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

Phase 1

Completed

• Conditions: Cystic Fibrosis
• Interventions: Drug: Normal saline; Drug: N6022

• Registration Number: NCT01746784
• Lead Sponsor: Nivalis Therapeutics, Inc.

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.

Study Timeline

• Study First Submitted: 2012-12-06
• Study First Submitted QC: 2012-12-10
• Study First Posted: 2012-12-11
• Study Start: 2014-02
• Primary Completion: 2014-04
• Study Completion: 2014-05
• Status Verified: 2014-11
• Results First Submitted: 2014-11-17
• Results First Submitted QC: 2014-11-21
• Last Update Submitted: 2014-11-21
• Results First Posted: 2014-11-24
• Last Update Posted: 2014-11-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 66

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normal saline	Normal saline	Subjects randomized to placebo will receive normal saline administered intravenously using the same volume as the active drug group
N6022	N6022	Subjects randomized to study drug will receive N6022 by intravenous infusion once per day for 7 days

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability	Over 7 treatment days and 7 days of follow-up	Assessments are based on numbers of subjects with abnormal clinical evaluations, abnormal laboratory assessments, and adverse events.

Secondary Outcome Measures

Name	Time	Method
Change in Biomarkers of CFTR Function	Change from baseline at Day 7	Sweat chloride millequivalents/Liter (mEq/L)
Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)	Change from baseline at Day 7	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).

Trial Locations

Locations (17)

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States

Cincinnati Children's Hospital; 🇺🇸 Cincinnati, Ohio, United States

Rainbow Babies and Children's Hospital - Case Medical Center; 🇺🇸 Cleveland, Ohio, United States

University of Alabama; 🇺🇸 Birmingham, Alabama, United States

Providence Alaska Medical Center; 🇺🇸 Anchorage, Alaska, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

University of Iowa Children's Hospital; 🇺🇸 Iowa City, Iowa, United States

Washington University; 🇺🇸 St. Louis, Missouri, United States

University of North Carolina; 🇺🇸 Chapel Hill, North Carolina, United States

Children's Hospital of Pittsburgh of UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States

Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

National Jewish Health; 🇺🇸 Denver, Colorado, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States