Tocilizumab (TCZ) in New-onset Type 1 Diabetes | NCT02293837 | Trialant
NCT02293837
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Status
Completed
Last Update Posted
Sep 8, 2021Actual
Enrollment
136Actual
Phase
Phase 2
Conditions
Type 1 Diabetes Mellitus
New-onset Type 1 Diabetes Mellitus
T1DM
T1D
Interventions
Tocilizumab (TCZ)
Placebo
Standard of Care
Countries
United States
Australia
Protocol Section
Identification Module
NCT ID
NCT02293837
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
DAIT ITN058AI
Secondary IDs
Not provided
Brief Title
Tocilizumab (TCZ) in New-onset Type 1 Diabetes
Official Title
Preserving Beta-Cell Function With Tocilizumab in New-onset Type 1 Diabetes (ITN058AI)
Acronym
EXTEND
Organization
National Institute of Allergy and Infectious Diseases (NIAID)NIH
Status Module
Record Verification Date
Aug 2021
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Mar 12, 2015Actual
Primary Completion Date
Jul 10, 2019Actual
Completion Date
Aug 31, 2020Actual
First Submitted Date
Nov 13, 2014
First Submission Date that Met QC Criteria
Nov 17, 2014
First Posted Date
Nov 18, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
Jul 22, 2021
Results First Submitted that Met QC Criteria
Jul 22, 2021
Results First Posted Date
Aug 17, 2021Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Jan 22, 2020
Certification/Extension First Submitted that Passed QC Review
Jan 22, 2020
Certification/Extension First Posted Date
Feb 5, 2020Actual
Last Update Submitted Date
Aug 16, 2021
Last Update Posted Date
Sep 8, 2021Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)NIH
Collaborators
Name
Class
Immune Tolerance Network (ITN)
NETWORK
PPD Development, LP
INDUSTRY
Rho Federal Systems Division, Inc.
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
Type 1 diabetes mellitus (T1DM) is an autoimmune disease. Based on previous research, study doctors think that giving medicines to affect the immune system soon after diabetes is diagnosed may stop, delay or decrease the destruction of beta cells, resulting in better glucose control.
Researchers believe that tocilizumab could have some effect on the cells in the immune system that are thought to be involved in the development of type 1 diabetes. This study will test whether tocilizumab can help preserve or delay destruction of remaining beta cells in people recently diagnosed type 1 diabetes.
Detailed Description
Staggered enrollment is planned for this trial.
Prior to initiating the study in the pediatric age group (6-17 years old), 30-99 eligible adults (ages 18-45 years) will be randomized 2:1 to tocilizumab or placebo, respectively. Once the first thirty adult participants have completed 12 weeks of treatment, the FDA and Data and Safety Monitoring Board (DSMB) will review available data (e.g., interim analysis) to weigh potential risks and benefits before opening the trial to pediatric participants.
As of ≥ May 15, 2017: Study enrollment limited to participants ages 6 to 17 years inclusive.
Conditions Module
Conditions
Type 1 Diabetes Mellitus
New-onset Type 1 Diabetes Mellitus
T1DM
T1D
Keywords
interleukin-6 (IL-6) receptor inhibitor
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
136Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Tocilizumab (TCZ) + SOC
Experimental
Subjects will receive intravenous (IV) infusions of either 8.0 mg/kg (body weight ≥30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. Participants will also receive standard intensive diabetes management (in accordance with the American Diabetes Association guidelines [Standard of Care, SOC])
Drug: Tocilizumab (TCZ)
Other: Standard of Care
Tocilizumab Placebo Group + SOC
Placebo Comparator
Subjects will receive IV infusions of either 8.0 mg/kg (body weight ≥ 30kg) or 10.0 mg/kg (body weight <30kg) placebo every 4 weeks for 24 weeks. Participants will also receive standard intensive diabetes management (in accordance with the American Diabetes Association guidelines [Standard of Care, SOC])
Drug: Placebo
Other: Standard of Care
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Tocilizumab (TCZ)
Drug
Subjects assigned to this group will receive tocilizumab intravenous (IV) infusions of either 8.0 mg/kg (body weight ≥ 30kg) or 10.0 mg/kg (body weight <30kg) every 4 weeks for 24 weeks.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC) in Pediatric Participants
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 2-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
Baseline (Pre-treatment) to Week 52
Secondary Outcomes
Measure
Description
Time Frame
Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC)
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 2-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Male or female aged 6-45 years*
-*Current Institutional Review Board (IRB)-approved age eligibility criteria is restricted to subjects 6 to 17 years of age at time of study enrollment
Diagnosis of type 1 diabetes mellitus (T1DM), using the American Diabetes Association T1DM criteria, within 100 days of study enrollment
Positive for at least one diabetes-related autoantibody, including but not limited to:
Glutamate decarboxylase (GAD-65)
Insulin, if obtained within 10 days of the onset of exogenous insulin therapy
Insulinoma antigen-2 (IA-2)
Zinc transporter-8 (ZnT8)
Peak stimulated C-peptide level ≥ 0.2 pmol/mL following a mixed-meal tolerance test (MMTT) conducted at least 21 days from diagnosis and within 37 days of randomization (V0)
Signed informed consent (and informed assent of minor, if applicable).
Exclusion Criteria:
Severe reaction or anaphylaxis to human, humanized or murine monoclonal antibodies
History of malignancy or serious uncontrolled cardiovascular, nervous system, pulmonary, renal, or gastrointestinal disease, or significant dyslipidemia
Any history of recent serious bacterial, viral, fungal, or other opportunistic infections
Have serologic evidence of current or past HIV (Human immunodeficiency virus), Hepatitis B, or Hepatitis C
Positive QuantiFERON Tuberculosis (TB) test, history of TB, or active TB infection
Active infection with Epstein-Barr virus (EBV) as defined by EBV viral load ≥10,000 copies per mL of whole blood
Active infection with Cytomegalovirus (CMV) as defined by CMV viral load ≥10,000 copies per mL of whole blood
Diagnosis of liver disease or elevated hepatic enzymes, as defined by Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), or both > 1.5 x the upper limit of age-determined normal (ULN) or total bilirubin > ULN
Current or prior treatment that is known to cause a significant, ongoing change in the course of T1D or immunologic status
Current or prior (within last 30 days) use of drugs other than insulin to treat hyperglycemia (e.g. metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, Dipeptidyl peptidase-4 Intravenous (DPP-IV) inhibitors, or amylin)
Current use of any medication known to significantly influence glucose tolerance (e.g., atypical antipsychotics, diphenylhydantoin, niacin)
Any of the following hematologic abnormalities, confirmed by repeat tests:
White blood count <3,000/microL or >14,000/microL
Lymphocyte count <500/microL
Platelet count <150,000 /microL
Hemoglobin <8.5 g/dL
. Neutrophil count <2,000 cells/microL.
