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Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Lumacaftor in Combination With Ivacaftor

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
LUM/IVA
LUM/IVA
Sponsored by
Vertex Pharmaceuticals Incorporated
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects entering the Treatment Cohort must meet both of the following criteria:

  • Completed study visits up to Week 24 of Study 109 or Week 26 of Study 011B and did not permanently discontinue treatment
  • Willing to remain on a stable CF medication through the Safety Follow-up Visit.

Subjects entering the Observational Cohort must meet 1 of the following criteria:

  • Completed 24 weeks of study drug treatment in Study 109 or completed 24 weeks of study drug treatment and the Week 26 Safety Follow up in Study 011B.
  • Received at least 4 weeks of study drug and completed visits up to Week 24 of Study 109 or Week 26 of Study 011B.

Exclusion Criteria (Treatment Cohort Only):

  • History of 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 subject (e.g., cirrhosis with portal hypertension).
  • Pregnant and nursing females.
  • Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements.
  • History of drug intolerance in the prior study that would pose an additional risk to the subject in the opinion of investigator
  • History of poor compliance with study drug and/or procedure in the previous study as deemed by the investigator.
  • Participation in an investigational drug trial (including studies investigating lumacaftor and/or ivacaftor).

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

No Intervention

Experimental

Arm Label

Treatment Period 1: LUM/IVA to LUM/IVA

Treatment Period 1: Placebo (PBO) to LUM/IVA

Treatment Period 1: Observational Cohort

Treatment Period 2: LUM/IVA

Arm Description

Outcomes

Primary Outcome Measures

Treatment Period 1 (Treatment Cohorts): Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Secondary Outcome Measures

Absolute Change in Lung Clearance Index (LCI) 2.5
LCI 2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Absolute Change in Sweat Chloride
Sweat samples were collected using an approved collection device.
Absolute Change in Body Mass Index (BMI)
BMI was defined as weight in kilograms divided by height in square meter (m^2).
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
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, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Observational Cohort: Safety as Assessed by Serious Adverse Events (SAEs)
Absolute Change in LCI 5.0
LCI 5.0 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/20th of its starting value.
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Relative Change in ppFEV1
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Absolute Change in BMI-for-age Z-score
BMI was defined as weight in kilograms divided by height in m^2. z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Absolute Change in Weight
Absolute Change in Weight-for-age Z-score
z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Absolute Change in Height
Absolute Change in Height-for-age Z-score
z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Absolute Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Total Domain Score
The TSQM measures participants' experiences with their medication on four dimensions: effectiveness, side effects, convenience and global satisfaction. For each dimension, responses are added and transformed in the total domain score, which ranges from 0 to 100, where higher scores indicate greater satisfaction.
Time-to-first Pulmonary Exacerbation
Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Percentage of Participants Having At Least 1 Pulmonary Exacerbation Event
Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Number of Pulmonary Exacerbation Events Per Patient-year
Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Rate of Change in LCI 2.5
Rate of change analysis evaluates the change in LCI 2.5 after long term treatment with LUM/IVA. A rate of change equal to zero would indicate that treatment effects were stable.
Rate of Change in LCI 5.0
Rate of change analysis evaluates the change in LCI 5.0 after long term treatment with LUM/IVA. A rate of change equal to zero would indicate that treatment effects were stable.
Rate of Change in ppFEV1
Rate of change analysis evaluates the change in ppFEV1 after long term treatment with LUM/IVA. A rate of change equal to zero would indicate that treatment effects were stable.
Treatment Period 2: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Full Information

First Posted
September 1, 2015
Last Updated
April 27, 2021
Sponsor
Vertex Pharmaceuticals Incorporated
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1. Study Identification

