Protege Encore Study- Clinical Trial of Teplizumab (MGA03... | NCT00920582

NCT00920582

Status Module

Name	Class
Eli Lilly and Company	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Herold Regimen	Experimental	14-day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-14. Repeat at Week 26	Biological: Teplizumab Herold Regimen
33.3% Herold Regimen	Experimental	Subjects received a 14-day cycle of teplizumab consisting of daily IV doses of 17 µg/m2, 34 µg/m2, 68 µg/m2, and 136 µg/m2 on Study Days 1-4, respectively, and one dose of 273 µg/m2 on each of Study Days 5-14. Repeat at Week 26	Biological: Teplizumab 33.3% Herold Regimen
Curtailed Herold Regimen	Experimental	Subjects received a 6 day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-6, followed by 8 days of IV placebo (Study Days 7-14). Repeat at Week 26	Biological: Teplizumab Curtailed Herold Regimen
Placebo	Placebo Comparator	14-day cycle of placebo consisting of daily IV doses. Repeat at Week 26	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Teplizumab Herold Regimen	Biological	Full dose of teplizumab IV for 14 days, repeated at Week 26	Herold Regimen

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Proportion of Subjects With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%.		52 weeks after randomization
Mean Change From Baseline in HbA1c Between Teplizumab and Placebo		52 weeks after randomization

Secondary Outcomes

Measure	Description	Time Frame
The Change in Beta-cell Function as Measured by C-peptide Secretory Response Following a Mixed Meal		52 weeks after randomization
The Change in Beta-cell Function as Measured by C-peptide Secretory Response Following a Mixed Meal		104 weeks after randomization

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects 8-35 years old
Body weight > 36 Kg
Diagnosis of diabetes mellitus according to the American Diabetes Association (ADA) criteria
Randomization on Study Day 0 within 12 weeks of first visit to any physician for symptoms or signs of diabetes
Requires insulin for T1DM or has required insulin at some time between diagnosis and administration of study drug
Detectable fasting or stimulated C-peptide level (above the lower limit of the reportable range of the assay) at screening
Diagnosis of T1DM as evidenced by one positive result on testing for any of the following antibodies at screening:
- Islet-cell autoantibodies 512 (ICA512)/islet antigen-2 (IA-2),
- Glutamic acid decarboxylase (GAD) autoantibodies, or
- Insulin autoantibodies (in subjects on insulin for more than 2 weeks, ICA512/IA-2 or GAD must be positive).

Exclusion Criteria:

Prior administration of a monoclonal antibody-within the 1 year before randomization
Participation in any type of therapeutic drug or vaccine clinical trial within the last 12 weeks before randomization at Study Day 0
Any medical condition that, in the opinion of the investigator, would interfere with safe completion of the trial
Pregnant females or lactating females who intend to provide their own breast milk to the baby during the study
Current therapy with GLP-1 receptor agonists (e.g., exenatide or pramlintide), or any other agents that might stimulate pancreatic beta cell regeneration or insulin secretion
Current treatment with oral antidiabetic agents
Evidence of active or latent tuberculosis
Vaccination with a live virus or organism within the 8 weeks before randomization continuing through Week 52 of the study.
- Influenza vaccination with a killed virus, including booster vaccinations, within 4 weeks before or after each dosing cycle.
- Vaccination with other antigens or killed organisms within 8 weeks before or after each dosing cycle
Any infectious mononucleosis-like illness within the 6 months before randomization

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35233	United States
NEA Clinic

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Herold Regimen	14-day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab Herold Regimen: Full dose of teplizumab IV for 14 days, repeated at Week 26
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Herold Regimen	14-day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab Herold Regimen: Full dose of teplizumab IV for 14 days, repeated at Week 26
BG001	33.3% Herold Regimen	Subjects received a 14-day cycle of teplizumab consisting of daily IV doses of 17 µg/m2, 34 µg/m2, 68 µg/m2, and 136 µg/m2 on Study Days 1-4, respectively, and one dose of 273 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab 33.3% Herold Regimen: One third full dose of teplizumab IV for 14 days, repeated at Week 26
BG002	Curtailed Herold Regimen	Subjects received a 6 day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-6, followed by 8 days of IV placebo (Study Days 7-14). Repeat at Week 26 Teplizumab Curtailed Herold Regimen: Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26
BG003	Placebo	14-day cycle of placebo consisting of daily IV doses. Repeat at Week 26 Placebo: IV dosing daily for 14 days repeated at Week 26
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00016.0(8.0 to 23.0) BG00116.0(8.0 to 35.0) BG00215.0(8.0 to 33.0) BG003

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

8-11 years

Title	Measurements
	BG00013 BG00112 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00025 BG00120 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0011 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Romania

Title	Measurements
	BG0003 BG0013 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Proportion of Subjects With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%.

