Evaluation of the Efficacy and Safety of VX-864 in Subjects With the PiZZ Genotype

A Phase 2, Randomized, Double-blind, Placebo-controlled Study of the Efficacy and Safety of VX-864 in PiZZ Subjects

This study will evaluate the efficacy, safety and pharmacokinetics (PK) of VX-864 in PiZZ subjects.

Study Overview

• Status: Completed
• Conditions: Alpha1-Antitrypsin Deficiency
• Intervention / Treatment: Drug: VX-864; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Halifax, Canada
    • Queen Elizabeth II Health Sciences Center
  • Toronto, Canada
    • Inspiration Research Ltd
• Germany
  • Aachen, Germany
    • University Hospital RWTH Aachen
  • Essen, Germany
    • Universitätsklinikum Essen
  • Hannover, Germany
    • Medizinische Hochschule Hannover
• Ireland
  • Beaumont, Ireland
    • Royal College of Surgeons in Ireland Clinical Research Centre, Beaumont Hospital
• Sweden
  • Malmö, Sweden
    • Skånes Universitetssjukhus, Malmo
• United Kingdom
  • Soham Ely, United Kingdom
    • Staploe Medical Centre
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicine at UCLA
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Florida
    • Gainesville, Florida, United States, 11735
      • University of Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
    • Orlando, Florida, United States, 32803
      • Central Florida Pulmonary
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • The University of Iowa Hospitals and Clinics
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Hannibal, Missouri, United States, 63401
      • Blessing Corporate Services, Inc., dba Blessing Health System
    • Saint Louis, Missouri, United States, 63104
      • Cardinal Glennon Children's Hospital - St. Louis University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Baptist Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • University of Cincinnati
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77380
      • Renovatio Clinical
    • Tyler, Texas, United States, 75708
      • The University of Texas Health Science Center at Tyler
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Health
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received placebo matched to VX-864 in the treatment period for 28 days.	Drug: Placebo; Placebo matched to VX-864 for oral administration.
Experimental: VX-864 100 mg; Participants received VX-864 100 milligrams (mg) every 12 hours (q12h) in the treatment period for 28 days.	Drug: VX-864; Tablets for oral administration.
Experimental: VX-864 300 mg; Participants received VX-864 300 mg q12h in the treatment period for 28 days.	Drug: VX-864; Tablets for oral administration.
Experimental: VX-864 500 mg; Participants received VX-864 500 mg q12h in the treatment period for 28 days.	Drug: VX-864; Tablets for oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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 Adverse Events (AEs) and Serious Adverse Events (SAEs)	Day 1 up to Week 8

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Plasma Antigenic AAT Levels	From Baseline at Day 28
Observed Pre-dose Plasma Concentration (Ctrough) of VX-864	Pre-dose at Day 7, Day 14, Day 21 and Day 28

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2020
• Primary Completion (Actual): May 4, 2021
• Study Completion (Actual): May 4, 2021

Study Registration Dates

• First Submitted: July 13, 2020
• First Submitted That Met QC Criteria: July 13, 2020
• First Posted (Actual): July 16, 2020

Study Record Updates

• Last Update Posted (Actual): May 26, 2022
• Last Update Submitted That Met QC Criteria: May 3, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Liver Diseases; Genetic Diseases, Inborn; Subcutaneous Emphysema; Emphysema; Alpha 1-Antitrypsin Deficiency
• Other Study ID Numbers: VX19-864-101; 2019-004881-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No