Study of VX-661 Alone and in Combination With Ivacaftor in Subjects Homozygous or Heterozygous to the F508del-Cystic Fibrosis Transmembrane Conductance Regulator(CFTR) Mutation

NCT01531673 | Completed Phase 2 Results DMC

• 2 other identifiers: VX11-661-1012011-003821-93
• Study Type: interventional
• Target: 194
• Locations: 4 countries
• Sites: 36

Brief Summary

The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) effects of VX-661 alone and when coadministered with ivacaftor in participants with cystic fibrosis (CF) who are homozygous or heterozygous for the F508del-CFTR mutation.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (4)

• Safety as Determined by Adverse Events (AEs)

  An AE is defined as any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the Informed Consent Form is signed. AE includes serious as well as non-serious AEs. Serious Adverse Event (SAE) is any AE that results in any of the following: death; life-threatening condition; inpatient hospitalization or prolongation of hospitalization; persistent or significant disability or incapacity; congenital anomaly or birth defect; or other important medical event. Treatment-emergent adverse events are defined as adverse events that were reported or worsened on or after start of study drug through the Follow-up Visit (28 days after last dose of study drug) or premature discontinuation.

  Start of study drug through the Follow-up Visit (Up to Day 56)

• Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b

  Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.

  Baseline through Day 28

• Change in Sweat Chloride From Baseline Through Study Day 28 for Group 6

  Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.

  Baseline through Day 28

• Change in Sweat Chloride From Baseline Through Study Day 28 for Group 7

  Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.

  Baseline through Day 28

Secondary Outcomes (14)

• Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b

  Baseline, Day 7, Day 14, Day 21, Day 28

• Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6

  Baseline, Day 7, Day 14, Day 21, Day 28

• Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 7

  Baseline, Day 7, Day 14, Day 21, Day 28

• Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b

  Baseline, Day 7, Day 14, Day 21, Day 28

• Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6

  Baseline, Day 7, Day 14, Day 21, Day 28

Study Arms (13)

Group 1-6d Combined: Placebo

PLACEBO COMPARATOR

All participants in group 1, 2a, 2b, 3a, 3b, 4, 5a, 5b, 6a and 6d who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days.

Drug: Placebo matched to VX-661; Drug: Placebo matched to ivacaftor

Group 1: VX-661 10 mg qd

EXPERIMENTAL

All participants in group 1 who received VX-661 10 milligram (mg) tablet orally once daily (qd) for up to 28 days.

Drug: VX-661

Group 2a: VX-661 30 mg qd

EXPERIMENTAL

All participants in group 2a who received VX-661 30 mg tablet orally qd and placebo matched to Ivacaftor tablet every 12 hours (q12h) for up to 28 days.

Drug: VX-661; Drug: Placebo matched to ivacaftor

Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h

EXPERIMENTAL

All participants in group 2b who received VX-661 10 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.

Drug: VX-661; Drug: Ivacaftor

Group 3a: VX-661 100 mg qd

EXPERIMENTAL

All participants in group 3a who received VX-661 100 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.

Drug: VX-661; Drug: Placebo matched to ivacaftor

Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h

EXPERIMENTAL

All participants in group 3b who received VX-661 30 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.

Drug: VX-661; Drug: Ivacaftor

Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h

EXPERIMENTAL

All participants in group 4 who received VX-661 100 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.

Drug: VX-661; Drug: Ivacaftor

Group 5a: VX-661 150 mg qd

EXPERIMENTAL

All participants in group 5a who received VX-661 150 mg tablet orally qd for up to 28 days.

Drug: VX-661

Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h

EXPERIMENTAL

All participants in group 5b who received VX-661 150 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.

Drug: VX-661; Drug: Ivacaftor

Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h

EXPERIMENTAL

All participants in group 6a who received VX-661 100 mg tablet qd and Ivacaftor 50 mg tablet q12h orally for up to 28 days.

Drug: VX-661; Drug: Ivacaftor

Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h

EXPERIMENTAL

All participants in group 6d who received VX-661 50 mg tablet and Ivacaftor 150 mg tablet q12h orally for up to 28 days.

Drug: VX-661; Drug: Ivacaftor

Group 7: Placebo

PLACEBO COMPARATOR

All participants in group 7 who received placebo matched to VX-661 tablet orally qd in combination with physician-prescribed Kalydeco (Ivacaftor) for up to 28 days.

Drug: Ivacaftor; Drug: Placebo matched to VX-661

Group 7: VX-661 100 mg qd

EXPERIMENTAL

All participants in group 7 who received VX-661 100 mg tablet orally qd in combination with physician-prescribed Kalydeco (Ivacaftor) for up to 28 days.

