Clinical trial NCT02846545: A Study of SIMPONI® to Arrest Beta-cell Loss in Type 1 Diabetes
Official title: SIMPONI® to Arrest β-cell Loss in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 1
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2016-07-27
Enrollment: 84
Sex: ALL
Minimum age (years): 6
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: 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
timeFrame: Week 52
Secondary outcomes:
measure: Active Treatment Period: Change From Baseline in Insulin Use in Units Per Kilogram Body Weight Per Day
timeFrame: Baseline and Week 52
measure: Active Treatment Period: Change From Baseline in Glycosylated Haemoglobin (HbA1c) at Week 52
timeFrame: Baseline and Week 52
measure: Hypoglycemic Event Rates
timeFrame: Up to Week 52
measure: Active Treatment Period: C-peptide Area Under the Concentration-time Curve (AUC) Calculated From a 4 Hour Mixed Meal Tolerance Test (MMTT) Over Time
timeFrame: Baseline, Weeks 12, 26, 38, 52, 78 and 104
measure: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability
timeFrame: Up to Week 52 (Active treatment period), Up to Week 104 (Active treatment + Off therapy follow-up period)
measure: Percentage of Participants With Serious Adverse Events
timeFrame: Up to Week 52 (Active treatment period), Up to Week 104 (Active treatment + Off therapy follow-up period)
measure: Percentage of Participants With Severe Infections Through Week 52 and Week 104
timeFrame: Up to Week 52 (Active treatment period), Up to Week 104 (Active treatment + Off therapy follow-up period)
measure: Active Treatment Period: Percentage of Participants With Study Agent Injection Site Reactions Up to Week 52
timeFrame: Up to Week 52
measure: Serum Golimumab Concentrations
timeFrame: 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
measure: Number of Participants With Antibodies to Golimumab
timeFrame: Up to Week 52 (Active treatment period), Up to Week 104 (Active treatment + Off therapy follow-up period)
measure: Titers of Antibodies to Golimumab
timeFrame: Up to Week 52 (Active treatment period), Up to Week 104 (Active treatment + Off therapy follow-up period)
Other outcomes:
Locations:
city: Little Rock
country: United States
state: Arkansas
city: Newport Beach
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: New Haven
country: United States
state: Connecticut
city: Doral
country: United States
state: Florida
city: Gainesville
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Columbus
country: United States
state: Georgia
city: Boise
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Lexington
country: United States
state: Kentucky
city: Louisville
country: United States
state: Kentucky
city: Baton Rouge
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Worcester
country: United States
state: Massachusetts
city: Morristown
country: United States
state: New Jersey
city: Bronx
country: United States
state: New York
city: Buffalo
country: United States
state: New York
city: Mentor
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Sioux Falls
country: United States
state: South Dakota
city: Dallas
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Schertz
country: United States
state: Texas
city: Webster
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Tacoma
country: United States
state: Washington
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Quattrin T, Haller MJ, Steck AK, Felner EI, Li Y, Xia Y, Leu JH, Zoka R, Hedrick JA, Rigby MR, Vercruysse F; T1GER Study Investigators. Golimumab and Beta-Cell Function in Youth with New-Onset Type 1 Diabetes. N Engl J Med. 2020 Nov 19;383(21):2007-2017. doi: 10.1056/NEJMoa2006136.