A Phase 3 Rollover Study of Lumacaftor in Combination With Ivacaftor in Subjects 12 Years and Older With Cystic Fibrosis

A Phase 3, Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Lumacaftor in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation

Sponsors

Lead Sponsor: Vertex Pharmaceuticals Incorporated

Source Vertex Pharmaceuticals Incorporated
Brief Summary

The purpose of this study is to evaluate the efficacy and safety of long-term treatment with lumacaftor in combination with ivacaftor in people 12 years and older with Cystic Fibrosis.

Detailed Description

This is a Phase 3, parallel group, multicenter, rollover study in participants with CF who are homozygous or heterozygous for the F508del CFTR mutation and who previously participated in Study 103 (Study VX12-809-103, NCT01807923), Study 104 (Study VX12-809-104, NCT01807949), or Cohort 4 of Study 102 (Study VX09-809-102, NCT01225211).

Overall Status Completed
Start Date October 2013
Completion Date April 2016
Primary Completion Date April 2016
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Part A Treatment Cohort: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Day 1 up to Week 105 (Study 105)
Part B Treatment Cohort: Number of Participants With Treatment-Emergent AEs and SAEs Day 1 up to Week 105 (Study 105)
Secondary Outcome
Measure Time Frame
Part A Treatment Cohort: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) At Day 15, Week 8, 16, 24, 36, 48, 60 and 72 Baseline (Study 103/104/105); Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)
Part B Treatment Cohort: Absolute Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72 Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)
Part A Treatment Cohort: Relative Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72 Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)
Part B Treatment Cohort: Relative Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72 Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)
Part A Treatment Cohort: Absolute Change From Baseline in Body Mass Index (BMI) at Day 15, Week 8, 16, 24, 36, 48, 60 and 72 Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)
Part B Treatment Cohort: Absolute Change From Baseline in BMI at Day 15, Week 8, 16, 24, 36, 48, 60 and 72 Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)
Part A Treatment Cohort: Number of Pulmonary Exacerbations Events Per Patient-Year Baseline (Study 103/104) up to Week 100 (Study 105) for Arm 1 and 3 (Cumulative study period); Baseline (Study 105) up to Week 100 (Study 105) for Arm 2 and 4 (current study period)
Part A Treatment Cohort: Absolute Change From Baseline in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Domain Score at Day 15, Week 8, 16, 24, 48 and 72 Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 48, 72 (Study 105)
Part B Treatment Cohort: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 15, Week 8, 16, 24, 48 and 72 Baseline (Study 102 Study), Day 15, Week 8, 16, 24, 48, 72 (Study 105)
Part A Treatment Cohort: Absolute Change From Baseline in BMI Z-score at Day 15, Week 8, 16, 24, 36, 48, 60 and 72 Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)
Part A Treatment Cohort: Absolute Change From Baseline in Body Weight at Day 15, Week 8, 16, 24, 36, 48, 60 and 72 Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)
Part B Treatment Cohort: Absolute Change From Baseline in Body Weight at Day 15, Week 8, 16, 24, 36, 48, 60 and 72 Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)
Part A Treatment Cohort: Time-to-First Pulmonary Exacerbation Baseline (Study 103/104) up to Week 100 (Study 105) for Arm 1 and 3 (Cumulative study period); Baseline (Study 105) up to Week 100 (Study 105) for Arm 2 and 4 (current study period)
Part A Treatment Cohort: Percentage of Participants With at Least 1 Pulmonary Exacerbation Baseline (Study 103/104) up to Week 100 (Study 105) for Arm 1 and 3 (Cumulative study period); Baseline (Study 105) up to Week 100 (Study 105) for Arm 2 and 4 (current study period)
Part A Treatment Cohort: Percentage of Participants With Response Based on Relative Change in Percent Predicted FEV1 From Baseline Baseline (Study 103/104/105); Day 15, Week 8, 16, 24, 36, 48, 60, 72, 84, 96 (Study 105)
Part B Treatment Cohort: Percentage of Participants With Response Based on Relative Change in Percent Predicted FEV1 From Baseline Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)
Part A Observation Cohort: Number of Participants With Serious Adverse Events (SAEs) up to 2 years
Enrollment 1164
Condition
Intervention

Intervention Type: Drug

Intervention Name: Lumacaftor Plus Ivacaftor Combination

Description: Fixed dose combination tablet, oral use

Intervention Type: Drug

Intervention Name: Ivacaftor

Description: Film-coated tablet, oral use

Eligibility

Criteria:

Inclusion Criteria:

- Signed informed consent form (ICF), and where appropriate, signed assent form.

- Participants entering the Part A Treatment Cohort: Completed 24 weeks of study drug treatment in Study 103 or Study 104 and elect to enroll in Part A treatment cohort.

- Participants entering the Part B Treatment Cohort: Completed 56 days of study drug treatment in Cohort 4 of Study 102 and elect to enroll in Part B treatment cohort.

