Clinical Application of Stem Cell Educator Therapy in Type 1 Diabetes

NCT ID: NCT04011020

Last Updated: 2024-04-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-20
• Study Completion Date: 2025-06-20

Brief Summary

Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that causes a deficit of pancreatic islet beta cells. Millions of individuals worldwide have T1D, and incidence increases annually. Several recent clinical trials point to the need for an approach that produces comprehensive immune modulation at both the local pancreatic and systemic levels. Stem Cell Educator (SCE) therapy offers comprehensive immune modulation at both the local and systemic levels in T1D by using a patient's own immune cells (including platelets) that are "educated" by cord blood stem cells. Tested clinically in more than 200 patients, SCE therapy has shown lasting reversal in autoimmunity in T1D patients, including improved C-peptide levels, reduced median glycated hemoglobin A1C (HbA1C) values, and decreased median daily usage of insulin. SCE therapy circulates a patient's blood through a blood cell separator, briefly cocultures the patient's immune cells with adherent Cord Blood Stem Cells (CB-SCs) in vitro, and returns the "educated" autologous immune cells to the patient's circulation.

Detailed Description

The SCE device is made of a hydrophobic material from FDA-approved (USP Class VI) dishes that tightly binds stem cells CB-SCs without interfering with their immune modulating capability. We originally designed a chamber for co-culture of lymphocytes and CB-SCs that included nine discs of the material with a flow pathway and adherent CB-SCs sandwiched between a top cover plate and a bottom collecting plate. In this trial, we are going to use the 12-layer SCE device.

The SCE therapy carried a lower risk of infection than a typical blood transfusion, and did not introduce stem cells or reagents into the patients. In addition, CB-SCs have very low immunogenicity, and the CB-SCs cultured in the device are a highly restricted population and contain no CD3+ T cells or other lymphocyte subsets, eliminating the need for human leukocyte antigen (HLA) matching prior to treatment. This innovative approach has the potential to provide CB-SC-mediated immune modulation therapy for multiple autoimmune diseases while mitigating the safety and ethical concerns associated with other approaches such as T1D, type 2 diabetes (T2D), and alopecia areata (AA) in clinics. The relative simplicity of the approach may also provide cost and time savings relative to other approaches.

Conditions

Type 1 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Treatment of T1D with Stem Cell Educator therapy

Recruited T1D subjects will receive one treatment with SCE therapy.

Group Type: EXPERIMENTAL

Stem Cell Educator therapy

Intervention Type: COMBINATION_PRODUCT

Patients with T1D will be evaluated by the study principal investigator or co-investigators. Informed consent will be obtained at the initial screening visit. The initial screening visit will occur within 30 days of initiation of SCE therapy. The second screening visit will occur within 7 days of therapy. Subjects who meet all criteria will be scheduled for treatment. All enrolled subjects will receive treatment with the SCE system consisting of a single session of mononuclear cells (MNC) collection by apheresis where 10 L of blood will be processed on day -1. The MNC product will then be exposed over to the SCE and on day 0 the product will be infused intravenously back to the patient.

Conventional insulin therapy

Control group will receive conventional insulin therapy.

Group Type: EXPERIMENTAL

Stem Cell Educator therapy

Intervention Type: COMBINATION_PRODUCT

Patients with T1D will be evaluated by the study principal investigator or co-investigators. Informed consent will be obtained at the initial screening visit. The initial screening visit will occur within 30 days of initiation of SCE therapy. The second screening visit will occur within 7 days of therapy. Subjects who meet all criteria will be scheduled for treatment. All enrolled subjects will receive treatment with the SCE system consisting of a single session of mononuclear cells (MNC) collection by apheresis where 10 L of blood will be processed on day -1. The MNC product will then be exposed over to the SCE and on day 0 the product will be infused intravenously back to the patient.

Interventions

Stem Cell Educator therapy

Patients with T1D will be evaluated by the study principal investigator or co-investigators. Informed consent will be obtained at the initial screening visit. The initial screening visit will occur within 30 days of initiation of SCE therapy. The second screening visit will occur within 7 days of therapy. Subjects who meet all criteria will be scheduled for treatment. All enrolled subjects will receive treatment with the SCE system consisting of a single session of mononuclear cells (MNC) collection by apheresis where 10 L of blood will be processed on day -1. The MNC product will then be exposed over to the SCE and on day 0 the product will be infused intravenously back to the patient.

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

Inclusion Criteria

1. Adult patients ( 14 years)

2. Must have a diagnosis of type 1 diabetes mellitus based on the 2015 American Diabetes Association criteria for the Clarification and Diagnosis of diabetes.

3. Must have a blood test confirming the presence of at least one autoantibody to pancreatic islet Cells (IAA, IA2, GAD 65, ZnT8).

4. Fasting C-peptide level > 0.3 ng/ml

5. HbA1C < 10% at enrollment

6. Recent diagnosis (within two years of enrollment)

7. Adequate venous access for apheresis

8. Must be equipped with a continuous glucose monitoring system (CGMS)

9. Ability to provide informed consent

10. For female patients only, willingness to use FDA-recommended birth control (http://www.fda.gov/downloads/ForConsumers/ByAudience/ForWomen/FreePublications/UCM356451.pdf) until 6 months post treatment.

