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

• Register: ClinicalTrials.gov
• Last refreshed on: 20 June 2023
• Main ID: NCT03145298
• Date of registration: 02/05/2017
• Prospective Registration: Yes
• Primary sponsor: Cedars-Sinai Medical Center
• Public title: ALlogeneic Cardiosphere-derived Stem Cells (CDCs) for Pulmonary Hypertension therApy ALPHA
• Scientific 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
• Date of first enrolment: October 1, 2017
• Target sample size: 26
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03145298
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Michael I Lewis, MD
• Affiliation: Cedars-Sinai Medical Center

Key inclusion & exclusion criteria

Inclusion Criteria:

- Confirmed clinical diagnosis of IPAH, HPAH, PAH-CTD, PAH-HIV

- NYHA Functional Class: II or III

- 6MWD > 150 m

- Able to maintain O2 saturation at rest = 90% (with or without supplemental O2). O2 use
during the course of the study is permitted.

- The subjects must be on PAH-specific therapies for at least 4 months and on a stable
dose for at least 4 weeks prior to enrollment into study. PAH-specific agents can
include: prostanoids, prostacyclin receptor agonist, endothelin receptor antagonists,
phosphodiesterase-5 inhibitors and soluble guanylate cyclase stimulator agents alone
or in combination

- All patients with PAH-HIV must be on a stable and effective HAART combination regimen

- Pulmonary capillary wedge pressure (PCWP) or LVEDP < 15 mm Hg

- Age: 18 -75 years

- Ability to provide informed consent and follow-up with protocol procedures

Exclusion Criteria:

- Diagnosis of PAH other than IPAH, HPAH, PAH-CTD or PAH-HIV

- Right atrial pressure > 20 mmHg as measured by right heart catheterization (RHC) on
day of pre-infusion

- History of clinically-significant coronary artery disease, including myocardial
infarction, coronary stent placement or coronary artery bypass surgery within the
previous 5 years, LV dysfunction

- History or demonstration of significant ventricular tachy-arrhythmias or conduction
abnormalities

- Significant interstitial lung disease (on imaging and PFTs; FVC: < 60%;

- Chronic thromboembolic pulmonary hypertension (CTEPH)

- Estimated glomerular filtration rate (GFR) = 50 mL/min

- Active uncontrolled infection

- Non-pulmonary vascular disease with life expectancy of < 3 years

- Hypersensitivity to contrast agents

- Active allergic reactions

- History of previous stem cell therapy

- Participation in an on-going protocol studying an experimental drug or device

- Current alcohol or drug abuse because of anticipated difficulty in complying with
protocol-related procedures

- Pregnant/nursing women as well as men and women of child-bearing potential without use
of active and highly reliable contraception

- Known history of viral hepatitis

- Abnormal liver function (transaminases > 3 times the upper reference range; total
bilirubin > 2 times the upper reference range without a reversible, identifiable cause

- Evidence of tumor on screening of chest/abdominal/pelvic (body) CT scan

- History of malignancy within the last 5 years, except for resected skin basal cell or
squamous cell carcinoma, treated cervical dysplasia or treated in-situ cervical cancer
grade 1

- Any prior organ transplant

- Being actively listed for, or under active consideration for, an organ transplant of
any kind, including lung transplantation

- Known hypersensitivity to bovine products

- Known hypersensitivity to dimethyl sulfoxide (DMSO)

- Any condition or treatment which (in the opinion of investigator), places the patient
at an unacceptable risk if enrolled

- Patients with PAH-HIV will be excluded with any of the following clinical conditions:

- CD4 T-cell count < 200 /mm3 within 90 days prior to screening

- A detectable viral load within 90 days prior to screening

- Active opportunistic infections within 90 days prior to screening

- Changes in antiretroviral regimen within 90 days prior to screening

- Significant anemia or a falling Hb would make patient ineligible. Platelet counts =
100,000/mm3 and absolute neutrophil count < 1,500/mm3 excludes the patient

- History of heparin induced thrombocytopenia (HIT) (unless current HIT Panel is
negative)

NOTE: Those eligible individuals who have had four or more previous gadolinium contrast
scans will have a cardiac MRI without contrast



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension (PAH)

Intervention(s)

Biological: Placebo

Biological: Allogeneic Human Cardiosphere-Derived Stem Cells

Primary Outcome(s)

Primary Safety (Early) endpoints including the determination of Gas Exchange and Hemodynamics; Detection of Arrhythmias; Sudden unexpected death and Mortality and Morbidity [Time Frame: Within 72 hours of infusion]

Secondary Outcome(s)

Exploratory Secondary Efficacy Endpoints measuring right ventricular function and pressure estimates [Time Frame: One year]

Secondary Safety (Long Term) endpoints including ongoing monitoring of events listed for primary safety endpoints as well as long term monitoring for a composite of time to clinical worsening. [Time Frame: One year]

Secondary ID(s)

IND 16686

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

California Institute for Regenerative Medicine (CIRM)