Pulmonary Arterial HypertensionPhase 2LIBERTYNCT02664558

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

A Phase 2 study testing ubenimex in people with Pulmonary Arterial Hypertension, run by Eiger BioPharmaceuticals at 31 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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… Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Pulmonary Arterial Hypertension
What is being tested?: ubenimex
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 61 participants
Where: 31 sitesin 2 countries
Study dates: Apr 2016to Jan 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female, 18-75 years old.
Has a diagnosis of WHO Group 1 PAH.
Right heart catheterization performed at Screening with results that are:
Mean pulmonary arterial pressure ≥25 mmHg (at rest) and
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
Pulmonary vascular resistance (PVR) ≥300 dyn•s/cm5 (3.75 Wood units)

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Has WHO/NYHA-FC of II or III.
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.
Has a 6-minute walk distance that is ≥150 and ≤500 meters.
Have a ventilation-perfusion scan that rules out thromboembolic disease.

Who cannot join

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

Show all 33Show fewer

Exclusions Related to Pulmonary Disease
Newly diagnosed with PAH and not on PAH-specific therapy.
Pulmonary hypertension due to:
Uncorrected congenital systemic-to-pulmonary shunt.
Pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis
Persistent pulmonary hypertension of the newborn
WHO clinical classification Groups 2-5
Evidence of significant airway and/or parenchymal lung disease.
Chronic infection related to tuberculosis or fungal or mycobacterial disease.
Exclusions Based on Other Medical Conditions
Chronic infections including, but not limited to tuberculosis (TB), hepatitis B virus (HBV) or hepatitis C virus (HCV).
History of portal hypertension or chronic liver disease, including positive serology for infection with HCV and/or HBV.
Evidence of active infection requiring intravenous or oral antibiotics within 4 weeks of Screening.
Body mass index ≥35.0 at Screening.
History of obstructive sleep apnea.
History of malignancy within the last 5 years, except nonmelanoma skin cancer and cervical carcinoma in situ treated with curative intent.
Neuropsychiatric disorders/symptoms or psychological conditions.
Pregnancy or breast-feeding
Prior treatment with B cell or lymphocyte-depleting agents (eg, rituximab, Campath)
Exclusions Based on Concomitant Medication Use
Concurrent regular use of another leukotriene pathway inhibitor, including over-the-counter medications or herbal remedies.
Exclusions Based on Laboratory Values
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.
Hepatic dysfunction as defined by Child-Pugh Class B or C

Trial locations and contacts

31 sites in 2 countries.

Country

City, postcode or hospital

31 sites in 2 countries

United States28 sites

University of Michigan
Ann Arbor, Michigan, 48109
University of Colorado Denver
Aurora, Colorado, 80045
Johns Hopkins University, Pulmonary and Critical Care Medicine
Baltimore, Maryland, 21205
California Heart Center Foundation, An Affiliate of Cedars-Sinai Heart Institute, Cedars-Sinai Medical Care Foundation
Beverly Hills, California, 90211
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Tufts Medical Center
Boston, Massachusetts, 02111
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Boston University School of Medicine
Boston, Massachusetts, 02118
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Cleveland Clinic Respiratory Institute
Cleveland, Ohio, 44195
UT Southwestern Medical Center
Dallas, Texas, 75390
Duke University Medical Center
Durham, North Carolina, 27710
University of Florida
Gainesville, Florida, 32610
Houston Methodist Hospital
Houston, Texas, 77030
UCSD Medical Center
La Jolla, California, 92103
Kentuckiana Pulmonary Associates
Louisville, Kentucky, 40202
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Weill Cornell Medicine
New York, New York, 10065
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
University of Pennsylvania Medical Center
Pittsburgh, Pennsylvania, 15213
Alpert Medical School of Brown University Rhode Island Hospital
Providence, Rhode Island, 02903
Mayo Clinic College of Medicine
Rochester, Minnesota, 55905
University Texas Health Science Center
San Antonio, Texas, 78229
Chest Medicine Associates
South Portland, Maine, 04106
Washington University
St Louis, Missouri, 63130
Stanford University Medical Center
Stanford, California, 94305
Cleveland Clinic, Florida
Weston, Florida, 33331

Other trials in United States

Canada3 sites

London Health Sciences Centre
London, Ontario, N6A 5W9
University of Ottawa Heart Institute
Ottawa, Ontario, K1Y 4W7
Toronto General Hospital
Toronto, Ontario, M5G 2N2

Other trials in Canada

About this study

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

Read the 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.

