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EXTEND: Tocilizumab (TCZ) in New-onset Type 1 Diabetes

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
Overall Status
Completed
CT.gov ID
NCT02293837
Collaborator
Immune Tolerance Network (ITN) (Other), PPD (Industry), Rho Federal Systems Division, Inc. (Industry)
136
Enrollment
19
Locations
2
Arms
65.7
Actual Duration (Months)
7.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Tocilizumab (TCZ)
  • Drug: Placebo
  • Other: Standard of Care
 Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
136 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Preserving Beta-Cell Function With Tocilizumab in New-onset Type 1 Diabetes (ITN058AI)
Actual Study Start Date :
Mar 12, 2015
Actual Primary Completion Date :
Jul 10, 2019
Actual Study Completion Date :
Aug 31, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Tocilizumab (TCZ) + SOC

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)
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.
Other Names:
  • Actemra®

    • Other: Standard of Care
    Participants will also receive standard intensive diabetes management (in accordance with the American Diabetes Association guidelines [Standard of Care, SOC])
    Other Names:
  • SOC

    		•
    Placebo Comparator: Tocilizumab Placebo Group + SOC

    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
    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.
    Other Names:
  • Placebo for Tocilizumab

    • Other: Standard of Care
    Participants will also receive standard intensive diabetes management (in accordance with the American Diabetes Association guidelines [Standard of Care, SOC])
    Other Names:
  • SOC

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC) in Pediatric Participants [Baseline (Pre-treatment) to Week 52]

      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.

    Secondary Outcome Measures

    1. Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC) [Baseline (Pre-treatment) to Weeks 24, 52, and 104]

      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.

    2. 2-Hour C-peptide Mean Area Under the Curve (mAUC), Mixed Model [Baseline (Pre-treatment), Weeks 12, 24, 39, 52, 78, and 104]

      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.

    3. Change From Baseline in 4-Hour C-peptide Mean Area Under the Curve (mAUC) [Baseline (Pre-treatment) to Weeks 52 and 104]

      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.

    4. Change From Baseline in Average Insulin Use in Units Per Kilogram Body Weight Per Day [Baseline (Pre-treatment) to Weeks 24, 52, and 104]

      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.

    5. Change From Baseline in Average Insulin Use Per Kg, Mixed Model [Baseline (Pre-treatment) to Weeks 12, 24, 39, 52, 78, and 104]

      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.

    6. Change From Baseline in Hemoglobin A1c [Baseline (Pre-treatment) to Weeks 24, 52, and 104]

      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.

    7. Change From Baseline in Hemoglobin A1C (HbA1c) Level in Participants, Mixed Model [Baseline (Pre-treatment) to Weeks 12, 24, 39, 52, 78, and 104]

      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.

    8. Number of Participants Who Experienced at Least One Major Hypoglycemic Event After Treatment Initiation [Day 0 (Treatment Initiation) to Weeks 52 and 104]

      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

    9. Number of Participants Who Experienced Infusion-Related Adverse Events [Day 0 (Treatment Initiation) to Week 52]

      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.

    10. Number of Participants Who Experienced Hypersensitivity Adverse Events [Day 0 (Treatment Initiation) to Week 52]

      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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    6 Years to 17 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. 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

    1. Diagnosis of type 1 diabetes mellitus (T1DM), using the American Diabetes Association T1DM criteria, within 100 days of study enrollment

    2. Positive for at least one diabetes-related autoantibody, including but not limited to:

    3. Glutamate decarboxylase (GAD-65)

    4. Insulin, if obtained within 10 days of the onset of exogenous insulin therapy

    5. Insulinoma antigen-2 (IA-2)

    6. Zinc transporter-8 (ZnT8)

    7. 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)

    8. Signed informed consent (and informed assent of minor, if applicable).

    Exclusion Criteria:

    1. Severe reaction or anaphylaxis to human, humanized or murine monoclonal antibodies

    2. History of malignancy or serious uncontrolled cardiovascular, nervous system, pulmonary, renal, or gastrointestinal disease, or significant dyslipidemia

    3. Any history of recent serious bacterial, viral, fungal, or other opportunistic infections

    4. Have serologic evidence of current or past HIV (Human immunodeficiency virus), Hepatitis B, or Hepatitis C

    5. Positive QuantiFERON Tuberculosis (TB) test, history of TB, or active TB infection

    6. Active infection with Epstein-Barr virus (EBV) as defined by EBV viral load ≥10,000 copies per mL of whole blood

    7. Active infection with Cytomegalovirus (CMV) as defined by CMV viral load ≥10,000 copies per mL of whole blood

    8. 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

    9. Current or prior treatment that is known to cause a significant, ongoing change in the course of T1D or immunologic status

    10. 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)

    11. Current use of any medication known to significantly influence glucose tolerance (e.g., atypical antipsychotics, diphenylhydantoin, niacin)

    12. Any of the following hematologic abnormalities, confirmed by repeat tests:

    13. White blood count <3,000/microL or >14,000/microL

    14. Lymphocyte count <500/microL

    15. Platelet count <150,000 /microL

    16. Hemoglobin <8.5 g/dL

    17. . Neutrophil count <2,000 cells/microL.

    18. Females who are pregnant, lactating, or planning on pregnancy during the 2- year study period

    19. History or diagnoses of other autoimmune diseases with the exception of stable thyroid or celiac disease

    20. History of alcohol, drug or chemical abuse within 1 year prior to study eligibility screening evaluation

    21. Any medical or psychological condition that in the opinion of the principal investigator would interfere with safe completion of the trial

    22. Prior participation in a clinical trial that could increase risks associated with this clinical trial

    23. Receipt of live vaccine (e.g. varicella, measles, mumps, rubella, cold-attenuated intranasal influenza vaccine, bacillus Calmette-Guérin, and small pox) in the 6 weeks before randomization

    24. High lipid levels (fasting Low-density lipoprotein (LDL) cholesterol ≥160 mg/dL)

    25. History of significant allergy (e.g. anaphylaxis) to milk or soy proteins.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of California San Francisco San Francisco California United States 94143
    2 Stanford University Stanford California United States 94305
    3 Yale University School of Medicine: Diabetes Endocrinology Research Center New Haven Connecticut United States 06519
    4 University of Florida Gainesville Florida United States 32610
    5 University of Miami: Diabetes Research Institute Miami Florida United States 33136
    6 University of South Florida: Diabetes Center Tampa Florida United States 33612
    7 Indiana University Health - Riley Hospital for Children Indianapolis Indiana United States 46202
    8 University of Iowa Iowa City Iowa United States 52242
    9 Harvard University, Joslin Diabetes Center Boston Massachusetts United States 002215
    10 University of Minnesota Minneapolis Minnesota United States 55455
    11 Children's Mercy Hospital Kansas City Missouri United States 64111
    12 Columbia University, Naomi Berrie Diabetes Center New York New York United States 10032
    13 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    14 Sanford Research Sioux Falls South Dakota United States 57104
    15 Vanderbilt University Nashville Tennessee United States 37232
    16 University of Texas Southwestern Medical Center Dallas Texas United States 75390
    17 Benaroya Research Institute Seattle Washington United States 98101
    18 The Children's Hospital at Westmead: Kids Research Institute Westmead New South Wales Australia Westmead 2145
    19 Lady Cilento Children's Hospital: Department of Endocrinology South Brisbane Queensland Australia 4101

