We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 15 for:    cedars sinai | pulmonary hypertension | United States, California
Previous Study | Return to List | Next Study

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

This study is currently recruiting participants.
Verified August 2017 by Eduardo Marban, MD, PhD, Cedars-Sinai Medical Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT03145298
First Posted: May 9, 2017
Last Update Posted: August 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
California Institute for Regenerative Medicine
Information provided by (Responsible Party):
Eduardo Marban, MD, PhD, Cedars-Sinai Medical Center
  Purpose
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.

Condition Intervention Phase
Pulmonary Arterial Hypertension (PAH) Biological: Allogeneic Human Cardiosphere-Derived Stem Cells Biological: Placebo Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
The study is divided into two portions. The first (Phase 1a) evaluates safety and efficacy of 2 different doses of cells (50 and 100 million cells). The second phase (Phase 1b) takes place after an independent data safety monitoring board has reviewed all the data from Phase 1a and deems it safe and appropriate to proceed to Phase 1b. The latter is a randomized double-blind study in which subjects receive either CAP-1002 or placebo in a 1:1 ratio.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
Notification of subject randomization will be received by an independent storage/distribution center; the storage/distribution center will have password protected access to the randomization in order to retrieve the treatment assignment. The storage/distribution center will randomly assign an appropriate donor (or placebo) once they receive the designation of active treatment vs. placebo from the interactive system. All Sponsor staff will remain blinded to treatment (CAP-1002 or placebo) assignments. The only time other Sponsor staff will become aware of individual treatments is in the case of an emergency blind break resulting from an SAE.
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eduardo Marban, MD, PhD, Cedars-Sinai Medical Center:

Primary Outcome Measures:
  • 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 ]
    • 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 screening. (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).


Secondary Outcome Measures:
  • 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 ]

    Clinical Worsening is described as:

    • Death (all-cause mortality)
    • Hospitalization for worsening PAH:
    • Non-elective hospitalization for ≥ 24 hours
    • Signs and symptoms of RV failure to include one or more of: increased dyspnea, clinically significant deterioration in exercise capacity, syncope or pre-syncope, hypoxemia, edema, hepatomegaly, ascites
    • Initiation of parenteral prostanoids or chronic O2 therapy if not previously receiving
    • Decrease in Functional Class:
    • ≥ 15% reduction in 6MWD from screening (confirmed on 2 tests on different
    • days over 2 weeks)
    • Need for additional PAH-specific therapy
    • Progressive disease requiring balloon atrial septostomy +/- lung transplantation

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

    Transthoracic Echo (TTE):

    • Tricuspid annular plane systolic excursion (TAPSE)
    • RV (Right Ventricular) Fractional Area Change
    • Tricuspid Tissue Doppler Velocity
    • Pulmonary and right atrial pressure estimates

    Right Heart Catheterization:

    • Right atrial pressure (RAP)
    • RV systolic, diastolic pressures
    • PA systolic, diastolic and mean pressures
    • Pulmonary capillary wedge pressure
    • Total pulmonary arterial compliance
    • Cardiac Output (CO)/Cardiac Input (CI)


Estimated Enrollment: 26
Anticipated Study Start Date: August 30, 2017
Estimated Study Completion Date: December 31, 2020
Estimated Primary Completion Date: January 1, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Biological: Allogeneic Human Cardiosphere-Derived Cells (CDCs)
The Phase 1a portion (N=6 subjects) consists of an open-label, single-arm, study design - dose escalation. The potentially conducted Phase 1b portion of the study (N=20 subjects) consists of a double-blind, randomized, placebo-controlled study design.
Biological: Allogeneic Human Cardiosphere-Derived Stem Cells
Human Allogeneic Cardiosphere-Derived Cells is a biologic product consisting largely of cells grown from donated human heart muscle tissue
Other Name: CAP-1002
Placebo Comparator: Placebo
The placebo study arm only applies to the Phase Ib portion of the study design. The Phase Ia portion (N=6 subjects) consists of an open-label, single-arm, study design. The potentially conducted Phase Ib portion of the study (N=20 subjects) consists of a double-blind, randomized, placebo-controlled study design with a 1:1 ratio.
Biological: Placebo
For use in Phase 1b - Double-blind randomized control portion of the study

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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
  • Pulmonary capillary wedge pressure or LVEDP > 15 mm Hg
  • Right atrial pressure > 20 mmHg with initial research RHC
  • 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

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03145298


Contacts
Contact: Tracey Early, BA, MA, CCRP 310-423-1231 Tracey.Early@cshs.org

Locations
United States, California
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Tracey Early, BA, MA, CCRP    310-423-1231    Tracey.Early@cshs.org   
Sponsors and Collaborators
Cedars-Sinai Medical Center
California Institute for Regenerative Medicine
Investigators
Principal Investigator: Michael I Lewis, MD Cedars-Sinai Medical Center
  More Information

Responsible Party: Eduardo Marban, MD, PhD, Director, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT03145298     History of Changes
Other Study ID Numbers: IND 16686
First Submitted: May 2, 2017
First Posted: May 9, 2017
Last Update Posted: August 17, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Uncertain

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eduardo Marban, MD, PhD, Cedars-Sinai Medical Center:
HPAH (heritable)
IPAH (idiopathic)
PAH-CTD (connective tissue diseases)
PAH-HIV (human immunodeficiency virus)

Additional relevant MeSH terms:
Hypertension
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases