Trial Outcomes & Findings for Tocilizumab (TCZ) in New-onset Type 1 Diabetes (NCT NCT02293837)

NCT ID: NCT02293837

Last Updated: 2021-09-08

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 136 participants
• Primary outcome timeframe: Baseline (Pre-treatment) to Week 52
• Results posted on: 2021-09-08

Participant Flow

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.

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.

Participant milestones

Measure	Tocilizumab (TCZ) in Pediatric Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.	Placebo in Pediatric Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.	Tocilizumab (TCZ) in Adult Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.	Placebo in Adult Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.
Overall Study STARTED	54	27	35	20
Overall Study COMPLETED	51	23	31	19
Overall Study NOT COMPLETED	3	4	4	1

Reasons for withdrawal

Measure	Tocilizumab (TCZ) in Pediatric Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.	Placebo in Pediatric Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.	Tocilizumab (TCZ) in Adult Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.	Placebo in Adult Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.
Overall Study Lost to Follow-up	0	2	1	0
Overall Study Withdrawal by Subject	2	1	2	1
Overall Study COVID-19 Related	1	1	0	0
Overall Study Participant ill and could not be infused	0	0	1	0

Baseline Characteristics

Tocilizumab (TCZ) in New-onset Type 1 Diabetes

Baseline characteristics by cohort

Measure	Tocilizumab (TCZ) in Pediatric Participants n=54 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.	Placebo in Pediatric Participants n=27 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.	Tocilizumab (TCZ) in Adult Participants n=35 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.	Placebo in Adult Participants n=20 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.	Total n=136 Participants Total of all reporting groups
Age, Continuous	11.1 years STANDARD_DEVIATION 2.9 • n=5 Participants	11.1 years STANDARD_DEVIATION 2.5 • n=7 Participants	27.9 years STANDARD_DEVIATION 7.4 • n=5 Participants	29.2 years STANDARD_DEVIATION 9.3 • n=4 Participants	18.1 years STANDARD_DEVIATION 10.2 • n=21 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants	7 Participants n=4 Participants	57 Participants n=21 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	15 Participants n=7 Participants	23 Participants n=5 Participants	13 Participants n=4 Participants	79 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	9 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	53 Participants n=5 Participants	21 Participants n=7 Participants	32 Participants n=5 Participants	19 Participants n=4 Participants	125 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) White	47 Participants n=5 Participants	20 Participants n=7 Participants	32 Participants n=5 Participants	19 Participants n=4 Participants	118 Participants n=21 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
Region of Enrollment United States	52 Participants n=5 Participants	24 Participants n=7 Participants	35 Participants n=5 Participants	20 Participants n=4 Participants	131 Participants n=21 Participants
Region of Enrollment Australia	2 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	5 Participants n=21 Participants
Body Mass Index (BMI)	19.8 kg/m^2 STANDARD_DEVIATION 3.8 • n=5 Participants	19.1 kg/m^2 STANDARD_DEVIATION 3.3 • n=7 Participants	24.2 kg/m^2 STANDARD_DEVIATION 3.9 • n=5 Participants	25.4 kg/m^2 STANDARD_DEVIATION 3.5 • n=4 Participants	21.6 kg/m^2 STANDARD_DEVIATION 4.4 • n=21 Participants
2-hour C-peptide Mean Area Under the Curve (mAUC) Result in Response to Standardized Mixed Meal Tol	0.73 pmol/mL STANDARD_DEVIATION 0.44 • n=5 Participants	0.66 pmol/mL STANDARD_DEVIATION 0.32 • n=7 Participants	0.77 pmol/mL STANDARD_DEVIATION 0.24 • n=5 Participants	0.97 pmol/mL STANDARD_DEVIATION 0.69 • n=4 Participants	0.76 pmol/mL STANDARD_DEVIATION 0.43 • n=21 Participants
Hemoglobin A1C (HbA1c) Level	6.79 percent (%) STANDARD_DEVIATION 1.03 • n=5 Participants	6.86 percent (%) STANDARD_DEVIATION 0.55 • n=7 Participants	6.48 percent (%) STANDARD_DEVIATION 1.08 • n=5 Participants	6.28 percent (%) STANDARD_DEVIATION 0.73 • n=4 Participants	6.65 percent (%) STANDARD_DEVIATION 0.94 • n=21 Participants
Average Insulin Use Per Kilogram Body Weight	0.39 Units per Kilogram Body Weight per Day STANDARD_DEVIATION 0.24 • n=5 Participants	0.38 Units per Kilogram Body Weight per Day STANDARD_DEVIATION 0.19 • n=7 Participants	0.28 Units per Kilogram Body Weight per Day STANDARD_DEVIATION 0.15 • n=5 Participants	0.30 Units per Kilogram Body Weight per Day STANDARD_DEVIATION 0.21 • n=4 Participants	0.35 Units per Kilogram Body Weight per Day STANDARD_DEVIATION 0.21 • n=21 Participants
Days from Type 1 Diabetes Mellitus (T1DM) Diagnosis to Randomization	85.9 Days STANDARD_DEVIATION 15.5 • n=5 Participants	83.9 Days STANDARD_DEVIATION 16.7 • n=7 Participants	82.5 Days STANDARD_DEVIATION 13.6 • n=5 Participants	84.6 Days STANDARD_DEVIATION 12.4 • n=4 Participants	84.4 Days STANDARD_DEVIATION 14.7 • n=21 Participants

PRIMARY outcome

Timeframe: Baseline (Pre-treatment) to Week 52

Population: The modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.

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.

Outcome measures

Measure	Tocilizumab (TCZ) in Pediatric Participants n=54 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.	Placebo in Pediatric Participants n=27 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.	Tocilizumab (TCZ) in Adult Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.	Placebo in Adult Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.	Tocilizumab (TCZ) in Pooled Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.	Placebo in Pooled Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC) in Pediatric Participants	-0.337 pmol/mL Interval -0.39 to -0.28	-0.391 pmol/mL Interval -0.47 to -0.31	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Pre-treatment) to Weeks 24, 52, and 104

Population: Modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.

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.