    Sponsors and Collaborators

    • National Institute of Allergy and Infectious Diseases (NIAID)
    • Immune Tolerance Network (ITN)
    • PPD
    • Rho Federal Systems Division, Inc.

    Investigators

    • Study Chair: Carla Greenbaum, Benaroya Research Institute at Virginia Mason: Diabetes Research Program
    • Study Chair: Jane Buckner, M.D., Benaroya Research Institute at Virginia Mason: Diabetes Research Program

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    National Institute of Allergy and Infectious Diseases (NIAID)
    ClinicalTrials.gov Identifier:
    NCT02293837
    Other Study ID Numbers:
    • DAIT ITN058AI
    First Posted:
    Nov 18, 2014
    Last Update Posted:
    Sep 8, 2021
    Last Verified:
    Aug 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID)
    interleukin-6 (IL-6) receptor inhibitor
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Diabetes Mellitus, Type 1

    Study Results

    Participant Flow

    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.
    Pre-assignment Detail 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.
    Arm/Group Title Tocilizumab (TCZ) in Pediatric Participants Placebo in Pediatric Participants Tocilizumab (TCZ) in Adult Participants Placebo in Adult Participants
    Arm/Group Description 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive. 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.
    Period Title: Overall Study
    STARTED 54 27 35 20
    COMPLETED 51 23 31 19
    NOT COMPLETED 3 4 4 1

    Baseline Characteristics

    Arm/Group Title Tocilizumab (TCZ) in Pediatric Participants Placebo in Pediatric Participants Tocilizumab (TCZ) in Adult Participants Placebo in Adult Participants Total
    Arm/Group Description 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive. 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive. Total of all reporting groups
    Overall Participants 54 27 35 20 136
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    11.1
    (2.9)
    11.1
    (2.5)
    27.9
    (7.4)
    29.2
    (9.3)
    18.1
    (10.2)
    Sex: Female, Male (Count of Participants)
    Female
    26
    48.1%
    12
    44.4%
    12
    34.3%
    7
    35%
    57
    41.9%
    Male
    28
    51.9%
    15
    55.6%
    23
    65.7%
    13
    65%
    79
    58.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    1.9%
    4
    14.8%
    3
    8.6%
    1
    5%
    9
    6.6%
    Not Hispanic or Latino
    53
    98.1%
    21
    77.8%
    32
    91.4%
    19
    95%
    125
    91.9%
    Unknown or Not Reported
    0
    0%
    2
    7.4%
    0
    0%
    0
    0%
    2
    1.5%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    1
    3.7%
    1
    2.9%
    0
    0%
    2
    1.5%
    Asian
    1
    1.9%
    2
    7.4%
    0
    0%
    1
    5%
    4
    2.9%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    3.7%
    0
    0%
    1
    2.9%
    0
    0%
    3
    2.2%
    White
    47
    87%
    20
    74.1%
    32
    91.4%
    19
    95%
    118
    86.8%
    More than one race
    2
    3.7%
    2
    7.4%
    1
    2.9%
    0
    0%
    5
    3.7%
    Unknown or Not Reported
    2
    3.7%
    2
    7.4%
    0
    0%
    0
    0%
    4
    2.9%
    Region of Enrollment (Count of Participants)
    United States
    52
    96.3%
    24
    88.9%
    35
    100%
    20
    100%
    131
    96.3%
    Australia
    2
    3.7%
    3
    11.1%
    0
    0%
    0
    0%
    5
    3.7%
    Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    19.8
    (3.8)
    19.1
    (3.3)
    24.2
    (3.9)
    25.4
    (3.5)
    21.6
    (4.4)
    2-hour C-peptide Mean Area Under the Curve (mAUC) Result in Response to Standardized Mixed Meal Tol (pmol/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [pmol/mL]
    0.73
    (0.44)
    0.66
    (0.32)
    0.77
    (0.24)
    0.97
    (0.69)
    0.76
    (0.43)
    Hemoglobin A1C (HbA1c) Level (percent (%)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percent (%)]
    6.79
    (1.03)
    6.86
    (0.55)
    6.48
    (1.08)
    6.28
    (0.73)
    6.65
    (0.94)
    Average Insulin Use Per Kilogram Body Weight (Units per Kilogram Body Weight per Day) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Units per Kilogram Body Weight per Day]
    0.39
    (0.24)
    0.38
    (0.19)
    0.28
    (0.15)
    0.30
    (0.21)
    0.35
    (0.21)
    Days from Type 1 Diabetes Mellitus (T1DM) Diagnosis to Randomization (Days) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Days]
    85.9
    (15.5)
    83.9
    (16.7)
    82.5
    (13.6)
    84.6
    (12.4)
    84.4
    (14.7)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC) in Pediatric Participants
    Description 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.
    Time Frame Baseline (Pre-treatment) to Week 52

    Outcome Measure Data

    Analysis Population Description
    The modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.
    Arm/Group Title Tocilizumab (TCZ) in Pediatric Participants Placebo in Pediatric Participants
    Arm/Group Description 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.
    Measure Participants 54 27
    Least Squares Mean (95% Confidence Interval) [pmol/mL]
    -0.337
    -0.391
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pediatric Participants, Placebo in Pediatric Participants
    Comments Week 52; Primary imputation method used for missing Week 52 mAUC.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.277
    Comments 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.
    Method ANCOVA
    Comments
    2. Secondary Outcome
    Title Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC)
    Description 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.
    Time Frame Baseline (Pre-treatment) to Weeks 24, 52, and 104

