Study to Evaluate Safety and Efficacy of VX-661 in Combination With Ivacaftor in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation With an Open-Label Expansion

NCT02070744 | Completed Phase 2 Results DMC

• 1 other identifier: VX13-661-103
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 23

Brief Summary

The objective of this study was to evaluate the safety and efficacy of VX-661in combination with ivacaftor in participants with cystic fibrosis (CF) who are homozygous for F508del cystic fibrosis transmembrane conductance regulator (CFTR) mutation

Conditions

Cystic Fibrosis

Keywords

CF

Outcome Measures

Primary Outcomes (2)

• PC Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  AE: 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. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of PC Phase.

  Baseline (PC Phase) up to 112 days

• OLE Phase: Number of Participants With Treatment-Emergent AEs and SAEs

  AE: 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. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of the OLE Phase.

  Baseline (OLE Phase) up to 364 days

Secondary Outcomes (16)

• PC Phase: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12

  Baseline (PC Phase), Through Week 12

• OLE Phase: Absolute Change From Baseline in Percent Predicted FEV1 Through Week 40

  Baseline (OLE Phase), Through Week 40

• PC Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 12

  Baseline (PC Phase), Through Week 12

• OLE Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 40

  Baseline (OLE Phase), Through Week 40

• PC Phase: Absolute Change From Baseline in Sweat Chloride Through Week 12

  Baseline (PC Phase), Through Week 12

Study Arms (5)

PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h

EXPERIMENTAL

Participants received VX-661 50 milligram (mg) tablet plus Ivacaftor (IVA) 150 mg tablet every 12 hours (q12h) for 12 weeks.

Drug: VX-661; Drug: Ivacaftor

PC Phase: VX 661 placebo q12h + IVA placebo q12h

PLACEBO COMPARATOR

Participants received placebo matched to VX-661 tablet plus placebo matched to IVA tablet q12h for 12 weeks.

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

PC Phase: VX-661 100 mg qd + IVA 150 mg q12h

EXPERIMENTAL

Participants received two VX-661 50 mg tablets once daily (qd) plus IVA 150 mg tablet q12h for 12 weeks.

Drug: VX-661; Drug: Ivacaftor

PC Phase: VX -661 placebo qd + IVA placebo q12h

PLACEBO COMPARATOR

Participants received two placebo matched to VX-661 tablets qd plus placebo matched to IVA tablet q12h for 12 weeks.

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

OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h

EXPERIMENTAL

Participants who completed 12 week PC phase underwent a washout period of at least 4 weeks before entering the OLE phase and received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 48 weeks in OLE phase.

Drug: VX-661; Drug: Ivacaftor

Interventions

VX-661 DRUG

Tablet, oral use

OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h; PC Phase: VX-661 100 mg qd + IVA 150 mg q12h; PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h

Ivacaftor DRUG

Film coated tablet, oral use

OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h; PC Phase: VX-661 100 mg qd + IVA 150 mg q12h; PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h

Placebo matched to VX-661 DRUG

Tablet, oral use

PC Phase: VX -661 placebo qd + IVA placebo q12h; PC Phase: VX 661 placebo q12h + IVA placebo q12h

Placebo matched to Ivacaftor DRUG

Film coated tablet, oral use

PC Phase: VX -661 placebo qd + IVA placebo q12h; PC Phase: VX 661 placebo q12h + IVA placebo q12h

Eligibility Criteria

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

You may qualify if:

• Homozygous for the F508del CFTR mutation
• FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height
• Stable CF disease as judged by the investigator

You may not qualify if:

• History of any comorbidity 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
• Pregnant and nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1 of the PC Phase and Day -7 or Day 1 of the OLE Phase (whichever was applicable)
• Sexually active participants of reproductive potential who are not willing to follow the contraception requirements
• The participant or a close relative of the participant is the investigator or sub investigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the study.

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (23)

Unknown Facility

Birmingham, Alabama, United States

Location

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Palo Alto, California, United States

Location

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Stanford, California, United States

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Altamonte Springs, Florida, 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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Boise, Idaho, United States

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Chicago, Illinois, United States

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Boston, Massachusetts, United States

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New Brunswick, New Jersey, United States

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New York, New York, United States

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Durham, North Carolina, United States

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Cincinnati, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Pittsburgh, Pennsylvania, United States

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Charleston, South Carolina, United States

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Memphis, Tennessee, United States

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Houston, Texas, United States

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Burlington, Vermont, United States

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Colchester, Vermont, United States

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Seattle, Washington, United States

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Milwaukee, Wisconsin, United States

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

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2014
• First Posted: February 25, 2014
• Study Start: March 1, 2014
• Primary Completion: May 27, 2016
• Study Completion: May 27, 2016
• Last Updated: September 24, 2025
• Results First Posted: April 13, 2018

Record last verified: 2025-09

Locations

US (23)