Outcome measures

Measure	Tocilizumab (TCZ) in Pediatric Participants n=54 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.	Placebo in Pediatric Participants n=27 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.	Tocilizumab (TCZ) in Adult Participants n=34 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.	Placebo in Adult Participants n=20 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.	Tocilizumab (TCZ) in Pooled Participants n=88 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.	Placebo in Pooled Participants n=47 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC) Week 24	-0.200 pmol/mL Interval -0.26 to -0.14	-0.164 pmol/mL Interval -0.25 to -0.08	-0.072 pmol/mL Interval -0.17 to 0.03	-0.097 pmol/mL Interval -0.23 to 0.03	-0.152 pmol/mL Interval -0.2 to -0.1	-0.134 pmol/mL Interval -0.21 to -0.06
Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC) Week 52	-0.339 pmol/mL Interval -0.4 to -0.28	-0.397 pmol/mL Interval -0.48 to -0.31	-0.186 pmol/mL Interval -0.29 to -0.08	-0.267 pmol/mL Interval -0.4 to -0.13	-0.287 pmol/mL Interval -0.34 to -0.23	-0.328 pmol/mL Interval -0.41 to -0.25
Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC) Week 104	-0.495 pmol/mL Interval -0.55 to -0.44	-0.556 pmol/mL Interval -0.64 to -0.47	-0.384 pmol/mL Interval -0.49 to -0.28	-0.388 pmol/mL Interval -0.52 to -0.25	-0.461 pmol/mL Interval -0.52 to -0.4	-0.463 pmol/mL Interval -0.54 to -0.38

SECONDARY outcome

Timeframe: Baseline (Pre-treatment), Weeks 12, 24, 39, 52, 78, and 104

Population: 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.

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.

Outcome measures

Measure	Tocilizumab (TCZ) in Pediatric Participants n=54 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.	Placebo in Pediatric Participants n=26 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.	Tocilizumab (TCZ) in Adult Participants n=34 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.	Placebo in Adult Participants n=20 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.	Tocilizumab (TCZ) in Pooled Participants n=88 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.	Placebo in Pooled Participants n=46 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
2-Hour C-peptide Mean Area Under the Curve (mAUC), Mixed Model Week 12	0.60 pmol/mL Interval 0.51 to 0.69	0.55 pmol/mL Interval 0.42 to 0.68	0.72 pmol/mL Interval 0.56 to 0.89	0.88 pmol/mL Interval 0.67 to 1.09	0.65 pmol/mL Interval 0.57 to 0.74	0.69 pmol/mL Interval 0.57 to 0.81
2-Hour C-peptide Mean Area Under the Curve (mAUC), Mixed Model Week 24	0.55 pmol/mL Interval 0.46 to 0.63	0.49 pmol/mL Interval 0.37 to 0.61	0.68 pmol/mL Interval 0.52 to 0.84	0.83 pmol/mL Interval 0.62 to 1.04	0.60 pmol/mL Interval 0.52 to 0.69	0.63 pmol/mL Interval 0.52 to 0.75
2-Hour C-peptide Mean Area Under the Curve (mAUC), Mixed Model Week 39	0.48 pmol/mL Interval 0.4 to 0.56	0.42 pmol/mL Interval 0.3 to 0.53	0.63 pmol/mL Interval 0.47 to 0.79	0.77 pmol/mL Interval 0.56 to 0.98	0.54 pmol/mL Interval 0.46 to 0.62	0.56 pmol/mL Interval 0.45 to 0.67
2-Hour C-peptide Mean Area Under the Curve (mAUC), Mixed Model Week 52	0.42 pmol/mL Interval 0.34 to 0.5	0.35 pmol/mL Interval 0.24 to 0.46	0.59 pmol/mL Interval 0.43 to 0.75	0.72 pmol/mL Interval 0.51 to 0.93	0.49 pmol/mL Interval 0.41 to 0.57	0.50 pmol/mL Interval 0.39 to 0.61
2-Hour C-peptide Mean Area Under the Curve (mAUC), Mixed Model Week 78	0.30 pmol/mL Interval 0.23 to 0.37	0.23 pmol/mL Interval 0.12 to 0.33	0.50 pmol/mL Interval 0.33 to 0.66	0.61 pmol/mL Interval 0.4 to 0.82	0.38 pmol/mL Interval 0.3 to 0.46	0.38 pmol/mL Interval 0.28 to 0.49
2-Hour C-peptide Mean Area Under the Curve (mAUC), Mixed Model Week 104	0.18 pmol/mL Interval 0.11 to 0.25	0.10 pmol/mL Interval 0.0 to 0.21	0.41 pmol/mL Interval 0.24 to 0.58	0.50 pmol/mL Interval 0.28 to 0.72	0.27 pmol/mL Interval 0.19 to 0.35	0.27 pmol/mL Interval 0.16 to 0.38

SECONDARY outcome

Timeframe: Baseline (Pre-treatment) to Weeks 52 and 104

Population: The modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.

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.

Outcome measures

Measure	Tocilizumab (TCZ) in Pediatric Participants n=54 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.	Placebo in Pediatric Participants n=27 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.	Tocilizumab (TCZ) in Adult Participants n=34 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.	Placebo in Adult Participants n=20 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.	Tocilizumab (TCZ) in Pooled Participants n=88 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.	Placebo in Pooled Participants n=47 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Change From Baseline in 4-Hour C-peptide Mean Area Under the Curve (mAUC) Week 52	-0.325 pmol/mL Interval -0.42 to -0.23	-0.448 pmol/mL Interval -0.6 to -0.29	-0.195 pmol/mL Interval -0.3 to -0.09	-0.262 pmol/mL Interval -0.4 to -0.13	-0.252 pmol/mL Interval -0.32 to -0.18	-0.321 pmol/mL Interval -0.42 to -0.22
Change From Baseline in 4-Hour C-peptide Mean Area Under the Curve (mAUC) Week 104	-0.521 pmol/mL Interval -0.62 to -0.42	-0.635 pmol/mL Interval -0.82 to -0.45	-0.382 pmol/mL Interval -0.49 to -0.27	-0.390 pmol/mL Interval -0.53 to -0.25	-0.449 pmol/mL Interval -0.53 to -0.37	-0.448 pmol/mL Interval -0.56 to -0.33

SECONDARY outcome

Timeframe: Baseline (Pre-treatment) to Weeks 24, 52, and 104

Population: The modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.

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.

