A Study of Ubenimex in Patients With Pulmonary Arterial Hypertension (WHO Group 1)

NCT ID: NCT02664558

Last Updated: 2023-03-06

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

61 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-04-30

Study Completion Date

2018-01-31

Brief Summary

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This proof-of-concept study is designed as a Phase 2, multicenter, randomized, double-blind, placebo controlled study comparing ubenimex with placebo in patients with pulmonary arterial hypertension (PAH) (World Health Organization \[WHO\] Group 1) and have a WHO/New York Heart Association (NYHA) Functional Classification (WHO/NYHA-FC) of II or III.

Detailed Description

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Ubenimex is being developed for the treatment of PAH (WHO Group 1) to improve exercise capacity and delay clinical worsening. This proof-of-concept study is designed as a Phase 2, multicenter, randomized, double-blind, placebo controlled study comparing ubenimex with placebo in patients with PAH (WHO Group 1) and have a WHO/NYHA Functional Classification (WHO/NYHA-FC) of II or III. The Primary Objectives for the study are:

* To evaluate the efficacy of ubenimex in patients with PAH (WHO Group 1).
* To evaluate the safety and tolerability of ubenimex in patients with WHO Group 1 PAH.

Conditions

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Pulmonary Arterial Hypertension

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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ubenimex

ubenimex capsules 150 mg three times a day (TID), administered orally for a total of 24 weeks.

Group Type EXPERIMENTAL

ubenimex

Intervention Type DRUG

placebo

placebo capsules TID, administered orally for a total of 24 weeks

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type OTHER

Interventions

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ubenimex

Intervention Type DRUG

placebo

Intervention Type OTHER

Other Intervention Names

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UBX

Eligibility Criteria

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Inclusion Criteria

1. Male or female, 18-75 years old.
2. Has a diagnosis of WHO Group 1 PAH.
3. Right heart catheterization performed at Screening with results that are:

1. Mean pulmonary arterial pressure ≥25 mmHg (at rest) and
2. Pulmonary venous hypertension (measured as pulmonary capillary wedge pressure (PCWP) ≤15 mmHg. If PCWP is not available, then mean left atrial pressure or left ventricular end-diastolic pressure ≤15 mmHg in the absence of left atrial obstruction. and
3. Pulmonary vascular resistance (PVR) ≥300 dyn•s/cm5 (3.75 Wood units)
4. Has WHO/NYHA-FC of II or III.
5. Be on stable dose of at least one of the following PAH-specific therapies: endothelin receptor antagonist, an agent acting on the nitric oxide pathway (phosphodiesterase type 5 inhibitor or soluble guanylate cyclase stimulator), and/or a prostacyclin or prostacyclin analog.
6. Has a 6-minute walk distance that is ≥150 and ≤500 meters.
7. Have a ventilation-perfusion scan that rules out thromboembolic disease.

Exclusion Criteria

Exclusions Related to Cardiovascular Disease

1. History of uncontrolled hypertension
2. Persistent hypotension at Screening.
3. Evidence or history of left-sided heart disease and/or clinically significant cardiac disease in which pulmonary hypertension is more likely WHO Group 2.
4. Acute decompensated heart failure within 1 month of Screening.
5. Recent initiation (\<8 weeks from Screening) or planned initiation of cardiopulmonary rehabilitation exercise program.

Exclusions Related to Pulmonary Disease
6. Newly diagnosed with PAH and not on PAH-specific therapy.
7. Pulmonary hypertension due to:

1. Uncorrected congenital systemic-to-pulmonary shunt.
2. Pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis
3. Persistent pulmonary hypertension of the newborn
4. WHO clinical classification Groups 2-5
8. Evidence of significant airway and/or parenchymal lung disease.
9. Chronic infection related to tuberculosis or fungal or mycobacterial disease.

Exclusions Based on Other Medical Conditions
10. Chronic infections including, but not limited to tuberculosis (TB), hepatitis B virus (HBV) or hepatitis C virus (HCV).
11. History of portal hypertension or chronic liver disease, including positive serology for infection with HCV and/or HBV.
12. Evidence of active infection requiring intravenous or oral antibiotics within 4 weeks of Screening.
13. Body mass index ≥35.0 at Screening.
14. History of obstructive sleep apnea.
15. History of malignancy within the last 5 years, except nonmelanoma skin cancer and cervical carcinoma in situ treated with curative intent.
16. Neuropsychiatric disorders/symptoms or psychological conditions.
17. Pregnancy or breast-feeding
18. Prior treatment with B cell or lymphocyte-depleting agents (eg, rituximab, Campath)

Exclusions Based on Concomitant Medication Use
19. Concurrent regular use of another leukotriene pathway inhibitor, including over-the-counter medications or herbal remedies.

Exclusions Based on Laboratory Values
20. Significant/chronic renal insufficiency.
21. Transaminases (alanine transaminase, aspartate transaminase) levels \>3 × upper limit of normal (ULN) and/or bilirubin level \>2 × ULN.
22. Absolute neutrophil count \<1500 mm3.
23. Hemoglobin concentration \<9 g/dL at Screening.
24. Hepatic dysfunction as defined by Child-Pugh Class B or C
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eiger BioPharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

California Heart Center Foundation, An Affiliate of Cedars-Sinai Heart Institute, Cedars-Sinai Medical Care Foundation

Beverly Hills, California, United States

Site Status

UCSD Medical Center

La Jolla, California, United States

Site Status

Stanford University Medical Center

Stanford, California, United States

Site Status

University of Colorado Denver

Aurora, Colorado, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Cleveland Clinic, Florida

Weston, Florida, United States

Site Status

Kentuckiana Pulmonary Associates

Louisville, Kentucky, United States

Site Status

Chest Medicine Associates

South Portland, Maine, United States

Site Status

Johns Hopkins University, Pulmonary and Critical Care Medicine

Baltimore, Maryland, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Boston University School of Medicine

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Mayo Clinic College of Medicine

Rochester, Minnesota, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

Weill Cornell Medicine

New York, New York, United States

Site Status

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Cleveland Clinic Respiratory Institute

Cleveland, Ohio, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

University of Pennsylvania Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Alpert Medical School of Brown University Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

Houston Methodist Hospital

Houston, Texas, United States

Site Status

University Texas Health Science Center

San Antonio, Texas, United States

Site Status

London Health Sciences Centre

London, Ontario, Canada

Site Status

University of Ottawa Heart Institute

Ottawa, Ontario, Canada

Site Status

Toronto General Hospital

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type BACKGROUND
PMID: 23986401 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26558820 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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EIG-UBX-001

Identifier Type: -

Identifier Source: org_study_id

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