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Study to Evaluate Lumacaftor and Ivacaftor Combination Therapy in Subjects 12 Years and Older With Advanced Lung Disease

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02390219
First Posted: March 17, 2015
Last Update Posted: November 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
  Purpose
The purpose of this study is to evaluate the safety and tolerability of LUM/IVA combination therapy in subjects 12 years and older with CF and advanced lung disease and who are homozygous for the F508del CFTR mutation

Condition Intervention Phase
Cystic Fibrosis Advanced Lung Disease Drug: Lumacaftor Drug: Ivacaftor Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3b, Open-Label Study to Evaluate Lumacaftor and Ivacaftor Combination Therapy in Subjects 12 Years and Older With Cystic Fibrosis and Advanced Lung Disease, Homozygous for the F508del-CFTR Mutation

Resource links provided by NLM:


Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • Number of Participants With Treatment Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Day 1 up to Week 28 ]
    AE: any untoward medical occurrence in a participant during the study; event does not necessarily have a causal relationship with treatment. This includes any newly occurring event/previous condition that has increased in severity/frequency after informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event, which falls into any of the following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. TEAEs: AEs that started/ worsened on/after the start of study drug through the Safety Follow up Visit (4 weeks after the last dose of study drug). Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.


Secondary Outcome Measures:
  • Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Up to Week 24 [ Time Frame: Baseline, Up to Week 24 ]
    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 participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.

  • Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Up to Week 24 [ Time Frame: Baseline, Up to Week 24 ]
    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 FEV1 (for age, gender, race, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.

  • Duration For Which Participants Received Intravenous (IV) Antibiotics [ Time Frame: Baseline through Week 24 ]
    The duration for which participants received IV antibiotics for sinopulmonary signs and symptoms were reported. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.

  • Number of Hospitalizations [ Time Frame: Baseline through Week 24 ]
    Number of hospitalizations (all causes) through Week 24 was summarized. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.

  • Absolute Change From Baseline in Sweat Chloride at Average of Day 15 and Week 4 [ Time Frame: Baseline, Day 15 and Week 4 ]
    Sweat samples were collected using an approved collection device. Baseline was defined as the average of the measurements at screening and on Day 1 pre-dose. The average absolute change from baseline in sweat chloride was derived as: (Average of Day 15 and Week 4 value) minus Baseline value. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.

  • Absolute Change From Baseline in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Domain Score Through Week 24 [ Time Frame: Baseline, Through Week 24 ]
    The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), the scaled score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.


Enrollment: 46
Study Start Date: March 2015
Study Completion Date: October 2016
Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lumacaftor/Ivacaftor combination
Lumacaftor 400 milligram (mg) and ivacaftor 250 mg combination tablet orally twice daily for 24 weeks.
Drug: Lumacaftor
Other Name: VX-809
Drug: Ivacaftor
Other Name: VX-770

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Homozygous for the F508del-CFTR mutation; historical genotype must be documented in the participant's source documents.
  • Percent predicted FEV1 <40 of adjusted for age, sex, and height at Screening

Exclusion Criteria:

  • Participant currently receiving invasive mechanical ventilation.
  • History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant
  • Any clinically significant laboratory abnormalities at screening that would interfere with the study assessments or pose an undue risk for the subject
  • A 12-lead electrocardiograms (ECG) demonstrating QTcF >450 msec at Screening
  • History of solid organ or hematological transplantation
  • History of alcohol or drug abuse in the past year
  • Ongoing or prior participation in an investigational drug study (including studies investigating lumacaftor and/or ivacaftor) within 30 days of screening.
  • Use of strong inhibitors, moderate inducers, or strong inducers of CYP3A
  • Pregnant and nursing females: Females of childbearing potential must have a negative pregnancy test at Screening and Day 1.
  • Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements
  • Use of beta blockers or the equivalent at Screening.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02390219


Locations
United States, Colorado
Denver, Colorado, United States
United States, Florida
Tampa, Florida, United States
United States, Illinois
Chicago, Illinois, United States
United States, Missouri
Saint Louis, Missouri, United States
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States
United States, Texas
Houston, Texas, United States
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
  More Information

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT02390219     History of Changes
Other Study ID Numbers: VX14-809-106
First Submitted: March 11, 2015
First Posted: March 17, 2015
Results First Submitted: October 4, 2017
Results First Posted: November 1, 2017
Last Update Posted: November 1, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Fibrosis
Cystic Fibrosis
Lung Diseases
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Ivacaftor
Chloride Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action