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

Vertex Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Cystic Fibrosis

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01531673

VX11-661-101

2011-003821-93 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

This is a Phase 2, randomized, multicenter, double-blinded, placebo-controlled, study of VX-661 monotherapy, and VX-661/ivacaftor co-therapy in participants with CF who are homozygous or heterozygous for the F508del CFTR mutation.

This study is separated into seven groups: Group 1-7, respectively. Approximately 180 participants were randomized in a ratio of 4:1; active drug to matching placebo in each group.

Enrollment: 194 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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194 participants in 13 patient groups, including a placebo group

Group 1-6d Combined: Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo matched to VX-661

Drug: Placebo matched to ivacaftor

Group 1: VX-661 10 mg qd

Experimental group

Description:

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

Treatment:

Drug: VX-661

Group 2a: VX-661 30 mg qd

Experimental group

Description:

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.

Treatment:

Drug: Placebo matched to ivacaftor

Drug: VX-661

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

Experimental group

Description:

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.

Treatment:

Drug: VX-661

Drug: Ivacaftor

Group 3a: VX-661 100 mg qd

Experimental group

Description:

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.

Treatment:

Drug: Placebo matched to ivacaftor

Drug: VX-661

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

Experimental group

Description:

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.

Treatment:

Drug: VX-661

Drug: Ivacaftor

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

Experimental group

Description:

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.

Treatment:

Drug: VX-661

Drug: Ivacaftor

Group 5a: VX-661 150 mg qd

Experimental group

Description:

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

Treatment:

Drug: VX-661

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

Experimental group

Description:

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.

Treatment:

Drug: VX-661

Drug: Ivacaftor

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

Experimental group

Description:

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.

Treatment:

Drug: VX-661

Drug: Ivacaftor

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

Experimental group

Description:

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

Treatment:

Drug: VX-661

Drug: Ivacaftor

Group 7: Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo matched to VX-661

Drug: Ivacaftor

Group 7: VX-661 100 mg qd

Experimental group

Description:

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.

Treatment:

Drug: VX-661

Drug: Ivacaftor