Back to results

Clinical Application of Stem Cell Educator Therapy in Type 1 Diabetes

Primary Purpose

Type 1 Diabetes

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Stem Cell Educator therapy

About this trial

This is an interventional treatment trial for Type 1 Diabetes

Eligibility Criteria

14 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Adult patients ( 14 years)
Must have a diagnosis of type 1 diabetes mellitus based on the 2015 American Diabetes Association criteria for the Clarification and Diagnosis of diabetes.
Must have a blood test confirming the presence of at least one autoantibody to pancreatic islet Cells (IAA, IA2, GAD 65, ZnT8).
Fasting C-peptide level > 0.3 ng/ml
HbA1C < 10% at enrollment
Recent diagnosis (within two years of enrollment)
Adequate venous access for apheresis
Must be equipped with a continuous glucose monitoring system (CGMS)
Ability to provide informed consent
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.
Must agree to comply with all study requirements and be willing to complete all study visits

Exclusion Criteria:

AST or ALT 2 > x upper limit of normal.
Abnormal bilirubin (total bilirubin > 1.2 mg/dL, direct bilirubin > 0.4 mg/dL)
Creatinine > 2.0 mg/dl.
Known coronary artery disease or EKG suggestive of coronary artery disease unless cardiac clearance for apheresis is obtained from a cardiologist.
Known active infection such as Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV)
Pregnancy assessed by a positive serum pregnancy test or breastfeeding mothers
Use of immunosuppressive medication within one month of enrollment including but not limited to prednisone, cyclosporine, tacrolimus, sirolimus, and chemotherapy.
Presence of any other autoimmune diseases (lupus, rheumatoid arthritis, scleroderma, etc.)
Anticoagulation other than ASA.
Hemoglobin < 10 g/dl or platelets < 100 k/ml
Is unable or unwilling to provide informed consent
Presence of any other physical or psychological medical condition that, in the opinion of the investigator, would preclude participation

Sites / Locations

Hackensack Meridian Health
Throne BiotechnologiesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Treatment of T1D with Stem Cell Educator therapy

Conventional insulin therapy

Arm Description

Recruited T1D subjects will receive one treatment with SCE therapy.

Control group will receive conventional insulin therapy.

Outcomes

Primary Outcome Measures

Incidence of Treatment Adverse Events in T1D Subjects

The occurrence of treatment-related adverse events will be evaluated post the treatment with SCE therapy.

Secondary Outcome Measures

Preliminary efficacy of SCE therapy to improve beta cell function

Preliminary efficacy as measured by Area under the C-peptide curve (AUC) over the first 2 hours of a 3-hour mixed meal tolerance test (MMTT)

Preliminary efficacy of SCE therapy to improve glucose control

Change in HbA1C levels over time

Preliminary efficacy of SCE therapy to reduce insulin dose

Change in daily insulin requirements

Efficacy of SCE therapy in immune modulation

Measurements of immune markers at baseline, 1, 3, 6, 9, and 12 months. Peripheral blood mononuclear cells (PBMC) will be collected and tested by flow cytometry.

Full Information

NCT ID

NCT04011020

First Posted

July 4, 2019

Last Updated

September 19, 2022

Sponsor

Throne Biotechnologies Inc.

Collaborators

Hackensack Meridian Health

1. Study Identification

Unique Protocol Identification Number

NCT04011020

Brief Title

Clinical Application of Stem Cell Educator Therapy in Type 1 Diabetes

Official Title

Clinical Application of Stem Cell Educator Therapy in Type 1 Diabetes

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Recruiting

Study Start Date

September 20, 2022 (Actual)

Primary Completion Date

March 20, 2023 (Anticipated)

Study Completion Date

March 20, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Throne Biotechnologies Inc.

Collaborators

Hackensack Meridian Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 1 Diabetes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Model Description

Treatment group receive Stem Cell Educator therapy, control group receive conventional insulin therapy.

Masking

Care ProviderInvestigator

Masking Description

All recruited T1D subjects will receive the treatment with Stem Cell Educator therapy.

Allocation

Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment of T1D with Stem Cell Educator therapy

Arm Type

Experimental

Arm Description

Recruited T1D subjects will receive one treatment with SCE therapy.

