Diabetes Islet Preservation Immune Treatment

NCT02586831 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 20150856
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

To assess whether there is a difference in endogenous insulin secretion, measured as stimulated C-peptide secretion (area under the curve during a 4-hour mixed meal tolerance test), at the 1 year visit, for study subjects receiving combinational therapy versus those receiving placebo. The study will also examine the effect of the proposed treatments on immunological outcomes, specifically proportion of regulatory T cells at the 1 year visit.

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia; Autoimmune Diseases; Diabetes Mellitus

Outcome Measures

Primary Outcomes (2)

• Simulated C-peptide AUC

  Endogenous insulin secretion as measured as stimulated C-peptide section Area Under the Curve (AUC) during a 4 hour mixed meal tolerance test (MMTT)

  1 Year Visit

• Proportion of regulatory T cells

  As measured from blood samples

  1 Year Visit

Secondary Outcomes (4)

• Hemoglobin A1c (HbA1c) levels

  Up to 18 months

• Insulin dose

  Up to 18 months

• Mean daily plasma glucose levels

  Up to 18 months

• Incidence of immune response adverse events

  Up to 18 months

Study Arms (2)

Arm A

EXPERIMENTAL

Participants in this group will receive Thymoglobulin, Aldesleukin, Adalimumab, and Exenatide over a period of 52 weeks. * Anti-Thymocyte Globulin (ATG or Thymoglobulin®) will be administered at a dose of 2.5mg/kg (2 infusions, 0.5 and 2mg/kg) Days 1 and 2 * Adalimumab (Humira®) will be administered at a dose of 50 mg every month, for 1 year * Low-dose Interleukin 2 (Aldesleukin; IL-2 or Proleukin®) will be administered 1 million IU/dose; 5 consecutive days (days 10-14), \& then every 2 weeks, for 52 weeks * Exenatide (Bydureon®): 2 mg SC weekly up to 52 weeks.

Drug: Anti-Thymocyte Globulin (ATG); Drug: Interleukin 2; Drug: Exenatide; Drug: Adalimumab

Arm B

PLACEBO COMPARATOR

Participants in this group will receive the placebos for Thymoglobulin, Aldesleukin, Adalimumab, Exenatide, and Neulasta over a period of 52 weeks.

Other: ATG Placebo; Other: IL-2 Placebo; Other: Adalimumab Placebo; Other: Exenatide Placebo

Interventions

Anti-Thymocyte Globulin (ATG) DRUG

2.5 mg/kg administered as two divided infusions of 0.5 mg/kg and 2 mg/kg on Days 1 and 2.

Also known as: Thymoglobulin

Arm A

Interleukin 2 DRUG

1 million IU per dose administered subcutaneously for 5 consecutive days on Days 10-14, and then every two weeks.

Also known as: Aldesleukin; IL-2 or Proleukin®

Arm A

Exenatide DRUG

2 mg administered subcutaneously weekly for up to 52 weeks.

Also known as: Bydureon®

Arm A

Adalimumab DRUG

50 mg administered subcutaneously once a month for 1 year.

Also known as: HUMIRA®

Arm A

ATG Placebo OTHER

ATG placebo mimicking Thymoglobulin administered intravenously.

Arm B

IL-2 Placebo OTHER

IL-2 placebo mimicking Aldesleukin administered subcutaneously.

Arm B

Adalimumab Placebo OTHER

Placebo mimicking Adalimumab administered subcutaneously.

Arm B

Exenatide Placebo OTHER

Placebo mimicking Exenatide administered subcutaneously.

Arm B

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients must meet all of the following criteria to be eligible to participate in this study:
• Subject must be able to understand and provide informed consent.
• Males and females, 18-35 years of age.
• New onset T1D for no longer than 120 days at the time of randomization.
• Affected by T1D, according to ADA standard criteria, and confirmed by positivity of at least one T1D-associated autoantibody, to GAD65, IA-2, ZnT8, or insulin autoantibodies (if patient has been treated with insulin for less than 2 weeks).
• Being on insulin therapy.
• Stimulated C-peptide peak level \>0.2 nmol/L at the baseline 1 visit MMTT.
• Female subjects of childbearing potential must have a negative pregnancy test upon study entry.
• Female (and male) subjects with reproductive potential must agree to use two FDA approved methods of birth control for the entire duration of the study.
• Adequate venous access to support study required blood draws.

You may not qualify if:

• Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
• BMI\>30 Kg/m2.
• Contra-indications to ATG, GCSF, exenatide, etanercept and IL-2 (as per package insert, e.g., knowledge of hypersensitivity to drugs or its excipients).
• Uncompensated heart failure, fluid overload, myocardial infarction or liver disease or severe impairment of a vital organ within the last 6 weeks before enrollment.
• Any of the following laboratory findings: hemoglobin \<10.0 g/dL; leukocytes \<3,000/μL; neutrophils \<1,500/μL; lymphocytes \<800/μL; platelets \<100,000/μL.
• Any sign or diagnosis of significant chronic active infection (e.g., hepatitis, tuberculosis, EBV, or CMV), or screening laboratory evidence consistent with a significant chronic active infection (such as positive for HIV, IGRA test for TB, or hepatitis B-C).
• Ongoing acute infections, e.g., acute respiratory tract urinary tract, or gastrointestinal tract infections.
• Ongoing or anticipated use of diabetes medications other than insulin.
• Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within prior 7 days of screening.
• Current or prior use of immunomodulators or systemic steroids in the last 2 months that could potentially affect diabetes or immunologic status.
• Recent recipient of any licensed or investigational live attenuated vaccine(s) within 6 weeks of randomization.
• Use of investigational drugs within 3 months of participation.
• Concomitant therapy with immunosuppressive drugs, immunomodulators, or cytotoxic agents, or previous therapy less than 3 months from randomization.
• History or diagnosis of malignancy. Any history of gastroparesis or other severe gastrointestinal disease, pancreatitis, thyroid nodules or malignancy with the exception of a history of localized basal cell carcinoma.
• Presence of an allograft.

Sponsors & Collaborators

• Camillo Ricordi and Jay Skyler: lead
• Diabetes Research Institute Foundation: collaborator

Related Publications (2)

• Skyler JS. Prevention and reversal of type 1 diabetes--past challenges and future opportunities. Diabetes Care. 2015 Jun;38(6):997-1007. doi: 10.2337/dc15-0349.

  PMID: 25998292 BACKGROUND

• Skyler JS, Ricordi C. Stopping type 1 diabetes: attempts to prevent or cure type 1 diabetes in man. Diabetes. 2011 Jan;60(1):1-8. doi: 10.2337/db10-1114. No abstract available.

  PMID: 21193733 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia; Autoimmune Diseases; Diabetes Mellitus

Interventions

Antilymphocyte Serum; thymoglobulin; Interleukin-2; aldesleukin; Exenatide; Adalimumab

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Lymphokines; Biological Factors; Venoms; Toxins, Biological; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal

Study Officials

• Rodolfo Alejandro, M.D.

  Diabetes Research Institute, University of Miami

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professors, University of Miami Miller School of Medicine and Director/Deputy Director, Diabetes Research Institute

Study Record Dates

• First Submitted: October 23, 2015
• First Posted: October 26, 2015
• Study Start: June 1, 2024
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2024
• Last Updated: January 15, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share