11. Must agree to comply with all study requirements and be willing to complete all study visits

Exclusion Criteria

1. AST or ALT 2 > x upper limit of normal.

2. Abnormal bilirubin (total bilirubin > 1.2 mg/dL, direct bilirubin > 0.4 mg/dL)

3. Creatinine > 2.0 mg/dl.

4. Known coronary artery disease or EKG suggestive of coronary artery disease unless cardiac clearance for apheresis is obtained from a cardiologist.

5. Known active infection such as Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV)

6. Pregnancy assessed by a positive serum pregnancy test or breastfeeding mothers

7. Use of immunosuppressive medication within one month of enrollment including but not limited to prednisone, cyclosporine, tacrolimus, sirolimus, and chemotherapy.

8. Presence of any other autoimmune diseases (lupus, rheumatoid arthritis, scleroderma, etc.)

9. Anticoagulation other than ASA.

10. Hemoglobin < 10 g/dl or platelets < 100 k/ml

11. Is unable or unwilling to provide informed consent

12. Presence of any other physical or psychological medical condition that, in the opinion of the investigator, would preclude participation

• Minimum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hackensack Meridian Health

OTHER

Sponsor Role: collaborator

Throne Biotechnologies Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

YONG ZHAO, MD,PhD

Role: STUDY_CHAIR

Throne Biotechnologies Inc.

Locations

Hackensack Meridian Health

Hackensack, New Jersey, United States

Site Status: ACTIVE_NOT_RECRUITING

Throne Biotechnologies

Paramus, New Jersey, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

YONG ZHAO, MD,PhD

Role: CONTACT

Yong.Zhao@ThroneBio.com

201 988 0290

Facility Contacts

Yong Zhao, MD,PhD

Role: primary

yong.zhao@thronebio.com

201-988-0290

References

Zhao Y, Knight CM, Jiang Z, Delgado E, Van Hoven AM, Ghanny S, Zhou Z, Zhou H, Yu H, Hu W, Li H, Li X, Perez-Basterrechea M, Zhao L, Zhao Y, Giangola J, Weinberg R, Mazzone T. Stem Cell Educator therapy in type 1 diabetes: From the bench to clinical trials. Autoimmun Rev. 2022 May;21(5):103058. doi: 10.1016/j.autrev.2022.103058. Epub 2022 Jan 31.

Reference Type: BACKGROUND

PMID: 35108619 (View on PubMed)

Zhao Y, Jiang Z, Zhao T, Ye M, Hu C, Yin Z, Li H, Zhang Y, Diao Y, Li Y, Chen Y, Sun X, Fisk MB, Skidgel R, Holterman M, Prabhakar B, Mazzone T. Reversal of type 1 diabetes via islet beta cell regeneration following immune modulation by cord blood-derived multipotent stem cells. BMC Med. 2012 Jan 10;10:3. doi: 10.1186/1741-7015-10-3.

Reference Type: RESULT

PMID: 22233865 (View on PubMed)

Zhao Y. Stem cell educator therapy and induction of immune balance. Curr Diab Rep. 2012 Oct;12(5):517-23. doi: 10.1007/s11892-012-0308-1.

Reference Type: RESULT

PMID: 22833322 (View on PubMed)

Delgado E, Perez-Basterrechea M, Suarez-Alvarez B, Zhou H, Revuelta EM, Garcia-Gala JM, Perez S, Alvarez-Viejo M, Menendez E, Lopez-Larrea C, Tang R, Zhu Z, Hu W, Moss T, Guindi E, Otero J, Zhao Y. Modulation of Autoimmune T-Cell Memory by Stem Cell Educator Therapy: Phase 1/2 Clinical Trial. EBioMedicine. 2015 Nov 5;2(12):2024-36. doi: 10.1016/j.ebiom.2015.11.003. eCollection 2015 Dec.

Reference Type: RESULT

PMID: 26844283 (View on PubMed)

Zhao Y, Jiang Z, Delgado E, Li H, Zhou H, Hu W, Perez-Basterrechea M, Janostakova A, Tan Q, Wang J, Mao M, Yin Z, Zhang Y, Li Y, Li Q, Zhou J, Li Y, Martinez Revuelta E, Maria Garcia-Gala J, Wang H, Perez-Lopez S, Alvarez-Viejo M, Menendez E, Moss T, Guindi E, Otero J. Platelet-Derived Mitochondria Display Embryonic Stem Cell Markers and Improve Pancreatic Islet beta-cell Function in Humans. Stem Cells Transl Med. 2017 Aug;6(8):1684-1697. doi: 10.1002/sctm.17-0078. Epub 2017 Jul 7.

Reference Type: RESULT

PMID: 28685960 (View on PubMed)

Related Links

https://thronebio.com/

Throne Biotechnologies Inc

Other Identifiers

2019-TH-002

Identifier Type: -

Identifier Source: org_study_id