Oral CXA-10 in Pulmonary Arterial Hypertension
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension
Intervention: CXA-10
Intervention description: Each subject will receive oral CXA-10 at the dose of 300 mg once daily for 12 weeks
Intervention MeSH terms: CXA-10
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: One-arm, open-label
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      The main objective of this study is to evaluate the safety and tolerability of 12-week oral
      CXA-10 therapy in subjects with pulmonary arterial hypertension, with additional evaluation
      on the clinical efficacy of oral CXA-10 on changes in hemodynamics, exercise capacity,
      cardiovascular function and patient reported outcomes.
    

Eligibility criteria:

        INCLUSION CRITERIA

        The following criteria will be required on ALL subjects:

          -  Male or female between 18-80 years of age inclusive at Screening

          -  Weight ≥ 40 kg or 88 lbs

          -  Have a WHO Classification of Functional Status Class II or III

          -  Must meet all of the following hemodynamic criteria by means of a right heart
             catheterization: mPAP of ≥ 25 mmHg, PVR ≥ 3 wood units, PAWP of ≤ 15 mmHg. A clinical
             RHC done within 2 months is acceptable to determine eligibility

          -  Meet all of the following pulmonary function test parameters, completed no more than
             12 months before Screening or at screening: forced expiratory volume in one second
             (FEV1) > 60% of predicted normal and forced vital capacity (FVC) ≥ 60%

          -  A 6 MWD test of ≥ 100 m and ≤ 600 m at Screening

          -  Participants enrolled in an exercise program for pulmonary rehabilitation must be in a
             stable program 1 month prior to Screening and must agree to maintain their current
             level of rehabilitation throughout the study. If subjects are not enrolled in an
             exercise training program for pulmonary rehabilitation they cannot enroll during the
             Screening/Baseline Period or throughout the study

          -  If receiving 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors
             (i.e., statins) subjects must not have changed their dose < 4 weeks prior to Screening

          -  If receiving simvastatin-containing products: simvastatin (Zocor), Vytorin, or any
             other combination therapy containing simvastatin, the subject's simvastatin dose
             should not exceed 20 mg/day Note: Subjects using a simvastatin product at dose > 20
             mg/day may be rescreened if their dose has been adjusted to ≤ 20 mg/day, at least 4
             weeks prior to Screening with no dose or regimen changes within 4 weeks prior to
             Baseline

          -  Subjects must be receiving one or more of the following previously approved PAH
             therapies: phosphodiesterase type 5 inhibitors (PDE5), endothelin receptor antagonist
             (ERA), soluble guanylate cyclase (sGC) stimulator, prostanoids, prostacyclin receptor
             agonists and must be on stable doses ≥ 3 months) with no dose adjustment within 1
             month of Screening

          -  Ability to provide written informed consent

        EXCLUSION CRITERIA

        Subjects meeting any of the following exclusion criteria at baseline will be excluded from
        participating in study:

          -  Portopulmonary hypertension and pulmonary veno-occlusive diseases

          -  Congenital heart defects (i.e., atrial septal defects, ventricular septal defects, and
             patent ductus arteriosus) repaired < 1 year prior to Screening (Group 1 classification
             of Pulmonary Hypertension)

          -  Systolic blood pressure > 160 or < 90 mmHg or diastolic blood pressure > 110 mmHg at
             Screening

          -  An average QTcF on supine triplicate ECGs at Screening (Visit 1) of > 500 msec Acute
             myocardial infarction or acute coronary syndrome (ST-Elevation Myocardial Infarction
             (STEMI), Non STEMI (NSTEMI) and/or unstable angina) within the last 90 days prior to
             Screening

          -  Recent cerebrovascular accident/transient ischemic attack (CVA/TIA) within the last 90
             days prior to Screening

          -  Recent hospitalization for left heart failure within the last 90 days prior to
             Screening

          -  Clinically significant aortic or mitral valve disease defined as greater than moderate
             regurgitation or moderate 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 in the opinion of the investigator

          -  Evidence of a life-threatening cardiac arrhythmias on ECG at Screening as determined
             by the physician investigator

          -  Personal or family history of congenital prolonged QTc syndrome or sudden unexpected
             death due to a cardiac reason

          -  Receiving intravenous inotropes (e.g. dopamine, dobutamine) 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

          -  The subject has a history of herbal or natural medication use (including fish oil)
             within 2 weeks or 5 half-lives, whichever is longer, prior to Baseline

          -  Subject has taken prednisone at doses > 15 mg/day; if immunosuppressive medications
             are used the dose must be stable within 12 weeks prior to Screening and throughout the
             study

          -  The subject is currently taking a drug that may affect the assay measurement of serum
             creatinine (e.g. cimetidine, Bactrim, Pyridium)

          -  Newly prescribed drug or increased dose of an existing drug that is known to prolong
             the QTc interval and has been associated with Torsades de Pointes Note: Stable doses
             of these drugs are permitted (i.e., subject has received the same dose and regimen for
             at least 30 days prior to Screening with no anticipated changes to the dose or regimen
             during the course of the study)

          -  The subject is currently taking dimethyl fumarate (Tecfidera™)

          -  Females with a positive urine pregnancy test at Screening or prior to dosing or who
             are pregnant or breastfeeding or who are trying to conceive

          -  Recent (within 6 months) history of abusing alcohol or illicit drugs

          -  History of any primary malignancy, including a history of melanoma or suspicious
             undiagnosed skin lesions, with the exception of basal cell or squamous cell carcinomas
             of the skin or cervical carcinoma in situ or other malignancies curatively treated and
             with no evidence of disease for at least 5 years or prostate cancer who is not
             currently or expected, during the study, to undergo radiation therapy, chemotherapy,
             and/or surgical intervention, or to initiate hormonal treatment

          -  Cardiovascular, liver, renal, hematologic, gastrointestinal, immunologic, endocrine,
             metabolic, central nervous system or psychiatric disease that, in the opinion of the
             investigator, may adversely affect the safety of the subject and/or efficacy of the
             investigational product or severely limit the lifespan of the subject other than the
             condition being studied

          -  Clinically significant hyperthyroidism or hypothyroidism not adequately treated

          -  Any other condition and/or situation that causes the Investigator to deem a subject
             unsuitable for the study (e.g., due to expected study medication non-compliance,
             inability to medically tolerate the study procedures, or a subject's unwillingness to
             comply with study-related procedures)

          -  The subject has known hypersensitivity to the CXA-10, the metabolites, or formulation
             excipients

          -  The subject has had treatment with any investigational drug within 30 days or 5
             half-lives (whichever is longer) prior to Screening or plans to participate in an
             investigational drug study at any time during this study

        Subjects who fail inclusion/exclusion criteria may be re-screened once.