Females who are pregnant, lactating, or planning on pregnancy during the 2- year study period
History or diagnoses of other autoimmune diseases with the exception of stable thyroid or celiac disease
History of alcohol, drug or chemical abuse within 1 year prior to study eligibility screening evaluation
Any medical or psychological condition that in the opinion of the principal investigator would interfere with safe completion of the trial
Prior participation in a clinical trial that could increase risks associated with this clinical trial
Greenbaum CJ, Serti E, Lambert K, Weiner LJ, Kanaparthi S, Lord S, Gitelman SE, Wilson DM, Gaglia JL, Griffin KJ, Russell WE, Raskin P, Moran A, Willi SM, Tsalikian E, DiMeglio LA, Herold KC, Moore WV, Goland R, Harris M, Craig ME, Schatz DA, Baidal DA, Rodriguez H, Utzschneider KM, Nel HJ, Soppe CL, Boyle KD, Cerosaletti K, Keyes-Elstein L, Long SA, Thomas R, McNamara JG, Buckner JH, Sanda S; ITN058AI EXTEND Study Team. IL-6 receptor blockade does not slow beta cell loss in new-onset type 1 diabetes. JCI Insight. 2021 Nov 8;6(21):e150074. doi: 10.1172/jci.insight.150074.
The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
Types
Not provided
Time Frame
On average, within 24 months after database lock for the trial.
Before initiating the study in the pediatric group (6-17 years old), adults (18-45 years old) were randomized 2:1 to tocilizumab or placebo, respectively. After at least 30 adults completed 12 weeks of treatment, the Data and Safety Monitoring Board (DSMB) and FDA reviewed the available data and allowed the enrollment of children 6-17 years old.
Recruitment Details
Participants were screened from February 11, 2015 to Jun 21, 2018 at 17 sites in the US and two sites in Australia. March 12, 2015 was the actual date on which the first participant was enrolled in this clinical study.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Tocilizumab (TCZ) in Pediatric Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.
Subjects assigned to this group will receive placebo intravenous (IV) infusions of either 8.0 mg/kg (body weight ≥ 30kg) or 10.0 mg/kg (body weight <30kg) every 4 weeks for 24 weeks.
Tocilizumab Placebo Group + SOC
Placebo for Tocilizumab
Standard of Care
Other
Participants will also receive standard intensive diabetes management (in accordance with the American Diabetes Association guidelines [Standard of Care, SOC])
Tocilizumab (TCZ) + SOC
Tocilizumab Placebo Group + SOC
SOC
Baseline (Pre-treatment) to Weeks 24, 52, and 104
2-Hour C-peptide Mean Area Under the Curve (mAUC), Mixed Model
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 2-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
Baseline (Pre-treatment), Weeks 12, 24, 39, 52, 78, and 104
Change From Baseline in 4-Hour C-peptide Mean Area Under the Curve (mAUC)
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 4-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
Baseline (Pre-treatment) to Weeks 52 and 104
Change From Baseline in Average Insulin Use in Units Per Kilogram Body Weight Per Day
The need to use exogenous insulin is an indication that the body is not producing enough endogenous insulin. Higher amounts of insulin use indicate higher disease activity. Insulin use was collected each day for 5 days prior to the visit. Average insulin use per kg is the average insulin use over the 5 days prior to the visit divided by the participant's weight in kg.
Baseline (Pre-treatment) to Weeks 24, 52, and 104
Change From Baseline in Average Insulin Use Per Kg, Mixed Model
The need to use exogenous insulin is an indication that the body is not producing enough endogenous insulin. Higher amounts of insulin use indicate higher disease activity. Insulin use was collected each day for 5 days prior to the visit. Average insulin use per kg is the average insulin use over the 5 days prior to the visit divided by the participant's weight in kg.
Baseline (Pre-treatment) to Weeks 12, 24, 39, 52, 78, and 104
Change From Baseline in Hemoglobin A1c
Glycosylated hemoglobin (HbA1c) is a measure of the average plasma concentration of blood sugar (glucose) over the previous three months and measures the level of optimal management of underlying disease. An HbA1c of 5.6% or less is considered normal. HbA1c of 6.5% or higher is typical for individuals with Type 1 Diabetes mellitus (T1DM). The closer HbA1c levels are to normal, the better controlled the disease is.
Baseline (Pre-treatment) to Weeks 24, 52, and 104
Change From Baseline in Hemoglobin A1C (HbA1c) Level in Participants, Mixed Model
Glycosylated hemoglobin (HbA1c) is a measure of the average plasma concentration of blood sugar (glucose) over the previous three months and measures the level of optimal management of underlying disease. An HbA1c of 5.6% or less is considered normal. HbA1c of 6.5% or higher is typical for individuals with Type 1 Diabetes mellitus (T1DM). The closer HbA1c levels are to normal, the better controlled the disease is.
Baseline (Pre-treatment) to Weeks 12, 24, 39, 52, 78, and 104
Number of Participants Who Experienced at Least One Major Hypoglycemic Event After Treatment Initiation
Major hypoglycemic adverse events are defined as: Blood glucose concentration < 40 mg/dL (Grades 3-5, NCI-CTCAE version 4.03*), or hypoglycemic events involving seizure or loss of consciousness (coma) or requiring assistance from another individual in order to recover.
*NCI-CTCAE: National Cancer Institute Common Terminology Criteria for Adverse Events
Day 0 (Treatment Initiation) to Weeks 52 and 104
Number of Participants Who Experienced Infusion-Related Adverse Events
An infusion/dose reaction is defined as an adverse event occurring during and within 24 hours after the infusion or subcutaneous injection of tocilizumab. This may include hypersensitivity reactions or anaphylactic reactions.
Day 0 (Treatment Initiation) to Week 52
Number of Participants Who Experienced Hypersensitivity Adverse Events
Signs of a possible hypersensitivity reaction to the study drug include but are not limited to:
Fever, chills, pruritus, urticaria, angioedema, and skin rash
Cardiopulmonary reactions, including chest pain, dyspnea, hypotension or hypertension
Day 0 (Treatment Initiation) to Week 52
Stanford
California
94305
United States
Yale University School of Medicine: Diabetes Endocrinology Research Center
New Haven
Connecticut
06519
United States
University of Florida
Gainesville
Florida
32610
United States
University of Miami: Diabetes Research Institute
Miami
Florida
33136
United States
University of South Florida: Diabetes Center
Tampa
Florida
33612
United States
Indiana University Health - Riley Hospital for Children
Indianapolis
Indiana
46202
United States
University of Iowa
Iowa City
Iowa
52242
United States
Harvard University, Joslin Diabetes Center
Boston
Massachusetts
002215
United States
University of Minnesota
Minneapolis
Minnesota
55455
United States
Children's Mercy Hospital
Kansas City
Missouri
64111
United States
Columbia University, Naomi Berrie Diabetes Center
New York
New York
10032
United States
Children's Hospital of Philadelphia
Philadelphia
Pennsylvania
19104
United States
Sanford Research
Sioux Falls
South Dakota
57104
United States
Vanderbilt University
Nashville
Tennessee
37232
United States
University of Texas Southwestern Medical Center
Dallas
Texas
75390
United States
Benaroya Research Institute
Seattle
Washington
98101
United States
The Children's Hospital at Westmead: Kids Research Institute
Westmead
New South Wales
Westmead 2145
Australia
Lady Cilento Children's Hospital: Department of Endocrinology
South Brisbane
Queensland
4101
Australia
Derived
Hundhausen C, Roth A, Whalen E, Chen J, Schneider A, Long SA, Wei S, Rawlings R, Kinsman M, Evanko SP, Wight TN, Greenbaum CJ, Cerosaletti K, Buckner JH. Enhanced T cell responses to IL-6 in type 1 diabetes are associated with early clinical disease and increased IL-6 receptor expression. Sci Transl Med. 2016 Sep 14;8(356):356ra119. doi: 10.1126/scitranslmed.aad9943.
