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

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

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.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: PLX-PAD

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia
    • The Alfred Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4032
      • The Prince Charles Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: United Therapeutics
• Investigators: Principal Investigator: Daniel Chambers, MRCP FRACP MD, The Prince Charles Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: February 12, 2013
• First Submitted That Met QC Criteria: February 18, 2013
• First Posted (Estimate): February 21, 2013

Study Record Updates

• Last Update Posted (Estimate): February 17, 2016
• Last Update Submitted That Met QC Criteria: February 15, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: cell therapy; Pulmonary arterial hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension
• Other Study ID Numbers: PLX-PH-101