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Completed

NCT Number: NCT01531673

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

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.

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Key information

Conditions

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

Age range

12 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Vertex Investigational Site, Calgary, Alberta, Canada

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

VX-661

Drug

Ivacaftor

Drug

Placebo matched to VX-661

Drug

Placebo matched to Ivacaftor

Drug

Primary outcomes

  1. Safety as Determined by Adverse Events (AEs)

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

    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.

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

    Time frame: Baseline through Day 28

    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.

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

    Time frame: Baseline through Day 28

    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.

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

    Time frame: Baseline through Day 28

    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.

Secondary outcomes

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

    Time frame: Baseline, Day 7, Day 14, Day 21, Day 28

    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.

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

    Time frame: Baseline, Day 7, Day 14, Day 21, Day 28

    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.

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

    Time frame: Baseline, Day 7, Day 14, Day 21, Day 28

    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.

  4. 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

    Time frame: Baseline, Day 7, Day 14, Day 21, Day 28

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  5. 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

    Time frame: Baseline, Day 7, Day 14, Day 21, Day 28

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.

  6. 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 7

    Time frame: Baseline, Day 7, Day 14, Day 21, Day 28

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  7. Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b

    Time frame: Baseline, Day 7, Day 14, Day 21, Day 28

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  8. Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6

    Time frame: Baseline, Day 7, Day 14, Day 21, Day 28

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.

  9. Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7

    Time frame: Baseline, Day 7, Day 14, Day 21, Day 28

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  10. Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b

    Time frame: Baseline, Day 14, Day 28

    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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

  11. Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6

    Time frame: Baseline, Day 14, Day 28

    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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.

  12. Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7

    Time frame: Baseline, Day 14, Day 28

    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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

  13. Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 After Administration of VX-661 Monotherapy

    Time frame: Day 28

    Participants who received VX-661 monotherapy (Group 1, 2a, 3a and 5a) were analyzed for this outcome measure. PK analysis (AUC0-24h) was not planned for placebo reporting arms.

  14. AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor

    Time frame: Day 28

    Participants who received VX-661 in combination with Ivacaftor (Group 2b, 3b, 4, 5b, 6a, 6d and 7) were analyzed for this outcome measure. PK analysis was not planned for placebo reporting arms.

Sponsors and collaborators

Lead sponsor

Vertex Pharmaceuticals Incorporated

Industry

Registry information

Official study title

A Phase 2, Multicenter, Double-Blinded, Placebo Controlled Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-661 Monotherapy and VX-661/Ivacaftor Cotherapy in Subjects With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation

Important dates

Study start
2012
Primary completion
2014
Study completion
2014
First posted
Feb 13, 2012
Registry last updated
Apr 13, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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