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

Cystic Fibrosis Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01746784
• Other study ID #: N6022-1CF1-04
• Status: Completed
• Phase: Phase 1
• First received: December 6, 2012
• Last updated: November 21, 2014
• Start date: February 2014
• Est. completion date: May 2014

Study information

• Verified date: November 2014
• Source: Nivalis Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: May 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

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

Locations

Country	Name	City	State
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Alabama	Birmingham	Alabama
United States	Boston Children's Hospital	Boston	Massachusetts
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	Rainbow Babies and Children's Hospital - Case Medical Center	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	National Jewish Health	Denver	Colorado
United States	University of Iowa Children's Hospital	Iowa City	Iowa
United States	University of Minnesota	Minneapolis	Minnesota
United States	Stanford University	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Washington University	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Nivalis Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability	Assessments are based on numbers of subjects with abnormal clinical evaluations, abnormal laboratory assessments, and adverse events.	Over 7 treatment days and 7 days of follow-up	Yes
Secondary	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 from baseline at Day 7	No
Secondary	Change in Biomarkers of CFTR Function	Sweat chloride millequivalents/Liter (mEq/L)	Change from baseline at Day 7	No

External Links

•   Home page of Sponsor