Safety Study of PLX-PAD Cells to Treat Pulmonary Arterial Hypertension (PAH)

Study Overview
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Brief Summary
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The purpose of this clinical study is to assess the safety of PLX-PAD to treat pulmonary arterial hypertension (PAH). PLX-PAD is a cell-based product made of allogeneic Mesenchymal-like Adherent Stromal Cells (ASCs), derived from human full-term placentas following an elective caesarean section. This year-long study will evaluate the safety of three different dose levels of PLX-PAD, each given as a single intravenous infusion. This study will also evaluate effects that PLX-PAD may have on PAH, such as changes in the ability to exercise and on other tests used to measure the disease severity.

Official Title
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A Phase I Safety and Pharmacodynamic Study of Intravenous Infusion of PLX-PAD Cells in Patients With PAH

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: PLX-PAD


Participation Criteria
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Eligibility Criteria
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Summary of inclusion and exclusion criteria. Eligible subjects: Are between 18 and 75 years of age Have a minimum weight of 45 kg Have a diagnosis of idiopathic or heritable PAH, PAH associated with connective tissue disease (CTD), PAH associated with repaired congenital systemic-to-pulmonary cardiac shunt (at least one year since repair), or PAH associated with appetite suppressant/drug or toxin use confirmed by RHC Have a current WHO functional class II or III designation Have been stabilized, without dose changes for at least 30 days prior to the Screening visit on at least two approved PAH medications (e.g., PDE-5 inhibitor, ERA, prostanoid [as inhalation or infusion]); or IV prostanoid monotherapy. Subjects on an IV prostanoid must have been receiving therapy for at least three months prior to the Screening visit. Have a 6MWD equal to or greater than 200 meters (m) at the Screening and Baseline Visits. Subjects must not: Have any evidence of pulmonary thrombus, significant coronary artery disease (CAD), left ventricular dysfunction, or a restrictive or congestive cardiomyopathy Have a history of malignancies within the past 5 years,with the exception of individuals with localized, non-metastatic basal cell carcinoma of the skin, in situ carcinoma of the cervix, or prostate cancer who are not currently or expected to undergo radiation therapy, chemotherapy and/or surgical intervention, or to initiate hormonal treatment during the study Be listed for transplantation Be pregnant or nursing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.5 M PLX-PAD<br>0.5 million (M) PLX-PAD cells per kg body weight | Drug: PLX-PAD<br>* intravenous administration of a single dose of PLX-PAD cells<br>* Other names: allogeneic Mesenchymal-like Adherent Stromal Cells (ASCs);|
| Experimental: 1 M PLX-PAD<br>1.0 million (M) PLX-PAD cells per kg body weight | Drug: PLX-PAD<br>* intravenous administration of a single dose of PLX-PAD cells<br>* Other names: allogeneic Mesenchymal-like Adherent Stromal Cells (ASCs);|
| Experimental: 2 M PLX-PAD<br>2.0 million (M) PLX-PAD cells per kg body weight | Drug: PLX-PAD<br>* intravenous administration of a single dose of PLX-PAD cells<br>* Other names: allogeneic Mesenchymal-like Adherent Stromal Cells (ASCs);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent AEs (frequency and severity at each dose level) |  | 12 weeks | 
| Incidence of SAEs |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Six Minute Walk distance |  | Baseline and 6 weeks | 
| Change in Dyspnea Score | Change in maximum level of dyspnea experienced during the six minute walk test using a 10 point scale. | Baseline and 6 weeks | 
| Change in WHO Functional Classification |  | Baseline and 6 weeks | 
| Change in Plasma NT-pro-BNP levels |  | Baseline and 6 weeks | 
| Change from Baseline in echocardiography parameters | Change in RV area at end systole and end diastole (for calculation of estimated RV ejection fraction, RV basal and mid diameter at end systole and end diastole, RV free wall thickness, tricuspid annular plane systolic excursion (TAPSE), maximal tricuspid regurgitant jet velocity TRJV) and pulmonary artery end diastolic pressure (PAEDP) | Baseline and 6 weeks | 
| Change in cardiopulmonary hemodynamics | mean pulmonary arterial pressure (PAPm), heart rate (HR), systolic systemic arterial pressure (SAPs), diastolic systemic arterial pressure (SAPd), mean systemic arterial pressure (SAPm), pulmonary artery systolic pressure (PAPs), pulmonary artery diastolic pressure (PAPd), mean right atrial pressure (RAPm), mean pulmonary capillary wedge pressure (PCWPm), and cardiac output (CO) | Baseline and 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cell therapy, Pulmonary arterial hypertension