Study of Ivacaftor in Subjects With Cystic Fibrosis (CF) Who Have a Non-G551D CF Transmembrane Conductance Regulator (CFTR) Gating Mutation

NCT01614470 | Completed Phase 3 Results DMC

• 1 other identifier: VX12-770-111
• Study Type: interventional
• Target: 39
• Locations: 3 countries
• Sites: 12

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of ivacaftor in subjects with cystic fibrosis (CF) who have a non-G551D cystic fibrosis transmembrane regulator (CFTR) gating mutation (any one of the following CFTR mutations: G178R, G551S, S549N, S549R, G970R, G1244E, S1251N, S1255P, or G1349D).

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (2)

• Part 1: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8

  FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male subjects 18 years and older and female subjects 16 years and older. The Wang standard was used for male subjects aged 6 to 17 years and for female subjects aged 6 to 15 years. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1.

  Part 1: Baseline (pre-dose Day 1), Week 8

• Part 2: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through 24 Weeks of Treatment (Week 36 Visit)

  FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male subjects 18 years and older and female subjects 16 years and older. The Wang standard was used for male subjects aged 6 to 17 years and for female subjects aged 6 to 15 years. Absolute change in percent predicted FEV1 over 24 weeks of ivacaftor treatment (from Week 12 \[Part 1: Treatment Period 2\] through Week 36 \[Part 2\]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2, as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2.

  Baseline (pre-dose Week 12), Week 36

Secondary Outcomes (8)

• Part 1: Change From Baseline in Body Mass Index (BMI) at Week 8

  Part 1: Baseline (pre-dose Day 1), Week 8

• Part 2: Change From Baseline in Body Mass Index (BMI) at 24 Weeks of Treatment (Week 36 Visit)

  Baseline (pre-dose Week 12), Week 36

• Part 1: Change From Baseline in Sweat Chloride Through Week 8

  Part 1: Baseline (pre-dose Day 1), Week 8

• Part 2: Change From Baseline in Sweat Chloride Through 24 Weeks of Treatment (Week 36 Visit)

  Baseline (pre-dose Week 12), Week 36

• Part 1: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 8

  Part 1: Baseline (pre-dose Day 1), Week 8

Study Arms (3)

Part 1: Ivacaftor First, Then Placebo

EXPERIMENTAL

Ivacaftor 150 milligram (mg) tablet orally twice daily for 8 weeks in treatment period 1 followed by placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period.

Drug: Ivacaftor; Drug: Placebo

Part 1: Placebo First, Then Ivacaftor

EXPERIMENTAL

Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 1 followed by ivacaftor 150 mg tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period.

Drug: Ivacaftor; Drug: Placebo

Part 2: Ivacaftor

EXPERIMENTAL

Ivacaftor 150 mg tablet orally twice daily for 16 weeks.

Drug: Ivacaftor

Interventions

Ivacaftor DRUG

150 mg tablet, oral use, administered twice a day (q12h)

Also known as: Kalydeco, VX-770

Part 1: Ivacaftor First, Then Placebo; Part 1: Placebo First, Then Ivacaftor; Part 2: Ivacaftor

Placebo DRUG

oral use, administered twice a day (q12h)

Part 1: Ivacaftor First, Then Placebo; Part 1: Placebo First, Then Ivacaftor

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female with confirmed diagnosis of CF
• At least 1 allele of the following CFTR gating mutations: G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P, G1349D
• Percent predicted forced expiratory volume in 1 second (FEV1) greater than or equal to (\>=) 40 percent (%) predicted normal for age, sex, and height
• years of age or older
• Minimum weight of 15 kilogram (kg) at screening
• Females of childbearing potential must not be pregnant
• Willing to comply with contraception requirements

You may not qualify if:

• G551D-CFTR mutation on at least 1 allele
• History of any illness or condition that might confound the results of the study or pose an additional risk in administering ivacaftor to the subject
• An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before the first dose of study drug
• History of solid organ or hematological transplantation
• History of alcohol, medication or illicit drug abuse within 1 year before the first dose of study drug
• Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days before screening
• Use of inhaled hypertonic saline treatment
• Use of any inhibitors or inducers of cytochrome (CYP) P450 3A
• Evidence of cataract or lens opacity at screening

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (12)

Unknown Facility

Tampa, Florida, United States

Location

Unknown Facility

Atlanta, Georgia, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

Ann Arbor, Michigan, United States

Location

Unknown Facility

Minneapolis, Minnesota, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

Houston, Texas, United States

Location

Unknown Facility

Leuven, Belgium

Location

Unknown Facility

Lyon, France

Location

Unknown Facility

Montpellier, France

Location

Unknown Facility

Paris, France

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

ivacaftor

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Medical Monitor
• Organization: Vertex Pharmaceuticals Incorporated

medicalinfo@vrtx.com

617-341-6777

Study Officials

• Christine De Boeck, MD, PhD

  University of Leuven

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2012
• First Posted: June 8, 2012
• Study Start: July 1, 2012
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: October 29, 2014
• Results First Posted: October 29, 2014

Record last verified: 2014-10

Locations

US (8); FR (3); BE (1)