Intervention: Ubenimex
Trial phase: Phase 2
SMILES: CC(C)C[C@H](NC(=O)[C@@H](O)[C@H](N)Cc1ccccc1)C(=O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 41
Group description: ubenimex capsules 150 mg three times a day (TID), administered orally for a total of 24 weeks.

ubenimex
Eligibility criteria:
Inclusion Criteria:

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)
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.

Exclusion Criteria:

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.

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