Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older With the G551D Mutation - Full Text View

Purpose

The purpose of this study was to evaluate the efficacy and safety of ivacaftor in subjects with cystic fibrosis aged 12 years and older who have the G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Ivacaftor is a potent and selective CFTR potentiator of wild-type, G551D, F508del, and R117H forms of human CFTR protein. Potentiators are pharmacological agents that increase the chloride ion transport properties of the channel in the presence of cyclic AMP-dependent protein kinase A (PKA) activation.

Condition	Intervention	Phase
Cystic Fibrosis	Drug: Ivacaftor Drug: Placebo	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of VX-770 in Subjects With Cystic Fibrosis and the G551D Mutation

Resource links provided by NLM:

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Ivacaftor

Genetic and Rare Diseases Information Center resources: Cystic Fibrosis

U.S. FDA Resources

Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:

Absolute Mean Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24 [ Time Frame: baseline through 24 weeks ] [ Designated as safety issue: No ]
Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.

Secondary Outcome Measures:

Absolute Mean Change From Baseline in Percent Predicted FEV1 Through Week 48 [ Time Frame: baseline through 48 weeks ] [ Designated as safety issue: No ]
Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.
Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score Through Week 24 and Week 48 (Respiratory Domain Score, Pooled) [ Time Frame: baseline through 24 weeks and 48 weeks ] [ Designated as safety issue: No ]
The CFQ-R is a health-related quality of life measure for subjects with cystic fibrosis. Each domain is scored from 0 (worst) to 100 (best). A difference of at least 4 points in the respiratory domain score of the CFQ-R is considered a minimal clinically important difference (MCID).
Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48 [ Time Frame: baseline through 24 weeks and 48 weeks ] [ Designated as safety issue: No ]
The sweat chloride (quantitative pilocarpine iontophoresis) test is a standard diagnostic tool for cystic fibrosis (CF), serving as an indicator of cystic fibrosis transmembrane conductance regulator (CFTR) activity.
Time-to-first Pulmonary Exacerbation Through Week 24 and Week 48 [ Time Frame: baseline through 24 weeks and 48 weeks ] [ Designated as safety issue: No ]
Pulmonary exacerbation was defined as a change in antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of signs/symptoms such as change in sputum; new or increased hemoptysis; increased cough or dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees C; anorexia or weight loss; sinus pain/tenderness and discharge; change in physical examination of the chest; decreased pulmonary function by 10%; and radiographic changes indicative of pulmonary infection.
Absolute Change From Baseline in Weight at Week 24 and Week 48 [ Time Frame: baseline to 24 weeks and 48 weeks ] [ Designated as safety issue: No ]
As malnutrition is common in patients with cystic fibrosis (CF) because of increased energy expenditures due to lung disease and fat malabsorption, body weight is an important clinical measure of nutritional status.


Enrollment:	167
Study Start Date:	June 2009
Study Completion Date:	November 2012
Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Placebo Subjects who received placebo every 12 hours (q12h) for up to 48 weeks.	Drug: Placebo Tablet given orally q12h for up to 48 weeks
Experimental: 150 mg Ivacaftor q12h Subjects who received 150 mg of ivacaftor q12h for up to 48 weeks.	Drug: Ivacaftor 150-mg tablets given orally q12h for up to 48 weeks Other Name: VX-770

Detailed Description:

This was a phase 3 study in subjects with cystic fibrosis (CF) age 12 years and older who have a G551D-CFTR mutation and percent predicted forced expiratory volumn in 1 second (FEV1) between 40% and 90%.

Based on in vitro studies and pharmacologic, pharmacokinetic (PK), and safety profiles, ivacaftor was selected for clinical development as a possible treatment for patients with CF. Patients with the G551D mutation were the targeted population for this study because ivacaftor is a potentiator of the gating function of the CFTR protein, and the most prevalent mutation with a gating defect in CF is the G551D mutation.

This study was designed to further evaluate the efficacy of ivacaftor in subjects with CF who have a G551D-CFTR gene mutation and to evaluate safety in this population over a longer period than previously studied.

Eligibility


Ages Eligible for Study:	12 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Confirmed diagnosis of cystic fibrosis (CF) and G551D mutation in at least 1 allele
Forced expiratory volume in 1 second (FEV1) of 40% to 90% (inclusive) of predicted normal for age, gender, and height at Screening.
No clinically significant abnormalities that would have interfered with the study assessments, as judged by the investigator
Willing to use highly effective birth control methods during the study

Exclusion Criteria:

History of any illness or condition that might confound the results of the study or pose an additional risk in administering study drug to the subject
Acute respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks of Day 1 of the study
History of alcohol, medication or illicit drug abuse within one year prior to Day 1
Abnormal liver function ≥ 3x the upper limit of normal
Abnormal renal function at Screening
History of solid organ or hematological transplantation
Pregnant, planning a pregnancy, breast-feeding, or unwilling to follow contraception requirements
Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days prior to Screening
Use of inhaled hypertonic saline treatment
Concomitant use of any inhibitors or inducers of cytochrome P450 3A4 (CYP 3A4)

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00909532

Show 65 Study Locations

Sponsors and Collaborators

Vertex Pharmaceuticals Incorporated

Cystic Fibrosis Foundation Therapeutics

Investigators


Principal Investigator:	Bonnie W. Ramsey, MD	Children's Hospital and Regional Medical Center, Seattle, Washington, USA
Principal Investigator:	Stuart Elborn, MD	Respiratory Medicine Group, Queen's University of Belfast, Belfast, Northern Ireland, UK

More Information

Additional Information:

Genetics Home Reference This link exits the ClinicalTrials.gov site

Medline Plus This link exits the ClinicalTrials.gov site

U.S. FDA Resources This link exits the ClinicalTrials.gov site

Publications:

Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Dřevínek P, Griese M, McKone EF, Wainwright CE, Konstan MW, Moss R, Ratjen F, Sermet-Gaudelus I, Rowe SM, Dong Q, Rodriguez S, Yen K, Ordoñez C, Elborn JS; VX08-770-102 Study Group. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011 Nov 3;365(18):1663-72. doi: 10.1056/NEJMoa1105185.


Responsible Party:	Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:	NCT00909532 History of Changes
Other Study ID Numbers:	VX08-770-102
Study First Received:	May 26, 2009
Results First Received:	February 27, 2012
Last Updated:	January 14, 2013
Health Authority:	United States: Food and Drug Administration United Kingdom: Medicines and Healthcare Products Regulatory Agency Ireland: Irish Medicines Board France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices Czech Republic: State Institute for Drug Control Australia: Department of Health and Ageing Therapeutic Goods Administration Canada: Health Canada

Keywords provided by Vertex Pharmaceuticals Incorporated:


Fibrosis Pancreatic Diseases Lung Diseases Respiratory Tract Diseases	Genetic Diseases, Inborn Infant, Newborn, Diseases Pathologic Processes

Additional relevant MeSH terms:


Cystic Fibrosis Fibrosis Digestive System Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases	Lung Diseases Pancreatic Diseases Pathologic Processes Respiratory Tract Diseases

ClinicalTrials.gov processed this record on February 25, 2015

Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older With the G551D Mutation (STRIVE)