A Study of SIMPONI® to Arrest Beta-cell Loss in Type 1 Diabetes

Study Overview
=================
Brief Summary
-----------------
The primary purpose of this study is to determine if golimumab can preserve beta-cell function in children and young adults with newly diagnosed Type 1 Diabetes (T1D).

Official Title
-----------------
SIMPONI® to Arrest β-cell Loss in Type 1 Diabetes

Conditions
-----------------
Diabetes Mellitus, Type 1

Intervention / Treatment
-----------------
* Biological: Golimumab
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Double-blind Period: Be positive for at least 1 of the following diabetes-related autoantibodies obtained at study screening: Glutamic acid decarboxylase (GAD-65), islet antigen 2 (IA-2), zinc transporter 8 (ZnT8), Islet Cell Cytoplasmic Autoantibodies (ICA), or Insulin (if obtained within 10 days of the onset of exogenous insulin therapy) Have a peak stimulated C-peptide level greater than or equal to (>=) 0.2 picomole per milliliter (pmol/mL) following a 4-hour Mixed-meal Tolerance Test (MMTT) obtained at study screening Be medically stable on the basis of physical examination, medical history, and vital signs performed at screening. If there are abnormalities, they must be consistent with the underlying illness in the study population Females of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) test at screening and a negative urine pregnancy test at the Week 0 visit Participants (or their legally acceptable representatives) are willing and able to adhere to requirements, prohibitions, and restrictions specified in this protocol Open-Label Extension Period: - Participants must meet the responder criteria based on C-peptide area under the concentration-time curve (AUC) and insulin dose-adjusted HbA1c (IDAAC) remission score Exclusion Criteria: Double-blind Period: Has a history of significant renal, vascular, pulmonary, gastrointestinal, neurologic, hematologic, rheumatologic, or psychiatric disease or immune suppression or immune deficiency. Has significant cardiovascular disease, including history of myocardial infarction, congestive heart failure, angina, abnormal electrocardiogram or abnormal stress test 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 (example [eg.], bronchiectasis), sinusitis, recurrent urinary tract infection (eg., recurrent pyelonephritis, chronic cystitis), 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 viral load >=10,000 copies per milliliter (mL) of plasma obtained at study screening. Has a clinically active infection with cytomegalovirus (CMV) or a CMV viral load >= 10,000 copies per milliliter (mL) of plasma obtained at study screening Current or prior (within 30 days of screening) treatment that is known to cause a significant, ongoing change in the course of T1D or immunologic status, including high-dose inhaled, extensive topical, or systemic glucocorticoids Has another autoimmune disease (eg, rheumatoid arthritis [RA], polyarticular juvenile idiopathic arthritis [pJIA], psoriatic arthritis [PsA], ankylosing spondylitis [AS], multiple sclerosis [MS], systemic lupus erythematosus [SLE], celiac disease [clinically symptomatic and antibody positive, that is, tissue transglutaminase Immunoglobulin A [IgA]) excluding clinically stable autoimmune thyroiditis whether treated or untreated Has any of the following tuberculosis [TB] screening criteria: A history of latent or active TB prior to screening (including but not limited to a positive QuantiFERON®-TB Gold test), signs or symptoms suggestive of active TB upon medical history and/or physical examination, recent close contact with a person with known or suspected active TB Has known allergies, intolerance and/or hypersensitivity to human immunoglobulin proteins, golimumab or any of its components or its excipients Open-Label Extension Period: Participants having reported clinically significant AEs or serious adverse events (SAEs) deemed to be related to the study agent during the double blind period (for example. severe infections or hypersensitivity reactions), precluding renewed exposure to golimumab Participants who discontinued study agent administration prior to Week 52 or who have completed the Week 104 visit of the double-blind period or discontinued early from study