Division of Allergy, Immunology, and Transplantation (DAIT) website
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.
FG002
Tocilizumab (TCZ) in Adult Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.
FG003
Placebo in Adult Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.
FG00054 subjects
FG00127 subjects
FG00235 subjects1 randomized adult was never treated
FG00320 subjects
COMPLETED
FG00051 subjects
FG00123 subjects
FG00231 subjects
FG00319 subjects
NOT COMPLETED
FG0003 subjects
FG0014 subjects
FG0024 subjects
FG0031 subjects
Type
Comment
Reasons
Lost to Follow-up
FG0000 subjects
FG0012 subjects
FG0021 subjects
FG0030 subjects
Withdrawal by Subject
FG0002 subjects
FG0011 subjects
FG0022 subjects
FG0031 subjects
COVID-19 Related
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
Participant ill and could not be infused
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
Randomized participants in each cohort were randomized 2:1 to tocilizumab or placebo, respectively.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Tocilizumab (TCZ) in Pediatric Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.
BG001
Placebo in Pediatric Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.
BG002
Tocilizumab (TCZ) in Adult Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.
BG003
Placebo in Adult Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.
BG004
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00054
BG00127
BG00235
BG00320
BG004136
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00011.1± 2.9
BG00111.1± 2.5
BG00227.9± 7.4
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00026
BG00112
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0001
BG0014
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0011
BG002
Region of Enrollment
Count of Participants
Participants
Title
Denominators
Categories
United States
Title
Measurements
BG00052
BG00124
BG002
Body Mass Index (BMI)
BMI is a person's weight in kilograms divided by the square of height in meters. For more information regarding BMI, visit the Centers for Disease Control and Prevention (CDC) website, "How Do I Interpret Body Mass Index Information" at:
2-hour C-peptide Mean Area Under the Curve (mAUC) Result in Response to Standardized Mixed Meal Tol
C-peptide is released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and various minutes post-meal. C-peptide AUC was calculated using the trapezoidal rule over the 2-hour time period. Results of the stimulated 2-hour (e.g., 120 minutes) post-meal C-peptide AUC are provided. Larger numbers are preferable (better) in these AUC results: more insulin being produced reflects less severe disease.
Mean
Standard Deviation
pmol/mL
Title
Denominators
Categories
Title
Measurements
BG0000.73± 0.44
BG001
Hemoglobin A1C (HbA1c) Level
Glycosylated hemoglobin (HbA1c) is a measure of the average plasma concentration of blood sugar (glucose) over the previous three months and measures the level of optimal management of underlying disease. An HbA1c of 5.6% or less is considered normal. HbA1c of 6.5% or higher is typical for individuals with Type 1 Diabetes mellitus (T1DM). The closer HbA1c levels are to normal, the better controlled the disease is.
Mean
Standard Deviation
percent (%)
Title
Denominators
Categories
Title
Measurements
BG0006.79± 1.03
BG001
Average Insulin Use Per Kilogram Body Weight
The need to use exogenous insulin is an indication that the body is not producing enough endogenous insulin. Higher amounts of insulin use indicate higher disease activity.
Mean
Standard Deviation
Units per Kilogram Body Weight per Day
Title
Denominators
Categories
Title
Measurements
BG0000.39± 0.24
BG001
Days from Type 1 Diabetes Mellitus (T1DM) Diagnosis to Randomization
Inclusion criteria included being diagnosed with type 1 diabetes within 100 days of enrollment. Diagnosis was based on the American Diabetes Association T1DM criteria.
Mean
Standard Deviation
Days
Title
Denominators
Categories
Title
Measurements
BG00085.9± 15.5
BG001
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC) in Pediatric Participants
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 2-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
The modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.
Posted
Least Squares Mean
95% Confidence Interval
pmol/mL
Baseline (Pre-treatment) to Week 52
ID
Title
Description
OG000
Tocilizumab (TCZ) in Pediatric Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.
OG001
Placebo in Pediatric Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.
Units
Counts
Participants
OG00054
OG00127
Title
Denominators
Categories
Title
Measurements
OG000-0.337(-0.39 to -0.28)
OG001-0.391(-0.47 to -0.31)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Week 52; Primary imputation method used for missing Week 52 mAUC.
ANCOVA
0.277
P-value comes from an analysis of covariance with outcome variable of change in mAUC from screening and covariates of treatment, screening mAUC, and age.
Superiority
Secondary
Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC)
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 2-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
Modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.
Posted
Least Squares Mean
95% Confidence Interval
pmol/mL
Baseline (Pre-treatment) to Weeks 24, 52, and 104
ID
Title
Description
OG000
Tocilizumab (TCZ) in Pediatric Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.
Secondary
2-Hour C-peptide Mean Area Under the Curve (mAUC), Mixed Model
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 2-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
The modified intent to treat population includes all randomized participants who received any dose of assigned study treatment. The model only included subjects with at least 1 post-screening assessment. One mITT subject did not have a post-screening MMTT and this subject is not included.
Posted
Least Squares Mean
95% Confidence Interval
pmol/mL
Baseline (Pre-treatment), Weeks 12, 24, 39, 52, 78, and 104
ID
Title
Description
OG000
Tocilizumab (TCZ) in Pediatric Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.
Secondary
Change From Baseline in 4-Hour C-peptide Mean Area Under the Curve (mAUC)
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210, and 240 minutes post-meal. C-peptide mAUC was calculated using the trapezoidal rule over the 4-hour time period. Larger numbers are preferable (better) in these mAUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., mAUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
The modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.
Posted
Least Squares Mean
95% Confidence Interval
pmol/mL
Baseline (Pre-treatment) to Weeks 52 and 104
ID
Title
Description
OG000
Tocilizumab (TCZ) in Pediatric Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.
Secondary
Change From Baseline in Average Insulin Use in Units Per Kilogram Body Weight Per Day
The need to use exogenous insulin is an indication that the body is not producing enough endogenous insulin. Higher amounts of insulin use indicate higher disease activity. Insulin use was collected each day for 5 days prior to the visit. Average insulin use per kg is the average insulin use over the 5 days prior to the visit divided by the participant's weight in kg.
The modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.
Posted
Least Squares Mean
95% Confidence Interval
Units per Kilogram Body Weight per Day
Baseline (Pre-treatment) to Weeks 24, 52, and 104
ID
Title
Description
OG000
Tocilizumab (TCZ) in Pediatric Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.
OG001
Placebo in Pediatric Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.
OG002
Tocilizumab (TCZ) in Adult Participants
Secondary
Change From Baseline in Average Insulin Use Per Kg, Mixed Model
The need to use exogenous insulin is an indication that the body is not producing enough endogenous insulin. Higher amounts of insulin use indicate higher disease activity. Insulin use was collected each day for 5 days prior to the visit. Average insulin use per kg is the average insulin use over the 5 days prior to the visit divided by the participant's weight in kg.
The modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.
Posted
Least Squares Mean
95% Confidence Interval
Units per Kilogram Body Weight per Day
Baseline (Pre-treatment) to Weeks 12, 24, 39, 52, 78, and 104
ID
Title
Description
OG000
Tocilizumab (TCZ) in Pediatric Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.
OG001
Placebo in Pediatric Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.
