects of child bearing potential willing to follow contraception requirements

Exclusion Criteria:

  • Previous enrollment in another cohort for this study.
  • Any acute infection, including acute upper or lower respiratory infections and pulmonary exacerbations that require treatment within 4 weeks of Study Day 1.
  • Any change in chronic therapies for CF lung disease within 4 weeks of Study Day 1.
  • 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) in three or more of the following: AST, ALT, GGT, ALP, total bilirubin at screening.
  • History of abnormal renal function (creatinine clearance < 50 mL/min using Cockcroft-Gault equation) within a year at screening.
  • History, including the screening assessment, of ventricular tachycardia or other ventricular arrhythmias.
  • History, including the screening assessment, of prolonged QT and/or QTcF interval (> 450 msec).
  • History of solid organ or hematological transplantation.
  • Intranasal medication changes within 14 days prior to Study Day 1
  • Required Use of continuous (24 hr/d) or nocturnal supplemental oxygen.
  • Concomitant use of any inhibitors or inducers of CYP3A4.

Sites / Locations

  • University of Alabama
  • Providence Alaska Medical Center
  • Stanford University
  • Children's Hospital Colorado
  • National Jewish Health
  • Northwestern University
  • University of Iowa Children's Hospital
  • Johns Hopkins Hospital
  • Boston Children's Hospital
  • University of Minnesota
  • Washington University
  • University of North Carolina
  • Cincinnati Children's Hospital
  • Rainbow Babies and Children's Hospital - Case Medical Center
  • Nationwide Children's Hospital
  • Children's Hospital of Philadelphia
  • Children's Hospital of Pittsburgh of UPMC

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

N6022

Normal saline

Arm Description

Subjects randomized to study drug will receive N6022 by intravenous infusion once per day for 7 days

Subjects randomized to placebo will receive normal saline administered intravenously using the same volume as the active drug group

Outcomes

Primary Outcome Measures

Safety and Tolerability
Assessments are based on numbers of subjects with abnormal clinical evaluations, abnormal laboratory assessments, and adverse events.

Secondary Outcome Measures

Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson standards were used to calculate percent predicted FEV1 (for age, sex, and height).
Change in Biomarkers of CFTR Function
Sweat chloride millequivalents/Liter (mEq/L)

Full Information

First Posted
December 6, 2012
Last Updated
November 21, 2014
Sponsor
Nivalis Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01746784
Brief Title
Safety and Pharmacokinetic Study of N6022 in Subjects With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation
Acronym
SNO-1
Official Title
A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study of N6022 to Evaluate Safety and Pharmacokinetics in Subjects With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation (SNO1)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2014
Overall Recruitment Status
Completed
Study Start Date
February 2014 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
May 2014 (Actual)

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
The purpose of this study is to investigate the safety, tolerability and pharmacokinetics of N6022, and to obtain descriptive information on the effect of N6022 on biomarkers of CFTR function and inflammation in adult cystic fibrosis subjects who are homozygous for the F508del-CFTR mutation.
Detailed Description
This is a double-blind, randomized, placebo-controlled, multicenter, sequential dose-escalation study which will occur in two parts. All selection criteria, assessments and procedures described in this protocol will be applied to both parts. Up to 5 cohorts will be studied with a total of 67 patients at approximately 18 clinical sites in the United States.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
Cystic Fibrosis, F508del-CFTR, N6022, S-Nitrosoglutathione

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
66 (Actual)

8. Arms, Groups, and Interventions

Arm Title
N6022
Arm Type
Experimental
Arm Description
Subjects randomized to study drug will receive N6022 by intravenous infusion once per day for 7 days
Arm Title
Normal saline
Arm Type
Placebo Comparator
Arm Description
Subjects randomized to placebo will receive normal saline administered intravenously using the same volume as the active drug group
Intervention Type
Drug
Intervention Name(s)
N6022
Other Intervention Name(s)
GSNORi
Intervention Description
Intravenous solution of N6022 in normal saline administered by infusion pump over 1-8 minutes depending on the dose
Intervention Type
Drug
Intervention Name(s)
Normal saline
Other Intervention Name(s)
Placebo
Intervention Description
Intravenous solution of 0.9% (weight/volume) NaCl administered by infusion pump over 1-8 minutes depending on dose of active drug used in same cohort
Primary Outcome Measure Information:
Title
Safety and Tolerability
Description
Assessments are based on numbers of subjects with abnormal clinical evaluations, abnormal laboratory assessments, and adverse events.
Time Frame
Over 7 treatment days and 7 days of follow-up
Secondary Outcome Measure Information:
Title
Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson standards were used to calculate percent predicted FEV1 (for age, sex, and height).
Time Frame
Change from baseline at Day 7
Title
Change in Biomarkers of CFTR Function
Description
Sweat chloride millequivalents/Liter (mEq/L)
Time Frame
Change from baseline at Day 7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Homozygous for F508del-CFTR gene Sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis Body weight ≥ 40 kg FEV1 ≥ 40% predicted Oxygen saturation ≥ 90% breathing ambient air Hematology and clinical chemistry of blood and urine results with no clinically significant abnormalities that would interfere with the study assessments Negative pregnancy test for women of child bearing potential Sexually active subjects of child bearing potential willing to follow contraception requirements Exclusion Criteria: Previous enrollment in another cohort for this study. Any acute infection, including acute upper or lower respiratory infections and pulmonary exacerbations that require treatment within 4 weeks of Study Day 1. Any change in chronic therapies for CF lung disease within 4 weeks of Study Day 1. 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) in three or more of the following: AST, ALT, GGT, ALP, total bilirubin at screening. History of abnormal renal function (creatinine clearance < 50 mL/min using Cockcroft-Gault equation) within a year at screening. History, including the screening assessment, of ventricular tachycardia or other ventricular arrhythmias. History, including the screening assessment, of prolonged QT and/or QTcF interval (> 450 msec). History of solid organ or hematological transplantation. Intranasal medication changes within 14 days prior to Study Day 1 Required Use of continuous (24 hr/d) or nocturnal supplemental oxygen. Concomitant use of any inhibitors or inducers of CYP3A4.
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
Providence Alaska Medical Center
City
Anchorage
State/Province
Alaska
ZIP/Postal Code
99508
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
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
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
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
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 Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Washington University
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
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
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

12. IPD Sharing Statement

Citations:
PubMed Identifier
33331662
Citation
Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
Results Reference
derived
Links:
URL
http://www.n30pharma.com/
Description
Home page of Sponsor

Learn more about this trial

Safety and Pharmacokinetic Study of N6022 in Subjects With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation

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