Evaluation of the Efficacy and Safety of VX-814 in Subjects With the PiZZ Genotype

Study Overview
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Brief Summary
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This study will evaluate the efficacy, safety and pharmacokinetics (PK) of VX-814 in PiZZ subjects.

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled Study of the Efficacy and Safety of VX-814 in PiZZ Subjects

Conditions
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Alpha 1-Antitrypsin Deficiency

Intervention / Treatment
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* Drug: VX-814
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subjects must have a PiZZ genotype confirmed at screening Plasma AAT levels indicating severe deficiency at screening Key Exclusion Criteria: History of a medical condition that could negatively impact the ability to complete the study Solid organ, or hematological transplantation or is currently on a transplant list History of use of gene therapy or RNAi therapy at any time previously Other protocol defined Inclusion/Exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Parts A1, A2 and B Combined: Placebo<br>Participants received placebo matched to VX-814 in the treatment period for 28 days. | Drug: Placebo<br>* Placebo matched to VX-814 for oral administration.<br>|
| Experimental: Part A1: VX-814 100 milligrams (mg)<br>Participants received VX-814 100 mg every 12 hours (q12h) in the treatment period for 28 days. | Drug: VX-814<br>* Tablet for oral administration.<br>|
| Experimental: Part A1: VX-814 200 mg<br>Participants received VX-814 200 mg q12h in the treatment period for 28 days. | Drug: VX-814<br>* Tablet for oral administration.<br>|
| Experimental: Parts A1 and A2 Combined: VX-814 400 mg<br>Participants received VX-814 400 mg q12h in the treatment period for 28 days. | Drug: VX-814<br>* Tablet for oral administration.<br>|
| Experimental: Part B: VX-814 600 mg<br>Participants received VX-814 600 mg q12h in the treatment period for 28 days. | Drug: VX-814<br>* Tablet for oral administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Plasma Functional Alpha-1 Antitrypsin (AAT) Levels |  | From Baseline at Day 28 | 
| Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Day 1 up to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Plasma Antigenic AAT Levels |  | From Baseline at Day 28 | 
| Observed Pre-dose Plasma Concentration of VX-814 |  | Pre-dose at Day 7, Day 14, Day 21, and Day 28 |