Back to resultsA Study of SIMPONI® to Arrest Beta-cell Loss in Type 1 Diabetes (T1GER)
Primary Purpose
Diabetes Mellitus, Type 1
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Golimumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 1
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Group 1: Golimumab
Group 2: Placebo
Arm Description
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).
Participants will receive a matching placebo to golimumab.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Active Treatment Period: Change From Baseline in Glycosylated Haemoglobin (HbA1c) at Week 52
Change from baseline in glycosylated HbA1c at Week 52 was reported.
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.
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.
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.
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.
Percentage of Participants With Severe Infections Through Week 52 and Week 104
Participants having 1 or more severe infections were evaluated and reported.
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.
Serum Golimumab Concentrations
Serum samples were collected for the measurement of golimumab concentrations.
Number of Participants With Antibodies to Golimumab
Number of participants with antibodies to golimumab were reported.
Titers of Antibodies to Golimumab
Titers of antibodies to golimumab were evaluated.
Full Information
NCT ID
NCT02846545
First Posted
July 22, 2016
Last Updated
December 20, 2022
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT02846545
Brief Title
A Study of SIMPONI® to Arrest Beta-cell Loss in Type 1 Diabetes
Acronym
T1GER
Official Title
SIMPONI® to Arrest β-cell Loss in Type 1 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
August 26, 2016 (Actual)
Primary Completion Date
May 21, 2019 (Actual)
Study Completion Date
January 5, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
84 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1: Golimumab
Arm Type
Experimental
Arm Description
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).
Arm Title
Group 2: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive a matching placebo to golimumab.
Intervention Type
Biological
Intervention Name(s)
Golimumab
Other Intervention Name(s)
SIMPONI
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Matching Placebo to golimumab.
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Week 52
Secondary Outcome Measure Information:
Title
Active Treatment Period: Change From Baseline in Insulin Use in Units Per Kilogram Body Weight Per Day
Description
Change from baseline in daily insulin use at Week 52 was reported.
Time Frame
Baseline and Week 52
Title
Active Treatment Period: Change From Baseline in Glycosylated Haemoglobin (HbA1c) at Week 52
Description
Change from baseline in glycosylated HbA1c at Week 52 was reported.
Time Frame
Baseline and Week 52
Title
Hypoglycemic Event Rates
Description
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.
Time Frame
Up to Week 52
Title
Active Treatment Period: C-peptide Area Under the Concentration-time Curve (AUC) Calculated From a 4 Hour Mixed Meal Tolerance Test (MMTT) Over Time
Description
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.
Time Frame
Baseline, Weeks 12, 26, 38, 52, 78 and 104
Title
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability
Description
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.
Time Frame
Up to Week 52 (Active treatment period), Up to Week 104 (Active treatment + Off therapy follow-up period)
Title
Percentage of Participants With Serious Adverse Events
Description
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.
Time Frame
Up to Week 52 (Active treatment period), Up to Week 104 (Active treatment + Off therapy follow-up period)
Title
Percentage of Participants With Severe Infections Through Week 52 and Week 104
Description
Participants having 1 or more severe infections were evaluated and reported.
Time Frame
Up to Week 52 (Active treatment period), Up to Week 104 (Active treatment + Off therapy follow-up period)
Title
Active Treatment Period: Percentage of Participants With Study Agent Injection Site Reactions Up to Week 52
Description
Percentage of participants with study agent injection site reactions up to Week 52 were reported.
Time Frame
Up to Week 52
Title
Serum Golimumab Concentrations
Description
Serum samples were collected for the measurement of golimumab concentrations.
Time Frame
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
Title
Number of Participants With Antibodies to Golimumab
Description
Number of participants with antibodies to golimumab were reported.
Time Frame
Up to Week 52 (Active treatment period), Up to Week 104 (Active treatment + Off therapy follow-up period)
Title
Titers of Antibodies to Golimumab
Description
Titers of antibodies to golimumab were evaluated.
Time Frame
Up to Week 52 (Active treatment period), Up to Week 104 (Active treatment + Off therapy follow-up period)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Little Rock
State/Province
Arkansas
Country
United States
City
Newport Beach
State/Province
California
Country
United States
City
Sacramento
State/Province
California
Country
United States
City
San Diego
State/Province
California
Country
United States
City
San Francisco
State/Province
California
Country
United States
City
Walnut Creek
State/Province
California
Country
United States
City
Aurora
State/Province
Colorado
Country
United States
City
New Haven
State/Province
Connecticut
Country
United States
City
Doral
State/Province
Florida
Country
United States
City
Gainesville
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Columbus
State/Province
Georgia
Country
United States
City
Boise
State/Province
Idaho
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Indianapolis
State/Province
Indiana
Country
United States
City
Lexington
State/Province
Kentucky
Country
United States
City
Louisville
State/Province
Kentucky
Country
United States
City
Baton Rouge
State/Province
Louisiana
Country
United States
City
Baltimore
State/Province
Maryland
Country
United States
City
Boston
State/Province
Massachusetts
Country
United States
City
Worcester
State/Province
Massachusetts
Country
United States
City
Morristown
State/Province
New Jersey
Country
United States
City
Bronx
State/Province
New York
Country
United States
City
Buffalo
State/Province
New York
Country
United States
City
Mentor
State/Province
Ohio
Country
United States
City
Philadelphia
State/Province
Pennsylvania
Country
United States
City
Sioux Falls
State/Province
South Dakota
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
San Antonio
State/Province
Texas
Country
United States
City
Schertz
State/Province
Texas
Country
United States
City
Webster
State/Province
Texas
Country
United States
City
Seattle
State/Province
Washington
Country
United States
City
Tacoma
State/Province
Washington
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
33207093
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.
Results Reference
derived
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A Study of SIMPONI® to Arrest Beta-cell Loss in Type 1 Diabetes
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