    Outcome Measure Data

    Analysis Population Description
    Modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.
    Arm/Group Title Tocilizumab (TCZ) in Pediatric Participants Placebo in Pediatric Participants Tocilizumab (TCZ) in Adult Participants Placebo in Adult Participants Tocilizumab (TCZ) in Pooled Participants Placebo in Pooled Participants
    Arm/Group Description 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive. 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive. 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. 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.
    Measure Participants 54 27 34 20 88 47
    Week 24
    -0.200
    -0.164
    -0.072
    -0.097
    -0.152
    -0.134
    Week 52
    -0.339
    -0.397
    -0.186
    -0.267
    -0.287
    -0.328
    Week 104
    -0.495
    -0.556
    -0.384
    -0.388
    -0.461
    -0.463
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pediatric Participants, Placebo in Pediatric Participants
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.499
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pediatric Participants, Placebo in Pediatric Participants
    Comments Week 52
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.267
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pediatric Participants, Placebo in Pediatric Participants
    Comments Week 104
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.226
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Adult Participants, Placebo in Adult Participants
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.758
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Adult Participants, Placebo in Adult Participants
    Comments Week 52
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.341
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Adult Participants, Placebo in Adult Participants
    Comments Week 104
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.969
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pooled Participants, Placebo in Pooled Participants
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.689
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pooled Participants, Placebo in Pooled Participants
    Comments Week 52
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.400
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pooled Participants, Placebo in Pooled Participants
    Comments Week 104
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.969
    Comments 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.
    Method ANCOVA
    Comments
    3. Secondary Outcome
    Title 2-Hour C-peptide Mean Area Under the Curve (mAUC), Mixed Model
    Description 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.
    Time Frame Baseline (Pre-treatment), Weeks 12, 24, 39, 52, 78, and 104

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Tocilizumab (TCZ) in Pediatric Participants Placebo in Pediatric Participants Tocilizumab (TCZ) in Adult Participants Placebo in Adult Participants Tocilizumab (TCZ) in Pooled Participants Placebo in Pooled Participants
    Arm/Group Description 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive. 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive. 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. 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.
    Measure Participants 54 26 34 20 88 46
    Week 12
    0.60
    0.55
    0.72
    0.88
    0.65
    0.69
    Week 24
    0.55
    0.49
    0.68
    0.83
    0.60
    0.63
    Week 39
    0.48
    0.42
    0.63
    0.77
    0.54
    0.56
    Week 52
    0.42
    0.35
    0.59
    0.72
    0.49
    0.50
    Week 78
    0.30
    0.23
    0.50
    0.61
    0.38
    0.38
    Week 104
    0.18
    0.10
    0.41
    0.50
    0.27
    0.27
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pediatric Participants, Placebo in Pediatric Participants
    Comments Screening to Week 104
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.679
    Comments 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.
    Method Longitudinal mixed model
    Comments Random within-subject effects for intercept and study week were included assuming an unstructured covariance matrix.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Adult Participants, Placebo in Adult Participants
    Comments Screening to Week 104
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.373
    Comments 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.
    Method Longitudinal mixed model
    Comments Random within-subject effects for intercept and study week were included assuming an unstructured covariance matrix.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pooled Participants, Placebo in Pooled Participants
    Comments Screening to Week 104
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.395
    Comments 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.
    Method Longitudinal mixed model
    Comments Random within-subject effects for intercept and study week were included assuming an unstructured covariance matrix.
    4. Secondary Outcome
    Title Change From Baseline in 4-Hour C-peptide Mean Area Under the Curve (mAUC)
    Description 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.
    Time Frame Baseline (Pre-treatment) to Weeks 52 and 104

    Outcome Measure Data

    Analysis Population Description
    The modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.
    Arm/Group Title Tocilizumab (TCZ) in Pediatric Participants Placebo in Pediatric Participants Tocilizumab (TCZ) in Adult Participants Placebo in Adult Participants Tocilizumab (TCZ) in Pooled Participants Placebo in Pooled Participants
    Arm/Group Description 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive. 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive. 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. 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.
    Measure Participants 54 27 34 20 88 47
    Week 52
    -0.325
    -0.448
    -0.195
    -0.262
    -0.252
    -0.321
    Week 104
    -0.521
    -0.635
    -0.382
    -0.390
    -0.449
    -0.448
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pediatric Participants, Placebo in Pediatric Participants
    Comments Week 52. Only participants >=12 years old had the 4-hour MMTT performed.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.176
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pediatric Participants, Placebo in Pediatric Participants
    Comments Week 104. Only participants >=12 years old had the 4-hour MMTT performed.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.285
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Adult Participants, Placebo in Adult Participants
    Comments Week 52
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.435
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Adult Participants, Placebo in Adult Participants
    Comments Week 104
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.931
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pooled Participants, Placebo in Pooled Participants
    Comments Week 52. Only participants >=12 years old had the 4-hour MMTT performed.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.280
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pooled Participants, Placebo in Pooled Participants
    Comments Week 104. Only participants >=12 years old had the 4-hour MMTT performed.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.985
    Comments 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.
    Method ANCOVA
    Comments
    5. Secondary Outcome
    Title Change From Baseline in Average Insulin Use in Units Per Kilogram Body Weight Per Day
    Description 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.
    Time Frame Baseline (Pre-treatment) to Weeks 24, 52, and 104

    Outcome Measure Data

    Analysis Population Description
    The modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.
    Arm/Group Title Tocilizumab (TCZ) in Pediatric Participants Placebo in Pediatric Participants Tocilizumab (TCZ) in Adult Participants Placebo in Adult Participants Tocilizumab (TCZ) in Pooled Participants Placebo in Pooled Participants
    Arm/Group Description 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive. 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive. 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. 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.
    Measure Participants 54 27 34 20 88 47
    Week 24
    0.139
    0.126
    0.015
    0.146
    0.090
    0.139
    Week 52
    0.300
    0.326
    0.081
    0.112
    0.211
    0.243
    Week 104
    0.403
    0.493
    0.116
    0.129
    0.288
    0.354
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pediatric Participants, Placebo in Pediatric Participants
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.762
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pediatric Participants, Placebo in Pediatric Participants
    Comments Week 52
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.640
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pediatric Participants, Placebo in Pediatric Participants
    Comments Week 104
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.145
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Adult Participants, Placebo in Adult Participants
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.033
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Adult Participants, Placebo in Adult Participants
    Comments Week 52
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.591
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Adult Participants, Placebo in Adult Participants
    Comments Week 104
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.810
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pooled Participants, Placebo in Pooled Participants
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.178
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pooled Participants, Placebo in Pooled Participants
    Comments Week 52
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.430
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pooled Participants, Placebo in Pooled Participants
    Comments Week 104
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.149
    Comments 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.
    Method ANCOVA
    Comments
    6. Secondary Outcome
    Title Change From Baseline in Average Insulin Use Per Kg, Mixed Model
    Description 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.
    Time Frame Baseline (Pre-treatment) to Weeks 12, 24, 39, 52, 78, and 104

