Ignite Creation Date:
2024-05-06 @ 10:02 AM
Last Modification Date:
2024-10-26 @ 12:23 PM
Study NCT ID:
NCT03145298
Status:
COMPLETED
Last Update Posted:
2023-06-12
First Post:
2017-05-02
Brief Title:
ALlogeneic Cardiosphere-derived Stem Cells CDCs for Pulmonary Hypertension therApy
Sponsor:
Cedars-Sinai Medical Center
Organization:
Cedars-Sinai Medical Center
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2023-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ALPHA
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 Description:
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
Heritable PAH HPAH This diagnosis is based on a family history of PAH with or without a documented genetic mutation associated with PAH such as BMPR2 mutations that are present in up to 75 of HPAH patients No other PAH association is present
PAH - Connective Tissue Disease PAH-CTD These patients have a confirmed diagnosis of PAH as well as firm evidence to support a diagnosis of a connective tissue disease In the REVEAL registry scleroderma-associated PAH accounted for 60 of PAH-CTD All PAH-CTD cases will be referred by or evaluated by a rheumatologist to ensure a firm diagnosis While all CTDs can be complicated by PAH the most common associations are described below
1 Scleroderma SSc We use the ACREULAR criteria for the diagnosis and classification of systemic sclerosis Patients with SSc-APAH may exhibit features of limited scleroderma such as calcinosis Reynauds esophageal dysmotility sclerodactyly with skin thickening of the fingers of both hands extending proximal to the metacarpophalangeal joints and telangiectasia In those with limited scleroderma anticentromere antibodies are commonly positive In patients with diffuse cutaneous scleroderma SSc-PAH can also be seen They exhibit diffuse skin thickening and tightening Anti-topoisomerase antibodies anti Scl70 may be positive but interestingly their absence is more likely to be associated with PAH Other autoantibodies that are associated with an increased risk of SSc-PAH include anti-U1-ribonucleoprotein antibodies RNP nucleolar pattern of anti-nuclear antibody nucleolar-ANA and rarely antiphospholipid antibodies
2 Systemic Lupus Erythematosus SLE We use the Systemic Lupus International Collaborating Clinics SLICC classification which requires at least 417 criteria including at least 1 clinical criterion and 1 immunologic criterion or biopsy proven lupus nephritis On history and physical exam the following are highly suggestive Photosensitive skin lesions malar rash or discoid lesions painless ulcers oral or nasal features of a serositis alopecia Raynauds arthralgiaarthritis often migratory etc Immunologic antibody studies included in SLICC are Positive ANA anti-dsDNA anti-Sm antiphospholipid low complement positive direct Coombs test
3 Mixed Connective Tissue Disease MCTD This is characterized by overlapping features of SLE SSc and polymyositis PM as well as high titers of anti-U1 ribonucleoprotein RNP The old term for this is anti-extractable nuclear protein anti-ENA
4 Rheumatoid Arthritis RA RA is a symmetrical distal inflammatory poly arthritis condition The criteria developed and validated by the American College of Rheumatology ACR has been used in numerous drug studies which requires at least four of these seven criteria for diagnosis morning stiffness arthritis of three or more joint areas arthritis of the hands symmetric arthritis rheumatoid nodules and classic radiographic erosive changes Immunologic studies include positive rheumatoid factor RF and anti-cyclic citrullinated peptide CCP antibody
PAH- Human Immunodeficiency Virus HIV Patients will have a firm diagnosis with positive HIV testing ie positive 4th generation immunoassay and positive confirmatory testing such as Western Blot or HIV-1HIV-2 antibody differentiation immunoassay and managed by an infectious diseaseHIV specialist These patients have hemodynamic criteria for PAH present but the only association on workup is the presence of HIV
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
Heritable PAH HPAH This diagnosis is based on a family history of PAH with or without a documented genetic mutation associated with PAH such as BMPR2 mutations that are present in up to 75 of HPAH patients No other PAH association is present
PAH - Connective Tissue Disease PAH-CTD These patients have a confirmed diagnosis of PAH as well as firm evidence to support a diagnosis of a connective tissue disease In the REVEAL registry scleroderma-associated PAH accounted for 60 of PAH-CTD All PAH-CTD cases will be referred by or evaluated by a rheumatologist to ensure a firm diagnosis While all CTDs can be complicated by PAH the most common associations are described below
1 Scleroderma SSc We use the ACREULAR criteria for the diagnosis and classification of systemic sclerosis Patients with SSc-APAH may exhibit features of limited scleroderma such as calcinosis Reynauds esophageal dysmotility sclerodactyly with skin thickening of the fingers of both hands extending proximal to the metacarpophalangeal joints and telangiectasia In those with limited scleroderma anticentromere antibodies are commonly positive In patients with diffuse cutaneous scleroderma SSc-PAH can also be seen They exhibit diffuse skin thickening and tightening Anti-topoisomerase antibodies anti Scl70 may be positive but interestingly their absence is more likely to be associated with PAH Other autoantibodies that are associated with an increased risk of SSc-PAH include anti-U1-ribonucleoprotein antibodies RNP nucleolar pattern of anti-nuclear antibody nucleolar-ANA and rarely antiphospholipid antibodies
2 Systemic Lupus Erythematosus SLE We use the Systemic Lupus International Collaborating Clinics SLICC classification which requires at least 417 criteria including at least 1 clinical criterion and 1 immunologic criterion or biopsy proven lupus nephritis On history and physical exam the following are highly suggestive Photosensitive skin lesions malar rash or discoid lesions painless ulcers oral or nasal features of a serositis alopecia Raynauds arthralgiaarthritis often migratory etc Immunologic antibody studies included in SLICC are Positive ANA anti-dsDNA anti-Sm antiphospholipid low complement positive direct Coombs test
3 Mixed Connective Tissue Disease MCTD This is characterized by overlapping features of SLE SSc and polymyositis PM as well as high titers of anti-U1 ribonucleoprotein RNP The old term for this is anti-extractable nuclear protein anti-ENA
4 Rheumatoid Arthritis RA RA is a symmetrical distal inflammatory poly arthritis condition The criteria developed and validated by the American College of Rheumatology ACR has been used in numerous drug studies which requires at least four of these seven criteria for diagnosis morning stiffness arthritis of three or more joint areas arthritis of the hands symmetric arthritis rheumatoid nodules and classic radiographic erosive changes Immunologic studies include positive rheumatoid factor RF and anti-cyclic citrullinated peptide CCP antibody
PAH- Human Immunodeficiency Virus HIV Patients will have a firm diagnosis with positive HIV testing ie positive 4th generation immunoassay and positive confirmatory testing such as Western Blot or HIV-1HIV-2 antibody differentiation immunoassay and managed by an infectious diseaseHIV specialist These patients have hemodynamic criteria for PAH present but the only association on workup is the presence of HIV
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None