Outcome measures

Measure	Tocilizumab (TCZ) in Pediatric Participants n=54 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.	Placebo in Pediatric Participants n=27 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.	Tocilizumab (TCZ) in Adult Participants n=34 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.	Placebo in Adult Participants n=20 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.	Tocilizumab (TCZ) in Pooled Participants n=88 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.	Placebo in Pooled Participants n=47 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Change From Baseline in Average Insulin Use in Units Per Kilogram Body Weight Per Day Week 24	0.139 Units per Kilogram Body Weight per Day Interval 0.09 to 0.19	0.126 Units per Kilogram Body Weight per Day Interval 0.05 to 0.2	0.015 Units per Kilogram Body Weight per Day Interval -0.06 to 0.09	0.146 Units per Kilogram Body Weight per Day Interval 0.05 to 0.24	0.090 Units per Kilogram Body Weight per Day Interval 0.05 to 0.13	0.139 Units per Kilogram Body Weight per Day Interval 0.08 to 0.2
Change From Baseline in Average Insulin Use in Units Per Kilogram Body Weight Per Day Week 52	0.300 Units per Kilogram Body Weight per Day Interval 0.24 to 0.36	0.326 Units per Kilogram Body Weight per Day Interval 0.24 to 0.42	0.081 Units per Kilogram Body Weight per Day Interval 0.01 to 0.15	0.112 Units per Kilogram Body Weight per Day Interval 0.02 to 0.2	0.211 Units per Kilogram Body Weight per Day Interval 0.16 to 0.26	0.243 Units per Kilogram Body Weight per Day Interval 0.18 to 0.31
Change From Baseline in Average Insulin Use in Units Per Kilogram Body Weight Per Day Week 104	0.403 Units per Kilogram Body Weight per Day Interval 0.33 to 0.47	0.493 Units per Kilogram Body Weight per Day Interval 0.39 to 0.59	0.116 Units per Kilogram Body Weight per Day Interval 0.05 to 0.18	0.129 Units per Kilogram Body Weight per Day Interval 0.05 to 0.21	0.288 Units per Kilogram Body Weight per Day Interval 0.24 to 0.34	0.354 Units per Kilogram Body Weight per Day Interval 0.28 to 0.43

SECONDARY outcome

Timeframe: Baseline (Pre-treatment) to Weeks 12, 24, 39, 52, 78, and 104

Population: The modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.

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.

Outcome measures

Measure	Tocilizumab (TCZ) in Pediatric Participants n=54 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.	Placebo in Pediatric Participants n=27 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.	Tocilizumab (TCZ) in Adult Participants n=34 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.	Placebo in Adult Participants n=20 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.	Tocilizumab (TCZ) in Pooled Participants n=88 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.	Placebo in Pooled Participants n=47 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Change From Baseline in Average Insulin Use Per Kg, Mixed Model Week 104	0.84 Units per Kilogram Body Weight per Day Interval 0.77 to 0.91	0.94 Units per Kilogram Body Weight per Day Interval 0.83 to 1.04	0.43 Units per Kilogram Body Weight per Day Interval 0.32 to 0.55	0.57 Units per Kilogram Body Weight per Day Interval 0.42 to 0.72	0.68 Units per Kilogram Body Weight per Day Interval 0.62 to 0.74	0.79 Units per Kilogram Body Weight per Day Interval 0.7 to 0.87
Change From Baseline in Average Insulin Use Per Kg, Mixed Model Week 12	0.45 Units per Kilogram Body Weight per Day Interval 0.4 to 0.51	0.45 Units per Kilogram Body Weight per Day Interval 0.37 to 0.53	0.29 Units per Kilogram Body Weight per Day Interval 0.22 to 0.35	0.37 Units per Kilogram Body Weight per Day Interval 0.29 to 0.46	0.39 Units per Kilogram Body Weight per Day Interval 0.35 to 0.43	0.42 Units per Kilogram Body Weight per Day Interval 0.36 to 0.48
Change From Baseline in Average Insulin Use Per Kg, Mixed Model Week 24	0.50 Units per Kilogram Body Weight per Day Interval 0.45 to 0.56	0.51 Units per Kilogram Body Weight per Day Interval 0.44 to 0.59	0.31 Units per Kilogram Body Weight per Day Interval 0.24 to 0.37	0.40 Units per Kilogram Body Weight per Day Interval 0.31 to 0.48	0.43 Units per Kilogram Body Weight per Day Interval 0.38 to 0.47	0.47 Units per Kilogram Body Weight per Day Interval 0.41 to 0.53
Change From Baseline in Average Insulin Use Per Kg, Mixed Model Week 39	0.57 Units per Kilogram Body Weight per Day Interval 0.51 to 0.62	0.59 Units per Kilogram Body Weight per Day Interval 0.52 to 0.67	0.33 Units per Kilogram Body Weight per Day Interval 0.26 to 0.4	0.43 Units per Kilogram Body Weight per Day Interval 0.34 to 0.52	0.47 Units per Kilogram Body Weight per Day Interval 0.43 to 0.52	0.53 Units per Kilogram Body Weight per Day Interval 0.47 to 0.59
Change From Baseline in Average Insulin Use Per Kg, Mixed Model Week 52	0.62 Units per Kilogram Body Weight per Day Interval 0.57 to 0.68	0.66 Units per Kilogram Body Weight per Day Interval 0.58 to 0.74	0.35 Units per Kilogram Body Weight per Day Interval 0.27 to 0.43	0.46 Units per Kilogram Body Weight per Day Interval 0.36 to 0.56	0.51 Units per Kilogram Body Weight per Day Interval 0.47 to 0.56	0.58 Units per Kilogram Body Weight per Day Interval 0.52 to 0.64
Change From Baseline in Average Insulin Use Per Kg, Mixed Model Week 78	0.73 Units per Kilogram Body Weight per Day Interval 0.67 to 0.79	0.80 Units per Kilogram Body Weight per Day Interval 0.71 to 0.89	0.39 Units per Kilogram Body Weight per Day Interval 0.3 to 0.49	0.51 Units per Kilogram Body Weight per Day Interval 0.39 to 0.64	0.60 Units per Kilogram Body Weight per Day Interval 0.54 to 0.65	0.68 Units per Kilogram Body Weight per Day Interval 0.61 to 0.76

SECONDARY outcome

Timeframe: Baseline (Pre-treatment) to Weeks 24, 52, and 104

Population: The modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.

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.

Outcome measures

Measure	Tocilizumab (TCZ) in Pediatric Participants n=54 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.	Placebo in Pediatric Participants n=27 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.	Tocilizumab (TCZ) in Adult Participants n=34 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.	Placebo in Adult Participants n=20 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.	Tocilizumab (TCZ) in Pooled Participants n=88 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.	Placebo in Pooled Participants n=47 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Change From Baseline in Hemoglobin A1c Week 104	0.734 percent (%) Interval 0.33 to 1.14	1.042 percent (%) Interval 0.44 to 1.64	0.253 percent (%) Interval -0.21 to 0.71	0.583 percent (%) Interval 0.0 to 1.17	0.556 percent (%) Interval 0.25 to 0.86	0.812 percent (%) Interval 0.38 to 1.24
Change From Baseline in Hemoglobin A1c Week 24	0.065 percent (%) Interval -0.17 to 0.3	0.368 percent (%) Interval 0.02 to 0.71	-0.509 percent (%) Interval -0.8 to -0.21	-0.136 percent (%) Interval -0.51 to 0.24	-0.163 percent (%) Interval -0.34 to 0.02	0.169 percent (%) Interval -0.08 to 0.42
Change From Baseline in Hemoglobin A1c Week 52	0.650 percent (%) Interval 0.24 to 1.06	1.134 percent (%) Interval 0.53 to 1.74	0.152 percent (%) Interval -0.21 to 0.51	0.262 percent (%) Interval -0.19 to 0.72	0.459 percent (%) Interval 0.16 to 0.76	0.753 percent (%) Interval 0.34 to 1.17

SECONDARY outcome

Timeframe: Baseline (Pre-treatment) to Weeks 12, 24, 39, 52, 78, and 104

Population: The modified intent to treat population includes all randomized participants who received any dose of assigned study treatment.

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.

Outcome measures

Measure	Tocilizumab (TCZ) in Pediatric Participants n=54 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.	Placebo in Pediatric Participants n=27 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.	Tocilizumab (TCZ) in Adult Participants n=34 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.	Placebo in Adult Participants n=20 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.	Tocilizumab (TCZ) in Pooled Participants n=88 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.	Placebo in Pooled Participants n=47 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Change From Baseline in Hemoglobin A1C (HbA1c) Level in Participants, Mixed Model Week 12	6.74 percent (%) Interval 6.5 to 6.97	6.99 percent (%) Interval 6.65 to 7.32	5.88 percent (%) Interval 5.59 to 6.18	6.04 percent (%) Interval 5.65 to 6.43	6.40 percent (%) Interval 6.21 to 6.58	6.60 percent (%) Interval 6.35 to 6.86
Change From Baseline in Hemoglobin A1C (HbA1c) Level in Participants, Mixed Model Week 24	6.87 percent (%) Interval 6.65 to 7.1	7.20 percent (%) Interval 6.88 to 7.52	6.02 percent (%) Interval 5.71 to 6.34	6.19 percent (%) Interval 5.78 to 6.6	6.54 percent (%) Interval 6.35 to 6.72	6.79 percent (%) Interval 6.54 to 7.04
Change From Baseline in Hemoglobin A1C (HbA1c) Level in Participants, Mixed Model Week 39	7.05 percent (%) Interval 6.8 to 7.29	7.46 percent (%) Interval 7.11 to 7.82	6.19 percent (%) Interval 5.85 to 6.54	6.38 percent (%) Interval 5.93 to 6.83	6.71 percent (%) Interval 6.51 to 6.91	7.02 percent (%) Interval 6.75 to 7.3
Change From Baseline in Hemoglobin A1C (HbA1c) Level in Participants, Mixed Model Week 52	7.20 percent (%) Interval 6.91 to 7.48	7.69 percent (%) Interval 7.28 to 8.11	6.34 percent (%) Interval 5.96 to 6.73	6.54 percent (%) Interval 6.04 to 7.03	6.86 percent (%) Interval 6.63 to 7.09	7.23 percent (%) Interval 6.91 to 7.54
Change From Baseline in Hemoglobin A1C (HbA1c) Level in Participants, Mixed Model Week 78	7.50 percent (%) Interval 7.1 to 7.9	8.16 percent (%) Interval 7.57 to 8.74	6.64 percent (%) Interval 6.17 to 7.11	6.86 percent (%) Interval 6.26 to 7.47	7.16 percent (%) Interval 6.85 to 7.46	7.63 percent (%) Interval 7.21 to 8.05
Change From Baseline in Hemoglobin A1C (HbA1c) Level in Participants, Mixed Model Week 104	7.80 percent (%) Interval 7.26 to 8.34	8.62 percent (%) Interval 7.83 to 9.4	6.94 percent (%) Interval 6.37 to 7.51	7.19 percent (%) Interval 6.45 to 7.92	7.45 percent (%) Interval 7.06 to 7.85	8.04 percent (%) Interval 7.49 to 8.59

SECONDARY outcome

Timeframe: Day 0 (Treatment Initiation) to Weeks 52 and 104

Population: The safety population includes all participants who received any degree of study treatment. Safety analyses are based on actual treatment the participants receive.

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

Outcome measures

Measure	Tocilizumab (TCZ) in Pediatric Participants n=54 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.	Placebo in Pediatric Participants n=27 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.	Tocilizumab (TCZ) in Adult Participants n=34 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.	Placebo in Adult Participants n=20 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.	Tocilizumab (TCZ) in Pooled Participants n=88 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.	Placebo in Pooled Participants n=47 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Number of Participants Who Experienced at Least One Major Hypoglycemic Event After Treatment Initiation Day 0 to Week 52	19 Participants	11 Participants	10 Participants	3 Participants	29 Participants	14 Participants
Number of Participants Who Experienced at Least One Major Hypoglycemic Event After Treatment Initiation Day 0 to Week 104	28 Participants	14 Participants	15 Participants	8 Participants	43 Participants	22 Participants

SECONDARY outcome

Timeframe: Day 0 (Treatment Initiation) to Week 52

Population: The safety population includes all participants who received any degree of study treatment. Safety analyses are based on actual treatment the participants receive.

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.

Outcome measures

Measure	Tocilizumab (TCZ) in Pediatric Participants n=54 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.	Placebo in Pediatric Participants n=27 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.	Tocilizumab (TCZ) in Adult Participants n=34 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.	Placebo in Adult Participants n=20 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.	Tocilizumab (TCZ) in Pooled Participants n=88 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.	Placebo in Pooled Participants n=47 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Number of Participants Who Experienced Infusion-Related Adverse Events	4 Participants	0 Participants	5 Participants	0 Participants	9 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 0 (Treatment Initiation) to Week 52

Population: The safety population includes all participants who received any degree of study treatment. Safety analyses are based on actual treatment the participants receive.

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

Outcome measures

Measure	Tocilizumab (TCZ) in Pediatric Participants n=54 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pediatric participants were 6 to 17 years old inclusive.	Placebo in Pediatric Participants n=27 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.	Tocilizumab (TCZ) in Adult Participants n=34 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Adult participants were 18 to 45 years old inclusive.	Placebo in Adult Participants n=20 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.	Tocilizumab (TCZ) in Pooled Participants n=88 Participants Participants received intravenous (IV) infusions of either 8.0 mg/kg (body weight \>=30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. The dose was capped at 800 mg. Pooled participants are the pediatric and adult participants who received TCZ combined.	Placebo in Pooled Participants n=47 Participants Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pooled participants are the pediatric and adult participants who received placebo combined.
Number of Participants Who Experienced Hypersensitivity Adverse Events	3 Participants	0 Participants	0 Participants	0 Participants	3 Participants	0 Participants

Adverse Events

Tocilizumab (TCZ) in Pediatric Participants

Serious events: 3 serious events

Other events: 52 other events

Deaths: 0 deaths

Placebo in Pediatric Participants

Serious events: 3 serious events

Other events: 26 other events

Deaths: 0 deaths

Tocilizumab (TCZ) in Adult Participants

Serious events: 2 serious events

Other events: 31 other events

Deaths: 0 deaths

Placebo in Adult Participants

Serious events: 2 serious events

Other events: 19 other events

Deaths: 0 deaths

Tocilizumab (TCZ) in Pooled Participants

Serious events: 5 serious events

Other events: 83 other events

Deaths: 0 deaths

Placebo in Pooled Participants

Serious events: 5 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tocilizumab (TCZ) in Pediatric Participants n=54 participants at risk 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.	Placebo in Pediatric Participants n=27 participants at risk Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.	Tocilizumab (TCZ) in Adult Participants n=34 participants at risk 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.	Placebo in Adult Participants n=20 participants at risk Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.	Tocilizumab (TCZ) in Pooled Participants n=88 participants at risk 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.	Placebo in Pooled Participants n=47 participants at risk 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.
General disorders Vaccination site reaction	0.00% 0/54 • Up to 104 weeks.	3.7% 1/27 • Number of events 1 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Infections and infestations Gastroenteritis	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	0.00% 0/47 • Up to 104 weeks.
Infections and infestations Infectious mononucleosis	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	0.00% 0/47 • Up to 104 weeks.
Injury, poisoning and procedural complications Forearm fracture	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	0.00% 0/47 • Up to 104 weeks.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/54 • Up to 104 weeks.	3.7% 1/27 • Number of events 1 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Nervous system disorders Thoracic outlet syndrome	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	0.00% 0/47 • Up to 104 weeks.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/54 • Up to 104 weeks.	3.7% 1/27 • Number of events 1 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Vascular disorders Deep vein thrombosis	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	0.00% 0/47 • Up to 104 weeks.