    Outcome Measure Data

    Analysis Population Description
    The modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.
    Arm/Group Title Tocilizumab (TCZ) in Pediatric Participants Placebo in Pediatric Participants Tocilizumab (TCZ) in Adult Participants Placebo in Adult Participants Tocilizumab (TCZ) in Pooled Participants Placebo in Pooled Participants
    Arm/Group Description 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive. 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive. 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. 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.
    Measure Participants 54 27 34 20 88 47
    Week 12
    0.45
    0.45
    0.29
    0.37
    0.39
    0.42
    Week 24
    0.50
    0.51
    0.31
    0.40
    0.43
    0.47
    Week 39
    0.57
    0.59
    0.33
    0.43
    0.47
    0.53
    Week 52
    0.62
    0.66
    0.35
    0.46
    0.51
    0.58
    Week 78
    0.73
    0.80
    0.39
    0.51
    0.60
    0.68
    Week 104
    0.84
    0.94
    0.43
    0.57
    0.68
    0.79
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pediatric Participants, Placebo in Pediatric Participants
    Comments Screening to Week 104
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.103
    Comments 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.
    Method Longitudinal mixed model
    Comments Random within-subject effects for intercept and study week were included assuming an unstructured covariance matrix.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Adult Participants, Placebo in Adult Participants
    Comments Screening to Week 104
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.452
    Comments 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.
    Method Longitudinal mixed model
    Comments Random within-subject effects for intercept and study week were included assuming an unstructured covariance matrix.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pooled Participants, Placebo in Pooled Participants
    Comments Screening to Week 104
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.091
    Comments 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.
    Method Longitudinal mixed model
    Comments Random within-subject effects for intercept and study week were included assuming an unstructured covariance matrix.
    7. Secondary Outcome
    Title Change From Baseline in Hemoglobin A1c
    Description 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.
    Time Frame Baseline (Pre-treatment) to Weeks 24, 52, and 104

    Outcome Measure Data

    Analysis Population Description
    The modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.
    Arm/Group Title Tocilizumab (TCZ) in Pediatric Participants Placebo in Pediatric Participants Tocilizumab (TCZ) in Adult Participants Placebo in Adult Participants Tocilizumab (TCZ) in Pooled Participants Placebo in Pooled Participants
    Arm/Group Description 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive. 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive. 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. 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.
    Measure Participants 54 27 34 20 88 47
    Week 24
    0.065
    0.368
    -0.509
    -0.136
    -0.163
    0.169
    Week 52
    0.650
    1.134
    0.152
    0.262
    0.459
    0.753
    Week 104
    0.734
    1.042
    0.253
    0.583
    0.556
    0.812
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pediatric Participants, Placebo in Pediatric Participants
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.154
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pediatric Participants, Placebo in Pediatric Participants
    Comments Week 52
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.193
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pediatric Participants, Placebo in Pediatric Participants
    Comments Week 104
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.397
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Adult Participants, Placebo in Adult Participants
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.125
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Adult Participants, Placebo in Adult Participants
    Comments Week 52
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.705
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Adult Participants, Placebo in Adult Participants
    Comments Week 104
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.378
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pooled Participants, Placebo in Pooled Participants
    Comments Week 24
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.035
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pooled Participants, Placebo in Pooled Participants
    Comments Week 52
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.262
    Comments 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.
    Method ANCOVA
    Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pooled Participants, Placebo in Pooled Participants
    Comments Week 104
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.338
    Comments 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.
    Method ANCOVA
    Comments
    8. Secondary Outcome
    Title Change From Baseline in Hemoglobin A1C (HbA1c) Level in Participants, Mixed Model
    Description 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.
    Time Frame Baseline (Pre-treatment) to Weeks 12, 24, 39, 52, 78, and 104

    Outcome Measure Data

    Analysis Population Description
    The modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.
    Arm/Group Title Tocilizumab (TCZ) in Pediatric Participants Placebo in Pediatric Participants Tocilizumab (TCZ) in Adult Participants Placebo in Adult Participants Tocilizumab (TCZ) in Pooled Participants Placebo in Pooled Participants
    Arm/Group Description 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive. 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive. 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. 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.
    Measure Participants 54 27 34 20 88 47
    Week 12
    6.74
    6.99
    5.88
    6.04
    6.40
    6.60
    Week 24
    6.87
    7.20
    6.02
    6.19
    6.54
    6.79
    Week 39
    7.05
    7.46
    6.19
    6.38
    6.71
    7.02
    Week 52
    7.20
    7.69
    6.34
    6.54
    6.86
    7.23
    Week 78
    7.50
    8.16
    6.64
    6.86
    7.16
    7.63
    Week 104
    7.80
    8.62
    6.94
    7.19
    7.45
    8.04
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pediatric Participants, Placebo in Pediatric Participants
    Comments Screening to Week 104
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.493
    Comments 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.
    Method Longitudinal mixed model
    Comments Random within-subject effects for intercept, study week, and spline week were included assuming an unstructured covariance matrix.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Adult Participants, Placebo in Adult Participants
    Comments Screening to Week 104
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.659
    Comments 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.
    Method Longitudinal mixed model
    Comments Random within-subject effects for intercept, study week, and spline week were included assuming an unstructured covariance matrix.
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pooled Participants, Placebo in Pooled Participants
    Comments Screening to Week 104
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.407
    Comments 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.
    Method Longitudinal mixed model
    Comments Random within-subject effects for intercept, study week, and spline week were included assuming an unstructured covariance matrix.
    9. Secondary Outcome
    Title Number of Participants Who Experienced at Least One Major Hypoglycemic Event After Treatment Initiation
    Description 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
    Time Frame Day 0 (Treatment Initiation) to Weeks 52 and 104

