Clinical Trial: ALlogeneic Cardiosphere-derived Stem Cells (CDCs) for Pulmonary Hypertension therApy

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Phase I Study of the Safety and Feasibility of Central Intravenous Delivery of Allogeneic Human Cardiosphere-Derived Stem Cells in Patients With Pulmonary Arterial Hypertension ALPHA Trial

Brief Summary: Pulmonary Arterial Hypertension or PAH is a progressive condition for which there is no cure. Even with substantial pharmacologic advances in the modern treatment era, survival still remains unacceptably poor, as reported in large PAH registries. Preclinical studies suggest that the administration of allogeneic CDCs have the potential to reduce adverse arteriolar remodeling in PAH which was the basis for the approved investigational new drug (IND). The use of CDCs as an adjunctive therapy in patients comprising 4 sub-groups of patients with PAH in which inflammation and immune dysfunction are key pathophysiologic drivers of PAH.

Detailed Summary:

Patients with IPAH, HPAH, PAH-CTD and PAH-HIV meeting all inclusion and no exclusion criteria will be enrolled. An open label phase 1a study (evaluating dosage and safety) will be conducted. This will followed by a randomized double blind placebo controlled Phase 1b study after Data Safety and Monitoring Board (DSMB) review of the one-month safety data for all the Phase 1a subjects. All patients must have documented PAH diagnosed within the last 5 years and all need to be on stable background PAH specific agents for at least 4 months.

The 4 different etiologies of Pulmonary Arterial Hypertension (PAH) included in this (IND) (IPAH, HPAH, PAH-CTD, PAH-HIV) will be diagnosed based on the following:

i) clinical features and tests to support a diagnosis of PAH: the diagnosis of PAH requires right heart catheterization (RHC) to confirm a hemodynamic profile compatible with PAH. This includes a mean pulmonary artery pressure (PAP) ≥ than 25 mmHg at rest, with a pulmonary capillary wedge pressure < 15 mmHg. (If slightly elevated, will confirm with LVEDP measure as is our usual standard of care) and pulmonary vascular resistance (PVR) of > 3 Wood units. In addition, there should be no features to suggest other associations for PAH (also included in Group 1) or evidence to suggest PAH owing to left heart disease (Group 2), PH due to lung diseases (Group 3), Chronic thromboembolic pulmonary hypertension (Group 4) or miscellaneous disorders of unclear mechanism ii) clinical features and tests to support a specific designation of each subset of PAH:

• Idiopathic PAH (IPAH): This is a diagnosis of exclusion in which a firm diagnosis of PAH is made and there are no other etiologies or associations determined that fall into Group 1
• • Determination of Gas Exchange: Significant hypoxemia within the 1st 72 hours following the infusion of CAP-1002 cells as determined by arterial blood gas analysis or pulse oximetry on or off O2, which is a distinct change from values obtained at baseline. (PaO2 < 55mmHg; SPO2 < 85%).
  • Determination of Hemodynamics: Significant tachycardia and hypotension; while PA cath in-situ: fall in cardiac output; significant rise in PA systolic pressure, mean right atrial pressure. Note, hemodynamic measurements will be obtained, as clinically indicated over a 1-hour time frame post CDC infusion. If the patient is deemed stable after this 1-hour time frame, the PA catheter will be withdrawn in the cardiac catheterization laboratory, and the patient will be transferred to the ICU for further monitoring.
  • Detection of Arrhythmias: development of supra-ventricular tachyarrhythmias (atrial fibrillation being the most common) or ventricular tachyarrhythmias (such as ventricular tachycardia).