Posted

Count of Participants

Participants

52 weeks after randomization

ID	Title	Description
OG000	Herold Regimen	14-day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab Herold Regimen: Full dose of teplizumab IV for 14 days, repeated at Week 26
OG001	33.3% Herold Regimen	Subjects received a 14-day cycle of teplizumab consisting of daily IV doses of 17 µg/m2, 34 µg/m2, 68 µg/m2, and 136 µg/m2 on Study Days 1-4, respectively, and one dose of 273 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab 33.3% Herold Regimen: One third full dose of teplizumab IV for 14 days, repeated at Week 26
OG002	Curtailed Herold Regimen	Subjects received a 6 day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-6, followed by 8 days of IV placebo (Study Days 7-14). Repeat at Week 26 Teplizumab Curtailed Herold Regimen: Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26
OG003	Placebo	14-day cycle of placebo consisting of daily IV doses. Repeat at Week 26 Placebo: IV dosing daily for 14 days repeated at Week 26

Units	Counts
Participants	OG00063 OG00166 OG00263 OG003

Title

Denominators

Categories

Title	Measurements
	OG0008 OG0018 OG0029 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG003		Mantel Haenszel		0.609		Odds Ratio (OR)	1.348			2-Sided	95	0.431	4.219					Superiority
OG001 OG003		Mantel Haenszel		0.601

Primary

Mean Change From Baseline in HbA1c Between Teplizumab and Placebo

Analysis population includes all participants with available data at 52 weeks after randomization.

Posted

Mean

Standard Deviation

percent HbA1c

52 weeks after randomization

ID	Title	Description
OG000	Herold Regimen	14-day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab Herold Regimen: Full dose of teplizumab IV for 14 days, repeated at Week 26
OG001	33.3% Herold Regimen	Subjects received a 14-day cycle of teplizumab consisting of daily IV doses of 17 µg/m2, 34 µg/m2, 68 µg/m2, and 136 µg/m2 on Study Days 1-4, respectively, and one dose of 273 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab 33.3% Herold Regimen: One third full dose of teplizumab IV for 14 days, repeated at Week 26
OG002	Curtailed Herold Regimen	Subjects received a 6 day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-6, followed by 8 days of IV placebo (Study Days 7-14). Repeat at Week 26 Teplizumab Curtailed Herold Regimen: Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26

Secondary

The Change in Beta-cell Function as Measured by C-peptide Secretory Response Following a Mixed Meal

Posted

Mean

Standard Deviation

nmol/L

52 weeks after randomization

ID	Title	Description
OG000	Herold Regimen	14-day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab Herold Regimen: Full dose of teplizumab IV for 14 days, repeated at Week 26
OG001	33.3% Herold Regimen	Subjects received a 14-day cycle of teplizumab consisting of daily IV doses of 17 µg/m2, 34 µg/m2, 68 µg/m2, and 136 µg/m2 on Study Days 1-4, respectively, and one dose of 273 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab 33.3% Herold Regimen: One third full dose of teplizumab IV for 14 days, repeated at Week 26
OG002	Curtailed Herold Regimen	Subjects received a 6 day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-6, followed by 8 days of IV placebo (Study Days 7-14). Repeat at Week 26 Teplizumab Curtailed Herold Regimen: Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26

Secondary

The Change in Beta-cell Function as Measured by C-peptide Secretory Response Following a Mixed Meal

The study was terminated early and no data for C-peptide secretory response following a mixed meal was collected at Week 104. Measurement of C-peptide response after a mixed meal at selected timepoints up to Week 104 was replaced with measurement of fasting C-peptide levels at Day 365 by protocol amendment. Data were collected only at Days 141 and 365, due to the early termination of the study.

Posted

104 weeks after randomization

ID	Title	Description
OG000	Herold Regimen	14-day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab Herold Regimen: Full dose of teplizumab IV for 14 days, repeated at Week 26
OG001	33.3% Herold Regimen	Subjects received a 14-day cycle of teplizumab consisting of daily IV doses of 17 µg/m2, 34 µg/m2, 68 µg/m2, and 136 µg/m2 on Study Days 1-4, respectively, and one dose of 273 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab 33.3% Herold Regimen: One third full dose of teplizumab IV for 14 days, repeated at Week 26
OG002	Curtailed Herold Regimen

Secondary

Mean Number of Total, Major, Minor and Nocturnal Hypoglycemia Events

Number of hypoglycemic events by type per participant

Analysis of hypoglycemic events at 52 weeks and 104 weeks was combined in the statistical analysis plan. The presentation reflects the total hypoglycemic events throughout the study.

Posted

Mean

Standard Deviation

events

Throughout the study up to 2 years

ID	Title	Description
OG000	Herold Regimen	14-day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab Herold Regimen: Full dose of teplizumab IV for 14 days, repeated at Week 26
OG001	33.3% Herold Regimen	Subjects received a 14-day cycle of teplizumab consisting of daily IV doses of 17 µg/m2, 34 µg/m2, 68 µg/m2, and 136 µg/m2 on Study Days 1-4, respectively, and one dose of 273 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab 33.3% Herold Regimen: One third full dose of teplizumab IV for 14 days, repeated at Week 26
OG002	Curtailed Herold Regimen	Subjects received a 6 day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-6, followed by 8 days of IV placebo (Study Days 7-14). Repeat at Week 26 Teplizumab Curtailed Herold Regimen: Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26

Secondary

Mean Number of Daily Insulin Injections

The number of daily insulin injections was not collected. Insulin use was analyzed as units/kg/day, not by number of injections.