    Outcome Measure Data

    Analysis Population Description
    The safety population includes all participants who received any degree of study treatment. Safety analyses are based on actual treatment the participants receive.
    Arm/Group Title Tocilizumab (TCZ) in Pediatric Participants Placebo in Pediatric Participants Tocilizumab (TCZ) in Adult Participants Placebo in Adult Participants Tocilizumab (TCZ) in Pooled Participants Placebo in Pooled Participants
    Arm/Group Description 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive. 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive. 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. 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.
    Measure Participants 54 27 34 20 88 47
    Day 0 to Week 52
    19
    35.2%
    11
    40.7%
    10
    28.6%
    3
    15%
    29
    21.3%
    14
    NaN
    Day 0 to Week 104
    28
    51.9%
    14
    51.9%
    15
    42.9%
    8
    40%
    43
    31.6%
    22
    NaN
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pediatric Participants, Placebo in Pediatric Participants
    Comments Baseline to Week 52
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.634
    Comments P-value is from comparing the number of participants with a hypoglycemic event between the two treatment groups using Fisher's exact test.
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pediatric Participants, Placebo in Pediatric Participants
    Comments Baseline to Week 104/End of Study
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.000
    Comments P-value is from comparing the number of participants with a hypoglycemic event between the two treatment groups using Fisher's exact test.
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Adult Participants, Placebo in Adult Participants
    Comments Baseline to Week 52
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.329
    Comments P-value is from comparing the number of participants with a hypoglycemic event between the two treatment groups using Fisher's exact test.
    Method Fisher Exact
    Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Adult Participants, Placebo in Adult Participants
    Comments Baseline to Week 104/End of Study
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 1.000
    Comments P-value is from comparing the number of participants with a hypoglycemic event between the two treatment groups using Fisher's exact test.
    Method Fisher Exact
    Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pooled Participants, Placebo in Pooled Participants
    Comments Baseline to Week 52
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.847
    Comments P-value is from comparing the number of participants with a hypoglycemic event between the two treatment groups using Fisher's exact test.
    Method Fisher Exact
    Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pooled Participants, Placebo in Pooled Participants
    Comments Baseline to Week 104/End of Study
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.858
    Comments P-value is from comparing the number of participants with a hypoglycemic event between the two treatment groups using Fisher's exact test.
    Method Fisher Exact
    Comments
    10. Secondary Outcome
    Title Number of Participants Who Experienced Infusion-Related Adverse Events
    Description 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.
    Time Frame Day 0 (Treatment Initiation) to Week 52

    Outcome Measure Data

    Analysis Population Description
    The safety population includes all participants who received any degree of study treatment. Safety analyses are based on actual treatment the participants receive.
    Arm/Group Title Tocilizumab (TCZ) in Pediatric Participants Placebo in Pediatric Participants Tocilizumab (TCZ) in Adult Participants Placebo in Adult Participants Tocilizumab (TCZ) in Pooled Participants Placebo in Pooled Participants
    Arm/Group Description 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive. 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive. 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. 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.
    Measure Participants 54 27 34 20 88 47
    Number [Participants]
    4
    7.4%
    0
    0%
    5
    14.3%
    0
    0%
    9
    6.6%
    0
    NaN
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pediatric Participants, Placebo in Pediatric Participants
    Comments Treatment start to Week 52
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.296
    Comments P-value is from comparing the number of participants with the AEs of interest between the two treatment groups using Fisher's exact test.
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Adult Participants, Placebo in Adult Participants
    Comments Treatment start to Week 52
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.145
    Comments P-value is from comparing the number of participants with the AEs of interest between the two treatment groups using Fisher's exact test.
    Method Fisher Exact
    Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pooled Participants, Placebo in Pooled Participants
    Comments Treatment start to Week 52
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.027
    Comments P-value is from comparing the number of participants with the AEs of interest between the two treatment groups using Fisher's exact test.
    Method Fisher Exact
    Comments
    11. Secondary Outcome
    Title Number of Participants Who Experienced Hypersensitivity Adverse Events
    Description 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
    Time Frame Day 0 (Treatment Initiation) to Week 52

    Outcome Measure Data

    Analysis Population Description
    The safety population includes all participants who received any degree of study treatment. Safety analyses are based on actual treatment the participants receive.
    Arm/Group Title Tocilizumab (TCZ) in Pediatric Participants Placebo in Pediatric Participants Tocilizumab (TCZ) in Adult Participants Placebo in Adult Participants Tocilizumab (TCZ) in Pooled Participants Placebo in Pooled Participants
    Arm/Group Description 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive. 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive. 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. 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.
    Measure Participants 54 27 34 20 88 47
    Number [Participants]
    3
    5.6%
    0
    0%
    0
    0%
    0
    0%
    3
    2.2%
    0
    NaN
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pediatric Participants, Placebo in Pediatric Participants
    Comments Treatment start to Week 52
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.547
    Comments P-value is from comparing the number of participants with the AEs of interest between the two treatment groups using Fisher's exact test.
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tocilizumab (TCZ) in Pooled Participants, Placebo in Pooled Participants
    Comments Treatment start to Week 52
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.551
    Comments P-value is from comparing the number of participants with the AEs of interest between the two treatment groups using Fisher's exact test.
    Method Fisher Exact
    Comments

