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

• ClinicalTrials.gov Identifier: NCT03068312
• Recruitment Status: Completed
• First Posted: March 1, 2017
• Results First Posted: January 6, 2020
• Last Update Posted: February 26, 2020
• Sponsor: Vertex Pharmaceuticals Incorporated
• Information provided by (Responsible Party): Vertex Pharmaceuticals Incorporated

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: Ivacaftor; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: July 18, 2017
• Actual Primary Completion Date: December 18, 2018
• Actual Study Completion Date: December 18, 2018

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 6 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Israel

Hadassah Medical Organization

Jerusalem, Israel

Sponsors and Collaborators

Vertex Pharmaceuticals Incorporated

  Study Documents (Full-Text)

Documents provided by Vertex Pharmaceuticals Incorporated:

Study Protocol  [PDF] October 20, 2016

Statistical Analysis Plan  [PDF] October 19, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Vertex Pharmaceuticals Incorporated
• ClinicalTrials.gov Identifier: NCT03068312
• Other Study ID Numbers: VX16-770-127; 2017-000457-39 ( EudraCT Number )
• First Posted: March 1, 2017
• Results First Posted: January 6, 2020
• Last Update Posted: February 26, 2020
• Last Verified: February 2020

• 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

Additional relevant MeSH terms:

Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Ivacaftor; Chloride Channel Agonists; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action