OG002
Tocilizumab (TCZ) in Adult Participants
Secondary
Change From Baseline in Hemoglobin A1c
Glycosylated hemoglobin (HbA1c) is a measure of the average plasma concentration of blood sugar (glucose) over the previous three months and measures the level of optimal management of underlying disease. An HbA1c of 5.6% or less is considered normal. HbA1c of 6.5% or higher is typical for individuals with Type 1 Diabetes mellitus (T1DM). The closer HbA1c levels are to normal, the better controlled the disease is.
The modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.
Posted
Least Squares Mean
95% Confidence Interval
percent (%)
Baseline (Pre-treatment) to Weeks 24, 52, and 104
ID
Title
Description
OG000
Tocilizumab (TCZ) in Pediatric Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.
OG001
Placebo in Pediatric Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.
OG002
Tocilizumab (TCZ) in Adult Participants
Secondary
Change From Baseline in Hemoglobin A1C (HbA1c) Level in Participants, Mixed Model
Glycosylated hemoglobin (HbA1c) is a measure of the average plasma concentration of blood sugar (glucose) over the previous three months and measures the level of optimal management of underlying disease. An HbA1c of 5.6% or less is considered normal. HbA1c of 6.5% or higher is typical for individuals with Type 1 Diabetes mellitus (T1DM). The closer HbA1c levels are to normal, the better controlled the disease is.
The modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.
Posted
Least Squares Mean
95% Confidence Interval
percent (%)
Baseline (Pre-treatment) to Weeks 12, 24, 39, 52, 78, and 104
ID
Title
Description
OG000
Tocilizumab (TCZ) in Pediatric Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.
OG001
Placebo in Pediatric Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.
OG002
Tocilizumab (TCZ) in Adult Participants
Secondary
Number of Participants Who Experienced at Least One Major Hypoglycemic Event After Treatment Initiation
Major hypoglycemic adverse events are defined as: Blood glucose concentration < 40 mg/dL (Grades 3-5, NCI-CTCAE version 4.03*), or hypoglycemic events involving seizure or loss of consciousness (coma) or requiring assistance from another individual in order to recover.
*NCI-CTCAE: National Cancer Institute Common Terminology Criteria for Adverse Events
The safety population includes all participants who received any degree of study treatment. Safety analyses are based on actual treatment the participants receive.
Posted
Number
Participants
Day 0 (Treatment Initiation) to Weeks 52 and 104
ID
Title
Description
OG000
Tocilizumab (TCZ) in Pediatric Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.
OG001
Placebo in Pediatric Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.
OG002
Tocilizumab (TCZ) in Adult Participants
Secondary
Number of Participants Who Experienced Infusion-Related Adverse Events
An infusion/dose reaction is defined as an adverse event occurring during and within 24 hours after the infusion or subcutaneous injection of tocilizumab. This may include hypersensitivity reactions or anaphylactic reactions.
The safety population includes all participants who received any degree of study treatment. Safety analyses are based on actual treatment the participants receive.
Posted
Number
Participants
Day 0 (Treatment Initiation) to Week 52
ID
Title
Description
OG000
Tocilizumab (TCZ) in Pediatric Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.
OG001
Placebo in Pediatric Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.
OG002
Tocilizumab (TCZ) in Adult Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.
Secondary
Number of Participants Who Experienced Hypersensitivity Adverse Events
Signs of a possible hypersensitivity reaction to the study drug include but are not limited to:
Fever, chills, pruritus, urticaria, angioedema, and skin rash
Cardiopulmonary reactions, including chest pain, dyspnea, hypotension or hypertension
The safety population includes all participants who received any degree of study treatment. Safety analyses are based on actual treatment the participants receive.
Posted
Number
Participants
Day 0 (Treatment Initiation) to Week 52
ID
Title
Description
OG000
Tocilizumab (TCZ) in Pediatric Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.
OG001
Placebo in Pediatric Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.
OG002
Tocilizumab (TCZ) in Adult Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.
Time Frame
Up to 104 weeks.
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Tocilizumab (TCZ) in Pediatric Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.
0
54
3
54
52
54
EG001
Placebo in Pediatric Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.
0
27
3
27
26
27
EG002
Tocilizumab (TCZ) in Adult Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.
0
34
2
34
31
34
EG003
Placebo in Adult Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.
0
20
2
20
19
20
EG004
Tocilizumab (TCZ) in Pooled Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.
0
88
5
88
83
88
EG005
Placebo in Pooled Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
0
27
5
47
45
47
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Vaccination site reaction
General disorders
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0011 events1 affected27 at risk
EG0020 events0 affected34 at risk
EG0030 events0 affected20 at risk
EG0040 events0 affected88 at risk
EG0051 events1 affected47 at risk
Gastroenteritis
Infections and infestations
17.1
Systematic Assessment
EG0001 events1 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Infectious mononucleosis
Infections and infestations
17.1
Systematic Assessment
EG0001 events1 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Forearm fracture
Injury, poisoning and procedural complications
17.1
Systematic Assessment
EG0001 events1 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0011 events1 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0021 events1 affected34 at risk
EG003
Squamous cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Thoracic outlet syndrome
Nervous system disorders
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0021 events1 affected34 at risk
EG003
Sleep apnoea syndrome
Respiratory, thoracic and mediastinal disorders
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0011 events1 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Deep vein thrombosis
Vascular disorders
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0021 events1 affected34 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
17.1
Systematic Assessment
EG0001 events1 affected54 at risk
EG0010 events0 affected27 at risk
EG0021 events1 affected34 at risk
EG0031 events1 affected20 at risk
EG0042 events2 affected88 at risk
EG0051 events1 affected47 at risk
Splenomegaly
Blood and lymphatic system disorders
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Palpitations
Cardiac disorders
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0022 events1 affected34 at risk
EG003
Basedow's disease
Endocrine disorders
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Eye irritation
Eye disorders
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Abdominal distension
Gastrointestinal disorders
17.1
Systematic Assessment
EG0001 events1 affected54 at risk
EG0010 events0 affected27 at risk
EG0021 events1 affected34 at risk
EG003
Abdominal pain
Gastrointestinal disorders
17.1
Systematic Assessment
EG0003 events2 affected54 at risk
EG0014 events3 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
17.1
Systematic Assessment
EG0007 events5 affected54 at risk
EG0014 events3 affected27 at risk
EG0022 events2 affected34 at risk
EG003
Constipation
Gastrointestinal disorders
17.1
Systematic Assessment
EG0003 events3 affected54 at risk
EG0014 events4 affected27 at risk
EG0021 events1 affected34 at risk
EG003
Dental caries
Gastrointestinal disorders
17.1
Systematic Assessment
EG0002 events2 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Diarrhoea
Gastrointestinal disorders
17.1
Systematic Assessment
EG0005 events4 affected54 at risk
EG0011 events1 affected27 at risk
EG0024 events4 affected34 at risk
EG003
Dyspepsia
Gastrointestinal disorders
17.1
Systematic Assessment
EG0003 events3 affected54 at risk
EG0014 events4 affected27 at risk
EG0021 events1 affected34 at risk
EG003
Food poisoning
Gastrointestinal disorders
17.1
Systematic Assessment
EG0001 events1 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Gastritis
Gastrointestinal disorders
17.1
Systematic Assessment
EG0004 events3 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0011 events1 affected27 at risk
EG0022 events2 affected34 at risk
EG003
Haemorrhoids
Gastrointestinal disorders
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0021 events1 affected34 at risk
EG003
Nausea
Gastrointestinal disorders
17.1
Systematic Assessment
EG00020 events13 affected54 at risk
EG00111 events4 affected27 at risk
EG0028 events5 affected34 at risk
EG003
Vomiting
Gastrointestinal disorders
17.1
Systematic Assessment
EG00016 events10 affected54 at risk
EG0017 events6 affected27 at risk
