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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01931839




Registration number
NCT01931839
Ethics application status
Date submitted
26/08/2013
Date registered
29/08/2013
Date last updated
12/05/2017

Titles & IDs
Public title
A Phase 3 Rollover Study of Lumacaftor in Combination With Ivacaftor in Subjects 12 Years and Older With Cystic Fibrosis
Scientific 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 12 Years and Older With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation
Secondary ID [1] 0 0
VX12-809-105
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lumacaftor Plus Ivacaftor Combination
Treatment: Drugs - Ivacaftor

Experimental: Arm 1 Part A: LUM 600 mg qd/ IVA 250 mg q12h - 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.

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

Experimental: Arm 3 Part A: LUM 400 mg q12h/ IVA 250 mg q12h - 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.

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

No intervention: Arm 5 Part A: Observational Cohort - 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.

Experimental: Arm 6 Part B: LUM 400 mg q12h/ IVA 250 mg q12h - 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.

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


Treatment: Drugs: Lumacaftor Plus Ivacaftor Combination
Fixed dose combination tablet, oral use

Treatment: Drugs: Ivacaftor
Film-coated tablet, oral use
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A Treatment Cohort: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [1] 0 0
Day 1 up to Week 105 (Study 105)
Primary outcome [2] 0 0
Part B Treatment Cohort: Number of Participants With Treatment-Emergent AEs and SAEs
Timepoint [2] 0 0
Day 1 up to Week 105 (Study 105)
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Baseline (Study 103/104/105); Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)
Secondary outcome [2] 0 0
Part B Treatment Cohort: Absolute Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72
Timepoint [2] 0 0
Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)
Secondary outcome [3] 0 0
Part A Treatment Cohort: Relative Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72
Timepoint [3] 0 0
Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)
Secondary outcome [4] 0 0
Part B Treatment Cohort: Relative Change From Baseline in Percent Predicted FEV1 at Day 15, Week 8, 16, 24, 36, 48, 60 and 72
Timepoint [4] 0 0
Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)
Secondary outcome [6] 0 0
Part B Treatment Cohort: Absolute Change From Baseline in BMI at Day 15, Week 8, 16, 24, 36, 48, 60 and 72
Timepoint [6] 0 0
Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60 , 72 (Study 105)
Secondary outcome [7] 0 0
Part A Treatment Cohort: Number of Pulmonary Exacerbations Events Per Patient-Year
Timepoint [7] 0 0
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)
Secondary outcome [8] 0 0
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
Timepoint [8] 0 0
Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 48, 72 (Study 105)
Secondary outcome [9] 0 0
Part B Treatment Cohort: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 15, Week 8, 16, 24, 48 and 72
Timepoint [9] 0 0
Baseline (Study 102 Study), Day 15, Week 8, 16, 24, 48, 72 (Study 105)
Secondary outcome [10] 0 0
Part A Treatment Cohort: Absolute Change From Baseline in BMI Z-score at Day 15, Week 8, 16, 24, 36, 48, 60 and 72
Timepoint [10] 0 0
Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)
Secondary outcome [11] 0 0
Part A Treatment Cohort: Absolute Change From Baseline in Body Weight at Day 15, Week 8, 16, 24, 36, 48, 60 and 72
Timepoint [11] 0 0
Baseline (Study 103/104/105), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)
Secondary outcome [12] 0 0
Part B Treatment Cohort: Absolute Change From Baseline in Body Weight at Day 15, Week 8, 16, 24, 36, 48, 60 and 72
Timepoint [12] 0 0
Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)
Secondary outcome [13] 0 0
Part A Treatment Cohort: Time-to-First Pulmonary Exacerbation
Timepoint [13] 0 0
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)
Secondary outcome [14] 0 0
Part A Treatment Cohort: Percentage of Participants With at Least 1 Pulmonary Exacerbation
Timepoint [14] 0 0
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)
Secondary outcome [15] 0 0
Part A Treatment Cohort: Percentage of Participants With Response Based on Relative Change in Percent Predicted FEV1 From Baseline
Timepoint [15] 0 0
Baseline (Study 103/104/105); Day 15, Week 8, 16, 24, 36, 48, 60, 72, 84, 96 (Study 105)
Secondary outcome [16] 0 0
Part B Treatment Cohort: Percentage of Participants With Response Based on Relative Change in Percent Predicted FEV1 From Baseline
Timepoint [16] 0 0
Baseline (Study 102), Day 15, Week 8, 16, 24, 36, 48, 60, 72 (Study 105)
Secondary outcome [17] 0 0
Part A Observation Cohort: Number of Participants With Serious Adverse Events (SAEs)
Timepoint [17] 0 0
up to 2 years

Eligibility
Key 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).
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2016
Sample size
Target
Accrual to date
Final
1164
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
- New Lambton Heights
Recruitment hospital [2] 0 0
- Westmead
Recruitment hospital [3] 0 0
- Adelaide
Recruitment hospital [4] 0 0
- Chermside
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- Herston
Recruitment hospital [6] 0 0
- South Brisbane
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- Nedlands
Recruitment hospital [8] 0 0
- Subiaco
Recruitment postcode(s) [1] 0 0
- New Lambton Heights
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- Westmead
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- Adelaide
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- Chermside
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- Herston
Recruitment postcode(s) [6] 0 0
- South Brisbane
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- Nedlands
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- Subiaco
Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Vertex Pharmaceuticals Incorporated
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01931839
Trial related presentations / publications
Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
Konstan MW, McKone EF, Moss RB, Marigowda G, Tian S, Waltz D, Huang X, Lubarsky B, Rubin J, Millar SJ, Pasta DJ, Mayer-Hamblett N, Goss CH, Morgan W, Sawicki GS. Assessment of safety and efficacy of long-term treatment with combination lumacaftor and ivacaftor therapy in patients with cystic fibrosis homozygous for the F508del-CFTR mutation (PROGRESS): a phase 3, extension study. Lancet Respir Med. 2017 Feb;5(2):107-118. doi: 10.1016/S2213-2600(16)30427-1. Epub 2016 Dec 21.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
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Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01931839