Open-Label Extension Study of Ubenimex in Patients With Pulmonary Arterial Hypertension (WHO Group 1) (LIBERTY2)

A Phase 2, Open-Label, Extension Study to Evaluate the Long-Term Safety and Efficacy of Ubenimex in Patients With Pulmonary Arterial Hypertension (WHO Group 1)

Ubenimex is being developed for the treatment of pulmonary arterial hypertension (PAH) (World Health Organization [WHO] Group 1) to improve exercise capacity and delay clinical worsening.

This study is a Phase 2, open-label, extension study to evaluate long-term safety and efficacy of ubenimex in patients with PAH (WHO Group 1) who complete Study EIG-UBX-001.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: ubenimex

Detailed Description

This study is a Phase 2, open-label, multicenter, extension study to evaluate long-term safety and efficacy of ubenimex in patients with PAH (WHO Group 1) who complete Study EIG-UBX-001 (Study EIG-UBX-001 is a Phase 2, randomized, double-blind, placebo-controlled clinical trial) and meet the eligibility criteria for Study EIG-UBX-002. The primary objective for this study is:

- to obtain long-term safety and tolerability data for ubenimex (150 mg administered three times daily [TID]) in patients with PAH (WHO Group 1).

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • California Heart Center Foundation, An Affiliate of Cedars-Sinai Heart Institute, Cedars-Sinai Medical Care Foundation
    • La Jolla, California, United States, 92103
      • Ucsd Medical Center
    • Palo Alto, California, United States, 94305
      • Stanford University Medical Center
    • Torrance, California, United States, 90502
      • Harbor - UCLA Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • Florida
    • Weston, Florida, United States, 33331
      • Cleveland Clinic, Florida
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Kentuckiana Pulmonary Associates
  • Maine
    • South Portland, Maine, United States, 04106
      • Chest Medicine Associates
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University, Pulmonary and Critical Care Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02118
      • Boston University School of Medicine
  • Michigan
    • Ann Arbor, Michigan, United States, 48103
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic College of Medicine
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Washington University
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Respiratory Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pennsylvania Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Alpert Medical School of Brown University Rhode Island Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • San Antonio, Texas, United States, 78229
      • University Texas Health Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have completed Study EIG-UBX-001 through Week 24.
• In the opinion of the Principal Investigator, has been generally compliant with study requirements during Study EIG-UBX-001.
• Agrees to use a medically acceptable method of contraception throughout the entire study period.
• Willing and able to comply with scheduled visits, treatment plans, and laboratory tests and other study procedures.

Exclusion Criteria:

• Is pregnant or lactating.
• Concurrent regular use of another leukotriene pathway inhibitor.

• Any reason that, in the opinion of the investigator, precludes the patient from participating in the study.

  1. Any condition that is unstable or that could jeopardize the safety of the patient and his/her compliance in the study
  2. A serious uncontrolled medical disorder/condition that in the opinion of the investigator would impair the ability of the patient to receive protocol therapy
• An ongoing, drug-related, serious adverse event (SAE).
• Significant/chronic renal insufficiency.
• Transaminases (alanine transaminase, aspartate transaminase) levels >3 × upper limit of normal (ULN) and/or bilirubin level >2 × ULN.
• Absolute neutrophil count <1500 mm3.
• Hemoglobin concentration <9 g/dL at Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ubenimex; ubenimex capsules 150 mg three times a day (TID), administered orally, minimum of 24 weeks for all patients. The maximum anticipated time an individual patient will participate will vary because treatment will continue until the last patient enrolled has received at least 24 weeks of open-label treatment.	Drug: ubenimex; Other Names: UBX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-emergent Adverse Events (TEAEs)	Number of Patients with TEAEs collected for all patients and recorded on the Adverse Event Case Report Form	At least 24 weeks of open-label treatment with ubenimex followed by 4 weeks follow-up

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in pulmonary vascular resistance (PVR)	through study completion, an average of 1 year
Change in exercise capacity as measured by 6-minute walk distance (6MWD)	through study completion, an average of 1 year
Change in World Health Organization/New York Heart Association Functional Classification	through study completion, an average of 1 year
Change in disease biomarkers brain natriuretic peptide (BNP) /N-terminal pro-brain natriuretic peptide (NT-proBNP )	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Eiger BioPharmaceuticals

Publications and helpful links

General Publications

• Tian W, Jiang X, Tamosiuniene R, Sung YK, Qian J, Dhillon G, Gera L, Farkas L, Rabinovitch M, Zamanian RT, Inayathullah M, Fridlib M, Rajadas J, Peters-Golden M, Voelkel NF, Nicolls MR. Blocking macrophage leukotriene b4 prevents endothelial injury and reverses pulmonary hypertension. Sci Transl Med. 2013 Aug 28;5(200):200ra117. doi: 10.1126/scitranslmed.3006674.
• Qian J, Tian W, Jiang X, Tamosiuniene R, Sung YK, Shuffle EM, Tu AB, Valenzuela A, Jiang S, Zamanian RT, Fiorentino DF, Voelkel NF, Peters-Golden M, Stenmark KR, Chung L, Rabinovitch M, Nicolls MR. Leukotriene B4 Activates Pulmonary Artery Adventitial Fibroblasts in Pulmonary Hypertension. Hypertension. 2015 Dec;66(6):1227-1239. doi: 10.1161/HYPERTENSIONAHA.115.06370. Epub 2015 Oct 5.

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: April 4, 2016
• First Submitted That Met QC Criteria: April 7, 2016
• First Posted (Estimate): April 13, 2016

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Immunologic Factors; Protease Inhibitors; Anti-Bacterial Agents; Adjuvants, Immunologic; Antibiotics, Antineoplastic; Ubenimex
• Other Study ID Numbers: EIG-UBX-002