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

Phase 2

Completed

• Conditions: Pulmonary Arterial Hypertension
• Interventions: Other: placebo; Drug: ubenimex

• Registration Number: NCT02664558
• Lead Sponsor: Eiger BioPharmaceuticals

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2016-01-21
• Study First Submitted QC: 2016-01-26
• Study First Posted: 2016-01-27
• Study Start: 2016-04
• Primary Completion: 2017-11
• Study Completion: 2018-01
• Disposition First Submitted: 2018-10-11
• Disposition First Submitted QC: 2018-10-11
• Disposition First Posted: 2018-10-12
• Results First Submitted: 2022-11-03
• Status Verified: 2023-03
• Results First Submitted QC: 2023-03-03
• Last Update Submitted: 2023-03-03
• Results First Posted: 2023-03-06
• Last Update Posted: 2023-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 61

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Change in Pulmonary Vascular Resistance (PVR)	Baseline to Week 24	Change from Baseline at End of Treatment in PVR Using Worst Case Imputation in the Modified Intent to Treat Population. PVR was assessed by hemodynamic measurements obtained via right heart catheterization.

Secondary Outcome Measures

Name	Time	Method
Change in 6-minute Walk Distance (6MWD)	Baseline to Week 24	Change in exercise capacity from baseline to Week 24 as determined by the 6MWD

Trial Locations

Locations (31)

Kentuckiana Pulmonary Associates; 🇺🇸 Louisville, Kentucky, United States

Cleveland Clinic, Florida; 🇺🇸 Weston, Florida, United States

UCSD Medical Center; 🇺🇸 La Jolla, California, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

California Heart Center Foundation, An Affiliate of Cedars-Sinai Heart Institute, Cedars-Sinai Medical Care Foundation; 🇺🇸 Beverly Hills, California, United States

Johns Hopkins University, Pulmonary and Critical Care Medicine; 🇺🇸 Baltimore, Maryland, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Cleveland Clinic Respiratory Institute; 🇺🇸 Cleveland, Ohio, United States

Allegheny General Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

University Texas Health Science Center; 🇺🇸 San Antonio, Texas, United States

University of Ottawa Heart Institute; 🇨🇦 Ottawa, Ontario, Canada

Stanford University Medical Center; 🇺🇸 Stanford, California, United States

University of Colorado Denver; 🇺🇸 Aurora, Colorado, United States

Boston University School of Medicine; 🇺🇸 Boston, Massachusetts, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

Mayo Clinic College of Medicine; 🇺🇸 Rochester, Minnesota, United States

Weill Cornell Medicine; 🇺🇸 New York, New York, United States

University of Pennsylvania Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Alpert Medical School of Brown University Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States

Toronto General Hospital; 🇨🇦 Toronto, Ontario, Canada

Chest Medicine Associates; 🇺🇸 South Portland, Maine, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

The University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States