- Participants entering the Part A Observational Cohort: Completed 24 weeks of study drug treatment in Study 103 or Study 104, but do not elect to enroll in the Part A Treatment Cohort or do not qualify to enroll in Part A treatment cohort.

- Willing to remain on a stable CF medication regimen through the end of study (Part A and Part B Treatment Cohorts only).

Exclusion Criteria:

- Any comorbidity or laboratory abnormality 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 (e.g., cirrhosis with portal hypertension).

- Pregnant and nursing females. Females of childbearing potential must have a negative pregnancy test at the Day 1 Visit.

- History of drug intolerance in the prior study that would pose an additional risk to the participant in the opinion of investigator or Vertex.

- History of poor compliance with study drug and/or procedures in the previous study as deemed by the investigator.

- Participation in an investigational drug trial (including studies investigating lumacaftor and/or ivacaftor, or studies requiring blood collections with or without administration of study drug)

Gender: All

Minimum Age: 12 Years

Maximum Age: N/A

Healthy Volunteers: No

Location
Facility:
| Birmingham, Alabama, United States
| Anchorage, Alaska, United States
| Tucson, Arizona, United States
| Little Rock, Arkansas, United States
| La Jolla, California, United States
| Loma Linda, California, United States
| Longbeach, California, United States
| Los Angeles, California, United States
| Madera, California, United States
| Oakland, California, United States
| Palo Alto, California, United States
| Sacramento, California, United States
| Aurora, Colorado, United States
| Denver, Colorado, United States
| Hartford, Connecticut, United States
| New Haven, Connecticut, United States
| Altamonte Springs, Florida, United States
| Hollywood, Florida, United States
| Jacksonville, Florida, United States
| Miami, Florida, United States
| Orlando, Florida, United States
| Tampa, Florida, United States
| Atlanta, Georgia, United States
| Boise, Idaho, United States
| Chicago, Illinois, United States
| Park Ridge, Illinois, United States
| Peoria, Illinois, United States
| Indianapolis, Indiana, United States
| Iowa City, Iowa, United States
| Kansas City, Kansas, United States
| Lexington, Kentucky, United States
| New Orleans, Louisiana, United States
| South Portland, Maine, United States
| Baltimore, Maryland, United States
| Boston, Massachusetts, United States
| Worcester, Massachusetts, United States
| Ann Arbor, Michigan, United States
| Detroit, Michigan, United States
| Grand Rapids, Michigan, United States
| Minneapolis, Minnesota, United States
| Jackson, Mississippi, United States
| Kansas City, Missouri, United States
| St Louis, Missouri, United States
| St. Louis, Missouri, United States
| Omaha, Nebraska, United States
| Bedford, New Hampshire, United States
| Lebanon, New Hampshire, United States
| Long Branch, New Jersey, United States
| Morristown, New Jersey, United States
| New Brunswick, New Jersey, United States
| Albuquerque, New Mexico, United States
| Albany, New York, United States
| Buffalo, New York, United States
| Lake Success, New York, United States
| New York, New York, United States
| Rochester, New York, United States
| Syracuse, New York, United States
| Valhalla, New York, United States
| Chapel Hill, North Carolina, United States
| Durham, North Carolina, United States
| Akron, Ohio, United States
| Cincinnati, Ohio, United States
| Cleveland, Ohio, United States
| Columbus, Ohio, United States
| Dayton, Ohio, United States
| Toledo, Ohio, United States
| Oklahoma City, Oklahoma, United States
| Portland, Oregon, United States
| Hershey, Pennsylvania, United States
| Philadelphia, Pennsylvania, United States
| Pittsburgh, Pennsylvania, United States
| Charelston, South Carolina, United States
| Sioux Falls, South Dakota, United States
| Knoxville, Tennessee, United States
| Memphis, Tennessee, United States
| Nashville, Tennessee, United States
| Austin, Texas, United States
| Dallas, Texas, United States
| Fort Worth, Texas, United States
| Houston, Texas, United States
| San Antonio, Texas, United States
| Tyler, Texas, United States
| Salt Lake City, Utah, United States
| Colchester, Vermont, United States
| Charlottesville, Virginia, United States
| Norfolk, Virginia, United States
| Richmond, Virginia, United States
| Seattle, Washington, United States
| Spokane, Washington, United States
| Morgantown, West Virginia, United States
| Madison, Wisconsin, United States
| Milwaukee, Wisconsin, United States
| New Lambton Heights, New South Wales, Australia
| Westmead, New South Wales, Australia
| Adelaide, Queensland, Australia
| Chermside, Queensland, Australia
| Herston, Queensland, Australia
| South Brisbane, Queensland, Australia
| Nedlands, Australia
| Subiaco, Australia
| Innsbruck, Austria
| Wels, Austria
| Bruxelles, Belgium
| Gent, Belgium
| Leuven, Belgium
| Liège, Belgium
| Calgary, Alberta, Canada
| Edmonton, Alberta, Canada
| Vancouver, British Columbia, Canada
| Halifax, Nova Scotia, Canada
| Ottowa, Ontario, Canada
| Toronto, Ontario, Canada
| Montreal, Quebec, Canada
| Brno, Czech Republic
| Plzeň - Bory, Czech Republic
| Praha 5, Czech Republic
| Copenhagen, Denmark
| Strasbourg, Bas Rhin, France
| Marseille, Bouches-du-Rhone, France
| Toulouse, Haute Garonne, France
| Montpellier, Herault, France
| Lille, Nord, France
| Bron Cedex, Rhone, France
| Bordeaux, France
| Paris, France
| Pierre Benite, France
| Rhone, France
| Roscoff, France
| Muenchen, Bayem, Germany
| Muenchen, Bayern, Germany
| Berlin, Germany
| Bochum, Germany
| Erlangen, Germany
| Essen, Germany
| Frankfurt, Germany
| Giessen, Germany
| Hannover, Germany
| Jena, Germany
| Koeln, Germany
| Leipzig, Germany
| Muenchen, Germany
| Tuebingen, Germany
| Wuerzburg, Germany
| Dublin, Ireland
| Ancona, Italy
| Firenze, Italy
| Genova, Italy
| Milano, Italy
| Roma, Italy
| Verona, Italy
| Amsterdam, Netherlands
| Den Haag, Netherlands
| Nijmegen, Netherlands
| Rotterdam, Netherlands
| Barcelona, Spain
| Valencia, Spain
| Goteborg, Sweden
| Stockholm, Sweden
| Exeter, Devon, United Kingdom
| Belfast, United Kingdom
| Birmingham, United Kingdom
| Bristol, United Kingdom
| Leeds, United Kingdom
| London, United Kingdom
| Newcastle, United Kingdom
| Nottingham, United Kingdom
| Southampton, United Kingdom
Location Countries

