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

Pulmonary Arterial Hypertension Clinical Trial

— LIBERTY  

Official title:

A Phase 2, Randomized, Double-BLInd, Placebo- Controlled Study of UBEnimex in Patients With Pulmonary ARTerial HYpertension (WHO Group 1) (LIBERTY)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02664558
• Other study ID #: EIG-UBX-001
• Status: Completed
• Phase: Phase 2
• Start date: April 2016
• Est. completion date: January 2018

Study information

• Verified date: March 2023
• Source: Eiger BioPharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: January 2018
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• ubenimex

Other:
• placebo

Locations

Country	Name	City	State
Canada	London Health Sciences Centre	London	Ontario
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado Denver	Aurora	Colorado
United States	Johns Hopkins University, Pulmonary and Critical Care Medicine	Baltimore	Maryland
United States	California Heart Center Foundation, An Affiliate of Cedars-Sinai Heart Institute, Cedars-Sinai Medical Care Foundation	Beverly Hills	California
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston University School of Medicine	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Cleveland Clinic Respiratory Institute	Cleveland	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Florida	Gainesville	Florida
United States	Houston Methodist Hospital	Houston	Texas
United States	UCSD Medical Center	La Jolla	California
United States	Kentuckiana Pulmonary Associates	Louisville	Kentucky
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Weill Cornell Medicine	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
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	Mayo Clinic College of Medicine	Rochester	Minnesota
United States	Washington University	Saint Louis	Missouri
United States	University Texas Health Science Center	San Antonio	Texas
United States	Chest Medicine Associates	South Portland	Maine
United States	Stanford University Medical Center	Stanford	California
United States	Cleveland Clinic, Florida	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Eiger BioPharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Pulmonary Vascular Resistance (PVR)	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.	Baseline to Week 24
Secondary	Change in 6-minute Walk Distance (6MWD)	Change in exercise capacity from baseline to Week 24 as determined by the 6MWD	Baseline to Week 24