A Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy

Study Overview
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Brief Summary
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This study will evaluate the long-term safety and tolerability of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous or heterozygous for the F508del mutation

Official Title
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A Phase 3, Open-label Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Homozygous or Heterozygous for the F508del Mutation

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: VX-445
* Drug: TEZ
* Drug: IVA
* Drug: IVA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed study drug treatment in a parent study; or had study drug interruption(s) in a parent study but completed study visits up to the last scheduled visit of the Treatment Period in the parent study. Exclusion Criteria: History of drug intolerance in a parent study that would pose an additional risk to the subject in the opinion of the investigator. Current participation in an investigational drug trial (other than a parent study) Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-label Triple Combination<br>Subjects will receive 200 mg VX-445/ 100 mg TEZ/ 150 mg IVA as FDC tablets in the morning and 150 mg IVA as mono tablet in the evening. Parent studies are Phase 3 Vertex studies investigating VX-445 in combination with TEZ and IVA. This includes Studies VX17-445-102 and VX17-445-103. | Drug: VX-445<br>* Fixed-dose combination (FDC) tablets (VX-445/TEZ/IVA)<br>Drug: TEZ<br>* FDC tablets (VX-445/TEZ/IVA)<br>* Other names: tezacaftor; VX-661;Drug: IVA<br>* FDC tablets (VX-445/TEZ/IVA)<br>* Other names: ivacaftor; VX-770;Drug: IVA<br>* IVA tablet<br>* Other names: ivacaftor; VX-770;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability as assessed by number of subjects with adverse events (AEs) and serious adverse events (SAEs) |  | from baseline through safety follow-up (up to 196 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) |  | from baseline through last dose of study drug (up to 192 weeks) | 
| Absolute change in sweat chloride (SwCl) |  | from baseline through last dose of study drug (up to 192 weeks) | 
| Number of pulmonary exacerbations (PEx) |  | from baseline through last dose of study drug (up to 192 weeks) | 
| Time to first PEx |  | from baseline through last dose of study drug (up to 192 weeks) | 
| Absolute change in body mass index (BMI) |  | from baseline through last dose of study drug (up to 192 weeks) | 
| Absolute change in BMI z-score |  | from baseline through last dose of study drug (up to 192 weeks) | 
| Absolute change in body weight |  | from baseline through last dose of study drug (up to 192 weeks) | 
| Absolute change from baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score |  | from baseline through last dose of study drug (up to 192 weeks) |