Arm Title

Conventional insulin therapy

Arm Type

Experimental

Arm Description

Control group will receive conventional insulin therapy.

Intervention Type

Combination Product

Intervention Name(s)

Stem Cell Educator therapy

Intervention Description

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.

Primary Outcome Measure Information:

Title

Incidence of Treatment Adverse Events in T1D Subjects

Description

The occurrence of treatment-related adverse events will be evaluated post the treatment with SCE therapy.

Time Frame

6 month

Secondary Outcome Measure Information:

Title

Preliminary efficacy of SCE therapy to improve beta cell function

Description

Preliminary efficacy as measured by Area under the C-peptide curve (AUC) over the first 2 hours of a 3-hour mixed meal tolerance test (MMTT)

Time Frame

12 months

Title

Preliminary efficacy of SCE therapy to improve glucose control

Description

Change in HbA1C levels over time

Time Frame

12 months

Title

Preliminary efficacy of SCE therapy to reduce insulin dose

Description

Change in daily insulin requirements

Time Frame

12 months

Title

Efficacy of SCE therapy in immune modulation

Description

Measurements of immune markers at baseline, 1, 3, 6, 9, and 12 months. Peripheral blood mononuclear cells (PBMC) will be collected and tested by flow cytometry.

Time Frame

12 month

10. Eligibility

Sex

All

Minimum Age & Unit of Time

14 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adult patients ( 14 years) Must have a diagnosis of type 1 diabetes mellitus based on the 2015 American Diabetes Association criteria for the Clarification and Diagnosis of diabetes. Must have a blood test confirming the presence of at least one autoantibody to pancreatic islet Cells (IAA, IA2, GAD 65, ZnT8). Fasting C-peptide level > 0.3 ng/ml HbA1C < 10% at enrollment Recent diagnosis (within two years of enrollment) Adequate venous access for apheresis Must be equipped with a continuous glucose monitoring system (CGMS) Ability to provide informed consent 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. Must agree to comply with all study requirements and be willing to complete all study visits Exclusion Criteria: AST or ALT 2 > x upper limit of normal. Abnormal bilirubin (total bilirubin > 1.2 mg/dL, direct bilirubin > 0.4 mg/dL) Creatinine > 2.0 mg/dl. Known coronary artery disease or EKG suggestive of coronary artery disease unless cardiac clearance for apheresis is obtained from a cardiologist. Known active infection such as Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV) Pregnancy assessed by a positive serum pregnancy test or breastfeeding mothers Use of immunosuppressive medication within one month of enrollment including but not limited to prednisone, cyclosporine, tacrolimus, sirolimus, and chemotherapy. Presence of any other autoimmune diseases (lupus, rheumatoid arthritis, scleroderma, etc.) Anticoagulation other than ASA. Hemoglobin < 10 g/dl or platelets < 100 k/ml Is unable or unwilling to provide informed consent Presence of any other physical or psychological medical condition that, in the opinion of the investigator, would preclude participation

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

YONG ZHAO, MD,PhD

Phone

201 988 0290

Yong.Zhao@ThroneBio.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

YONG ZHAO, MD,PhD

Organizational Affiliation

Throne Biotechnologies Inc.

Official's Role

Study Chair

Facility Information:

Facility Name

Hackensack Meridian Health

City

Hackensack

State/Province

New Jersey

ZIP/Postal Code

07601

Country

United States

Individual Site Status

Active, not recruiting

Facility Name

Throne Biotechnologies

City

Paramus

State/Province

New Jersey

ZIP/Postal Code

07652

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yong Zhao, MD,PhD

Phone

201-988-0290

yong.zhao@thronebio.com

First Name & Middle Initial & Last Name & Degree

Boris Veysman, MD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35108619

Citation

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.

Results Reference

background

PubMed Identifier

22233865

Citation

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.

Results Reference

result

PubMed Identifier

22833322

Citation

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.

Results Reference

result

PubMed Identifier

26844283

Citation

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.

Results Reference

result

PubMed Identifier

28685960

Citation

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.

Results Reference

result

Links:

URL

https://thronebio.com/

Description

Throne Biotechnologies Inc

Learn more about this trial

Clinical Application of Stem Cell Educator Therapy in Type 1 Diabetes

We'll reach out to this number within 24 hrs