Clinical trial NCT01225211: Study of VX-809 Alone and in Combination With VX-770 in Cystic Fibrosis (CF) Patients Homozygous or Heterozygous for the F508del-CFTR Mutation
Official title: A Phase 2, Multicenter, Double-Blinded, Placebo-Controlled, Multiple-Dose Study to Evaluate Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Lumacaftor Monotherapy, and Lumacaftor and Ivacaftor Combination Therapy in Subjects With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2010-10-20
Enrollment: 312
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate of the safety, efficacy, pharmacokinetics (PK) and pharmacodynamic (PD) effects of lumacaftor (VX-809) alone and when coadministered with ivacaftor (VX-770) in participants with cystic fibrosis, homozygous or heterozygous for the F508del-CFTR mutation.


Eligibility criteria: Inclusion Criteria:

* Male or female participants with confirmed diagnosis of CF
* Must have the F508del-CFTR mutation on at least 1 allele.
* FEV1 greater than equal (\>=) 40% of predicted normal for age, gender, and height (Knudson standards)(Cohort 1, 2, and 3); FEV1 40-90% of predicted normal for age, gender, and height (Hankinson standards (Cohort 4)
* Participant of child-bearing potential and who are sexually active must meet the contraception requirements

Exclusion Criteria:

* History of any illness or condition 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).
* An acute illness including acute upper or lower respiratory infection, pulmonary exacerbation or changes in therapy (including antibiotics) for pulmonary disease within 14 days (Cohort 1, 2, and 3) or 28 days (Cohort 4) before receiving the first dose of study drug.
* History of solid organ or hematological transplantation.
* History of alcohol abuse or drug addiction in the past year, including cannabis, cocaine, and opiates.
* Ongoing participation in another therapeutic clinical study, or prior participation in an investigational drug study without appropriate washout
* Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of non-hormonal contraception
* Participants enrolled in Cohort 1 or Cohort 2 will not be eligible for Cohort 3
* Ongoing or prior participation in an investigational drug study within 30 days of the Screening Visit
* Heterozygous participants who participated in Cohort 2 and meet the eligibility criteria for Cohort 4 may participate in Cohort 4
* Evidence of lens opacity or cataract as determined by the ophthalmologic examination (Cohort 4 only)

Primary outcomes:
measure: Cohort 1: Safety and Tolerability Based on Adverse Events (AEs)
timeFrame: Cohort 1: Day 1 up to 28 days after last dose (Last dose = Day 21)
measure: Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs)
timeFrame: Cohort 2 and 3: Day 1 up to 28 days after last dose (Last dose = Day 56)
measure: Cohort 4: Safety and Tolerability Assessed by Number of Participants With AEs and SAEs
timeFrame: Cohort 4: Day 1 up to 28 days after last dose (Last dose = Day 56)
measure: Cohort 1: Absolute Change From Day 14 in Sweat Chloride at Day 21
timeFrame: Cohort 1: Day 14, Day 21
measure: Cohort 2 And 3: Absolute Change From Day 28 in Sweat Chloride at Day 56
timeFrame: Cohort 2 and 3: Day 28, Day 56
measure: Cohort 4: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 56
timeFrame: Cohort 4: Baseline, Day 56
Secondary outcomes:
measure: Cohort 1: Absolute Change From Baseline in Sweat Chloride at Day 14
timeFrame: Cohort 1: Baseline, Day 14
measure: Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14
timeFrame: Cohort 2: Baseline, Day 14
measure: Cohort 4: Absolute Change From Baseline in Sweat Chloride at Day 56
timeFrame: Cohort 4: Baseline, Day 56
measure: Cohort 1: Absolute Change From Day 14 in FEV1 at Day 21
timeFrame: Cohort 1: Day 14, Day 21
measure: Cohort 1: Absolute Change From Day 14 in ppFEV1 at Day 21
timeFrame: Cohort 1: Day 14, Day 21
measure: Cohort 2 and 3: Absolute Change From Day 28 in ppFEV1 at Day 56
timeFrame: Cohort 2 and 3: Day 28, Day 56
measure: Cohort 2 and 3: Relative Change From Day 28 in ppFEV1 at Day 56
timeFrame: Cohort 2 and 3: Day 28, Day 56
measure: Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56
timeFrame: Cohort 2 and 3: Baseline, Day 28 and 56
measure: Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56
timeFrame: Cohort 2 and 3: Baseline, Day 28 and 56
measure: Cohort 4: Relative Change From Baseline in Percent Predicted FEV1 at Day 56
timeFrame: Cohort 4: Baseline, Day 56
measure: Cohort 2 and 3: Absolute Change From Day 28 in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 56
timeFrame: Cohort 2 and 3: Day 28, Day 56
measure: Cohort 4: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 56
timeFrame: Cohort 4: Baseline, Day 56
measure: Cohort 4: Absolute Change From Baseline in Body Mass Index (BMI) at Day 56
timeFrame: Cohort 4: Baseline, Day 56
measure: Cohort 4: Absolute Change From Baseline in Weight at Day 56
timeFrame: Cohort 4: Baseline, Day 56
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Anchorage
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state: Alaska
city: La Jolla
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state: California
city: Long Beach
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state: California
city: Palo Alto
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state: California
city: Sacramento
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state: California
city: Denver
country: United States
state: Colorado
city: New Haven
country: United States
state: Connecticut
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Boise
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Iowa City
country: United States
state: Iowa
city: Kansas City
country: United States
state: Kansas
city: Lexington
country: United States
state: Kentucky
city: New Orleans
country: United States
state: Louisiana
city: Baltimore
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state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Minneapolis
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state: Minnesota
city: St. Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Lebanon
country: United States
state: New Hampshire
city: Buffalo
country: United States
state: New York
city: New Hyde Park
country: United States
state: New York
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Akron
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Pittsburg
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Sioux Falls
country: United States
state: South Dakota
city: Adelaide
country: Australia
city: Brisbane
country: Australia
city: Chermside
country: Australia
city: Nedlands
country: Australia
city: Parkville Victoria
country: Australia
city: Westmead
country: Australia
city: Leuven
country: Belgium
city: Pierre Benite Cedex
country: France
state: Rhone
city: Paris
country: France
city: Jena
country: Germany
state: Thueringen
city: Berlin
country: Germany
city: Bochum
country: Germany
city: Essen
country: Germany
city: Koeln
country: Germany
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: London
country: United Kingdom
Study officials:
References:
citation: 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.
citation: Rowe SM, McColley SA, Rietschel E, Li X, Bell SC, Konstan MW, Marigowda G, Waltz D, Boyle MP; VX09-809-102 Study Group. Lumacaftor/Ivacaftor Treatment of Patients with Cystic Fibrosis Heterozygous for F508del-CFTR. Ann Am Thorac Soc. 2017 Feb;14(2):213-219. doi: 10.1513/AnnalsATS.201609-689OC.
citation: Boyle MP, Bell SC, Konstan MW, McColley SA, Rowe SM, Rietschel E, Huang X, Waltz D, Patel NR, Rodman D; VX09-809-102 study group. A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: a phase 2 randomised controlled trial. Lancet Respir Med. 2014 Jul;2(7):527-38. doi: 10.1016/S2213-2600(14)70132-8. Epub 2014 Jun 24.