    Adverse Events

    Time Frame Up to 104 weeks.
    Adverse Event Reporting Description
    Arm/Group Title Tocilizumab (TCZ) in Pediatric Participants Placebo in Pediatric Participants Tocilizumab (TCZ) in Adult Participants Placebo in Adult Participants Tocilizumab (TCZ) in Pooled Participants Placebo in Pooled Participants
    Arm/Group Description 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive. 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. Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive. 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. 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.
    All Cause Mortality
    Tocilizumab (TCZ) in Pediatric Participants Placebo in Pediatric Participants Tocilizumab (TCZ) in Adult Participants Placebo in Adult Participants Tocilizumab (TCZ) in Pooled Participants Placebo in Pooled Participants
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/54 (0%) 0/27 (0%) 0/34 (0%) 0/20 (0%) 0/88 (0%) 0/27 (0%)
    Serious Adverse Events
    Tocilizumab (TCZ) in Pediatric Participants Placebo in Pediatric Participants Tocilizumab (TCZ) in Adult Participants Placebo in Adult Participants Tocilizumab (TCZ) in Pooled Participants Placebo in Pooled Participants
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/54 (5.6%) 3/27 (11.1%) 2/34 (5.9%) 2/20 (10%) 5/88 (5.7%) 5/47 (10.6%)
    General disorders
    Vaccination site reaction 0/54 (0%) 0 1/27 (3.7%) 1 0/34 (0%) 0 0/20 (0%) 0 0/88 (0%) 0 1/47 (2.1%) 1
    Infections and infestations
    Gastroenteritis 1/54 (1.9%) 1 0/27 (0%) 0 0/34 (0%) 0 0/20 (0%) 0 1/88 (1.1%) 1 0/47 (0%) 0
    Infectious mononucleosis 1/54 (1.9%) 1 0/27 (0%) 0 0/34 (0%) 0 0/20 (0%) 0 1/88 (1.1%) 1 0/47 (0%) 0
    Injury, poisoning and procedural complications
    Forearm fracture 1/54 (1.9%) 1 0/27 (0%) 0 0/34 (0%) 0 0/20 (0%) 0 1/88 (1.1%) 1 0/47 (0%) 0
    Metabolism and nutrition disorders
    Hyperglycaemia 0/54 (0%) 0 1/27 (3.7%) 1 0/34 (0%) 0 0/20 (0%) 0 0/88 (0%) 0 1/47 (2.1%) 1
    Hypoglycaemia 0/54 (0%) 0 0/27 (0%) 0 1/34 (2.9%) 1 1/20 (5%) 1 1/88 (1.1%) 1 1/47 (2.1%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous cell carcinoma 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Nervous system disorders
    Thoracic outlet syndrome 0/54 (0%) 0 0/27 (0%) 0 1/34 (2.9%) 1 0/20 (0%) 0 1/88 (1.1%) 1 0/47 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Sleep apnoea syndrome 0/54 (0%) 0 1/27 (3.7%) 1 0/34 (0%) 0 0/20 (0%) 0 0/88 (0%) 0 1/47 (2.1%) 1
    Vascular disorders
    Deep vein thrombosis 0/54 (0%) 0 0/27 (0%) 0 1/34 (2.9%) 1 0/20 (0%) 0 1/88 (1.1%) 1 0/47 (0%) 0
    Other (Not Including Serious) Adverse Events
    Tocilizumab (TCZ) in Pediatric Participants Placebo in Pediatric Participants Tocilizumab (TCZ) in Adult Participants Placebo in Adult Participants Tocilizumab (TCZ) in Pooled Participants Placebo in Pooled Participants
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 52/54 (96.3%) 26/27 (96.3%) 31/34 (91.2%) 19/20 (95%) 83/88 (94.3%) 45/47 (95.7%)
    Blood and lymphatic system disorders
    Anaemia 1/54 (1.9%) 1 0/27 (0%) 0 1/34 (2.9%) 1 1/20 (5%) 1 2/88 (2.3%) 2 1/47 (2.1%) 1
    Splenomegaly 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Cardiac disorders
    Palpitations 0/54 (0%) 0 0/27 (0%) 0 1/34 (2.9%) 2 1/20 (5%) 1 1/88 (1.1%) 2 1/47 (2.1%) 1
    Endocrine disorders
    Basedow's disease 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Eye disorders
    Eye irritation 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Gastrointestinal disorders
    Abdominal distension 1/54 (1.9%) 1 0/27 (0%) 0 1/34 (2.9%) 1 1/20 (5%) 1 2/88 (2.3%) 2 1/47 (2.1%) 1
    Abdominal pain 2/54 (3.7%) 3 3/27 (11.1%) 4 0/34 (0%) 0 1/20 (5%) 1 2/88 (2.3%) 3 4/47 (8.5%) 5
    Abdominal pain upper 5/54 (9.3%) 7 3/27 (11.1%) 4 2/34 (5.9%) 2 0/20 (0%) 0 7/88 (8%) 9 3/47 (6.4%) 4
    Constipation 3/54 (5.6%) 3 4/27 (14.8%) 4 1/34 (2.9%) 1 0/20 (0%) 0 4/88 (4.5%) 4 4/47 (8.5%) 4
    Dental caries 2/54 (3.7%) 2 0/27 (0%) 0 0/34 (0%) 0 2/20 (10%) 2 2/88 (2.3%) 2 2/47 (4.3%) 2
    Diarrhoea 4/54 (7.4%) 5 1/27 (3.7%) 1 4/34 (11.8%) 4 3/20 (15%) 3 8/88 (9.1%) 9 4/47 (8.5%) 4
    Dyspepsia 3/54 (5.6%) 3 4/27 (14.8%) 4 1/34 (2.9%) 1 2/20 (10%) 3 4/88 (4.5%) 4 6/47 (12.8%) 7
    Food poisoning 1/54 (1.9%) 1 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 1/88 (1.1%) 1 1/47 (2.1%) 1
    Gastritis 3/54 (5.6%) 4 0/27 (0%) 0 0/34 (0%) 0 0/20 (0%) 0 3/88 (3.4%) 4 0/47 (0%) 0
    Gastrooesophageal reflux disease 0/54 (0%) 0 1/27 (3.7%) 1 2/34 (5.9%) 2 0/20 (0%) 0 2/88 (2.3%) 2 1/47 (2.1%) 1
    Haemorrhoids 0/54 (0%) 0 0/27 (0%) 0 1/34 (2.9%) 1 1/20 (5%) 1 1/88 (1.1%) 1 1/47 (2.1%) 1
    Nausea 13/54 (24.1%) 20 4/27 (14.8%) 11 5/34 (14.7%) 8 2/20 (10%) 2 18/88 (20.5%) 28 6/47 (12.8%) 13
