A Study to Evaluate Efficacy of Ivacaftor in Subjects With Cystic Fibrosis Who Have a 3849 + 10KB C→T or D1152H CFTR Mutation

A Randomized, Double-blind, Placebo-controlled, Crossover Study to Evaluate the Efficacy of Ivacaftor in Subjects With Cystic Fibrosis Who Are 6 Years of Age and Older and Have Either a 3849 + 10KB C→T or D1152H-CFTR Mutation

This study will evaluate the efficacy of ivacaftor treatment in subjects with CF 6 years of age and older who have a 3849 + 10KB C→T or D1152H CFTR mutation.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Ivacaftor; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 3

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel
    • Hadassah Medical Organization

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed diagnosis of CF based on protocol-specified clinical features and at least one of the following: increased sweat chloride level, identification of 2 CF causing mutations, or demonstration of abnormal nasal epithelial ion transport.
• A 3849 + 10KB C→T or D1152H mutation on at least 1 CFTR allele.
• FEV1 ≥40% of predicted and ≤105% of predicted at screening.

Exclusion Criteria:

• A G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or R117H mutation.
• History of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject.
• Ongoing or prior participation in an investigational drug study within 30 days before the Screening Visit.
• Protocol-specified abnormal laboratory values at the Screening Visit
• For subjects <18 years of age at the Screening Visit, evidence of cataract/lens opacity determined to be clinically significant by the ophthalmologist or optometrist during the ophthalmologic examination (OE) at the Screening Visit.
• Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A, including consumption of certain herbal medications and certain fruit and fruit juices, within 14 days before Day 1.
• Pregnant, breastfeeding, or planning to become pregnant during the study.
• Sexually active subjects of reproductive potential must be willing to use appropriate contraception.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sequence 1: First Ivacaftor (IVA) Then Placebo; Participants received IVA 150 milligram (mg) every 12 hours (q12h) for 8 weeks in treatment period 1 followed by placebo matched to IVA for 8 weeks in treatment period 2. A washout period of 8 weeks was maintained between the 2 treatment periods.	Drug: Ivacaftor; IVA 150 mg tablet.; Other Names: VX-770; IVA; Drug: Placebo; Placebo matched to IVA tablet.
EXPERIMENTAL: Sequence 2: First Placebo Then IVA; Participants received placebo matched to IVA for 8 weeks in treatment period 1 followed by IVA 150 mg q12h for 8 weeks in treatment period 2. A washout period of 8 weeks was maintained between the 2 treatment periods.	Drug: Ivacaftor; IVA 150 mg tablet.; Other Names: VX-770; IVA; Drug: Placebo; Placebo matched to IVA tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Lung Clearance Index 2.5 (LCI2.5)	LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.	From baseline through 8 weeks

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Publications and helpful links

General Publications

• Kerem E, Cohen-Cymberknoh M, Tsabari R, Wilschanski M, Reiter J, Shoseyov D, Gileles-Hillel A, Pugatsch T, Davies JC, Short C, Saunders C, DeSouza C, Sullivan JC, Doyle JR, Chandarana K, Kinnman N. Ivacaftor in People with Cystic Fibrosis and a 3849+10kb C-->T or D1152H Residual Function Mutation. Ann Am Thorac Soc. 2021 Mar;18(3):433-441. doi: 10.1513/AnnalsATS.202006-659OC.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 18, 2017
• Primary Completion (ACTUAL): December 18, 2018
• Study Completion (ACTUAL): December 18, 2018

Study Registration Dates

• First Submitted: February 24, 2017
• First Submitted That Met QC Criteria: February 24, 2017
• First Posted (ACTUAL): March 1, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 26, 2020
• Last Update Submitted That Met QC Criteria: February 13, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Ivacaftor
• Other Study ID Numbers: VX16-770-127; 2017-000457-39 (EUDRACT_NUMBER)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes