A Study Evaluating the Safety and Efficacy of VX-440 Combination Therapy in Subjects With Cystic Fibrosis
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| ClinicalTrials.gov Identifier: NCT02951182 |
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Recruitment Status :
Completed
First Posted : November 1, 2016
Results First Posted : August 28, 2020
Last Update Posted : August 28, 2020
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Sponsor:
Vertex Pharmaceuticals Incorporated
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
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Brief Summary:
This is a Phase 2, randomized, double-blind, placebo- and active-controlled, parallel group, multicenter study to evaluate the safety, tolerability, and efficacy of VX-440 in dual and triple combination with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F508del/F508del), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ and/or IVA therapy (F508del/MF).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Cystic Fibrosis | Drug: TEZ Drug: IVA Drug: VX-440 Drug: Matched Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 74 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2, Randomized, Double-blind, Controlled Study to Evaluate the Safety and Efficacy of VX-440 Combination Therapy in Subjects Aged 12 Years and Older With Cystic Fibrosis |
| Actual Study Start Date : | October 2016 |
| Actual Primary Completion Date : | August 2017 |
| Actual Study Completion Date : | August 2017 |
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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Placebo Comparator: Part 1: Placebo - Cohort 1A and 1B Combined
Participants received placebo matched to VX-440/TEZ/IVA as triple combination for 4 weeks.
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Drug: Matched Placebo |
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Experimental: Part 1 Cohort 1A: Triple Combination (TC)
Participants received VX-440 200 milligram (mg) every 12 hours (q12h)/TEZ 100 mg once daily (qd)/IVA 150 mg q12h as triple combination for 4 weeks.
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Drug: TEZ
Other Names:
Drug: IVA Other Names:
Drug: VX-440 |
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Experimental: Part 1 Cohort 1B: TC Low Dose
Participants received VX-440 200 mg q12h/TEZ 50 mg q12h/IVA 150 mg q12h as triple combination for 4 weeks.
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Drug: TEZ
Other Names:
Drug: IVA Other Names:
Drug: VX-440 |
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Experimental: Part 1 Cohort 1B: TC High Dose
Participants received VX-440 600 mg q12h/TEZ 50 mg q12h/IVA 300 mg q12h as triple combination for 4 weeks.
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Drug: TEZ
Other Names:
Drug: IVA Other Names:
Drug: VX-440 |
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Active Comparator: Part 2: TEZ/IVA
Following a 4-week run-in period on TEZ 100 mg qd/IVA150 mg q12h, participants received placebo matched to VX-440 and TEZ 50 mg q12h/IVA 300 mg q12h for 4 weeks in treatment period and TEZ 100 mg qd/IVA150 mg q12h for 4 weeks in washout period.
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Drug: TEZ
Other Names:
Drug: IVA Other Names:
Drug: Matched Placebo |
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Experimental: Part 2: TC-2
Following a 4-week run-in period on TEZ 100 mg qd/IVA150 mg q12h, participants received VX-440 600 mg q12h/ TEZ 50 mg q12h/IVA 300 mg q12h for 4 weeks for 4 weeks in treatment period and TEZ 100 mg qd/IVA150 mg q12h for 4 weeks in washout period.
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Drug: TEZ
Other Names:
Drug: IVA Other Names:
Drug: VX-440 |
Primary Outcome Measures :
- 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 the Treatment Period through Safety Follow-up Visit (Up to Day 57 for Part 1 and Day 85 for Part 2) ]
- Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [ Time Frame: From Baseline through Day 29 ]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 Concentrations [ Time Frame: From Baseline through Day 29 ]Sweat samples were collected using an approved collection device.
- Relative Change in ppFEV1 [ Time Frame: From Baseline through Day 29 ]FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
- Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score [ Time Frame: From Baseline at Day 29 ]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.
- Pre-dose Plasma Concentration (Ctrough) of VX-440, TEZ, M1-TEZ, IVA and M1-IVA [ Time Frame: Predose at Day 8, Day 15 and Day 29 ]
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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:
- Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
- To prevent pregnancy, female participants of childbearing potential and their male partners will be required to use pre-specified, highly effective methods of non-hormonal contraception. Male participants with female partners of childbearing potential will be required to use a condom.
- Body weight ≥35 kg.
- Sweat chloride value ≥60 mmol/L from test results obtained during screening.
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Subjects must have an eligible CFTR genotype:
- Heterozygous for F508del and a minimal function (MF) mutation known or predicted not to be responsive to TEZ and/or IVA.
- Homozygous for F508del
- Subjects must have an FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height at the Screening Visit
- Stable CF disease as judged by the investigator.
- Willing to remain on a stable CF medication regimen through the planned end of treatment 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 subject.
- History of cirrhosis with portal hypertension.
- Risk factors for Torsade de Pointes
- History of hemolysis.
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.
- Clinically significant abnormal laboratory values at screening
- An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before the first dose of study drug.
- Lung infection with organisms associated with a more rapid decline in pulmonary status
- An acute illness not related to CF within 14 days before the first dose of study drug
- A standard digital ECG demonstrating QTc >450 msec at screening.
- History of solid organ or hematological transplantation.
- History or evidence of cataract or lens opacity determined to be clinically significant by the ophthalmologist or optometrist based on the ophthalmologic examination during the Screening Period.
- History of alcohol or drug abuse in the past year, including but not limited to, cannabis, cocaine, and opiates, as deemed by the investigator.
- Ongoing or prior participation in an investigational drug study, with certain exceptions. (e.g., ongoing participation in NCT02565914)
- Use of commercially available CFTR modulator (e.g., Kalydeco, Orkambi) within 14 days before screening (applies only to the Heterozygous F508del/MF cohorts; does not apply to the Homozygous F508del/F508del Cohort).
- Pregnant or nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1.
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): NCT02951182
Locations
Show 40 study locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Study Documents (Full-Text)
Documents provided by Vertex Pharmaceuticals Incorporated:
Documents provided by Vertex Pharmaceuticals Incorporated:
Statistical Analysis Plan [PDF] June 12, 2017
Study Protocol [PDF] September 16, 2016
| Responsible Party: | Vertex Pharmaceuticals Incorporated |
| ClinicalTrials.gov Identifier: | NCT02951182 |
| Other Study ID Numbers: |
VX15-440-101 2016-000454-36 ( EudraCT Number ) |
| First Posted: | November 1, 2016 Key Record Dates |
| Results First Posted: | August 28, 2020 |
| Last Update Posted: | August 28, 2020 |
| Last Verified: | August 2020 |
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 Chloride Channel Agonists Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action |