    Vomiting 10/54 (18.5%) 16 6/27 (22.2%) 7 4/34 (11.8%) 4 1/20 (5%) 1 14/88 (15.9%) 20 7/47 (14.9%) 8
    General disorders
    Adverse drug reaction 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Fatigue 0/54 (0%) 0 2/27 (7.4%) 2 1/34 (2.9%) 1 2/20 (10%) 2 1/88 (1.1%) 1 4/47 (8.5%) 4
    Influenza like illness 1/54 (1.9%) 1 3/27 (11.1%) 5 2/34 (5.9%) 3 2/20 (10%) 2 3/88 (3.4%) 4 5/47 (10.6%) 7
    Pain 1/54 (1.9%) 1 2/27 (7.4%) 2 0/34 (0%) 0 1/20 (5%) 1 1/88 (1.1%) 1 3/47 (6.4%) 3
    Pyrexia 7/54 (13%) 9 4/27 (14.8%) 5 1/34 (2.9%) 1 0/20 (0%) 0 8/88 (9.1%) 10 4/47 (8.5%) 5
    Temperature intolerance 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Immune system disorders
    Seasonal allergy 6/54 (11.1%) 7 2/27 (7.4%) 3 0/34 (0%) 0 2/20 (10%) 2 6/88 (6.8%) 7 4/47 (8.5%) 5
    Infections and infestations
    Bronchitis 2/54 (3.7%) 2 1/27 (3.7%) 1 2/34 (5.9%) 2 0/20 (0%) 0 4/88 (4.5%) 4 1/47 (2.1%) 1
    Ear infection 4/54 (7.4%) 4 0/27 (0%) 0 0/34 (0%) 0 0/20 (0%) 0 4/88 (4.5%) 4 0/47 (0%) 0
    Epstein-Barr virus infection 0/54 (0%) 0 0/27 (0%) 0 2/34 (5.9%) 2 1/20 (5%) 1 2/88 (2.3%) 2 1/47 (2.1%) 1
    Gastroenteritis 9/54 (16.7%) 9 3/27 (11.1%) 3 6/34 (17.6%) 6 2/20 (10%) 6 15/88 (17%) 15 5/47 (10.6%) 9
    Gastroenteritis viral 3/54 (5.6%) 4 0/27 (0%) 0 1/34 (2.9%) 1 1/20 (5%) 1 4/88 (4.5%) 5 1/47 (2.1%) 1
    Influenza 8/54 (14.8%) 8 5/27 (18.5%) 5 1/34 (2.9%) 1 2/20 (10%) 2 9/88 (10.2%) 9 7/47 (14.9%) 7
    Nasopharyngitis 7/54 (13%) 10 4/27 (14.8%) 6 5/34 (14.7%) 10 2/20 (10%) 2 12/88 (13.6%) 20 6/47 (12.8%) 8
    Oral herpes 1/54 (1.9%) 2 1/27 (3.7%) 1 2/34 (5.9%) 2 0/20 (0%) 0 3/88 (3.4%) 4 1/47 (2.1%) 1
    Otitis externa 3/54 (5.6%) 3 0/27 (0%) 0 0/34 (0%) 0 0/20 (0%) 0 3/88 (3.4%) 3 0/47 (0%) 0
    Otitis media 3/54 (5.6%) 4 2/27 (7.4%) 2 0/34 (0%) 0 1/20 (5%) 1 3/88 (3.4%) 4 3/47 (6.4%) 3
    Pharyngitis 5/54 (9.3%) 6 3/27 (11.1%) 4 4/34 (11.8%) 4 0/20 (0%) 0 9/88 (10.2%) 10 3/47 (6.4%) 4
    Pharyngitis streptococcal 6/54 (11.1%) 6 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 2 6/88 (6.8%) 6 1/47 (2.1%) 2
    Pneumonia mycoplasmal 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Respiratory tract infection 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Rhinitis 2/54 (3.7%) 2 2/27 (7.4%) 3 0/34 (0%) 0 0/20 (0%) 0 2/88 (2.3%) 2 2/47 (4.3%) 3
    Sinusitis 5/54 (9.3%) 11 1/27 (3.7%) 3 4/34 (11.8%) 4 0/20 (0%) 0 9/88 (10.2%) 15 1/47 (2.1%) 3
    Skin infection 1/54 (1.9%) 1 2/27 (7.4%) 2 1/34 (2.9%) 1 0/20 (0%) 0 2/88 (2.3%) 2 2/47 (4.3%) 2
    Upper respiratory tract infection 26/54 (48.1%) 82 13/27 (48.1%) 35 15/34 (44.1%) 42 12/20 (60%) 30 41/88 (46.6%) 124 25/47 (53.2%) 65
    Urinary tract infection 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Viral infection 0/54 (0%) 0 2/27 (7.4%) 2 1/34 (2.9%) 1 0/20 (0%) 0 1/88 (1.1%) 1 2/47 (4.3%) 2
    Viral upper respiratory tract infection 0/54 (0%) 0 1/27 (3.7%) 1 5/34 (14.7%) 6 3/20 (15%) 3 5/88 (5.7%) 6 4/47 (8.5%) 4
    Vulvovaginal mycotic infection 1/54 (1.9%) 1 0/27 (0%) 0 2/34 (5.9%) 2 0/20 (0%) 0 3/88 (3.4%) 3 0/47 (0%) 0
    Injury, poisoning and procedural complications
    Concussion 0/54 (0%) 0 2/27 (7.4%) 2 0/34 (0%) 0 0/20 (0%) 0 0/88 (0%) 0 2/47 (4.3%) 2
    Contusion 2/54 (3.7%) 2 2/27 (7.4%) 2 0/34 (0%) 0 0/20 (0%) 0 2/88 (2.3%) 2 2/47 (4.3%) 2
    Fall 0/54 (0%) 0 1/27 (3.7%) 1 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 2/47 (4.3%) 2
    Hand fracture 1/54 (1.9%) 1 1/27 (3.7%) 1 0/34 (0%) 0 1/20 (5%) 1 1/88 (1.1%) 1 2/47 (4.3%) 2
    Head injury 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Joint injury 0/54 (0%) 0 2/27 (7.4%) 2 1/34 (2.9%) 1 0/20 (0%) 0 1/88 (1.1%) 1 2/47 (4.3%) 2
    Ligament sprain 2/54 (3.7%) 2 2/27 (7.4%) 2 0/34 (0%) 0 0/20 (0%) 0 2/88 (2.3%) 2 2/47 (4.3%) 2
    Limb injury 3/54 (5.6%) 6 0/27 (0%) 0 1/34 (2.9%) 1 0/20 (0%) 0 4/88 (4.5%) 7 0/47 (0%) 0
    Muscle strain 1/54 (1.9%) 1 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 1/88 (1.1%) 1 1/47 (2.1%) 1
    Sunburn 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Traumatic haematoma 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Investigations
    Aspartate aminotransferase increased 0/54 (0%) 0 0/27 (0%) 0 1/34 (2.9%) 1 1/20 (5%) 1 1/88 (1.1%) 1 1/47 (2.1%) 1
    Body mass index increased 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Neutrophil count decreased 2/54 (3.7%) 2 0/27 (0%) 0 3/34 (8.8%) 5 0/20 (0%) 0 5/88 (5.7%) 7 0/47 (0%) 0
    Weight decreased 0/54 (0%) 0 2/27 (7.4%) 2 2/34 (5.9%) 2 0/20 (0%) 0 2/88 (2.3%) 2 2/47 (4.3%) 2
    Metabolism and nutrition disorders
    Hypoglycaemia 28/54 (51.9%) 85 14/27 (51.9%) 47 15/34 (44.1%) 42 7/20 (35%) 11 43/88 (48.9%) 127 21/47 (44.7%) 58