EG0024 events4 affected34 at risk
EG003
Adverse drug reaction
General disorders
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Fatigue
General disorders
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0012 events2 affected27 at risk
EG0021 events1 affected34 at risk
EG003
Influenza like illness
General disorders
17.1
Systematic Assessment
EG0001 events1 affected54 at risk
EG0015 events3 affected27 at risk
EG0023 events2 affected34 at risk
EG003
Pain
General disorders
17.1
Systematic Assessment
EG0001 events1 affected54 at risk
EG0012 events2 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Pyrexia
General disorders
17.1
Systematic Assessment
EG0009 events7 affected54 at risk
EG0015 events4 affected27 at risk
EG0021 events1 affected34 at risk
EG003
Temperature intolerance
General disorders
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Seasonal allergy
Immune system disorders
17.1
Systematic Assessment
EG0007 events6 affected54 at risk
EG0013 events2 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Bronchitis
Infections and infestations
17.1
Systematic Assessment
EG0002 events2 affected54 at risk
EG0011 events1 affected27 at risk
EG0022 events2 affected34 at risk
EG003
Ear infection
Infections and infestations
17.1
Systematic Assessment
EG0004 events4 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Epstein-Barr virus infection
Infections and infestations
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0022 events2 affected34 at risk
EG003
Gastroenteritis
Infections and infestations
17.1
Systematic Assessment
EG0009 events9 affected54 at risk
EG0013 events3 affected27 at risk
EG0026 events6 affected34 at risk
EG003
Gastroenteritis viral
Infections and infestations
17.1
Systematic Assessment
EG0004 events3 affected54 at risk
EG0010 events0 affected27 at risk
EG0021 events1 affected34 at risk
EG003
Influenza
Infections and infestations
17.1
Systematic Assessment
EG0008 events8 affected54 at risk
EG0015 events5 affected27 at risk
EG0021 events1 affected34 at risk
EG003
Nasopharyngitis
Infections and infestations
17.1
Systematic Assessment
EG00010 events7 affected54 at risk
EG0016 events4 affected27 at risk
EG00210 events5 affected34 at risk
EG003
Oral herpes
Infections and infestations
17.1
Systematic Assessment
EG0002 events1 affected54 at risk
EG0011 events1 affected27 at risk
EG0022 events2 affected34 at risk
EG003
Otitis externa
Infections and infestations
17.1
Systematic Assessment
EG0003 events3 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Otitis media
Infections and infestations
17.1
Systematic Assessment
EG0004 events3 affected54 at risk
EG0012 events2 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Pharyngitis
Infections and infestations
17.1
Systematic Assessment
EG0006 events5 affected54 at risk
EG0014 events3 affected27 at risk
EG0024 events4 affected34 at risk
EG003
Pharyngitis streptococcal
Infections and infestations
17.1
Systematic Assessment
EG0006 events6 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Pneumonia mycoplasmal
Infections and infestations
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Respiratory tract infection
Infections and infestations
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Rhinitis
Infections and infestations
17.1
Systematic Assessment
EG0002 events2 affected54 at risk
EG0013 events2 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Sinusitis
Infections and infestations
17.1
Systematic Assessment
EG00011 events5 affected54 at risk
EG0013 events1 affected27 at risk
EG0024 events4 affected34 at risk
EG003
Skin infection
Infections and infestations
17.1
Systematic Assessment
EG0001 events1 affected54 at risk
EG0012 events2 affected27 at risk
EG0021 events1 affected34 at risk
EG003
Upper respiratory tract infection
Infections and infestations
17.1
Systematic Assessment
EG00082 events26 affected54 at risk
EG00135 events13 affected27 at risk
EG00242 events15 affected34 at risk
EG003
Urinary tract infection
Infections and infestations
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Viral infection
Infections and infestations
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0012 events2 affected27 at risk
EG0021 events1 affected34 at risk
EG003
Viral upper respiratory tract infection
Infections and infestations
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0011 events1 affected27 at risk
EG0026 events5 affected34 at risk
EG003
Vulvovaginal mycotic infection
Infections and infestations
17.1
Systematic Assessment
EG0001 events1 affected54 at risk
EG0010 events0 affected27 at risk
EG0022 events2 affected34 at risk
EG003
Concussion
Injury, poisoning and procedural complications
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0012 events2 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Contusion
Injury, poisoning and procedural complications
17.1
Systematic Assessment
EG0002 events2 affected54 at risk
EG0012 events2 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Fall
Injury, poisoning and procedural complications
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0011 events1 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Hand fracture
Injury, poisoning and procedural complications
17.1
Systematic Assessment
EG0001 events1 affected54 at risk
EG0011 events1 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Head injury
Injury, poisoning and procedural complications
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Joint injury
Injury, poisoning and procedural complications
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0012 events2 affected27 at risk
EG0021 events1 affected34 at risk
EG003
Ligament sprain
Injury, poisoning and procedural complications
17.1
Systematic Assessment
EG0002 events2 affected54 at risk
EG0012 events2 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Limb injury
Injury, poisoning and procedural complications
17.1
Systematic Assessment
EG0006 events3 affected54 at risk
EG0010 events0 affected27 at risk
EG0021 events1 affected34 at risk
EG003
Muscle strain
Injury, poisoning and procedural complications
17.1
Systematic Assessment
EG0001 events1 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Sunburn
Injury, poisoning and procedural complications
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Traumatic haematoma
Injury, poisoning and procedural complications
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Aspartate aminotransferase increased
Investigations
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0021 events1 affected34 at risk
EG003
Body mass index increased
Investigations
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Neutrophil count decreased
Investigations
17.1
Systematic Assessment
EG0002 events2 affected54 at risk
EG0010 events0 affected27 at risk
EG0025 events3 affected34 at risk
EG003
Weight decreased
Investigations
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0012 events2 affected27 at risk
EG0022 events2 affected34 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
17.1
Systematic Assessment
EG00085 events28 affected54 at risk
EG00147 events14 affected27 at risk
EG00242 events15 affected34 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0021 events1 affected34 at risk
EG003
Hypophosphataemia
Metabolism and nutrition disorders
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
17.1
Systematic Assessment
EG0004 events3 affected54 at risk
EG0010 events0 affected27 at risk
EG0024 events4 affected34 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
17.1
Systematic Assessment
EG0001 events1 affected54 at risk
EG0011 events1 affected27 at risk
EG0024 events4 affected34 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
17.1
Systematic Assessment
EG0001 events1 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
17.1
Systematic Assessment
EG0002 events2 affected54 at risk
EG0010 events0 affected27 at risk
EG0022 events2 affected34 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
17.1
Systematic Assessment
EG0004 events4 affected54 at risk
EG0012 events1 affected27 at risk
EG0023 events3 affected34 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
17.1
Systematic Assessment
EG0004 events3 affected54 at risk
EG0011 events1 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
17.1
Systematic Assessment
EG0003 events2 affected54 at risk
EG0010 events0 affected27 at risk
EG0022 events2 affected34 at risk
EG003
Synovial cyst
Musculoskeletal and connective tissue disorders
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Temporomandibular joint syndrome
Musculoskeletal and connective tissue disorders
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Tendonitis
Musculoskeletal and connective tissue disorders
17.1
Systematic Assessment
EG0001 events1 affected54 at risk
EG0010 events0 affected27 at risk
EG0022 events2 affected34 at risk
EG003
Benign neoplasm of skin
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
17.1
Systematic Assessment
EG0000 events0 affected54 at risk
EG0010 events0 affected27 at risk
EG0020 events0 affected34 at risk
EG003
Skin papilloma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.