Other adverse events

Measure	Tocilizumab (TCZ) in Pediatric Participants n=54 participants at risk 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.	Placebo in Pediatric Participants n=27 participants at risk Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Pediatric participants were 6 to 17 years old inclusive.	Tocilizumab (TCZ) in Adult Participants n=34 participants at risk 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.	Placebo in Adult Participants n=20 participants at risk Participants received IV placebo infusions of saline of equal volume and appearance to the treatment. Adult participants were 18 to 45 years old inclusive.	Tocilizumab (TCZ) in Pooled Participants n=88 participants at risk 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.	Placebo in Pooled Participants n=47 participants at risk 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.
Skin and subcutaneous tissue disorders Papule	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Skin and subcutaneous tissue disorders Rash	13.0% 7/54 • Number of events 8 • Up to 104 weeks.	11.1% 3/27 • Number of events 4 • Up to 104 weeks.	14.7% 5/34 • Number of events 5 • Up to 104 weeks.	10.0% 2/20 • Number of events 2 • Up to 104 weeks.	13.6% 12/88 • Number of events 13 • Up to 104 weeks.	10.6% 5/47 • Number of events 6 • Up to 104 weeks.
Skin and subcutaneous tissue disorders Rash pruritic	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Skin and subcutaneous tissue disorders Skin fissures	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Skin and subcutaneous tissue disorders Skin mass	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Social circumstances Family stress	0.00% 0/54 • Up to 104 weeks.	7.4% 2/27 • Number of events 2 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	4.3% 2/47 • Number of events 2 • Up to 104 weeks.
Blood and lymphatic system disorders Anaemia	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	2.3% 2/88 • Number of events 2 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Blood and lymphatic system disorders Splenomegaly	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Cardiac disorders Palpitations	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	2.9% 1/34 • Number of events 2 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	1.1% 1/88 • Number of events 2 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Endocrine disorders Basedow's disease	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Eye disorders Eye irritation	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Gastrointestinal disorders Abdominal distension	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	2.3% 2/88 • Number of events 2 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Gastrointestinal disorders Abdominal pain	3.7% 2/54 • Number of events 3 • Up to 104 weeks.	11.1% 3/27 • Number of events 4 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	2.3% 2/88 • Number of events 3 • Up to 104 weeks.	8.5% 4/47 • Number of events 5 • Up to 104 weeks.
Gastrointestinal disorders Abdominal pain upper	9.3% 5/54 • Number of events 7 • Up to 104 weeks.	11.1% 3/27 • Number of events 4 • Up to 104 weeks.	5.9% 2/34 • Number of events 2 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	8.0% 7/88 • Number of events 9 • Up to 104 weeks.	6.4% 3/47 • Number of events 4 • Up to 104 weeks.
Gastrointestinal disorders Constipation	5.6% 3/54 • Number of events 3 • Up to 104 weeks.	14.8% 4/27 • Number of events 4 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	4.5% 4/88 • Number of events 4 • Up to 104 weeks.	8.5% 4/47 • Number of events 4 • Up to 104 weeks.
Gastrointestinal disorders Dental caries	3.7% 2/54 • Number of events 2 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	10.0% 2/20 • Number of events 2 • Up to 104 weeks.	2.3% 2/88 • Number of events 2 • Up to 104 weeks.	4.3% 2/47 • Number of events 2 • Up to 104 weeks.
Gastrointestinal disorders Diarrhoea	7.4% 4/54 • Number of events 5 • Up to 104 weeks.	3.7% 1/27 • Number of events 1 • Up to 104 weeks.	11.8% 4/34 • Number of events 4 • Up to 104 weeks.	15.0% 3/20 • Number of events 3 • Up to 104 weeks.	9.1% 8/88 • Number of events 9 • Up to 104 weeks.	8.5% 4/47 • Number of events 4 • Up to 104 weeks.
Gastrointestinal disorders Dyspepsia	5.6% 3/54 • Number of events 3 • Up to 104 weeks.	14.8% 4/27 • Number of events 4 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	10.0% 2/20 • Number of events 3 • Up to 104 weeks.	4.5% 4/88 • Number of events 4 • Up to 104 weeks.	12.8% 6/47 • Number of events 7 • Up to 104 weeks.
Gastrointestinal disorders Food poisoning	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Gastrointestinal disorders Gastritis	5.6% 3/54 • Number of events 4 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	3.4% 3/88 • Number of events 4 • Up to 104 weeks.	0.00% 0/47 • Up to 104 weeks.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/54 • Up to 104 weeks.	3.7% 1/27 • Number of events 1 • Up to 104 weeks.	5.9% 2/34 • Number of events 2 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	2.3% 2/88 • Number of events 2 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Gastrointestinal disorders Haemorrhoids	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Gastrointestinal disorders Nausea	24.1% 13/54 • Number of events 20 • Up to 104 weeks.	14.8% 4/27 • Number of events 11 • Up to 104 weeks.	14.7% 5/34 • Number of events 8 • Up to 104 weeks.	10.0% 2/20 • Number of events 2 • Up to 104 weeks.	20.5% 18/88 • Number of events 28 • Up to 104 weeks.	12.8% 6/47 • Number of events 13 • Up to 104 weeks.
Gastrointestinal disorders Vomiting	18.5% 10/54 • Number of events 16 • Up to 104 weeks.	22.2% 6/27 • Number of events 7 • Up to 104 weeks.	11.8% 4/34 • Number of events 4 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	15.9% 14/88 • Number of events 20 • Up to 104 weeks.	14.9% 7/47 • Number of events 8 • Up to 104 weeks.
General disorders Adverse drug reaction	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
General disorders Fatigue	0.00% 0/54 • Up to 104 weeks.	7.4% 2/27 • Number of events 2 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	10.0% 2/20 • Number of events 2 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	8.5% 4/47 • Number of events 4 • Up to 104 weeks.
General disorders Influenza like illness	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	11.1% 3/27 • Number of events 5 • Up to 104 weeks.	5.9% 2/34 • Number of events 3 • Up to 104 weeks.	10.0% 2/20 • Number of events 2 • Up to 104 weeks.	3.4% 3/88 • Number of events 4 • Up to 104 weeks.	10.6% 5/47 • Number of events 7 • Up to 104 weeks.
General disorders Pain	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	7.4% 2/27 • Number of events 2 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	6.4% 3/47 • Number of events 3 • Up to 104 weeks.
General disorders Pyrexia	13.0% 7/54 • Number of events 9 • Up to 104 weeks.	14.8% 4/27 • Number of events 5 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	9.1% 8/88 • Number of events 10 • Up to 104 weeks.	8.5% 4/47 • Number of events 5 • Up to 104 weeks.
General disorders Temperature intolerance	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Immune system disorders Seasonal allergy	11.1% 6/54 • Number of events 7 • Up to 104 weeks.	7.4% 2/27 • Number of events 3 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	10.0% 2/20 • Number of events 2 • Up to 104 weeks.	6.8% 6/88 • Number of events 7 • Up to 104 weeks.	8.5% 4/47 • Number of events 5 • Up to 104 weeks.
Infections and infestations Bronchitis	3.7% 2/54 • Number of events 2 • Up to 104 weeks.	3.7% 1/27 • Number of events 1 • Up to 104 weeks.	5.9% 2/34 • Number of events 2 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	4.5% 4/88 • Number of events 4 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Infections and infestations Ear infection	7.4% 4/54 • Number of events 4 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	4.5% 4/88 • Number of events 4 • Up to 104 weeks.	0.00% 0/47 • Up to 104 weeks.
Infections and infestations Epstein-Barr virus infection	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	5.9% 2/34 • Number of events 2 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	2.3% 2/88 • Number of events 2 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Infections and infestations Gastroenteritis	16.7% 9/54 • Number of events 9 • Up to 104 weeks.	11.1% 3/27 • Number of events 3 • Up to 104 weeks.	17.6% 6/34 • Number of events 6 • Up to 104 weeks.	10.0% 2/20 • Number of events 6 • Up to 104 weeks.	17.0% 15/88 • Number of events 15 • Up to 104 weeks.	10.6% 5/47 • Number of events 9 • Up to 104 weeks.