    Hyponatraemia 0/54 (0%) 0 0/27 (0%) 0 1/34 (2.9%) 1 1/20 (5%) 1 1/88 (1.1%) 1 1/47 (2.1%) 1
    Hypophosphataemia 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 3/54 (5.6%) 4 0/27 (0%) 0 4/34 (11.8%) 4 4/20 (20%) 8 7/88 (8%) 8 4/47 (8.5%) 8
    Back pain 1/54 (1.9%) 1 1/27 (3.7%) 1 4/34 (11.8%) 4 2/20 (10%) 2 5/88 (5.7%) 5 3/47 (6.4%) 3
    Muscle spasms 1/54 (1.9%) 1 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 1/88 (1.1%) 1 1/47 (2.1%) 1
    Musculoskeletal pain 2/54 (3.7%) 2 0/27 (0%) 0 2/34 (5.9%) 2 2/20 (10%) 2 4/88 (4.5%) 4 2/47 (4.3%) 2
    Myalgia 4/54 (7.4%) 4 1/27 (3.7%) 2 3/34 (8.8%) 3 2/20 (10%) 5 7/88 (8%) 7 3/47 (6.4%) 7
    Neck pain 3/54 (5.6%) 4 1/27 (3.7%) 1 0/34 (0%) 0 0/20 (0%) 0 3/88 (3.4%) 4 1/47 (2.1%) 1
    Pain in extremity 2/54 (3.7%) 3 0/27 (0%) 0 2/34 (5.9%) 2 1/20 (5%) 1 4/88 (4.5%) 5 1/47 (2.1%) 1
    Synovial cyst 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Temporomandibular joint syndrome 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Tendonitis 1/54 (1.9%) 1 0/27 (0%) 0 2/34 (5.9%) 2 0/20 (0%) 0 3/88 (3.4%) 3 0/47 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign neoplasm of skin 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Skin papilloma 3/54 (5.6%) 3 2/27 (7.4%) 2 0/34 (0%) 0 0/20 (0%) 0 3/88 (3.4%) 3 2/47 (4.3%) 2
    Nervous system disorders
    Dizziness 2/54 (3.7%) 2 2/27 (7.4%) 4 4/34 (11.8%) 4 1/20 (5%) 1 6/88 (6.8%) 6 3/47 (6.4%) 5
    Dizziness postural 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Headache 14/54 (25.9%) 24 6/27 (22.2%) 17 5/34 (14.7%) 8 6/20 (30%) 7 19/88 (21.6%) 32 12/47 (25.5%) 24
    Paraesthesia 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Peripheral sensory neuropathy 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Presyncope 1/54 (1.9%) 1 0/27 (0%) 0 1/34 (2.9%) 1 1/20 (5%) 1 2/88 (2.3%) 2 1/47 (2.1%) 1
    Syncope 1/54 (1.9%) 1 3/27 (11.1%) 4 2/34 (5.9%) 2 1/20 (5%) 1 3/88 (3.4%) 3 4/47 (8.5%) 5
    Psychiatric disorders
    Depression 1/54 (1.9%) 1 0/27 (0%) 0 4/34 (11.8%) 4 0/20 (0%) 0 5/88 (5.7%) 5 0/47 (0%) 0
    Stress 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Respiratory, thoracic and mediastinal disorders
    Cough 9/54 (16.7%) 9 7/27 (25.9%) 9 2/34 (5.9%) 4 2/20 (10%) 2 11/88 (12.5%) 13 9/47 (19.1%) 11
    Epistaxis 1/54 (1.9%) 1 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 1/88 (1.1%) 1 1/47 (2.1%) 1
    Nasal congestion 4/54 (7.4%) 6 2/27 (7.4%) 2 4/34 (11.8%) 4 3/20 (15%) 3 8/88 (9.1%) 10 5/47 (10.6%) 5
    Oropharyngeal pain 9/54 (16.7%) 17 4/27 (14.8%) 5 5/34 (14.7%) 6 1/20 (5%) 1 14/88 (15.9%) 23 5/47 (10.6%) 6
    Rhinorrhoea 1/54 (1.9%) 1 2/27 (7.4%) 2 0/34 (0%) 0 2/20 (10%) 2 1/88 (1.1%) 1 4/47 (8.5%) 4
    Tonsillolith 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Upper respiratory tract congestion 0/54 (0%) 0 0/27 (0%) 0 2/34 (5.9%) 8 0/20 (0%) 0 2/88 (2.3%) 8 0/47 (0%) 0
    Skin and subcutaneous tissue disorders
    Acne 1/54 (1.9%) 1 1/27 (3.7%) 1 0/34 (0%) 0 1/20 (5%) 1 1/88 (1.1%) 1 2/47 (4.3%) 2
    Alopecia 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Dermal cyst 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Dermatitis 3/54 (5.6%) 5 1/27 (3.7%) 2 0/34 (0%) 0 0/20 (0%) 0 3/88 (3.4%) 5 1/47 (2.1%) 2
    Dermatitis contact 3/54 (5.6%) 3 0/27 (0%) 0 2/34 (5.9%) 2 3/20 (15%) 3 5/88 (5.7%) 5 3/47 (6.4%) 3
    Dry skin 0/54 (0%) 0 1/27 (3.7%) 1 2/34 (5.9%) 2 0/20 (0%) 0 2/88 (2.3%) 2 1/47 (2.1%) 1
    Eczema 2/54 (3.7%) 2 1/27 (3.7%) 1 2/34 (5.9%) 2 0/20 (0%) 0 4/88 (4.5%) 4 1/47 (2.1%) 1
    Ingrowing nail 2/54 (3.7%) 2 2/27 (7.4%) 2 0/34 (0%) 0 0/20 (0%) 0 2/88 (2.3%) 2 2/47 (4.3%) 2
    Lipohypertrophy 2/54 (3.7%) 2 4/27 (14.8%) 5 2/34 (5.9%) 2 1/20 (5%) 1 4/88 (4.5%) 4 5/47 (10.6%) 6
    Papule 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Rash 7/54 (13%) 8 3/27 (11.1%) 4 5/34 (14.7%) 5 2/20 (10%) 2 12/88 (13.6%) 13 5/47 (10.6%) 6
    Rash pruritic 0/54 (0%) 0 0/27 (0%) 0 1/34 (2.9%) 1 1/20 (5%) 1 1/88 (1.1%) 1 1/47 (2.1%) 1
    Skin fissures 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Skin mass 0/54 (0%) 0 0/27 (0%) 0 0/34 (0%) 0 1/20 (5%) 1 0/88 (0%) 0 1/47 (2.1%) 1
    Social circumstances
    Family stress 0/54 (0%) 0 2/27 (7.4%) 2 0/34 (0%) 0 0/20 (0%) 0 0/88 (0%) 0 2/47 (4.3%) 2

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Director, Clinical Research Operations Program
    Organization DAIT/NIAID
    Phone 301-594-7669
    Email DAITClinicalTrialsGov@niaid.nih.gov
    Responsible Party:
    National Institute of Allergy and Infectious Diseases (NIAID)
    ClinicalTrials.gov Identifier:
    NCT02293837
    Other Study ID Numbers:
    • DAIT ITN058AI
    First Posted:
    Nov 18, 2014
    Last Update Posted:
    Sep 8, 2021
    Last Verified:
    Aug 1, 2021