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

NCT04167345 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: VX19-814-101
• Study Type: interventional
• Target: 48
• Locations: 4 countries
• Sites: 28

Brief Summary

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

Conditions

Alpha 1-Antitrypsin Deficiency

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• 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

Study Arms (5)

Parts A1, A2 and B Combined: Placebo

PLACEBO COMPARATOR

Participants received placebo matched to VX-814 in the treatment period for 28 days.

Drug: Placebo

Part A1: VX-814 100 milligrams (mg)

EXPERIMENTAL

Participants received VX-814 100 mg every 12 hours (q12h) in the treatment period for 28 days.

Drug: VX-814

Part A1: VX-814 200 mg

EXPERIMENTAL

Participants received VX-814 200 mg q12h in the treatment period for 28 days.

Drug: VX-814

Parts A1 and A2 Combined: VX-814 400 mg

EXPERIMENTAL

Participants received VX-814 400 mg q12h in the treatment period for 28 days.

Drug: VX-814

Part B: VX-814 600 mg

EXPERIMENTAL

Participants received VX-814 600 mg q12h in the treatment period for 28 days.

Drug: VX-814

Interventions

VX-814 DRUG

Tablet for oral administration.

Part A1: VX-814 100 milligrams (mg); Part A1: VX-814 200 mg; Part B: VX-814 600 mg; Parts A1 and A2 Combined: VX-814 400 mg

Placebo DRUG

Placebo matched to VX-814 for oral administration.

Parts A1, A2 and B Combined: Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have a PiZZ genotype confirmed at screening
• Plasma AAT levels indicating severe deficiency at screening

You may not qualify if:

• 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

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (28)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

University of Florida, Shands Hospital

Gainesville, Florida, 32610, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Central Florida Pulmonary Group, PA

Orlando, Florida, 32803, United States

Location

The University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Blessing Corporate Services, Inc., dba Blessing Health System

Hannibal, Missouri, 63401, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of North Carolina Medical Center

Chapel Hill, North Carolina, 27514, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Renovatio Clinical

Houston, Texas, 77380, United States

Location

The University of Texas Health Science Center at Tyler

Tyler, Texas, 75708, United States

Location

University of Utah Health

Salt Lake City, Utah, 84108, United States

Location

Inova Fairfax Medical Campus

Falls Church, Virginia, 22042, United States

Location

Queen Elizabeth II Health Sciences Center

Halifax, Canada

Location

Inspiration Research Ltd

Toronto, Canada

Location

University Hospital RWTH Aachen

Aachen, Germany

Location

Universitätsklinikum Essen

Essen, Germany

Location

Medizinische Hochschule Hannover

Hanover, Germany

Location

Royal College of Surgeons in Ireland Clinical Research Centre, Beaumont Hospital

Beaumont, Ireland

Location

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

During the study, elevated liver enzymes (AST/ALT) were observed in several participants and analysis of available pharmacokinetics data indicated that VX-814 exposures achieved were low. Based on these data, Vertex concluded that it would not be feasible to safely reach targeted exposure levels with VX-814. Thus, the study was terminated early at the sponsor's discretion. Given the study was terminated early, the data are incomplete, and results should be interpreted with caution.

Results Point of Contact

• Title: Medical Monitor
• Organization: Vertex Pharmaceuticals Incorporated

medicalinfo@vrtx.com

617-341-6777

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2019
• First Posted: November 18, 2019
• Study Start: January 13, 2020
• Primary Completion: November 14, 2020
• Study Completion: November 14, 2020
• Last Updated: February 2, 2022
• Results First Posted: February 2, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); DE (3); IE (1); US (22)