Infections and infestations Gastroenteritis viral	5.6% 3/54 • Number of events 4 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	4.5% 4/88 • Number of events 5 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Infections and infestations Influenza	14.8% 8/54 • Number of events 8 • Up to 104 weeks.	18.5% 5/27 • Number of events 5 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	10.0% 2/20 • Number of events 2 • Up to 104 weeks.	10.2% 9/88 • Number of events 9 • Up to 104 weeks.	14.9% 7/47 • Number of events 7 • Up to 104 weeks.
Infections and infestations Nasopharyngitis	13.0% 7/54 • Number of events 10 • Up to 104 weeks.	14.8% 4/27 • Number of events 6 • Up to 104 weeks.	14.7% 5/34 • Number of events 10 • Up to 104 weeks.	10.0% 2/20 • Number of events 2 • Up to 104 weeks.	13.6% 12/88 • Number of events 20 • Up to 104 weeks.	12.8% 6/47 • Number of events 8 • Up to 104 weeks.
Infections and infestations Oral herpes	1.9% 1/54 • Number of events 2 • Up to 104 weeks.	3.7% 1/27 • Number of events 1 • Up to 104 weeks.	5.9% 2/34 • Number of events 2 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	3.4% 3/88 • Number of events 4 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Infections and infestations Otitis externa	5.6% 3/54 • Number of events 3 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	3.4% 3/88 • Number of events 3 • Up to 104 weeks.	0.00% 0/47 • Up to 104 weeks.
Infections and infestations Otitis media	5.6% 3/54 • Number of events 4 • Up to 104 weeks.	7.4% 2/27 • Number of events 2 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	3.4% 3/88 • Number of events 4 • Up to 104 weeks.	6.4% 3/47 • Number of events 3 • Up to 104 weeks.
Infections and infestations Pharyngitis	9.3% 5/54 • Number of events 6 • Up to 104 weeks.	11.1% 3/27 • Number of events 4 • Up to 104 weeks.	11.8% 4/34 • Number of events 4 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	10.2% 9/88 • Number of events 10 • Up to 104 weeks.	6.4% 3/47 • Number of events 4 • Up to 104 weeks.
Infections and infestations Pharyngitis streptococcal	11.1% 6/54 • Number of events 6 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 2 • Up to 104 weeks.	6.8% 6/88 • Number of events 6 • Up to 104 weeks.	2.1% 1/47 • Number of events 2 • Up to 104 weeks.
Infections and infestations Pneumonia mycoplasmal	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Infections and infestations Respiratory tract infection	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Infections and infestations Rhinitis	3.7% 2/54 • Number of events 2 • Up to 104 weeks.	7.4% 2/27 • Number of events 3 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	2.3% 2/88 • Number of events 2 • Up to 104 weeks.	4.3% 2/47 • Number of events 3 • Up to 104 weeks.
Infections and infestations Sinusitis	9.3% 5/54 • Number of events 11 • Up to 104 weeks.	3.7% 1/27 • Number of events 3 • Up to 104 weeks.	11.8% 4/34 • Number of events 4 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	10.2% 9/88 • Number of events 15 • Up to 104 weeks.	2.1% 1/47 • Number of events 3 • Up to 104 weeks.
Infections and infestations Skin infection	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	7.4% 2/27 • Number of events 2 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	2.3% 2/88 • Number of events 2 • Up to 104 weeks.	4.3% 2/47 • Number of events 2 • Up to 104 weeks.
Infections and infestations Upper respiratory tract infection	48.1% 26/54 • Number of events 82 • Up to 104 weeks.	48.1% 13/27 • Number of events 35 • Up to 104 weeks.	44.1% 15/34 • Number of events 42 • Up to 104 weeks.	60.0% 12/20 • Number of events 30 • Up to 104 weeks.	46.6% 41/88 • Number of events 124 • Up to 104 weeks.	53.2% 25/47 • Number of events 65 • Up to 104 weeks.
Infections and infestations Urinary tract infection	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Infections and infestations Viral infection	0.00% 0/54 • Up to 104 weeks.	7.4% 2/27 • Number of events 2 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	4.3% 2/47 • Number of events 2 • Up to 104 weeks.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/54 • Up to 104 weeks.	3.7% 1/27 • Number of events 1 • Up to 104 weeks.	14.7% 5/34 • Number of events 6 • Up to 104 weeks.	15.0% 3/20 • Number of events 3 • Up to 104 weeks.	5.7% 5/88 • Number of events 6 • Up to 104 weeks.	8.5% 4/47 • Number of events 4 • Up to 104 weeks.
Infections and infestations Vulvovaginal mycotic infection	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	5.9% 2/34 • Number of events 2 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	3.4% 3/88 • Number of events 3 • Up to 104 weeks.	0.00% 0/47 • Up to 104 weeks.
Injury, poisoning and procedural complications Concussion	0.00% 0/54 • Up to 104 weeks.	7.4% 2/27 • Number of events 2 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	4.3% 2/47 • Number of events 2 • Up to 104 weeks.
Injury, poisoning and procedural complications Contusion	3.7% 2/54 • Number of events 2 • Up to 104 weeks.	7.4% 2/27 • Number of events 2 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	2.3% 2/88 • Number of events 2 • Up to 104 weeks.	4.3% 2/47 • Number of events 2 • Up to 104 weeks.
Injury, poisoning and procedural complications Fall	0.00% 0/54 • Up to 104 weeks.	3.7% 1/27 • Number of events 1 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	4.3% 2/47 • Number of events 2 • Up to 104 weeks.
Injury, poisoning and procedural complications Hand fracture	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	3.7% 1/27 • Number of events 1 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	4.3% 2/47 • Number of events 2 • Up to 104 weeks.
Injury, poisoning and procedural complications Head injury	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Injury, poisoning and procedural complications Joint injury	0.00% 0/54 • Up to 104 weeks.	7.4% 2/27 • Number of events 2 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	4.3% 2/47 • Number of events 2 • Up to 104 weeks.
Injury, poisoning and procedural complications Ligament sprain	3.7% 2/54 • Number of events 2 • Up to 104 weeks.	7.4% 2/27 • Number of events 2 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	2.3% 2/88 • Number of events 2 • Up to 104 weeks.	4.3% 2/47 • Number of events 2 • Up to 104 weeks.
Injury, poisoning and procedural complications Limb injury	5.6% 3/54 • Number of events 6 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	4.5% 4/88 • Number of events 7 • Up to 104 weeks.	0.00% 0/47 • Up to 104 weeks.
Injury, poisoning and procedural complications Muscle strain	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Injury, poisoning and procedural complications Sunburn	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Injury, poisoning and procedural complications Traumatic haematoma	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Investigations Aspartate aminotransferase increased	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Investigations Body mass index increased	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Investigations Neutrophil count decreased	3.7% 2/54 • Number of events 2 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	8.8% 3/34 • Number of events 5 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	5.7% 5/88 • Number of events 7 • Up to 104 weeks.	0.00% 0/47 • Up to 104 weeks.
Investigations Weight decreased	0.00% 0/54 • Up to 104 weeks.	7.4% 2/27 • Number of events 2 • Up to 104 weeks.	5.9% 2/34 • Number of events 2 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	2.3% 2/88 • Number of events 2 • Up to 104 weeks.	4.3% 2/47 • Number of events 2 • Up to 104 weeks.
Metabolism and nutrition disorders Hypoglycaemia	51.9% 28/54 • Number of events 85 • Up to 104 weeks.	51.9% 14/27 • Number of events 47 • Up to 104 weeks.	44.1% 15/34 • Number of events 42 • Up to 104 weeks.	35.0% 7/20 • Number of events 11 • Up to 104 weeks.	48.9% 43/88 • Number of events 127 • Up to 104 weeks.	44.7% 21/47 • Number of events 58 • Up to 104 weeks.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 3/54 • Number of events 4 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	11.8% 4/34 • Number of events 4 • Up to 104 weeks.	20.0% 4/20 • Number of events 8 • Up to 104 weeks.	8.0% 7/88 • Number of events 8 • Up to 104 weeks.	8.5% 4/47 • Number of events 8 • Up to 104 weeks.
