Study of VX-809 Alone and in Combination With VX-770 in Cystic Fibrosis (CF) Patients Homozygous or Heterozygous for the F508del-CFTR Mutation

NCT ID: NCT01225211

Last Updated: 2015-10-05

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

312 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-10-31

Study Completion Date

2014-04-30

Brief Summary

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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.

Detailed Description

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Conditions

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Cystic Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Cohort 1: Placebo

Participants homozygous (HO) for the F508del-CF transmembrane conductance regulator gene (CFTR) mutation received lumacaftor matched placebo once daily (qd) (Day 1 through Day 14), followed by lumacaftor matched placebo qd in combination with ivacaftor matched placebo every 12 hours (q12h) (Day 15 through Day 21).

Group Type PLACEBO_COMPARATOR

Lumacaftor Placebo

Intervention Type DRUG

Matching placebo tablet.

Ivacaftor Placebo

Intervention Type DRUG

Matching placebo tablet.

Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 150 mg q12h

Participants homozygous for the F508del-CFTR mutation received 200 milligram (mg) of lumacaftor (LUM) qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 150 mg of ivacaftor (IVA) q12h (Day 15 through Day 21).

Group Type EXPERIMENTAL

Lumacaftor

Intervention Type DRUG

Tablet

Ivacaftor

Intervention Type DRUG

Tablet.

Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h

Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 15 through Day 21).

Group Type EXPERIMENTAL

Lumacaftor

Intervention Type DRUG

Tablet

Ivacaftor

Intervention Type DRUG

Tablet.

Cohort 2 and 3: Placebo (HO and HE)

Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 28), followed by lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 29 through Day 56).

Group Type PLACEBO_COMPARATOR

Lumacaftor Placebo

Intervention Type DRUG

Matching placebo tablet.

Ivacaftor Placebo

Intervention Type DRUG

Matching placebo tablet.

Cohort 2: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h (HO)

Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).

Group Type EXPERIMENTAL

Lumacaftor

Intervention Type DRUG

Tablet

Ivacaftor

Intervention Type DRUG

Tablet.

Cohort 2: LUM 400 mg qd/LUM 400 mg qd+IVA 250 mg q12h (HO)

Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 400 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).

Group Type EXPERIMENTAL

Lumacaftor

Intervention Type DRUG

Tablet

Ivacaftor

Intervention Type DRUG

Tablet.

Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HO&HE)

Participants homozygous or heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).

Group Type EXPERIMENTAL

Lumacaftor

Intervention Type DRUG

Tablet

Ivacaftor

Intervention Type DRUG

Tablet.

Cohort 3: LUM 400 mg q12h/LUM 400 mg q12h+IVA 250 mg q12h (HO)

Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone q12h (Day 1 through Day 28), followed by 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).

Group Type EXPERIMENTAL

Lumacaftor

Intervention Type DRUG

Tablet

Ivacaftor

Intervention Type DRUG

Tablet.

Cohort 4: Placebo

Participants heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 1 through Day 56).

Group Type PLACEBO_COMPARATOR

Lumacaftor Placebo

Intervention Type DRUG

Matching placebo tablet.

Ivacaftor Placebo

Intervention Type DRUG

Matching placebo tablet.

Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h

Participants heterozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 1 through Day 56).

Group Type EXPERIMENTAL

Lumacaftor

Intervention Type DRUG

Tablet

Ivacaftor

Intervention Type DRUG

Tablet.

Interventions

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Lumacaftor

Tablet

Intervention Type DRUG

Ivacaftor

Tablet.

Intervention Type DRUG

Lumacaftor Placebo

Matching placebo tablet.

Intervention Type DRUG

Ivacaftor Placebo

Matching placebo tablet.

Intervention Type DRUG

Other Intervention Names

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VX-809, LUM VX-770, IVA

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vertex Pharmaceuticals Incorporated

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Birmingham, Alabama, United States

Site Status

Anchorage, Alaska, United States

Site Status

La Jolla, California, United States

Site Status

Long Beach, California, United States

Site Status

Palo Alto, California, United States

Site Status

Sacramento, California, United States

Site Status

Denver, Colorado, United States

Site Status

New Haven, Connecticut, United States

Site Status

Miami, Florida, United States

Site Status

Orlando, Florida, United States

Site Status

Tampa, Florida, United States

Site Status

Atlanta, Georgia, United States

Site Status

Boise, Idaho, United States

Site Status

Chicago, Illinois, United States

Site Status

Iowa City, Iowa, United States

Site Status

Kansas City, Kansas, United States

Site Status

Lexington, Kentucky, United States

Site Status

New Orleans, Louisiana, United States

Site Status

Baltimore, Maryland, United States

Site Status

Boston, Massachusetts, United States

Site Status

Minneapolis, Minnesota, United States

Site Status

St Louis, Missouri, United States

Site Status

Omaha, Nebraska, United States

Site Status

Lebanon, New Hampshire, United States

Site Status

Buffalo, New York, United States

Site Status

New Hyde Park, New York, United States

Site Status

New York, New York, United States

Site Status

Rochester, New York, United States

Site Status

Syracuse, New York, United States

Site Status

Chapel Hill, North Carolina, United States

Site Status

Akron, Ohio, United States

Site Status

Cleveland, Ohio, United States

Site Status

Columbus, Ohio, United States

Site Status

Oklahoma City, Oklahoma, United States

Site Status

Philadelphia, Pennsylvania, United States

Site Status

Pittsburgh, Pennsylvania, United States

Site Status

Charleston, South Carolina, United States

Site Status

Sioux Falls, South Dakota, United States

Site Status

Adelaide, , Australia

Site Status

Brisbane, , Australia

Site Status

Chermside, , Australia

Site Status

Nedlands, , Australia

Site Status

Parkville Victoria, , Australia

Site Status

Westmead, , Australia

Site Status

Leuven, , Belgium

Site Status

Pierre-Bénite, Rhone, France

Site Status

Paris, , France

Site Status

Jena, Thuringia, Germany

Site Status

Berlin, , Germany

Site Status

Bochum, , Germany

Site Status

Cologne, , Germany

Site Status

Essen, , Germany

Site Status

Auckland, , New Zealand

Site Status

Christchurch, , New Zealand

Site Status

London, , United Kingdom

Site Status

Countries

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United States Australia Belgium France Germany New Zealand United Kingdom

References

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Heneghan M, 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. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.

Reference Type DERIVED
PMID: 37983082 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33331662 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27898234 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24973281 (View on PubMed)

Other Identifiers

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2010-020413-90

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VX09-809-102

Identifier Type: -

Identifier Source: org_study_id

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