Clinical trial NCT00909532: Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older With the G551D Mutation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Keywords: Fibrosis
Pancreatic Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2009-05-28
Enrollment: 167
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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)

Primary outcomes:
measure: Absolute Mean Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24
timeFrame: baseline through 24 weeks
Secondary outcomes:
measure: Absolute Mean Change From Baseline in Percent Predicted FEV1 Through Week 48
timeFrame: baseline through 48 weeks
measure: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score Through Week 24 and Week 48 (Respiratory Domain Score, Pooled)
timeFrame: baseline through 24 weeks and 48 weeks
measure: Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48
timeFrame: baseline through 24 weeks and 48 weeks
measure: Time-to-first Pulmonary Exacerbation Through Week 24 and Week 48
timeFrame: baseline through 24 weeks and 48 weeks
measure: Absolute Change From Baseline in Weight at Week 24 and Week 48
timeFrame: baseline to 24 weeks and 48 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Oakland
country: United States
facility: Kaiser Permanente Medical Care Program
state: California
city: Palo Alto
country: United States
facility: Cystic Fibrosis Research Office, Stanford University
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: Denver
country: United States
facility: National Jewish Medical and Research Center
state: Colorado
city: Atlanta
country: United States
facility: Emory Cystic Fibrosis Center
state: Georgia
city: Boise
country: United States
facility: St. Luke's CF Clinic
state: Idaho
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Pulmonary, Allergy & Critical Care Medicine, University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: The Children's Mercy Hospital
state: Missouri
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: Adult Pulmonary/ CF, University of Nebraska Medical Center
state: Nebraska
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Women and Children's Hospital of Buffalo
state: New York
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Pediatric & Pulmonary Division, Rainbow Babies/Case Western
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Toledo
country: United States
facility: Toledo Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Sciences University
state: Oregon
city: Hershey
country: United States
facility: Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Knoxville
country: United States
facility: East Tennessee Children's Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Seattle
country: United States
facility: Division of Pulmonary and CCM, University of Washington
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Westmead
country: Australia
facility: The Children's Hospital Westmead
state: New South Wales
city: Chermside
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Children's Hospital Brisbane
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Adult Hospital
state: Queensland
city: Parkville
country: Australia
facility: Royal Children's Hospital Melbourne
state: Victoria
city: Nedlands
country: Australia
facility: Lung Institute of Western Australia
state: Western Australia
city: Subiaco
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: CF Center, Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Montreal Children's Hospital - MUHC
state: Quebec
city: Prague
country: Czech Republic
facility: FN Motol
city: Paris
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: Hopital Necker
city: Roscoff
country: France
facility: Centre de Perharidy
city: Erlangen
country: Germany
facility: Kinder- und Jugendklinik Universitätsklinikum Erlangen
city: Jena
country: Germany
facility: Mukoviszidose-Zentrum am Klinikum der Friedrich-Schiller-Universität Jena, Klinik für Kinder- und Jugendmedizin
city: Munich
country: Germany
facility: Klinikum der LMU München, Dr. von Haunersches Kinderspital (CHA)
city: Wurzburg
country: Germany
facility: Universitäts-Kinderklinik Würzburg
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: Our Lady's Children's Hospital
city: Dublin
country: Ireland
facility: The National Children's Hospital
city: Dublin
country: Ireland
facility: St. Vincent's University Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
state: Northern Ireland
city: London
country: United Kingdom
facility: Imperial College London
Study officials:
affiliation: Children's Hospital and Regional Medical Center, Seattle, Washington, USA
name: Bonnie W. Ramsey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Respiratory Medicine Group, Queen's University of Belfast, Belfast, Northern Ireland, UK
name: Stuart Elborn, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Drevinek P, Griese M, McKone EF, Wainwright CE, Konstan MW, Moss R, Ratjen F, Sermet-Gaudelus I, Rowe SM, Dong Q, Rodriguez S, Yen K, Ordonez 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.
citation: Flume PA, Wainwright CE, Elizabeth Tullis D, Rodriguez S, Niknian M, Higgins M, Davies JC, Wagener JS. Recovery of lung function following a pulmonary exacerbation in patients with cystic fibrosis and the G551D-CFTR mutation treated with ivacaftor. J Cyst Fibros. 2018 Jan;17(1):83-88. doi: 10.1016/j.jcf.2017.06.002. Epub 2017 Jun 24.
citation: Solem CT, Vera-Llonch M, Liu S, Botteman M, Castiglione B. Impact of pulmonary exacerbations and lung function on generic health-related quality of life in patients with cystic fibrosis. Health Qual Life Outcomes. 2016 Apr 21;14:63. doi: 10.1186/s12955-016-0465-z.
citation: Quittner A, Suthoff E, Rendas-Baum R, Bayliss MS, Sermet-Gaudelus I, Castiglione B, Vera-Llonch M. Effect of ivacaftor treatment in patients with cystic fibrosis and the G551D-CFTR mutation: patient-reported outcomes in the STRIVE randomized, controlled trial. Health Qual Life Outcomes. 2015 Jul 2;13:93. doi: 10.1186/s12955-015-0293-6.