Platform Trial in Stage 1 Diabetes: Comparing Golimumab vs Placebo

Adaptive Platform Trial to Delay Progression From Normoglycemia to Dysglycemia in Presymptomatic Type 1 Diabetes: Golimumab Substudy

The goal of this clinical trial is to learn if golimumab is effective at preventing progression to Stage 2 diabetes in participants with presymptomatic Type 1 Diabetes. The expected duration of this study is approximately 6 years.

Participants will:

• Take golimumab or placebo injections monthly for the duration of the study or until they are diagnosed with either stage 2 or stage 3 Type 1 Diabetes
• Visit a study clinic every 6 months for Oral Glucose Tolerance Tests (OGTTs) and other tests until the end of the study

Study Overview

• Status: Not yet recruiting
• Conditions: Type 1 Diabetes (T1D)
• Intervention / Treatment: Drug: Golimumab; Drug: Placebo (matching golimumab)

Detailed Description

This is a double-masked, multicenter, randomized, placebo-controlled trial to determine whether treatment of participants with presymptomatic T1D (two or more diabetes autoantibodies or IA2 alone) and normal glycemia with golimumab results in delay or prevention of progression to confirmed dysglycemia or symptomatic diabetes. 225 participants with presymptomatic T1D will be randomly assigned to placebo or golimumab at a 1:2 randomization (75 placebo and 150 study drug). Golimumab or a saline placebo will be given as a subcutaneous injection. A loading dose regimen at 0 and 2 weeks will be followed by monthly doses for the duration of the participant's enrollment in the study. Study visits will occur every 6 months with some additional remote monitoring in between visits. Study visit procedures include OGTTs, physical exams, questionnaires, and other laboratory tests. The primary outcome is to determine if intervention with golimumab will prevent or delay the progression to confirmed dysglycemia or overt diabetes in persons less than 18 years of age with presymptomatic T1D. The study is expected to recruit for 3 years followed by an additional 3 years of follow-up for the last participant enrolled.

• Study Type: Interventional
• Enrollment (Estimated): 255
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ariana Rojas; Phone Number: 813-974-6827; Email: Ariana.Rojas@epi.usf.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Joslin Diabetes Center
      • Principal Investigator: Jason Gaglia, MD
      • Contact: Samantha Kateman; Phone Number: 617-975-8269; Email: skateman@joslin.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Willing to provide informed consent or have a parent or legal guardians provide informed consent when the participant is <18 years of age.
2. Weight ≥15 kg at the time of screening.
3. Aged ≥2 to <45 years.
4. A confirmed history of either IA2A alone or at least two or more diabetes-related biochemical autoantibodies (mIAA, GADA, ICA, IA-2A, ZnT8A) present on the same sample. Confirmed autoantibody result means that the presence of the antibody has been verified on more than one occasion. For multiple autoantibody positivity, the same autoantibodies do not need to be present on the different tests. Confirmation must occur within the six months prior to screening. In the absence of other antibodies, ICA and GADA positivity alone will not suffice for eligibility in this study.
5. Oral glucose tolerance test (OGTT) results demonstrating normal glucose tolerance within 7 weeks (52 days) prior to randomization. If a participant has known previous abnormal glucose tolerance, the two most recent OGTTs must demonstrate normal glucose tolerance to be eligible.
6. CMV and/or EBV seronegative participants must be CMV and EBV PCR negative within 60 days of randomization and may not have had signs or symptoms of a CMV or EBV-compatible illness lasting longer than 7 days within 30 days of randomization.
7. CMV seropositive participants must be CMV PCR negative and all EBV seropositive participants must have EBV PCR < 2,000 IU/mL within 60 days of randomization and may not have had signs or symptoms of a CMV or EBV-compatible illness lasting longer than 7 days within 30 days of randomization.
8. Be at least 4 weeks from last live immunization.
9. Be willing to forgo live vaccines during treatment and for 3 months after study drug treatment period.
10. Must meet TrialNet eligibility minimum immunization recommendations found in Appendix A of the manual of operations (MOO).
11. Negative Coccidioides serology testing for those who have in the past resided in for at least 2 months, currently reside in, or within the past 2 months have visited an endemic area (as defined in Protocol MOO Appendix B).
12. If a female participant with reproductive potential, willing to avoid pregnancy (abstinence or adequate contraceptive method) through up to 3 months after last study drug administration and undergo pregnancy testing at each study visit.