Musculoskeletal and connective tissue disorders Back pain	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	3.7% 1/27 • Number of events 1 • Up to 104 weeks.	11.8% 4/34 • Number of events 4 • Up to 104 weeks.	10.0% 2/20 • Number of events 2 • Up to 104 weeks.	5.7% 5/88 • Number of events 5 • Up to 104 weeks.	6.4% 3/47 • Number of events 3 • Up to 104 weeks.
Musculoskeletal and connective tissue disorders Muscle spasms	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	3.7% 2/54 • Number of events 2 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	5.9% 2/34 • Number of events 2 • Up to 104 weeks.	10.0% 2/20 • Number of events 2 • Up to 104 weeks.	4.5% 4/88 • Number of events 4 • Up to 104 weeks.	4.3% 2/47 • Number of events 2 • Up to 104 weeks.
Musculoskeletal and connective tissue disorders Myalgia	7.4% 4/54 • Number of events 4 • Up to 104 weeks.	3.7% 1/27 • Number of events 2 • Up to 104 weeks.	8.8% 3/34 • Number of events 3 • Up to 104 weeks.	10.0% 2/20 • Number of events 5 • Up to 104 weeks.	8.0% 7/88 • Number of events 7 • Up to 104 weeks.	6.4% 3/47 • Number of events 7 • Up to 104 weeks.
Musculoskeletal and connective tissue disorders Neck pain	5.6% 3/54 • Number of events 4 • Up to 104 weeks.	3.7% 1/27 • Number of events 1 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	3.4% 3/88 • Number of events 4 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Musculoskeletal and connective tissue disorders Pain in extremity	3.7% 2/54 • Number of events 3 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	5.9% 2/34 • Number of events 2 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	4.5% 4/88 • Number of events 5 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Musculoskeletal and connective tissue disorders Synovial cyst	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Musculoskeletal and connective tissue disorders Temporomandibular joint syndrome	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Musculoskeletal and connective tissue disorders Tendonitis	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	5.9% 2/34 • Number of events 2 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	3.4% 3/88 • Number of events 3 • Up to 104 weeks.	0.00% 0/47 • Up to 104 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of skin	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	5.6% 3/54 • Number of events 3 • Up to 104 weeks.	7.4% 2/27 • Number of events 2 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	3.4% 3/88 • Number of events 3 • Up to 104 weeks.	4.3% 2/47 • Number of events 2 • Up to 104 weeks.
Nervous system disorders Dizziness	3.7% 2/54 • Number of events 2 • Up to 104 weeks.	7.4% 2/27 • Number of events 4 • Up to 104 weeks.	11.8% 4/34 • Number of events 4 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	6.8% 6/88 • Number of events 6 • Up to 104 weeks.	6.4% 3/47 • Number of events 5 • Up to 104 weeks.
Nervous system disorders Dizziness postural	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Nervous system disorders Headache	25.9% 14/54 • Number of events 24 • Up to 104 weeks.	22.2% 6/27 • Number of events 17 • Up to 104 weeks.	14.7% 5/34 • Number of events 8 • Up to 104 weeks.	30.0% 6/20 • Number of events 7 • Up to 104 weeks.	21.6% 19/88 • Number of events 32 • Up to 104 weeks.	25.5% 12/47 • Number of events 24 • Up to 104 weeks.
Nervous system disorders Paraesthesia	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Nervous system disorders Presyncope	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	2.9% 1/34 • Number of events 1 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	2.3% 2/88 • Number of events 2 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Nervous system disorders Syncope	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	11.1% 3/27 • Number of events 4 • Up to 104 weeks.	5.9% 2/34 • Number of events 2 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	3.4% 3/88 • Number of events 3 • Up to 104 weeks.	8.5% 4/47 • Number of events 5 • Up to 104 weeks.
Psychiatric disorders Depression	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	11.8% 4/34 • Number of events 4 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	5.7% 5/88 • Number of events 5 • Up to 104 weeks.	0.00% 0/47 • Up to 104 weeks.
Psychiatric disorders Stress	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Respiratory, thoracic and mediastinal disorders Cough	16.7% 9/54 • Number of events 9 • Up to 104 weeks.	25.9% 7/27 • Number of events 9 • Up to 104 weeks.	5.9% 2/34 • Number of events 4 • Up to 104 weeks.	10.0% 2/20 • Number of events 2 • Up to 104 weeks.	12.5% 11/88 • Number of events 13 • Up to 104 weeks.	19.1% 9/47 • Number of events 11 • Up to 104 weeks.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Respiratory, thoracic and mediastinal disorders Nasal congestion	7.4% 4/54 • Number of events 6 • Up to 104 weeks.	7.4% 2/27 • Number of events 2 • Up to 104 weeks.	11.8% 4/34 • Number of events 4 • Up to 104 weeks.	15.0% 3/20 • Number of events 3 • Up to 104 weeks.	9.1% 8/88 • Number of events 10 • Up to 104 weeks.	10.6% 5/47 • Number of events 5 • Up to 104 weeks.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	16.7% 9/54 • Number of events 17 • Up to 104 weeks.	14.8% 4/27 • Number of events 5 • Up to 104 weeks.	14.7% 5/34 • Number of events 6 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	15.9% 14/88 • Number of events 23 • Up to 104 weeks.	10.6% 5/47 • Number of events 6 • Up to 104 weeks.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	7.4% 2/27 • Number of events 2 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	10.0% 2/20 • Number of events 2 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	8.5% 4/47 • Number of events 4 • Up to 104 weeks.
Respiratory, thoracic and mediastinal disorders Tonsillolith	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	5.9% 2/34 • Number of events 8 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	2.3% 2/88 • Number of events 8 • Up to 104 weeks.	0.00% 0/47 • Up to 104 weeks.
Skin and subcutaneous tissue disorders Acne	1.9% 1/54 • Number of events 1 • Up to 104 weeks.	3.7% 1/27 • Number of events 1 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	1.1% 1/88 • Number of events 1 • Up to 104 weeks.	4.3% 2/47 • Number of events 2 • Up to 104 weeks.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Skin and subcutaneous tissue disorders Dermal cyst	0.00% 0/54 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	0.00% 0/88 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Skin and subcutaneous tissue disorders Dermatitis	5.6% 3/54 • Number of events 5 • Up to 104 weeks.	3.7% 1/27 • Number of events 2 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	3.4% 3/88 • Number of events 5 • Up to 104 weeks.	2.1% 1/47 • Number of events 2 • Up to 104 weeks.
Skin and subcutaneous tissue disorders Dermatitis contact	5.6% 3/54 • Number of events 3 • Up to 104 weeks.	0.00% 0/27 • Up to 104 weeks.	5.9% 2/34 • Number of events 2 • Up to 104 weeks.	15.0% 3/20 • Number of events 3 • Up to 104 weeks.	5.7% 5/88 • Number of events 5 • Up to 104 weeks.	6.4% 3/47 • Number of events 3 • Up to 104 weeks.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/54 • Up to 104 weeks.	3.7% 1/27 • Number of events 1 • Up to 104 weeks.	5.9% 2/34 • Number of events 2 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	2.3% 2/88 • Number of events 2 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Skin and subcutaneous tissue disorders Eczema	3.7% 2/54 • Number of events 2 • Up to 104 weeks.	3.7% 1/27 • Number of events 1 • Up to 104 weeks.	5.9% 2/34 • Number of events 2 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	4.5% 4/88 • Number of events 4 • Up to 104 weeks.	2.1% 1/47 • Number of events 1 • Up to 104 weeks.
Skin and subcutaneous tissue disorders Ingrowing nail	3.7% 2/54 • Number of events 2 • Up to 104 weeks.	7.4% 2/27 • Number of events 2 • Up to 104 weeks.	0.00% 0/34 • Up to 104 weeks.	0.00% 0/20 • Up to 104 weeks.	2.3% 2/88 • Number of events 2 • Up to 104 weeks.	4.3% 2/47 • Number of events 2 • Up to 104 weeks.
Skin and subcutaneous tissue disorders Lipohypertrophy	3.7% 2/54 • Number of events 2 • Up to 104 weeks.	14.8% 4/27 • Number of events 5 • Up to 104 weeks.	5.9% 2/34 • Number of events 2 • Up to 104 weeks.	5.0% 1/20 • Number of events 1 • Up to 104 weeks.	4.5% 4/88 • Number of events 4 • Up to 104 weeks.	10.6% 5/47 • Number of events 6 • Up to 104 weeks.

Additional Information

Director, Clinical Research Operations Program

DAIT/NIAID

Phone: 301-594-7669

Email: DAITClinicalTrialsGov@niaid.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place