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

NCT ID: NCT01746784

Last Updated: 2014-11-24

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-02-28

Study Completion Date

2014-05-31

Brief Summary

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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

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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.

Conditions

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Cystic Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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N6022

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

Group Type EXPERIMENTAL

N6022

Intervention Type DRUG

Intravenous solution of N6022 in normal saline administered by infusion pump over 1-8 minutes depending on the dose

Normal saline

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

Group Type PLACEBO_COMPARATOR

Normal saline

Intervention Type DRUG

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

Interventions

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N6022

Intravenous solution of N6022 in normal saline administered by infusion pump over 1-8 minutes depending on the dose

Intervention Type DRUG

Normal saline

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

Intervention Type DRUG

Other Intervention Names

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GSNORi Placebo

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nivalis Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Scott Donaldson, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

Providence Alaska Medical Center

Anchorage, Alaska, United States

Site Status

Stanford University

Palo Alto, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

National Jewish Health

Denver, Colorado, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Iowa Children's Hospital

Iowa City, Iowa, United States

Site Status

Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

Site Status

Rainbow Babies and Children's Hospital - Case Medical Center

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

References

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Heneghan M, 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. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.

Reference Type DERIVED
PMID: 37983082 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33331662 (View on PubMed)

Related Links

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http://www.n30pharma.com/

Home page of Sponsor

Other Identifiers

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N6022-1CF1-04

Identifier Type: -

Identifier Source: org_study_id