Oral CXA-10 in Pulmonary Arterial Hypertension

Phase 2

Terminated

Conditions: Pulmonary Arterial Hypertension

Interventions: Drug: CXA-10

Registration Number: NCT04125745

Lead Sponsor: Gladwin, Mark, MD

Brief 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.

Detailed Description: This is a single-center, one-arm, open-label proof of concept safety study and a phase 2a proof of efficacy pre- and post-assessment study of oral CXA-10 for the treatment of pulmonary arterial hypertension.

The investigators hypothesize that administration of CXA-10 for 12 weeks will improves exercise capacity, cardiovascular function and health related quality of life in pulmonary arterial hypertension patients with limited toxicity.

Subjects who meet the inclusion criteria and none of the exclusion criteria will be scheduled within 4 weeks of screening to receive oral CXA-10 at the dose of 300 mg once daily followed by 12 weeks of open-label CXA-10 treatment and then a 4-week safety follow-up. Additional follow-up assessments by telephone will occur in between each outpatient clinic visit.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CXA-10	CXA-10	Oral CXA-10 300 mg once daily for 12 weeks

Primary Outcome Measures

Name	Time	Method
Number of Treatment-Related Adverse Events as Assessed by CTCAE v4.0 in 12 Weeks	Baseline to 12 Weeks	Numbers of treatment-related adverse events is assessed by CTCAE v4.0

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Levels of Serum N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) at 12 Weeks	at Baseline and 12 Weeks	Blood samples will be collected for NT-proBNP analysis
Change From Baseline in Mean Pulmonary Artery Pressure is Measured at Baseline and 12 Weeks by Right Heart Catheterization	Baseline and 12 Weeks	Pulmonary Artery mean pressure will be measured by right heart catheterization
Change From Baseline in Functional Status of Patients as Assessed by New York Heart Association Functional Class	at Baseline and 12 Weeks	The New York Heart Association Classification of Functional Status of Patients with pulmonary hypertension will be used to classify disease severity in PAH. It places patients in one of four categories based on how much they are limited during physical activity. Measure Description: Class I: No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath). Class II: Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath). Class III: Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV: Unable to carry on any physical activity without discomfort. Symptoms of dyspnea at rest. If any physical activity is undertaken, discomfort increases.
Change From Baseline in Daily Physical Activity as Measured by a Accelerometer	Baseline and 12 Weeks	Continuous physical activity monitoring will be conducted using a noninvasive accelerometer. The device must be worn for a minimum of 7 days at home prior to receiving the first dose of the study drug and prior to the end of the study drug treatment at week 12.
Change From Baseline in Pulmonary Vascular Resistance is Measured at Baseline and 12 Weeks by Right Heart Catheterization	Baseline and 12 Weeks	Pulmonary vascular resistance (PVR) will be measured by right heart catheterization; results reported as changed from baseline in Woods units. PVR is calculated as (mean pulmonary artery pressure - pulmonary artery wedge pressure)/cardiac output, where pressures are in units of mm Hg and cardiac output is in units of L/min. Pulmonary hypertension is defined as PVR \> 3 Woods units. A negative change implies a decrease in PVR which would be considered an improvement.
Change From Baseline in RV Function as Measured by Tricuspid Annular Plane Systolic Excursion (TAPSE) as Assessed by Echocardiograms at 12 Weeks	at baseline and 12 weeks	Change from baseline in RV function as measured by tricuspid annular plane systolic excursion (TAPSE) as assessed by echocardiograms at 12 weeks
Changes From Baseline in Functional Exercise Capacity by Assessing 6 Minute Walk Distance Test	at baseline and 12 weeks	Change from baseline in 6 minute walk distance at 12 weeks