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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor

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ClinicalTrials.gov Identifier: NCT02347657
Recruitment Status : Completed
First Posted : January 27, 2015
Results First Posted : June 12, 2018
Last Update Posted : June 12, 2018
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Brief Summary:
This is a Phase 3, randomized, double blind, placebo controlled, parallel group, multicenter study in people with cystic fibrosis (CF) who are homozygous for the F508del CF transmembrane conductance regulator (CFTR) gene mutation.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: VX-661 Plus Ivacaftor Combination Drug: Ivacaftor Drug: VX-661 Plus Ivacaftor Combination Placebo Drug: Ivacaftor placebo Phase 3

Expanded Access : Vertex Pharmaceuticals Incorporated has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

Detailed Description:
This is a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study in people with CF who are homozygous for the F508del-CFTR mutation. This study is designed to evaluate the efficacy and safety of VX-661 in combination with Ivacaftor (IVA, VX-770). The active treatment regimen comprised of a morning dose of a fixed-dose combination (FDC) tablet of 100 milligram (mg) VX-661/150 mg IVA once daily (qd) and an evening dose of IVA 150 mg to be taken approximately 12 hours after the morning dose. The placebo regimen was visually matched tablets to be taken with the same schedule as the active treatment.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 510 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation
Actual Study Start Date : January 2015
Actual Primary Completion Date : January 20, 2017
Actual Study Completion Date : January 20, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis
Drug Information available for: Ivacaftor

Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.
Drug: VX-661 Plus Ivacaftor Combination Placebo
FDC tablet, oral use

Drug: Ivacaftor placebo
Tablet, oral use

Experimental: VX-661/IVA
VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.
Drug: VX-661 Plus Ivacaftor Combination
FDC tablet, oral use

Drug: Ivacaftor
Tablet, oral use




Primary Outcome Measures :
  1. Absolute Change From Baseline (Day 1) in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24 [ Time Frame: Day 1, Through Week 24 ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.


Secondary Outcome Measures :
  1. Relative Change From Baseline (Day 1) in ppFEV1 Through Week 24 [ Time Frame: Day 1, Through Week 24 ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  2. Number of Pulmonary Exacerbations Per Year [ Time Frame: Day 1 through Week 24 ]
    Pulmonary exacerbation was defined as a new event or change in antibiotic therapy for greater than or equal to 4 sinopulmonary signs/symptoms. Pulmonary exacerbation events per year (48 weeks) were reported.

  3. Absolute Change From Baseline (Day 1) Body Mass Index (BMI) at Week 24 [ Time Frame: Day 1, Week 24 ]
    BMI was defined as weight in kilograms (kg) divided by height in square meter (m^2).

  4. Absolute Change From Baseline (Day 1) in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24 [ Time Frame: Day 1, Through Week 24 ]
    The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

  5. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 up to Week 28 ]
    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. Any AE that increased in severity or newly developed at or after initial dosing of study drug to Week 28 was considered treatment-emergent.

  6. Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24 [ Time Frame: Day 1 through Week 24 ]
    Pulmonary exacerbation was defined as a new event or change in antibiotic therapy for greater than or equal to 4 sinopulmonary signs/symptoms. Time to event data was not collected and instead, Number of Subjects with first event were collected and are reported. Time-to-first pulmonary exacerbation was planned to be estimated using Kaplan-Meier (KM) estimates. However, due to less than 50% of events, time-to-first event data was not estimated. Instead, number of participants with at least one pulmonary exacerbation event were collected and are reported.

  7. Absolute Change From Baseline (Day 1) in Sweat Chloride Through Week 24 [ Time Frame: Day 1, Through Week 24 ]
    Sweat samples were collected using an approved collection device.

  8. Absolute Change From Baseline (Day 1) in BMI Z-score at Week 24 in Participants Less Than (<) 20 Years Old at the Time of Screening) [ Time Frame: Day 1, Week 24 ]
    BMI was defined as weight in kg divided by height in m^2. z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score (BMI z-score).

  9. Absolute Change From Baseline (Day 1) in Body Weight at Week 24 [ Time Frame: Day 1, Week 24 ]
  10. Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661 and M2-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA) [ Time Frame: Pre-morning dose on Week 16 ]
    This outcome was not planned to be assessed in Placebo arm.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Homozygous for the F508del CFTR mutation, genotype to be confirmed at the Screening Visit
  • Confirmed diagnosis of CF defined as a sweat chloride value ≥60 mmol/L by quantitative pilocarpine iontophoresis
  • Forced expiratory volume at one second (FEV1) ≥40% and ≤90% of predicted normal for age, sex, and height during screening
  • Stable CF disease as judged by the investigator
  • Willing to remain on a stable CF medication regimen through Week 24 or, if applicable, the Safety Follow up Visit

Exclusion Criteria:

  • 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.
  • An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug)
  • Pregnant or nursing females (females of childbearing potential must have a negative pregnancy test at Screening and Day 1)
  • Sexually active participants of reproductive potential who are not willing to follow the contraception requirements

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02347657


  Show 75 Study Locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
  Study Documents (Full-Text)

Documents provided by Vertex Pharmaceuticals Incorporated:
Study Protocol  [PDF] May 6, 2016
Statistical Analysis Plan  [PDF] February 9, 2017


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT02347657     History of Changes
Other Study ID Numbers: VX14-661-106
First Posted: January 27, 2015    Key Record Dates
Results First Posted: June 12, 2018
Last Update Posted: June 12, 2018
Last Verified: May 2018

Keywords provided by Vertex Pharmaceuticals Incorporated:
Homozygous for the F508del CFTR Mutation

Additional relevant MeSH terms:
Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Ivacaftor
Chloride Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action