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 |
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Recruitment Status :
Completed
First Posted : August 15, 2019
Results First Posted : July 2, 2021
Last Update Posted : July 2, 2021
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Sponsor:
Vertex Pharmaceuticals Incorporated
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
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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 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 Genetics related topics:
Cystic fibrosis
MedlinePlus related topics:
Cystic Fibrosis
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: IVA
Mono-tablet for oral administration.
Other Names:
Drug: TEZ/IVA Fixed-dose combination (FDC) tablet for oral administration.
Other Names:
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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.
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Drug: ELX/TEZ/IVA
FDC tablet for oral administration.
Other Names:
Drug: IVA Mono-tablet for oral administration.
Other Names:
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Primary Outcome Measures :
- 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 :
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 ]
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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
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
Show 93 study locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Study Documents (Full-Text)
Documents provided by Vertex Pharmaceuticals Incorporated:
Documents provided by Vertex Pharmaceuticals Incorporated:
Study Protocol [PDF] December 2, 2019
Statistical Analysis Plan [PDF] June 22, 2020
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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 |
| 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 |