Conditions: Pulmonary Arterial Hypertension
Being tested: ubenimex, placebo
Medical subject headings: Pulmonary Arterial Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ubenimexDrug
Also called UBX
placeboOther

Study groups in NCT02664558
Study group	Role	What they receive
ubenimex	Experimental	ubenimex capsules 150 mg three times a day (TID), administered orally for a total of 24 weeks. Receives: Drug: ubenimex
placebo	Placebo comparator	placebo capsules TID, administered orally for a total of 24 weeks Receives: Other: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline to Week 24

Secondary outcomes (1)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2016Jan 2018

First posted27 Jan 2016 (estimated)
Study startApr 2016
Primary completionNov 2017
Study completionJan 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 61 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02664558
Sponsor's protocol ID: EIG-UBX-001
Acronym: LIBERTY
Status last verified: Mar 2023
First submitted: 21 Jan 2016
Last updated: 6 Mar 2023
Results posted: Yes, on ClinicalTrials.gov

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.
PubMed 23986401
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.
PubMed 26558820

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
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All Pulmonary Arterial Hypertension trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, Randomized, Double-BLInd, Placebo- Controlled Study of UBEnimex in Patients With Pulmonary ARTerial HYpertension (WHO Group 1) (LIBERTY)
ClinicalTrials.gov ID: NCT02664558
Acronym / sponsor ID: LIBERTY / EIG-UBX-001
Conditions: Pulmonary Arterial Hypertension
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 61 participants (actual)
Lead sponsor: Eiger BioPharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Apr 2016
Primary completion: Nov 2017 (actual)
Study completion: Jan 2018 (actual)
First posted: 27 Jan 2016 (estimated)
Results: Posted 6 Mar 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
ubenimex	Experimental	Drug: ubenimexubenimex capsules 150 mg three times a day (TID), administered orally for a total of 24 weeks.
placebo	Placebo comparator	Other: placeboplacebo capsules TID, administered orally for a total of 24 weeks

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

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

Key exclusion criteria (33 listed)

Exclusions Related to Cardiovascular Disease
History of uncontrolled hypertension
Persistent hypotension at Screening.
Evidence or history of left-sided heart disease and/or clinically significant cardiac disease in which pulmonary hypertension is more likely WHO Group 2.
Acute decompensated heart failure within 1 month of Screening.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ubenimexAlso: UBX	Drug	ubenimex
placebo	Other	placebo

Primary outcome

Change in Pulmonary Vascular Resistance (PVR)
Time frame: 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.

1 secondary outcome

Change in 6-minute Walk Distance (6MWD)
Time frame: Baseline to Week 24

Results and safety

Results posted to the registry on 6 Mar 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ubenimex	41	36
Placebo	20	18

Primary outcome: Change in Pulmonary Vascular Resistance (PVR)

Time frame: Baseline to Week 24. Mean (Standard Deviation). Unit: dyn.sec/cm5

Measure	Ubenimex n = 41	Placebo n = 20
Value	73.1 (271.6)	46.6 (256.8)

Population analysed: Modified Intent to Treat Population: i.e., all randomized patients who received at least one dose of study drug and had a baseline assessment for the respective endpoint.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 7 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ubenimex	9 of 41 (22%)	39 of 41 (95.1%)	0 of 41
Placebo	2 of 20 (10%)	18 of 20 (90%)	0 of 20

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 23986401Tian 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.
Background: PubMed 26558820Qian 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.

Related trials for Pulmonary Arterial Hypertension

Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
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Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

31 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ubenimex in people with Pulmonary Arterial Hypertension, run by Eiger BioPharmaceuticals at 31 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Pulmonary Vascular Resistance (PVR) (time frame: Baseline to Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02664558, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2023.