A Study to Evaluate SIMPONI (Golimumab) Therapy in Children, Adolescents and Young Adults With Pre-Symptomatic Type 1 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and tolerability of golimumab in children, adolescents, and young adults with pre-symptomatic stage 2 type 1 diabetes mellitus (T1D).

Official Title
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A Phase 1b Study to Evaluate SIMPONI (Golimumab) Therapy in Children, Adolescents and Young Adults With Pre-Symptomatic Type 1 Diabetes

Conditions
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Pre-Symptomatic Type 1 Diabetes

Intervention / Treatment
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* Drug: Golimumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is positive for at least 2 of the following diabetes-related autoantibodies obtained at study screening: Glutamic acid decarboxylase-65 (GAD-65) Autoantibodies, Insulinoma-associated 2 Autoantibodies (IA-2A), Zinc Transporter-8 (ZnT8), Islet Cell Cytoplasmic Autoantibodies (ICA), or Insulin Autoantibodies (IAA). Participants with a confirmed documented history of at least 2 positive diabetes-related autoantibodies but who screen positive on only 1 autoantibody are considered to have met this criteria Has a plasma glucose of 7.8 to 11.0 millimoles per liter (mmol/L) (140 to 199 milligrams per deciliter (mg/dL)) at the 120-minute timepoint of a 2-hour(h)-oral glucose tolerance test (OGTT), OR have a plasma glucose of greater than (>) 200 mg/dL (> 11.1 mmol/L) at the 30, 60, or 90 minute timepoint of a 2h-OGTT OR have a hemoglobin A1c (HbA1c) greater than or equal to (>=) 5.7 percent (%) but less than (<) 6.5% ([>=] 39 to <48 millimoles per moles [mmol/mol]) evaluated at screening Is medically stable on the basis of physical examination, medical history, laboratory results, and vital signs performed at screening If a woman of childbearing potential must have a negative highly sensitive serum test (beta-human chorionic gonadotropin) at screening and a negative urine pregnancy test at the Week 0 visit Must be up-to-date or have initiated catch up vaccines with routine age-appropriate immunizations and have received vaccines, or at least initiated vaccine series and have a completion plan, that are recommended for immune suppressed individuals according to current local recommendations before the first dose of study treatment Exclusion Criteria: Has a current or prior diagnosis of diabetes mellitus (Type 1, Type 2, or gestational) or meet the metabolic criteria diagnostic of diabetes mellitus obtained at screening including: hemoglobin A1c (HbA1c) greater than or equal to 6.5 (%) (48 mmol/mol), or fasting plasma glucose (>=) 7.0 mmol/L (126 mg/dL) (fasting: no intake >= 8 hours), or plasma glucose >= 11.1 mmol/L (200 mg/dL) 2 hours post OGTT, or random plasma glucose >= 11.1 mmol/L (200 mg/dL) in those with symptoms consistent with hyperglycemia crisis Has a presence or history of malignancy Has an immune deficiency syndrome (for example, severe combined immunodeficiency syndrome, T-cell deficiency syndromes, B-cell deficiency syndromes, or chronic granulomatous disease), or bone marrow or organ transplantation, or a disease associated with lymphopenia Has other autoimmune diseases (for example, rheumatoid arthritis (RA), polyarticular juvenile idiopathic arthritis (pJIA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), multiple sclerosis, celiac disease, systemic lupus erythematosus) excluding clinically stable autoimmune thyroiditis whether treated or untreated Has active infections, is prone to infections or has chronic, recurrent or opportunistic infectious disease, including but not limited to, chronic renal infection, chronic chest infection, sinusitis, recurrent urinary tract infection, Pneumocystis carinii, aspergillosis, latent or active granulomatous infection, histoplasmosis, or coccidioidomycosis or an open, draining, or infected non healing skin wound or ulcer Has a clinically active infection with Epstein-Barr virus (EBV) or an EBV polymerase chain reaction (PCR) viral load serology of >= 10,000 copies per milliliter (mL) at study screening Has a clinically active infection with cytomegalovirus (CMV) or a CMV PCR viral load serology of >= 10,000 copies per mL at study screening Is infected with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) or at screening tests positive for HIV, HBV, or HCV Has any of the following tuberculosis (TB) screening criteria: a history of latent or active TB prior to screening; signs or symptoms suggestive of active TB upon medical history and/or physical examination; recent close contact (within 3 months) with a person with known or suspected active TB; a positive QuantiFERON-TB test result at screening, the participant should be excluded from the study; a chest radiograph taken within 3 months prior to the first administration of study treatment read by a qualified radiologist consistent with current, active TB or old, inactive TB Has a current or prior use of any type and form of exogenous insulin or oral/intravenous (IV) antihyperglycemic treatment Has known or suspected intolerance or hypersensitivity to human proteins, antibody fragments, or monoclonal antibodies, including golimumab or its excipients

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Golimumab<br>Participants will receive subcutaneous (SC) golimumab for 26 weeks, where doses will be based on weight and/or body surface area. | Drug: Golimumab<br>* Participants will receive subcutaneous golimumab for 26 weeks, where doses will be based on weight and/or body surface area.<br>* Other names: SIMPONI;|
| Placebo Comparator: Group 2: Placebo<br>Participants will receive a SC matching placebo to golimumab. | Drug: Placebo<br>* Matching placebo to golimumab.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Up to Week 26 | 
| Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Up to Week 52 | 
| Percentage of Participants With Treatment-Emergent Infections |  | Up to Week 26 | 
| Percentage of Participants With Treatment-Emergent Infections |  | Up to Week 52 | 
| Percentage of Participants With Study Treatment Injection Site Reactions |  | Up to Week 26 | 
| Number of Participants With Treatment Related AEs and SAEs Reported From Week 52 to Week 78 |  | Week 52 to Week 78 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Concentration of Golimumab |  | Through Week 52 | 
| Incidence of Antibodies to Golimumab |  | Through Week 52 |