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A Phase 3 Study of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03525444
Recruitment Status : Completed
First Posted : May 15, 2018
Results First Posted : May 19, 2020
Last Update Posted : May 19, 2020
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Study Description
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Brief Summary:
This study will evaluate the efficacy of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a minimal function mutation (F/MF subjects).

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: VX-445/TEZ/IVA Drug: IVA Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 405 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
Actual Study Start Date : June 15, 2018
Actual Primary Completion Date : April 24, 2019
Actual Study Completion Date : April 24, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arms and Interventions
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Arm Intervention/treatment
Placebo Comparator: Placebo
Participants who received placebo matched to VX-445/TEZ/IVA for 24 weeks in the TC treatment period.
 Drug: Placebo
Participants received placebo matched VX-445/TEZ/IVA orally once daily in the morning and placebo matched to IVA orally once daily in the evening.
Experimental: VX-445/TEZ/IVA TC
Participants who received VX-445 200 mg/TEZ 100 mg/IVA150 mg as fixed-dose combination (FDC) tablets in the morning and IVA 150 mg as mono tablet in the evening for 24 weeks in the TC treatment period.
 Drug: VX-445/TEZ/IVA
Participants received VX-445/TEZ/IVA orally once daily in the morning.
Other Names:
  • VX-445/VX-661/VX-770
  • VX-445/tezacaftor/ivacaftor

Drug: IVA
Participants received IVA orally once daily in the evening
Other Names:
  • VX-770
  • ivacaftor


Outcome Measures
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Primary Outcome Measures :
  1. Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [ Time Frame: From Baseline at Week 4 ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.


Secondary Outcome Measures :
  1. Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [ Time Frame: From Baseline 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 (PEx) [ Time Frame: From Baseline through Week 24 ]
    Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.

  3. Absolute Change in Sweat Chloride (SwCl) [ Time Frame: From Baseline through Week 24 ]
    Sweat samples were collected using an approved collection device.

  4. Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score [ Time Frame: From Baseline 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. Absolute Change in Body Mass Index (BMI) [ Time Frame: From Baseline at Week 24 ]
    BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).

  6. Absolute Change in Sweat Chloride [ Time Frame: From Baseline at Week 4 ]
    Sweat samples were collected using an approved collection device.

  7. Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score [ Time Frame: From Baseline at Week 4 ]
    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.

  8. Time-to-first Pulmonary Exacerbation (PEx) [ Time Frame: From Baseline through Week 24 ]
    Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.

  9. Absolute Change in BMI Z-score for Participants <=20 Years of Age at Baseline [ Time Frame: From Baseline at 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. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI.

  10. Absolute Change in Body Weight [ Time Frame: From Baseline at Week 24 ]
  11. Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 28 weeks) ]
  12. Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ, M1-TEZ, and IVA [ Time Frame: Pre-dose on Week 4, 8, 12, and 16 ]

Eligibility Criteria
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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

Key Inclusion Criteria:

  • Heterozygous for the F508del mutation (F/MF)
  • Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height

Key Exclusion Criteria:

  • Clinically significant cirrhosis with or without portal hypertension
  • Lung infection with organisms associated with a more rapid decline in pulmonary status
  • Solid organ or hematological transplantation

Other protocol defined Inclusion/Exclusion criteria may apply

Contacts and Locations
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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): NCT03525444


Locations
Show Show 115 study locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
  Study Documents (Full-Text)

Documents provided by Vertex Pharmaceuticals Incorporated:
Study Protocol  [PDF] July 19, 2018
Statistical Analysis Plan  [PDF] March 21, 2019

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT03525444    
Other Study ID Numbers: VX17-445-102
2018-000183-28 ( EudraCT Number )
First Posted: May 15, 2018    Key Record Dates
Results First Posted: May 19, 2020
Last Update Posted: May 19, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
 Genetic Diseases, Inborn
Infant, Newborn, Diseases
Ivacaftor
Elexacaftor
Chloride Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action