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Golimumab<br>Participants will receive subcutaneous (SC) golimumab intermittently for 52 weeks in double-blind period, where doses will be based on weight and/or body surface area. Participants meeting response criteria at Week 52, may enter in an open-label (OL) extension period to receive golimumab SC for 50 weeks (doses will be based on weight and/or body surface area). | Biological: Golimumab<br>* Participants will receive subcutaneous golimumab intermittently for 52 weeks in double-blind period, where doses will be based on weight and/or body surface area. Participants meeting response criteria at Week 52, may receive golimumab SC for 50 weeks (doses will be based on weight and/or body surface area) in an OL extension period.<br>* Other names: SIMPONI;|
| Placebo Comparator: Group 2: Placebo<br>Participants will receive a matching placebo to golimumab. | Biological: Placebo<br>* Matching Placebo to golimumab.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Active Treatment Period: C-peptide Area Under the Concentration-time Curve (AUC) Calculated From a 4 Hour Mixed Meal Tolerance Test (MMTT) at Week 52 | MMTT-Stimulated 4-Hour C-peptide AUC was defined as the mean area under the C-peptide level time curve over the 4-hour period divided by the duration after a mixed-meal tolerance test. | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Active Treatment Period: Change From Baseline in Insulin Use in Units Per Kilogram Body Weight Per Day | Change from baseline in daily insulin use at Week 52 was reported. | Baseline and Week 52 | 
| Active Treatment Period: Change From Baseline in Glycosylated Haemoglobin (HbA1c) at Week 52 | Change from baseline in glycosylated HbA1c at Week 52 was reported. | Baseline and Week 52 | 
| Hypoglycemic Event Rates | A hypoglycemic event was defined as either a biochemically confirmed hypoglycemic episode or a severe hypoglycemic event. The hypoglycemia event rate (number of hypoglycemia episodes per patient-year) was defined as blood glucose levels of less than and equal to (<=) 70, 55, and 35 mg/dL or clinical sequelae consistent with severe hypoglycemia in the absence of a BG reading. | Up to Week 52 | 
| Active Treatment Period: C-peptide Area Under the Concentration-time Curve (AUC) Calculated From a 4 Hour Mixed Meal Tolerance Test (MMTT) Over Time | MMTT-Stimulated 4-Hour C-peptide AUC is the mean area under the C-peptide level-time curve over the 4-hour period divided by the duration after a mixed-meal tolerance test. | Baseline, Weeks 12, 26, 38, 52, 78 and 104 | 
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability | An adverse event (AE) was defined as any untoward medical occurrence in clinical study subject administered medicinal product. It could be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product. Treatment emergent AEs were defined as AEs with onset during the treatment phase or that are a consequence of a pre-existing condition that has worsened since baseline. | Up to Week 52 (Active treatment period), Up to Week 104 (Active treatment + Off therapy follow-up period) | 
| Percentage of Participants With Serious Adverse Events | An AE was defined as any untoward medical occurrence in clinical study participant administered medicinal product. It could be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product. A serious AE was defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious treatment via medicinal product and was medically important. | Up to Week 52 (Active treatment period), Up to Week 104 (Active treatment + Off therapy follow-up period) | 
| Percentage of Participants With Severe Infections Through Week 52 and Week 104 | Participants having 1 or more severe infections were evaluated and reported. | Up to Week 52 (Active treatment period), Up to Week 104 (Active treatment + Off therapy follow-up period) | 
| Active Treatment Period: Percentage of Participants With Study Agent Injection Site Reactions Up to Week 52 | Percentage of participants with study agent injection site reactions up to Week 52 were reported. | Up to Week 52 | 
| Serum Golimumab Concentrations | Serum samples were collected for the measurement of golimumab concentrations. | Preinjection: Week 0, Week 2, Week 4, Week 8, Week 12, and Week 26, Week 33, Week 38 (preinjection),Week 45 and Week 52 (preinjection), for active treatment period; Weeks 78 and 104 for Off-therapy follow-up period | 
| Number of Participants With Antibodies to Golimumab | Number of participants with antibodies to golimumab were reported. | Up to Week 52 (Active treatment period), Up to Week 104 (Active treatment + Off therapy follow-up period) | 
| Titers of Antibodies to Golimumab | Titers of antibodies to golimumab were evaluated. | Up to Week 52 (Active treatment period), Up to Week 104 (Active treatment + Off therapy follow-up period) |