Australia

Austria

Belgium

Canada

Czech Republic

Denmark

France

Germany

Ireland

Italy

Netherlands

Spain

Sweden

United Kingdom

United States

Verification Date

April 2017

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 7
Arm Group

Label: Arm 1 Part A: LUM 600 mg qd/ IVA 250 mg q12h

Type: Experimental

Description: Participants who received lumacaftor (LUM, VX-809) 600 milligram (mg) plus ivacaftor (IVA, VX-770) 250 mg fixed-dose combination (FDC) tablet orally in the morning and IVA 250 mg film-coated tablet orally in the evening, in the previous study VX12-809-103 or VX12-809-104, and will receive the same treatment in this study VX12-809-105 up to Week 96.

Label: Arm 2 Part A: Placebo - LUM 600 mg qd/ IVA 250 mg q12h

Type: Experimental

Description: Participants who received placebo matched to LUM and IVA tablet in the previous study VX12-809-103 or VX12-809-104, and will receive LUM 600 mg plus IVA 250 mg FDC tablet orally in the morning and IVA 250 mg film-coated tablet orally in the evening in this study VX12-809-105 up to Week 96.

Label: Arm 3 Part A: LUM 400 mg q12h/ IVA 250 mg q12h

Type: Experimental

Description: Participants who received LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening in the previous study VX12-809-103 or VX12-809-104, and will receive the same treatment in this study VX12-809-105 up to Week 96.

Label: Arm 4 Part A: Placebo - LUM 400 mg q12h/ IVA 250 mg q12h

Type: Experimental

Description: Participants who received placebo matched to LUM and IVA tablet in the previous study VX12-809-103 or VX12-809-104, and will receive LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening in this study VX12-809-105 up to Week 96.

Label: Arm 5 Part A: Observational Cohort

Type: No Intervention

Description: Participants who received either LUM 600 mg plus IVA 250 mg FDC tablet orally in the morning and IVA 250 mg film-coated tablet orally in the evening OR LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening OR placebo matched to LUM and IVA in the morning and evening, in the previous study VX12-809-103 or VX12-809-104, and will be observed (will not receive study drug) in this study VX12-809-105 for up to 2 years.

Label: Arm 6 Part B: LUM 400 mg q12h/ IVA 250 mg q12h

Type: Experimental

Description: Participants who received LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening in Cohort 4 of the previous study VX09-809-102, and will receive the same treatment in this study VX12-809-105 up to Week 96.

Label: Arm 7 Part B: Placebo - LUM 400 mg q12h/ IVA 250 mg q12h

Type: Experimental

Description: Participants who received placebo matched to LUM and IVA tablet in Cohort 4 of the previous study VX09-809-102, and will receive LUM 400 mg plus IVA 250 mg FDC tablet orally in the morning and evening in this study VX12-809-105 up to Week 96.

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Triple (Participant, Care Provider, Investigator)

Source: ClinicalTrials.gov