OG002
Tocilizumab (TCZ) in Adult Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.
OG003
Placebo in Adult Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.
OG004
Tocilizumab (TCZ) in Pooled Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.
OG005
Placebo in Pooled Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Units
Counts
Participants
OG00054
OG00127
OG00234
OG00320
OG00488
OG00547
Title
Denominators
Categories
Week 24
ParticipantsOG00054
ParticipantsOG00126
ParticipantsOG00233
ParticipantsOG00320
ParticipantsOG00487
ParticipantsOG00546
Title
Measurements
OG000-0.200(-0.26 to -0.14)
OG001-0.164(-0.25 to -0.08)
OG002-0.072(-0.17 to 0.03)
OG003
Week 52
ParticipantsOG00053
ParticipantsOG00125
ParticipantsOG00233
ParticipantsOG00320
Week 104
ParticipantsOG00049
ParticipantsOG00122
ParticipantsOG00229
ParticipantsOG00319
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Week 24
ANCOVA
0.499
P-value comes from an analysis of covariance with outcome variable of change in mAUC from screening and covariates of treatment, screening mAUC, and age.
Superiority
OG000
OG001
Week 52
ANCOVA
0.267
P-value comes from an analysis of covariance with outcome variable of change in mAUC from screening and covariates of treatment, screening mAUC, and age.
Superiority
OG000
OG001
Week 104
ANCOVA
0.226
P-value comes from an analysis of covariance with outcome variable of change in mAUC from screening and covariates of treatment, screening mAUC, and age.
Superiority
OG002
OG003
Week 24
ANCOVA
0.758
P-value comes from an analysis of covariance with outcome variable of change in mAUC from screening and covariates of treatment, screening mAUC, and age.
Superiority
OG002
OG003
Week 52
ANCOVA
0.341
P-value comes from an analysis of covariance with outcome variable of change in mAUC from screening and covariates of treatment, screening mAUC, and age.
Superiority
OG002
OG003
Week 104
ANCOVA
0.969
P-value comes from an analysis of covariance with outcome variable of change in mAUC from screening and covariates of treatment, screening mAUC, and age.
Superiority
OG004
OG005
Week 24
ANCOVA
0.689
P-value comes from an analysis of covariance with outcome variable of change in mAUC from screening and covariates of treatment, screening mAUC, and age.
Superiority
OG004
OG005
Week 52
ANCOVA
0.400
P-value comes from an analysis of covariance with outcome variable of change in mAUC from screening and covariates of treatment, screening mAUC, and age.
Superiority
OG004
OG005
Week 104
ANCOVA
0.969
P-value comes from an analysis of covariance with outcome variable of change in mAUC from screening and covariates of treatment, screening mAUC, and age.
Superiority
OG001
Placebo in Pediatric Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.
OG002
Tocilizumab (TCZ) in Adult Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.
OG003
Placebo in Adult Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.
OG004
Tocilizumab (TCZ) in Pooled Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.
OG005
Placebo in Pooled Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Units
Counts
Participants
OG00054
OG00126
OG00234
OG00320
OG00488
OG00546
Title
Denominators
Categories
Week 12
Title
Measurements
OG0000.60(0.51 to 0.69)
OG0010.55(0.42 to 0.68)
OG0020.72(0.56 to 0.89)
OG0030.88(0.67 to 1.09)
OG0040.65(0.57 to 0.74)
OG0050.69(0.57 to 0.81)
Week 24
Title
Measurements
OG0000.55(0.46 to 0.63)
OG0010.49(0.37 to 0.61)
OG0020.68(0.52 to 0.84)
OG003
Week 39
Title
Measurements
OG0000.48(0.40 to 0.56)
OG0010.42(0.30 to 0.53)
OG0020.63(0.47 to 0.79)
OG003
Week 52
Title
Measurements
OG0000.42(0.34 to 0.50)
OG0010.35(0.24 to 0.46)
OG0020.59(0.43 to 0.75)
OG003
Week 78
Title
Measurements
OG0000.30(0.23 to 0.37)
OG0010.23(0.12 to 0.33)
OG0020.50(0.33 to 0.66)
OG003
Week 104
Title
Measurements
OG0000.18(0.11 to 0.25)
OG0010.10(0.00 to 0.21)
OG0020.41(0.24 to 0.58)
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Screening to Week 104
Longitudinal mixed model
Random within-subject effects for intercept and study week were included assuming an unstructured covariance matrix.
0.679
P-value is for group difference in time trends from a longitudinal mixed effects model. Response variable was 2-hour C-peptide mAUC and covariates were treatment, study week, age, treatment*study week, age*study week.
Superiority
OG002
OG003
Screening to Week 104
Longitudinal mixed model
Random within-subject effects for intercept and study week were included assuming an unstructured covariance matrix.
0.373
P-value is for group difference in time trends from a longitudinal mixed effects model. Response variable was 2-hour C-peptide mAUC and covariates were treatment, study week, age, treatment*study week, age*study week.
Superiority
OG004
OG005
Screening to Week 104
Longitudinal mixed model
Random within-subject effects for intercept and study week were included assuming an unstructured covariance matrix.
0.395
P-value is for group difference in time trends from a longitudinal mixed effects model. Response variable was 2-hour C-peptide mAUC and covariates were treatment, study week, age, treatment*study week, age*study week.
Superiority
OG001
Placebo in Pediatric Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.
OG002
Tocilizumab (TCZ) in Adult Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.
OG003
Placebo in Adult Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.
OG004
Tocilizumab (TCZ) in Pooled Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.
OG005
Placebo in Pooled Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Units
Counts
Participants
OG00054
OG00127
OG00234
OG00320
OG00488
OG00547
Title
Denominators
Categories
Week 52
ParticipantsOG00026
ParticipantsOG0019
ParticipantsOG00233
ParticipantsOG00320
ParticipantsOG00459
ParticipantsOG00529
Title
Measurements
OG000-0.325(-0.42 to -0.23)
OG001-0.448(-0.60 to -0.29)
OG002-0.195(-0.30 to -0.09)
OG003
Week 104
ParticipantsOG00024
ParticipantsOG0017
ParticipantsOG00229
ParticipantsOG00319
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Week 52. Only participants >=12 years old had the 4-hour MMTT performed.
ANCOVA
0.176
P-value comes from an analysis of covariance with outcome variable of change in mAUC from screening and covariates of treatment, screening mAUC, and age.
Superiority
OG000
OG001
Week 104. Only participants >=12 years old had the 4-hour MMTT performed.
ANCOVA
0.285
P-value comes from an analysis of covariance with outcome variable of change in mAUC from screening and covariates of treatment, screening mAUC, and age.
Superiority
OG002
OG003
Week 52
ANCOVA
0.435
P-value comes from an analysis of covariance with outcome variable of change in mAUC from screening and covariates of treatment, screening mAUC, and age.