Exclusion Criteria:

1. One or more screening laboratory values as stated:

   1. Leukocytes <3,500/μL or >14,000/μL
   2. Neutrophils <1,500/mL
   3. Platelet count <100,000 /μL
   4. Hemoglobin <6.2 mmol/L (10.0 g/dL)
   5. AST or ALT ≥ 2 times the upper limits of normal (2x ULN)

2. Abnormal Glucose Tolerance or Diabetes

   1. Fasting plasma glucose ≥100 mg/dL (6.1 mmol/L), or
   2. 2 hour plasma glucose ≥140 mg/dL (7.8 mmol/L), or
   3. 30, 60, or 90 minute plasma glucose during OGTT ≥200 mg/dL (11.1 mmol/L)
3. History of treatment with insulin except transient use during acute illness or hospitalization.
4. Vaccination with a live vaccine within the last 4 weeks or killed/inactivated vaccine within the last 2 weeks prior to randomization.
5. A history of confirmed infectious mononucleosis within the 3 months prior to randomization, as documented by EBV serology (EBV VCA-IgM and VCA-IgG; PCR would be confirmatory).

6. Evidence of prior or current tuberculosis (TB) infection through any one or more of the following:

   1. A history of latent or active TB
   2. Signs and/or symptoms of TB
   3. Recent close contact with a person with known or suspected active TB unless appropriate prophylaxis for TB was given
   4. A history of a chest X-ray consistent with active TB or old, inactive TB
   5. A history of a positive purified protein derivative (PPD) skin test result (>10 mm induration), or positive/repeatedly indeterminate on an interferon-gamma release assay (IGRA; e.g., QuantiFERON-TB test).
7. Prone to infections or has chronic, recurrent or opportunistic infectious disease, including but not limited to Pneumocystis carinii, aspergillosis, latent or active granulomatous infection, or an open, draining, or infected non-healing skin wound or ulcer.
8. Known active infection or active signs or symptoms of acute or chronic infection at the time of randomization including SARS-Cov-2.
9. Have or had a demyelinating disorder such as multiple sclerosis or Guillain-Barré syndrome.
10. Current diagnosis of other autoimmune diseases except stable and/or adequately treated hypothyroidism and/or celiac disease (participants must be well controlled for the previous 6 months).
11. Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within 14 days of the screening visit.
12. Has previously participated in a clinical trial for diabetes prevention and received active study agent within 6 months of treatment.
13. History of blastomycosis, histoplasmosis, or coccidioidomycosis.
14. A history of malignancies other than fully treated basal cell or squamous cell carcinoma of the skin.
15. Have or had moderate to severe congestive heart failure.
16. Ongoing or anticipated future use of any medications known to impact T1D progression.
17. Evidence of current or past HIV or Hepatitis B or current Hepatitis C infection.
18. Be pregnant or lactating or anticipate becoming pregnant during the study.
19. Any condition, prior treatment, or laboratory abnormality that in the investigator's opinion may adversely affect study participation or confound study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Golimumab; Participants assigned to this arm will receive golimumab injections	Drug: Golimumab; Golimumab will be given as a subcutaneous formulation based on the participant's weight at baseline. A loading dose regimen at 0 and 2 weeks will be followed by monthly maintenance doses for the duration of the participant's enrollment in the study. For those weighing 15kg to less than 40 kg the dosing will be: 100mg (week 0), followed by 50mg monthly thereafter. For those weighing 40kg or more the loading dose will be 200mg (week 0) followed by 100mg thereafter.; Other Names: Simponi
Placebo Comparator: Placebo; Participants assigned to this arm will receive saline (placebo) to match Golimumab injections	Drug: Placebo (matching golimumab); 0.9% Sodium Chloride Injection USP ("Normal" saline) is to be dispensed as the placebo for this study. A loading dose regimen at 0 and 2 weeks will be followed by monthly maintenance doses for the duration of the participant's enrollment in the study.; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression to Dysglycemia	The primary outcome is the elapsed time from random treatment assignment to the development of confirmed dysglycemia or overt hyperglycemia/symptomatic based upon ADA criteria.	From randomization to confirmed dysglycemia or clinical diagnosis of T1D, approximately 6 years from the first participant enrolled.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression to overt hyperglycemia/symptomatic Type 1 Diabetes	Elapsed time from study drug administration to the development of diabetes or time of last contact among those randomized	From Randomization to clinical diagnosis approximately 6 years from the first participant enrolled.

Collaborators and Investigators

• Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Study Chair: Jason Gaglia, MD, TrialNet

Publications and helpful links

Helpful Links

• TrialNet Public Website

Study record dates

Study Major Dates

• Study Start (Estimated): August 8, 2026
• Primary Completion (Estimated): September 1, 2032
• Study Completion (Estimated): September 1, 2032

Study Registration Dates

• First Submitted: June 24, 2026
• First Submitted That Met QC Criteria: June 30, 2026
• First Posted (Actual): July 6, 2026

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: June 30, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Golimumab; T1D; TrialNet
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 1; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Sodium Chloride; golimumab
• Other Study ID Numbers: TN39A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be available at the NIDDK Central Repository
• IPD Sharing Time Frame: Final datasets will be available at the NIDDK Central Repository 12 months from the last participant's follow-up visit
• IPD Sharing Access Criteria: IPD can be requested through the NIDDK Central Repository once submitted.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No