Drug: VX-661; Drug: Ivacaftor

Interventions

VX-661 DRUG

Group 1: VX-661 10 mg qd; Group 2a: VX-661 30 mg qd; Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h; Group 3a: VX-661 100 mg qd; Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h; Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h; Group 5a: VX-661 150 mg qd; Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h; Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h; Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h; Group 7: VX-661 100 mg qd

Ivacaftor DRUG

Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h; Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h; Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h; Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h; Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h; Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h; Group 7: Placebo; Group 7: VX-661 100 mg qd

Placebo matched to VX-661 DRUG

Group 1-6d Combined: Placebo; Group 7: Placebo

Placebo matched to ivacaftor DRUG

Group 1-6d Combined: Placebo; Group 2a: VX-661 30 mg qd; Group 3a: VX-661 100 mg qd

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female with confirmed diagnosis of CF
• Must have the F508del-CFTR gene mutation in both alleles (Groups 1, 2, 3, 4, 5, 6). Group 7 participants must have the F508del-CFTR mutation on 1 allele, and gating mutation G551D on the second allele and have been on their physician prescribed 150 mg KalydecoTM q12h (commercially available ivacaftor) for at least 28 days at the Screening Visit.
• Forced expiratory volume in 1 second(FEV1) 40% to 90% (inclusive) of predicted normal for age, gender, and height (Knudson standards) at screening
• Weight \>40 kg and BMI \>18.5
• Participants of child-bearing potential and who are sexually active must meet the contraception requirements.

You may not qualify if:

• History of any illness 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.
• An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Study Day 1.
• History of solid organ or hematological transplantation
• Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer) before screening
• History of alcohol, medication, or illicit drug abuse within 1 year prior to screening
• Pregnant, breast-feeding, or not willing to follow contraception requirements

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (36)

Vertex Investigational Site

Birmingham, Alabama, United States

Location

Vertex Investigational Site

Oakland, California, United States

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Vertex Investigational Site

Boise, Idaho, United States

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Vertex Investigational Site

Chicago, Illinois, United States

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Vertex Investigational Site

Boston, Massachusetts, United States

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Vertex Investigational Site

Grand Rapids, Michigan, United States

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Vertex Investigational Site

Kansas City, Missouri, United States

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Vertex Investigational Site

Long Branch, New Jersey, United States

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Vertex Investigational Site

New Hyde Park, New York, United States

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Vertex Investigational Site

Chapel Hill, North Carolina, United States

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Vertex Investigational Site

Cincinnati, Ohio, United States

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Vertex Investigational Site

Columbus, Ohio, United States

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Vertex Investigational Site

Oklahoma City, Oklahoma, United States

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Vertex Investigational Site

Hershey, Pennsylvania, United States

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Vertex Investigational Site

Pittsburgh, Pennsylvania, United States

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Vertex Investigational Site

Charleston, South Carolina, United States

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Vertex Investigational Site

Salt Lake City, Utah, United States

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Vertex Investigational Site

Burlington, Vermont, United States

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Vertex Investigational Site

Seattle, Washington, United States

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Vertex Investigational Site

Calgary, Alberta, Canada

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Vertex Investigational Site

Vancouver, British Columbia, Canada

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Vertex Investigational Site

Halifax, Nova Scotia, Canada

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Vertex Investigational Site

Toronto, Ontario, Canada

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Vertex Investigational Site

Erlangen, Bavaria, Germany

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Vertex Investigational Site

Frankfurt am Main, Hesse, Germany

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Vertex Investigational Site

Hanover, Lower Saxony, Germany

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Vertex Investigational Site

Cologne, North Rhine-Westphalia, Germany

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Vertex Investigational Site

Berlin, Germany

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Vertex Investigational Site

Bochum, Germany

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Vertex Investigational Site

Jena, Germany

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Vertex Investigational Site

Munich, Germany

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Vertex Investigational Site

Cambridge, Cambridgeshire, United Kingdom

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Vertex Investigational Site

London, Greater London, United Kingdom

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Vertex Investigational Site

Manchester, Greater Manchester, United Kingdom

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Vertex Investigational Site

Southhampton, Hampshire, United Kingdom

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Vertex Investigational Site

Cardiff, Vale of Glamorgen, United Kingdom

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

tezacaftor; 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

Limitations and Caveats

Pharmacokinetic (PK) final data are not yet available. Once the data are available for PK endpoints, the posting will be updated to include the same.

Results Point of Contact

• Title: Medical Monitor
• Organization: Vertex Pharmaceuticals Incorporated

medicalinfo@vrtx.com

617-341-6777

Study Officials

• Scott Donaldson, MD

  University of North Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: February 1, 2012
• First Posted: February 13, 2012
• Study Start: February 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: April 13, 2018
• Results First Posted: April 13, 2018

Record last verified: 2018-03

Locations

CA (4); GB (5); DE (8); US (19)