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

NCT01225211 | Completed Phase 2 Results DMC

• 2 other identifiers: VX09-809-1022010-020413-90
• Study Type: interventional
• Target: 312
• Locations: 7 countries
• Sites: 55

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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (6)

• Cohort 1: Safety and Tolerability Based on Adverse Events (AEs)

  AE: any untoward medical occurrence in a participant during study; irrespective of relationship with treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent. AE includes serious AEs (SAEs) as well as Non-SAEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Number of participants with AEs and SAEs are reported. AE that started at/after initial dosing of study drug, or increased in severity after initial dosing of study drug is considered treatment-emergent. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 14) and combination therapy period (Period 2: Day 15 to Day 21).

  Cohort 1: Day 1 up to 28 days after last dose (Last dose = Day 21)

• Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs)

  Detailed description is provided in Outcome Measure 1. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 28) and combination therapy period (Period 2: Day 29 to Day 56).

  Cohort 2 and 3: Day 1 up to 28 days after last dose (Last dose = Day 56)

• Cohort 4: Safety and Tolerability Assessed by Number of Participants With AEs and SAEs

  AEs and SAEs are defined in Outcome Measure 1.

  Cohort 4: Day 1 up to 28 days after last dose (Last dose = Day 56)

• Cohort 1: Absolute Change From Day 14 in Sweat Chloride at Day 21

  Cohort 1: Day 14, Day 21

• Cohort 2 And 3: Absolute Change From Day 28 in Sweat Chloride at Day 56

  Cohort 2 and 3: Day 28, Day 56

• Cohort 4: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 56

  FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) was calculated using the Hankinson method.

  Cohort 4: Baseline, Day 56

Secondary Outcomes (14)

• Cohort 1: Absolute Change From Baseline in Sweat Chloride at Day 14

  Cohort 1: Baseline, Day 14

• Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14

  Cohort 2: Baseline, Day 14

• Cohort 4: Absolute Change From Baseline in Sweat Chloride at Day 56

  Cohort 4: Baseline, Day 56

• Cohort 1: Absolute Change From Day 14 in FEV1 at Day 21

  Cohort 1: Day 14, Day 21

• Cohort 1: Absolute Change From Day 14 in ppFEV1 at Day 21

  Cohort 1: Day 14, Day 21

Study Arms (10)

Cohort 1: Placebo

PLACEBO COMPARATOR

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).

Drug: Lumacaftor Placebo; Drug: Ivacaftor Placebo

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

EXPERIMENTAL

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).

Drug: Lumacaftor; Drug: Ivacaftor

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

EXPERIMENTAL

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).

Drug: Lumacaftor; Drug: Ivacaftor

Cohort 2 and 3: Placebo (HO and HE)

PLACEBO COMPARATOR

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).

Drug: Lumacaftor Placebo; Drug: Ivacaftor Placebo

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

EXPERIMENTAL

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).

Drug: Lumacaftor; Drug: Ivacaftor

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

EXPERIMENTAL

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).

Drug: Lumacaftor; Drug: Ivacaftor

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

EXPERIMENTAL

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).

Drug: Lumacaftor; Drug: Ivacaftor

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

EXPERIMENTAL

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).

Drug: Lumacaftor; Drug: Ivacaftor

Cohort 4: Placebo

PLACEBO COMPARATOR

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

Drug: Lumacaftor Placebo; Drug: Ivacaftor Placebo

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

EXPERIMENTAL

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).

Drug: Lumacaftor; Drug: Ivacaftor

Interventions

Lumacaftor DRUG

Tablet

Also known as: VX-809, LUM

Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 150 mg q12h; Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h; Cohort 2: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h (HO); Cohort 2: LUM 400 mg qd/LUM 400 mg qd+IVA 250 mg q12h (HO); Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HO&HE); Cohort 3: LUM 400 mg q12h/LUM 400 mg q12h+IVA 250 mg q12h (HO); Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h

Ivacaftor DRUG

Tablet.

Also known as: VX-770, IVA

Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 150 mg q12h; Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h; Cohort 2: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h (HO); Cohort 2: LUM 400 mg qd/LUM 400 mg qd+IVA 250 mg q12h (HO); Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HO&HE); Cohort 3: LUM 400 mg q12h/LUM 400 mg q12h+IVA 250 mg q12h (HO); Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h

Lumacaftor Placebo DRUG

Matching placebo tablet.

Cohort 1: Placebo; Cohort 2 and 3: Placebo (HO and HE); Cohort 4: Placebo

Ivacaftor Placebo DRUG

Matching placebo tablet.

Cohort 1: Placebo; Cohort 2 and 3: Placebo (HO and HE); Cohort 4: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (55)

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Birmingham, Alabama, United States

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Anchorage, Alaska, United States

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La Jolla, California, United States

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Long Beach, California, United States

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Palo Alto, California, United States

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Sacramento, California, United States

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Denver, Colorado, United States

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New Haven, Connecticut, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Boise, Idaho, United States

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Chicago, Illinois, United States

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Iowa City, Iowa, United States

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Kansas City, Kansas, United States

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Lexington, Kentucky, United States

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New Orleans, Louisiana, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Minneapolis, Minnesota, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Lebanon, New Hampshire, United States

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Buffalo, New York, United States

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New Hyde Park, New York, United States

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New York, New York, United States

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Rochester, New York, United States

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Syracuse, New York, United States

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Chapel Hill, North Carolina, United States

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Akron, Ohio, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Charleston, South Carolina, United States

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Sioux Falls, South Dakota, United States

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Adelaide, Australia

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Brisbane, Australia

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Chermside, Australia

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Nedlands, Australia

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Parkville Victoria, Australia

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Westmead, Australia

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Leuven, Belgium

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Pierre-Bénite, Rhone, France

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Paris, France

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Jena, Thuringia, Germany

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Berlin, Germany

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Bochum, Germany

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Cologne, Germany

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Essen, Germany

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Auckland, New Zealand

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Christchurch, New Zealand

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London, United Kingdom

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Related Publications (4)

• 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.

  PMID: 37983082 DERIVED

• 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.

  PMID: 33331662 DERIVED

• 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.

  PMID: 27898234 DERIVED

• 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.

  PMID: 24973281 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

lumacaftor; ivacaftor

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Medical Monitor
• Organization: Vertex Pharmaceuticals Incorporated

medicalinfo@vrtx.com

617-341-6777

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2010
• First Posted: October 20, 2010
• Study Start: October 1, 2010
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: October 5, 2015
• Results First Posted: October 5, 2015

Record last verified: 2015-09

Locations

FR (2); DE (5); GB (1); NZ (2); US (38); AU (6); BE (1)