Clinical trial NCT01746784: Safety and Pharmacokinetic Study of N6022 in Subjects With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation
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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
F508del-CFTR
N6022
S-Nitrosoglutathione
Lead sponsor: Nivalis Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2012-12-11
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Safety and Tolerability
timeFrame: Over 7 treatment days and 7 days of follow-up
Secondary outcomes:
measure: Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Change from baseline at Day 7
measure: Change in Biomarkers of CFTR Function
timeFrame: Change from baseline at Day 7
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Anchorage
country: United States
facility: Providence Alaska Medical Center
state: Alaska
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Children's Hospital
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital - Case Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Scott Donaldson, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.