Superiority
OG002
OG003
Week 104
ANCOVA
0.931
P-value comes from an analysis of covariance with outcome variable of change in mAUC from screening and covariates of treatment, screening mAUC, and age.
Superiority
OG004
OG005
Week 52. Only participants >=12 years old had the 4-hour MMTT performed.
ANCOVA
0.280
P-value comes from an analysis of covariance with outcome variable of change in mAUC from screening and covariates of treatment, screening mAUC, and age.
Superiority
OG004
OG005
Week 104. Only participants >=12 years old had the 4-hour MMTT performed.
ANCOVA
0.985
P-value comes from an analysis of covariance with outcome variable of change in mAUC from screening and covariates of treatment, screening mAUC, and age.
Superiority
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.
OG003
Placebo in Adult Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.
OG004
Tocilizumab (TCZ) in Pooled Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.
OG005
Placebo in Pooled Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Units
Counts
Participants
OG00054
OG00127
OG00234
OG00320
OG00488
OG00547
Title
Denominators
Categories
Week 24
ParticipantsOG00054
ParticipantsOG00125
ParticipantsOG00233
ParticipantsOG00319
ParticipantsOG00487
ParticipantsOG00544
Title
Measurements
OG0000.139(0.09 to 0.19)
OG0010.126(0.05 to 0.20)
OG0020.015(-0.06 to 0.09)
OG003
Week 52
ParticipantsOG00051
ParticipantsOG00125
ParticipantsOG00233
ParticipantsOG00318
Week 104
ParticipantsOG00050
ParticipantsOG00123
ParticipantsOG00230
ParticipantsOG00317
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Week 24
ANCOVA
0.762
P-value comes from an analysis of covariance with outcome variable of change in average insulin use per kg from baseline and covariates of treatment, baseline average insulin use per kg, and age.
Superiority
OG000
OG001
Week 52
ANCOVA
0.640
P-value comes from an analysis of covariance with outcome variable of change in average insulin use per kg from baseline and covariates of treatment, baseline average insulin use per kg, and age.
Superiority
OG000
OG001
Week 104
ANCOVA
0.145
P-value comes from an analysis of covariance with outcome variable of change in avg insulin use per kg from baseline and covariates of treatment, baseline average insulin use per kg, and age.
Superiority
OG002
OG003
Week 24
ANCOVA
0.033
P-value comes from an analysis of covariance with outcome variable of change in average insulin use per kg from baseline and covariates of treatment, baseline average insulin use per kg, and age.
Superiority
OG002
OG003
Week 52
ANCOVA
0.591
P-value comes from an analysis of covariance with outcome variable of change in avg insulin use per kg from baseline and covariates of treatment, baseline avg insulin use per kg, and age.
Superiority
OG002
OG003
Week 104
ANCOVA
0.810
P-value comes from an analysis of covariance with outcome variable of change in average insulin use per kg from baseline and covariates of treatment, baseline average insulin use per kg, and age.
Superiority
OG004
OG005
Week 24
ANCOVA
0.178
P-value comes from an analysis of covariance with outcome variable of change in average insulin use per kg from baseline and covariates of treatment, baseline average insulin use per kg, and age.
Superiority
OG004
OG005
Week 52
ANCOVA
0.430
P-value comes from an analysis of covariance with outcome variable of change in average insulin use per kg from baseline and covariates of treatment, baseline average insulin use per kg, and age.
Superiority
OG004
OG005
Week 104
ANCOVA
0.149
P-value comes from an analysis of covariance with outcome variable of change in average insulin use per kg from baseline and covariates of treatment, baseline average insulin use per kg, and age.
Superiority
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.
OG003
Placebo in Adult Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.
OG004
Tocilizumab (TCZ) in Pooled Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.
OG005
Placebo in Pooled Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Units
Counts
Participants
OG00054
OG00127
OG00234
OG00320
OG00488
OG00547
Title
Denominators
Categories
Week 12
Title
Measurements
OG0000.45(0.40 to 0.51)
OG0010.45(0.37 to 0.53)
OG0020.29(0.22 to 0.35)
OG0030.37(0.29 to 0.46)
OG0040.39(0.35 to 0.43)
OG0050.42(0.36 to 0.48)
Week 24
Title
Measurements
OG0000.50(0.45 to 0.56)
OG0010.51(0.44 to 0.59)
OG0020.31(0.24 to 0.37)
OG003
Week 39
Title
Measurements
OG0000.57(0.51 to 0.62)
OG0010.59(0.52 to 0.67)
OG0020.33(0.26 to 0.40)
OG003
Week 52
Title
Measurements
OG0000.62(0.57 to 0.68)
OG0010.66(0.58 to 0.74)
OG0020.35(0.27 to 0.43)
OG003
Week 78
Title
Measurements
OG0000.73(0.67 to 0.79)
OG0010.80(0.71 to 0.89)
OG0020.39(0.30 to 0.49)
OG003
Week 104
Title
Measurements
OG0000.84(0.77 to 0.91)
OG0010.94(0.83 to 1.04)
OG0020.43(0.32 to 0.55)
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Screening to Week 104
Longitudinal mixed model
Random within-subject effects for intercept and study week were included assuming an unstructured covariance matrix.
0.103
P-value is for group difference in time trends from a longitudinal mixed effects model. Response variable was average insulin use per kg and covariates were treatment, study week, age, treatment*study week, age*study week.
Superiority
OG002
OG003
Screening to Week 104
Longitudinal mixed model
Random within-subject effects for intercept and study week were included assuming an unstructured covariance matrix.
0.452
P-value is for group difference in time trends from a longitudinal mixed effects model. Response variable was average insulin use per kg and covariates were treatment, study week, age, treatment*study week, age*study week.
Superiority
OG004
OG005
Screening to Week 104
Longitudinal mixed model
Random within-subject effects for intercept and study week were included assuming an unstructured covariance matrix.
0.091
P-value is for group difference in time trends from a longitudinal mixed effects model. Response variable was average insulin use per kg and covariates were treatment, study week, age, treatment*study week, age*study week.
Superiority
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.
OG003
Placebo in Adult Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.
OG004
Tocilizumab (TCZ) in Pooled Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.
OG005
Placebo in Pooled Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Units
Counts
Participants
OG00054
OG00127
OG00234
OG00320
OG00488
OG00547
Title
Denominators
Categories
Week 24
ParticipantsOG00054
ParticipantsOG00126
ParticipantsOG00233
ParticipantsOG00320
ParticipantsOG00487
ParticipantsOG00546
Title
Measurements
OG0000.065(-0.17 to 0.30)
OG0010.368(0.02 to 0.71)
OG002-0.509(-0.80 to -0.21)
OG003
Week 52
ParticipantsOG00053
ParticipantsOG00125
ParticipantsOG00232
ParticipantsOG00320
Week 104
ParticipantsOG00049
ParticipantsOG00122
ParticipantsOG00231
ParticipantsOG00319
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Week 24
ANCOVA
0.154
P-value comes from an analysis of covariance with outcome variable of change in HbA1c from baseline and covariates of treatment, baseline HbA1c, and age.
Superiority
OG000
OG001
Week 52
ANCOVA
0.193
P-value comes from an analysis of covariance with outcome variable of change in HbA1c from baseline and covariates of treatment, baseline HbA1c, and age.
