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A Phase 3 Study of VX-445 Combination Therapy in Cystic Fibrosis (CF) Subjects Heterozygous for F508del and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)

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ClinicalTrials.gov Identifier: NCT04058353
Recruitment Status : Completed
First Posted : August 15, 2019
Results First Posted : July 2, 2021
Last Update Posted : July 2, 2021
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Study Description
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Brief Summary:
This study will evaluate the efficacy, safety and pharmacodynamics of elexacaftor (ELX, 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 gating or residual function mutation (F/G and F/RF genotypes).

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: ELX/TEZ/IVA Drug: IVA Drug: TEZ/IVA Phase 3

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   More info ...

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 271 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 Gating or Residual Function Mutation (F/G and F/RF Genotypes)
Actual Study Start Date : August 28, 2019
Actual Primary Completion Date : June 12, 2020
Actual Study Completion Date : June 12, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Control: IVA or TEZ/IVA
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 milligrams (mg) every 12 hours (q12h) or TEZ 100 mg once daily (qd)/IVA 150 mg q12h in the treatment period for 8 weeks.
 Drug: IVA
Mono-tablet for oral administration.
Other Names:
  • VX-770
  • ivacaftor

Drug: TEZ/IVA
Fixed-dose combination (FDC) tablet for oral administration.
Other Names:
  • VX-661/VX-770
  • tezacaftor/ivacaftor
Experimental: TC: ELX/TEZ/IVA
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
 Drug: ELX/TEZ/IVA
FDC tablet for oral administration.
Other Names:
  • VX-445/VX-661/VX-770
  • elexacaftor/tezacaftor/ivacaftor

Drug: IVA
Mono-tablet for oral administration.
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) for ELX/TEZ/IVA Group [ Time Frame: From Baseline Through Week 8 ]
    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 Sweat Chloride (SwCl) for ELX/TEZ/IVA Group [ Time Frame: From Baseline Through Week 8 ]
    Sweat samples were collected using an approved collection device.

  2. Absolute Change in ppFEV1 for the ELX/TEZ/IVA Group Compared to the Control Group [ Time Frame: From Baseline Through Week 8 ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  3. Absolute Change in SwCl for ELX/TEZ/IVA Group Compared to the Control Group [ Time Frame: From Baseline Through Week 8 ]
    Sweat samples were collected using an approved collection device.

  4. Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for ELX/TEZ/IVA Group [ Time Frame: From Baseline Through Week 8 ]
    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 CFQ-R Respiratory Domain Score for ELX/TEZ/IVA Group Compared to the Control Group [ Time Frame: From Baseline Through Week 8 ]
    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.

  6. Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 up to Week 12 ]

Eligibility Criteria
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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

Key Inclusion Criteria:

  • Subject has a confirmed diagnosis of CF and is heterozygous for F508del and either a gating or residual function mutation (F/G and F/RF genotypes)
  • 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): NCT04058353


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

Documents provided by Vertex Pharmaceuticals Incorporated:
Study Protocol  [PDF] December 2, 2019
Statistical Analysis Plan  [PDF] June 22, 2020

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: NCT04058353    
Other Study ID Numbers: VX18-445-104
2018-002835-76 ( EudraCT Number )
First Posted: August 15, 2019    Key Record Dates
Results First Posted: July 2, 2021
Last Update Posted: July 2, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent research/clinical-trial-data-sharing

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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