PRIMEx - A Study of 2 Doses of Oral CXA-10 in Pulmonary Arterial Hypertension (PAH)

Study Overview
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Brief Summary
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This is a multicenter double-blind, placebo-controlled study to evaluate the safety, efficacy and pharmacokinetics of 2 doses of CXA-10 on stable background therapy in 96 subjects 18 to 80 years of age with PAH.

Detailed Description
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This is a multicenter double-blind, placebo-controlled study to evaluate the safety, efficacy and pharmacokinetics of 2 doses of CXA-10 on stable background therapy in 96 subjects 18 to 80 years of age with PAH. The study will be performed in approximately 50 study centers across the United States of America and Europe. The recruitment period is anticipated to be approximately 24 months. Approximately 115 subjects will be enrolled to ensure at least 96 subjects complete the study. Study participation for each subject will last approximately 8 months. The study will consist of a screening period (within 30 days prior to dosing), 180 days (approximately 6 months) treatment period and approximately 14 days follow-up period after the end of treatment visit.

Official Title
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Phase 2 Multicenter, Double-Blind, Placebo Controlled, Efficacy, Safety, and Pharmacokinetic Study of 2 Doses of CXA-10 on Stable Background Therapy in Subjects With Pulmonary Arterial Hypertension

Conditions
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PAH

Intervention / Treatment
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* Drug: 75mg CXA-10
* Drug: 150mg CXA-10
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between 18 to 80 years of age inclusive at Screening Weight ≥40 kg Must have a diagnosis of WHO Group 1 PH Have a World Health Organization (WHO) Classification of Functional Status Class II or III of patients with PH Must meet hemodynamic criteria by means of a right heart catheterization Meet pulmonary function test parameters A 6 MWD test of ≥125m and ≤550m at the visit Subjects must have a resting arterial oxygen saturation (SaO2) ≥90%, with or without supplemental oxygen, as measured by pulse oximetry at Screening Subjects enrolled in a prescribed exercise program for pulmonary rehabilitation must be in a stable program for 3 months prior to Screening (Visit 1) and must agree to maintain their current level of rehabilitation throughout the study. If subjects are not enrolled in a prescribed exercise training program for pulmonary rehabilitation, they cannot enroll during the Screening/Baseline Period or throughout the study If receiving simvastatin-containing products: dose should not exceed 20 mg/day Subjects must be receiving no more than three of the following previously approved PAH therapies: phosphodiesterase type 5 (PDE-5) inhibitors, endothelin receptor antagonist (ERA), soluble guanylate cyclase (sGC) stimulator, prostanoids, prostacyclin receptor agonists and must be on stable doses (≥3 months) at Screening (Visit 1) Exclusion Criteria: Contraindications for CMRI imaging WHO Groups 2, 3, 4 and 5 Pulmonary Hypertension Unrepaired congenital heart defects and significant congenital heart defects (i.e., atrial septal defects, ventricular septal defects, and patent ductus arteriosus) repaired less than 1 year prior to Screening (Visit 1) (Group 1 classification of Pulmonary Hypertension) QTcF > 500 msec Acute myocardial infarction or acute coronary syndrome within the last 90 days Cerebrovascular accident/transient ischemic attack (CVA/TIA) within the last 90 days Hospitalization for left heart failure within the last 90 days Clinically significant aortic or mitral valve disease defined as greater than mild regurgitation or mild stenosis; pericardial constriction; restrictive or constrictive cardiomyopathy; left ventricular dysfunction (LVEF < 50%); left ventricular outflow obstruction; symptomatic coronary artery disease; autonomic hypotension; or fluid depletion Chronic atrial fibrillation and life-threatening cardiac arrhythmias Personal or family history of congenital prolonged QTc syndrome or sudden or sudden unexpected death due to a cardiac reason Clinically significant anemia Severe hepatic impairment or active chronic hepatitis Receiving intravenous inotropes within 2 weeks prior to Screening History of angina pectoris or other condition that was treated with long or short acting nitrates <12 weeks of Screening Received prednisone doses >15mg/day or changes in immunosuppressive medications < 12 weeks prior to Screening (Visit 1) Recent (within 1 year) history of abusing alcohol or illicit drugs. History of any primary malignancy, with no evidence of disease for at least 5 years Treatment with any investigational drug or device within 30 days or 5 half-lives

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: CXA-10
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 75mg CXA-10<br>Once daily dosing of 75mg CXA-10 in the morning | Drug: 75mg CXA-10<br>* CXA-10 (10-nitro-9(E)-octadec-9-enoic acid) is a specific isomer of nitro-oleic acid (OA-NO2)<br>|
| Active Comparator: 150mg CXA-10<br>Once daily dosing of 150mg CXA-10 in the morning | Drug: 150mg CXA-10<br>* CXA-10 (10-nitro-9(E)-octadec-9-enoic acid) is a specific isomer of nitro-oleic acid (OA-NO2)<br>|
| Placebo Comparator: Placebo<br>Once daily dosing in the morning | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Right Ventricular Ejection Fraction (RVEF) | • To determine the efficacy of oral doses of CXA-10 on stable background therapy administered for 6 months in subjects with PAH assessed by right ventricular ejection fraction (RVEF) as measured by Cardiac MRI | 6 months | 
| Pulmonary Vascular Resistance (PVR) | • To determine the efficacy of oral doses of CXA-10 on stable background therapy administered for 6 months in subjects with PAH assessed by pulmonary vascular resistance (PVR) as measured by right heart catheterization (RHC) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 Minute Walk Distance (6MWD) | To determine the efficacy of oral doses of CXA-10 on stable background therapy administered for 6 months in subjects with PAH assessed by 6 minute walk distance (6MWD) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Arterial Hypertension, Pulmonary Hypertension, PAH, Connective Tissue Disease-Associated, 6 Minute Walk Test, 6 Minute Walk Distance, Pulmonary Vascular Resistance, Cardiac MRI, Right Ventricular Function, Hypertension, Familial Primary Pulmonary Hypertension, Connective Tissue Diseases, Vascular Diseases, Cardiovascular Diseases, Hypertension, Pulmonary, Lung Diseases