Unique Protocol Identification Number
NCT02544451
Brief Title
Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Lumacaftor in Combination With Ivacaftor
Official Title
A Phase 3, Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Lumacaftor in Combination With Ivacaftor in Subjects Aged 6 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
August 2015 (Actual)
Primary Completion Date
August 2018 (Actual)
Study Completion Date
April 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Study 110 is a Phase 3, multicenter study in subjects aged 6 years and older with cystic fibrosis (CF) who are homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation and who participated in Study 109 (NCT02514473) or Study 011B (NCT01897233). Study 110 is designed to evaluate the safety and efficacy of long term treatment of lumacaftor in combination with ivacaftor.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
246 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment Period 1: LUM/IVA to LUM/IVA
Arm Type
Experimental
Arm Title
Treatment Period 1: Placebo (PBO) to LUM/IVA
Arm Type
Experimental
Arm Title
Treatment Period 1: Observational Cohort
Arm Type
No Intervention
Arm Title
Treatment Period 2: LUM/IVA
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
LUM/IVA
Other Intervention Name(s)
VX-809/VX-770, lumacaftor/ivacaftor
Intervention Description
Lumacaftor (LUM) 200 mg every 12 hours (q12h)/ivacaftor (IVA) 250 mg q12h (for 6 through 11 years of age). LUM 400 mg q12h/IVA 250 mg q12h (for 12 years and older).
Intervention Type
Drug
Intervention Name(s)
LUM/IVA
Other Intervention Name(s)
VX-809/VX-770, lumacaftor/ivacaftor
Intervention Description
LUM 200 mg q12h/IVA 250 mg q12h (for 6 through 11 years of age).
Primary Outcome Measure Information:
Title
Treatment Period 1 (Treatment Cohorts): Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
Day 1 up to Week 100
Secondary Outcome Measure Information:
Title
Absolute Change in Lung Clearance Index (LCI) 2.5
Description
LCI 2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Time Frame
From Parent Study Baseline at Week 96
Title
Absolute Change in Sweat Chloride
Description
Sweat samples were collected using an approved collection device.
Time Frame
From Parent Study Baseline at Week 96
Title
Absolute Change in Body Mass Index (BMI)
Description
BMI was defined as weight in kilograms divided by height in square meter (m^2).
Time Frame
From Parent Study Baseline at Week 96
Title
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Description
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, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Time Frame
From Parent Study Baseline at Week 96
Title
Observational Cohort: Safety as Assessed by Serious Adverse Events (SAEs)
Time Frame
Day 1 up to Week 100
Title
Absolute Change in LCI 5.0
Description
LCI 5.0 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/20th of its starting value.
Time Frame
From Parent Study Baseline at Week 96
Title
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame
From Parent Study Baseline at Week 96
Title
Relative Change in ppFEV1
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame
From Parent Study Baseline at Week 96
Title
Absolute Change in BMI-for-age Z-score
Description
BMI was defined as weight in kilograms divided by height in m^2. z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Time Frame
From Parent Study Baseline at Week 96
Title
Absolute Change in Weight
Time Frame
From Parent Study Baseline at Week 96
Title
Absolute Change in Weight-for-age Z-score
Description
z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Time Frame
From Parent Study Baseline at Week 96
Title
Absolute Change in Height
Time Frame
From Parent Study Baseline at Week 96
Title
Absolute Change in Height-for-age Z-score
Description
z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Time Frame
From Parent Study Baseline at Week 96
Title
Absolute Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Total Domain Score
Description
The TSQM measures participants' experiences with their medication on four dimensions: effectiveness, side effects, convenience and global satisfaction. For each dimension, responses are added and transformed in the total domain score, which ranges from 0 to 100, where higher scores indicate greater satisfaction.
Time Frame
From Parent Study Baseline at Week 96
Title
Time-to-first Pulmonary Exacerbation
Description
Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Time Frame
From Parent Study Baseline through Week 96
Title
Percentage of Participants Having At Least 1 Pulmonary Exacerbation Event
Description
Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Time Frame
From Parent Study Baseline through Week 96
Title
Number of Pulmonary Exacerbation Events Per Patient-year
Description
Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Time Frame
From Parent Study Baseline through Week 96
Title
Rate of Change in LCI 2.5
Description
Rate of change analysis evaluates the change in LCI 2.5 after long term treatment with LUM/IVA. A rate of change equal to zero would indicate that treatment effects were stable.
Time Frame
Day 15 after first dose of LUM/IVA through Week 96
Title
Rate of Change in LCI 5.0
Description
Rate of change analysis evaluates the change in LCI 5.0 after long term treatment with LUM/IVA. A rate of change equal to zero would indicate that treatment effects were stable.
Time Frame
Day 15 after first dose of LUM/IVA through Week 96
Title
Rate of Change in ppFEV1
Description
Rate of change analysis evaluates the change in ppFEV1 after long term treatment with LUM/IVA. A rate of change equal to zero would indicate that treatment effects were stable.
Time Frame
Day 15 after first dose of LUM/IVA through Week 96
Title
Treatment Period 2: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
Day 1 up to Week 168

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects entering the Treatment Cohort must meet both of the following criteria: Completed study visits up to Week 24 of Study 109 or Week 26 of Study 011B and did not permanently discontinue treatment Willing to remain on a stable CF medication through the Safety Follow-up Visit. Subjects entering the Observational Cohort must meet 1 of the following criteria: Completed 24 weeks of study drug treatment in Study 109 or completed 24 weeks of study drug treatment and the Week 26 Safety Follow up in Study 011B. Received at least 4 weeks of study drug and completed visits up to Week 24 of Study 109 or Week 26 of Study 011B. Exclusion Criteria (Treatment Cohort Only): History of 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 subject (e.g., cirrhosis with portal hypertension). Pregnant and nursing females. Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements. History of drug intolerance in the prior study that would pose an additional risk to the subject in the opinion of investigator History of poor compliance with study drug and/or procedure in the previous study as deemed by the investigator. Participation in an investigational drug trial (including studies investigating lumacaftor and/or ivacaftor).
Facility Information:
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Birmingham
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Tucson
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Parkville
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Victoria
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Herston
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New Lambton Heights
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Subiaco
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Bron
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Giessen
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Koeln
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Belfast
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Edinburgh
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London
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United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
33516285
Citation
Chilvers MA, Davies JC, Milla C, Tian S, Han Z, Cornell AG, Owen CA, Ratjen F. Long-term safety and efficacy of lumacaftor-ivacaftor therapy in children aged 6-11 years with cystic fibrosis homozygous for the F508del-CFTR mutation: a phase 3, open-label, extension study. Lancet Respir Med. 2021 Jul;9(7):721-732. doi: 10.1016/S2213-2600(20)30517-8. Epub 2021 Jan 28. Erratum In: Lancet Respir Med. 2021 Apr;9(4):e38.
Results Reference
derived

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Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Lumacaftor in Combination With Ivacaftor

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