Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Homozygous for the F508del-CFTR Mutation

NCT00953706 | Terminated Phase 2 Results DMC

• 2 other identifiers: VX08-770-1042009-010261-23
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 34

Brief Summary

The purpose of this study was to evaluate the safety and efficacy of ivacaftor in participants with cystic fibrosis (CF) who were aged 12 years or older and were homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation. 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 adenosine monophosphate (AMP)-dependent protein kinase A (PKA) activation.

Conditions

Cystic Fibrosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16

  Spirometry (as measured by ppFEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) was calculated using the Knudson method.

  Part A baseline through Week 16

Secondary Outcomes (12)

• Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 16

  Part A baseline through Week 16

• Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration Through Week 16

  Part A baseline through Week 16

• Part A : Rate of Change From Baseline in Weight Through Week 16

  Part A baseline through Week 16

• Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64

  Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64

• Part B : Rate of Change From Part A Baseline in ppFEV1 Through Week 64

  Part A baseline through Week 64

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo matched to ivacaftor tablet orally every 12 hours (q12h) for 16 weeks during Part A (double-blind treatment period), followed by ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).

Drug: Ivacaftor; Drug: Placebo

Ivacaftor

EXPERIMENTAL

Ivacaftor 150 milligram (mg) tablet orally q12h for 16 weeks during Part A (double-blind treatment period), followed by ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).

Drug: Ivacaftor

Interventions

Ivacaftor DRUG

Tablet

Also known as: VX-770

Ivacaftor; Placebo

Placebo DRUG

Tablet

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of cystic fibrosis (CF) and homozygous for F508del-CFTR mutation
• Forced expiratory volume in 1 second (FEV1) of at least 40% of predicted normal for age, gender, and height
• Willing to use at least 2 highly effective birth control methods during the study
• No clinically significant abnormalities that would have interfered with the study assessments, as judged by the investigator
• Able to understand and comply with protocol requirements, restrictions, and instructions and likely to complete the study as planned, as judged by the investigator

You may not qualify if:

• 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 \>=3 x the upper limit of normal
• Abnormal renal function at Screening
• History of solid organ or hematological transplantation
• Pregnant or breast-feeding (for women)
• Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days prior to screening
• Previous participation in a VX-809 study
• Used inhaled hypertonic saline treatment
• Concomitant use of any inhibitors or inducers of cytochrome P450 3A4 (CYP3A4)

Sponsors & Collaborators

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

Study Sites (34)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

Providence Medical Center

Anchorage, Alaska, 99508, United States

Location

Kaiser Permanente Medical Care Program

Oakland, California, 94611, United States

Location

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Nemours Children's Clinic

Orlando, Florida, 32801, United States

Location

St. Luke's CF clinic

Boise, Idaho, 83712, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Massachussetts Medical School

Worcester, Massachusetts, 01655, United States

Location

Helen DeVos Children's Hospital; Spectrum Health Hospitals

Grand Rapids, Michigan, 49503, United States

Location

The Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Monmouth Medical Center

Long Branch, New Jersey, 07740, United States

Location

Morristown Memorial Hospital

Morristown, New Jersey, 07962, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

Women and Children's Hospital of Buffalo

Buffalo, New York, 14222, United States

Location

New York Medical College

Hawthorne, New York, 10532, United States

Location

The CF Center, Beth Israel Medical Center

New York, New York, 10003, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Toldedo Children's Hospital

Toledo, Ohio, 43606, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Tennessee

Memphis, Tennessee, 38103, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Univeristy of Utah

Salt Lake City, Utah, 84132, United States

Location

Vermont Lung Center at the University of Vermont

Colchester, Vermont, 05446, United States

Location

Medical College of Virginia

Richmond, Virginia, 23298, United States

Location

Related Publications (1)

• Flume PA, Liou TG, Borowitz DS, Li H, Yen K, Ordonez CL, Geller DE; VX 08-770-104 Study Group. Ivacaftor in subjects with cystic fibrosis who are homozygous for the F508del-CFTR mutation. Chest. 2012 Sep;142(3):718-724. doi: 10.1378/chest.11-2672.

  PMID: 22383668 DERIVED

Related Links

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

MeSH Terms

Conditions

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

Interventions

ivacaftor

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

In Part B, the treatment duration was 96 weeks; however, due to early study termination all analysis were performed up to Week 64, as planned.

Results Point of Contact

• Title: Medical Monitor
• Organization: Vertex

medicalinfo@vrtx.com

617-444-6777

Study Officials

• Patrick A Flume, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2009
• First Posted: August 6, 2009
• Study Start: September 1, 2009
• Primary Completion: July 1, 2010
• Study Completion: May 1, 2013
• Last Updated: September 11, 2015
• Results First Posted: August 21, 2012

Record last verified: 2015-08

Locations

US (34)