Superiority
OG000
OG001
Week 104
ANCOVA
0.397
P-value comes from an analysis of covariance with outcome variable of change in HbA1c from baseline and covariates of treatment, baseline HbA1c, and age.
Superiority
OG002
OG003
Week 24
ANCOVA
0.125
P-value comes from an analysis of covariance with outcome variable of change in HbA1c from baseline and covariates of treatment, baseline HbA1c, and age.
Superiority
OG002
OG003
Week 52
ANCOVA
0.705
P-value comes from an analysis of covariance with outcome variable of change in HbA1c from baseline and covariates of treatment, baseline HbA1c, and age.
Superiority
OG002
OG003
Week 104
ANCOVA
0.378
P-value comes from an analysis of covariance with outcome variable of change in HbA1c from baseline and covariates of treatment, baseline HbA1c, and age.
Superiority
OG004
OG005
Week 24
ANCOVA
0.035
P-value comes from an analysis of covariance with outcome variable of change in HbA1c from baseline and covariates of treatment, baseline HbA1c, and age.
Superiority
OG004
OG005
Week 52
ANCOVA
0.262
P-value comes from an analysis of covariance with outcome variable of change in HbA1c from baseline and covariates of treatment, baseline HbA1c, and age.
Superiority
OG004
OG005
Week 104
ANCOVA
0.338
P-value comes from an analysis of covariance with outcome variable of change in HbA1c from baseline and covariates of treatment, baseline HbA1c, and age.
Superiority
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.
OG003
Placebo in Adult Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.
OG004
Tocilizumab (TCZ) in Pooled Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.
OG005
Placebo in Pooled Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Units
Counts
Participants
OG00054
OG00127
OG00234
OG00320
OG00488
OG00547
Title
Denominators
Categories
Week 12
Title
Measurements
OG0006.74(6.50 to 6.97)
OG0016.99(6.65 to 7.32)
OG0025.88(5.59 to 6.18)
OG0036.04(5.65 to 6.43)
OG0046.40(6.21 to 6.58)
OG0056.60(6.35 to 6.86)
Week 24
Title
Measurements
OG0006.87(6.65 to 7.10)
OG0017.20(6.88 to 7.52)
OG0026.02(5.71 to 6.34)
OG003
Week 39
Title
Measurements
OG0007.05(6.80 to 7.29)
OG0017.46(7.11 to 7.82)
OG0026.19(5.85 to 6.54)
OG003
Week 52
Title
Measurements
OG0007.20(6.91 to 7.48)
OG0017.69(7.28 to 8.11)
OG0026.34(5.96 to 6.73)
OG003
Week 78
Title
Measurements
OG0007.50(7.10 to 7.90)
OG0018.16(7.57 to 8.74)
OG0026.64(6.17 to 7.11)
OG003
Week 104
Title
Measurements
OG0007.80(7.26 to 8.34)
OG0018.62(7.83 to 9.40)
OG0026.94(6.37 to 7.51)
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Screening to Week 104
Longitudinal mixed model
Random within-subject effects for intercept, study week, and spline week were included assuming an unstructured covariance matrix.
0.493
P-value is for group difference in time trends from a longitudinal mixed effects model. Response variable was HbA1c and covariates were treatment, study week, spline week (at week 4), age, treatment*spline week, treatment*study week, age*study week.
Superiority
OG002
OG003
Screening to Week 104
Longitudinal mixed model
Random within-subject effects for intercept, study week, and spline week were included assuming an unstructured covariance matrix.
0.659
P-value is for group difference in time trends from a longitudinal mixed effects model. Response variable was HbA1c and covariates were treatment, study week, spline week (at week 4), age, treatment*spline week, treatment*study week, age*study week.
Superiority
OG004
OG005
Screening to Week 104
Longitudinal mixed model
Random within-subject effects for intercept, study week, and spline week were included assuming an unstructured covariance matrix.
0.407
P-value is for group difference in time trends from a longitudinal mixed effects model. Response variable was HbA1c and covariates were treatment, study week, spline week (at week 4), age, treatment*spline week, treatment*study week, age*study week.
Superiority
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.
OG003
Placebo in Adult Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.
OG004
Tocilizumab (TCZ) in Pooled Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.
OG005
Placebo in Pooled Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Units
Counts
Participants
OG00054
OG00127
OG00234
OG00320
OG00488
OG00547
Title
Denominators
Categories
Day 0 to Week 52
Title
Measurements
OG00019
OG00111
OG00210
OG0033
OG00429
OG00514
Day 0 to Week 104
Title
Measurements
OG00028
OG00114
OG00215
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Baseline to Week 52
Fisher Exact
0.634
P-value is from comparing the number of participants with a hypoglycemic event between the two treatment groups using Fisher's exact test.
Superiority
OG000
OG001
Baseline to Week 104/End of Study
Fisher Exact
1.000
P-value is from comparing the number of participants with a hypoglycemic event between the two treatment groups using Fisher's exact test.
Superiority
OG002
OG003
Baseline to Week 52
Fisher Exact
0.329
P-value is from comparing the number of participants with a hypoglycemic event between the two treatment groups using Fisher's exact test.
Superiority
OG002
OG003
Baseline to Week 104/End of Study
Fisher Exact
1.000
P-value is from comparing the number of participants with a hypoglycemic event between the two treatment groups using Fisher's exact test.
Superiority
OG004
OG005
Baseline to Week 52
Fisher Exact
0.847
P-value is from comparing the number of participants with a hypoglycemic event between the two treatment groups using Fisher's exact test.
Superiority
OG004
OG005
Baseline to Week 104/End of Study
Fisher Exact
0.858
P-value is from comparing the number of participants with a hypoglycemic event between the two treatment groups using Fisher's exact test.
Superiority
OG003
Placebo in Adult Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.
OG004
Tocilizumab (TCZ) in Pooled Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.
OG005
Placebo in Pooled Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Units
Counts
Participants
OG00054
OG00127
OG00234
OG00320
OG00488
OG00547
Title
Denominators
Categories
Title
Measurements
OG0004
OG0010
OG0025
OG0030
OG0049
OG0050
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Treatment start to Week 52
Fisher Exact
0.296
P-value is from comparing the number of participants with the AEs of interest between the two treatment groups using Fisher's exact test.
Superiority
OG002
OG003
Treatment start to Week 52
Fisher Exact
0.145
P-value is from comparing the number of participants with the AEs of interest between the two treatment groups using Fisher's exact test.
Superiority
OG004
OG005
Treatment start to Week 52
Fisher Exact
0.027
P-value is from comparing the number of participants with the AEs of interest between the two treatment groups using Fisher's exact test.
Superiority
OG003
Placebo in Adult Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.
OG004
Tocilizumab (TCZ) in Pooled Participants
Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight >=30 kg) or 10.0 mg/kg (body weight <30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.
OG005
Placebo in Pooled Participants
Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Units
Counts
Participants
OG00054
OG00127
OG00234
OG00320
OG00488
OG00547
Title
Denominators
Categories
Title
Measurements
OG0003
OG0010
OG0020
OG0030
OG0043
OG0050
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Treatment start to Week 52
Fisher Exact
0.547
P-value is from comparing the number of participants with the AEs of interest between the two treatment groups using Fisher's exact test.
Superiority
OG004
OG005
Treatment start to Week 52
Fisher Exact
0.551
P-value is from comparing the number of participants with the AEs of interest between the two treatment groups using Fisher's exact test.