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

Cystic Fibrosis Clinical Trial

— STRIVE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00909532
• Other study ID #: VX08-770-102
• Status: Completed
• Phase: Phase 3
• First received: May 26, 2009
• Last updated: January 14, 2013
• Start date: June 2009
• Est. completion date: November 2012

Study information

• Verified date: January 2013
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyIreland: Irish Medicines BoardFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesCzech Republic: State Institute for Drug ControlAustralia: Department of Health and Ageing Therapeutic Goods AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 167
• Est. completion date: November 2012
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Ivacaftor
150-mg tablets given orally q12h for up to 48 weeks
• Placebo
Tablet given orally q12h for up to 48 weeks

Locations

Country	Name	City	State
Australia	The Prince Charles Hospital	Chermside	Queensland
Australia	Royal Children's Hospital Brisbane	Herston	Queensland
Australia	Lung Institute of Western Australia	Nedlands	Western Australia
Australia	Royal Children's Hospital Melbourne	Parkville	Victoria
Australia	Mater Adult Hospital	South Brisbane	Queensland
Australia	Princess Margaret Hospital for Children	Subiaco	Western Australia
Australia	The Children's Hospital Westmead	Westmead	New South Wales
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	Montreal Children's Hospital - MUHC	Montreal	Quebec
Canada	CF Center, Hospital for Sick Children	Toronto	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Czech Republic	FN Motol	Prague
France	Hopital Cochin	Paris
France	Hopital Necker	Paris
France	Centre de Perharidy	Roscoff
Germany	Kinder- und Jugendklinik Universitätsklinikum Erlangen	Erlangen
Germany	Mukoviszidose-Zentrum am Klinikum der Friedrich-Schiller-Universität Jena, Klinik für Kinder- und Jugendmedizin	Jena
Germany	Klinikum der LMU München, Dr. von Haunersches Kinderspital (CHA)	Munich
Germany	Universitäts-Kinderklinik Würzburg	Wurzburg
Ireland	Cork University Hospital	Cork
Ireland	Beaumont Hospital	Dublin
Ireland	Our Lady's Children's Hospital	Dublin
Ireland	St. Vincent's University Hospital	Dublin
Ireland	The National Children's Hospital	Dublin
United Kingdom	Belfast City Hospital	Belfast	Northern Ireland
United Kingdom	Imperial College London	London
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory Cystic Fibrosis Center	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Alabama	Birmingham	Alabama
United States	St. Luke's CF Clinic	Boise	Idaho
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Women and Children's Hospital of Buffalo	Buffalo	New York
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Pediatric & Pulmonary Division, Rainbow Babies/Case Western	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	National Jewish Medical and Research Center	Denver	Colorado
United States	Hershey Medical Center	Hershey	Pennsylvania
United States	Indiana University	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	The Children's Mercy Hospital	Kansas City	Missouri
United States	East Tennessee Children's Hospital	Knoxville	Tennessee
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Pulmonary, Allergy & Critical Care Medicine, University of Minnesota	Minneapolis	Minnesota
United States	West Virginia University	Morgantown	West Virginia
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Kaiser Permanente Medical Care Program	Oakland	California
United States	Adult Pulmonary/ CF, University of Nebraska Medical Center	Omaha	Nebraska
United States	Cystic Fibrosis Research Office, Stanford University	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Oregon Health & Sciences University	Portland	Oregon
United States	University of Utah	Salt Lake City	Utah
United States	Rady Children's Hospital	San Diego	California
United States	Division of Pulmonary and CCM, University of Washington	Seattle	Washington
United States	Seattle Children's Hospital	Seattle	Washington
United States	Washington University	St. Louis	Missouri
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Toledo Children's Hospital	Toledo	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated	Cystic Fibrosis Foundation Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czech Republic,  France,  Germany,  Ireland,  United Kingdom, 

References & Publications (1)

Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Drevínek 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute Mean Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24	Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.	baseline through 24 weeks	No
Secondary	Absolute Mean Change From Baseline in Percent Predicted FEV1 Through Week 48	Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.	baseline through 48 weeks	No
Secondary	Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score Through Week 24 and Week 48 (Respiratory Domain Score, Pooled)	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).	baseline through 24 weeks and 48 weeks	No
Secondary	Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48	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.	baseline through 24 weeks and 48 weeks	No
Secondary	Time-to-first Pulmonary Exacerbation Through Week 24 and Week 48	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.	baseline through 24 weeks and 48 weeks	No
Secondary	Absolute Change From Baseline in Weight at Week 24 and Week 48	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.	baseline to 24 weeks and 48 weeks	No

External Links

•   Genetics Home Reference
•   Medline Plus
•   U.S. FDA Resources