Posted

52 weeks after randomization

ID	Title	Description
OG000	Herold Regimen	14-day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab Herold Regimen: Full dose of teplizumab IV for 14 days, repeated at Week 26
OG001	33.3% Herold Regimen	Subjects received a 14-day cycle of teplizumab consisting of daily IV doses of 17 µg/m2, 34 µg/m2, 68 µg/m2, and 136 µg/m2 on Study Days 1-4, respectively, and one dose of 273 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab 33.3% Herold Regimen: One third full dose of teplizumab IV for 14 days, repeated at Week 26
OG002	Curtailed Herold Regimen	Subjects received a 6 day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-6, followed by 8 days of IV placebo (Study Days 7-14). Repeat at Week 26 Teplizumab Curtailed Herold Regimen: Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26

Secondary

Number of Subjects With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%.

Posted

Count of Participants

Participants

104 weeks after randomization

ID	Title	Description
OG000	Herold Regimen	14-day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab Herold Regimen: Full dose of teplizumab IV for 14 days, repeated at Week 26
OG001	33.3% Herold Regimen	Subjects received a 14-day cycle of teplizumab consisting of daily IV doses of 17 µg/m2, 34 µg/m2, 68 µg/m2, and 136 µg/m2 on Study Days 1-4, respectively, and one dose of 273 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab 33.3% Herold Regimen: One third full dose of teplizumab IV for 14 days, repeated at Week 26
OG002	Curtailed Herold Regimen	Subjects received a 6 day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-6, followed by 8 days of IV placebo (Study Days 7-14). Repeat at Week 26 Teplizumab Curtailed Herold Regimen: Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26

Secondary

The Proportion of Subjects Who Have Both a Total Daily Insulin Dose < 0.5 U/Kg/Day and Hemoglobin A1c (HbA1c) Level < 7.0%

Posted

Count of Participants

Participants

52 weeks after randomization

ID	Title	Description
OG000	Herold Regimen	14-day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab Herold Regimen: Full dose of teplizumab IV for 14 days, repeated at Week 26
OG001	33.3% Herold Regimen	Subjects received a 14-day cycle of teplizumab consisting of daily IV doses of 17 µg/m2, 34 µg/m2, 68 µg/m2, and 136 µg/m2 on Study Days 1-4, respectively, and one dose of 273 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab 33.3% Herold Regimen: One third full dose of teplizumab IV for 14 days, repeated at Week 26
OG002	Curtailed Herold Regimen	Subjects received a 6 day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-6, followed by 8 days of IV placebo (Study Days 7-14). Repeat at Week 26 Teplizumab Curtailed Herold Regimen: Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26

Secondary

The Mean HbA1c Change From Baseline

No statistical analysis was performed on the limited data collected at 104 weeks after randomization. Only descriptive statistics are provided.

Posted

Mean

Standard Deviation

percent glycosylated hemoglobin

104 weeks after randomization

ID	Title	Description
OG000	Herold Regimen	14-day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab Herold Regimen: Full dose of teplizumab IV for 14 days, repeated at Week 26
OG001	33.3% Herold Regimen	Subjects received a 14-day cycle of teplizumab consisting of daily IV doses of 17 µg/m2, 34 µg/m2, 68 µg/m2, and 136 µg/m2 on Study Days 1-4, respectively, and one dose of 273 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab 33.3% Herold Regimen: One third full dose of teplizumab IV for 14 days, repeated at Week 26
OG002	Curtailed Herold Regimen	Subjects received a 6 day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-6, followed by 8 days of IV placebo (Study Days 7-14). Repeat at Week 26 Teplizumab Curtailed Herold Regimen: Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26

Secondary

Number of Participants With Adverse Events

Posted

Count of Participants

Participants

throughout the study, up to 104 weeks

ID	Title	Description
OG000	Herold Regimen	14-day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab Herold Regimen: Full dose of teplizumab IV for 14 days, repeated at Week 26
OG001	33.3% Herold Regimen	Subjects received a 14-day cycle of teplizumab consisting of daily IV doses of 17 µg/m2, 34 µg/m2, 68 µg/m2, and 136 µg/m2 on Study Days 1-4, respectively, and one dose of 273 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab 33.3% Herold Regimen: One third full dose of teplizumab IV for 14 days, repeated at Week 26
OG002	Curtailed Herold Regimen	Subjects received a 6 day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-6, followed by 8 days of IV placebo (Study Days 7-14). Repeat at Week 26 Teplizumab Curtailed Herold Regimen: Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26

Secondary

Number of Participants With Serious Adverse Events

Posted

Count of Participants

Participants

throughout the study, up to 104 weeks

ID	Title	Description
OG000	Herold Regimen	14-day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab Herold Regimen: Full dose of teplizumab IV for 14 days, repeated at Week 26
OG001	33.3% Herold Regimen	Subjects received a 14-day cycle of teplizumab consisting of daily IV doses of 17 µg/m2, 34 µg/m2, 68 µg/m2, and 136 µg/m2 on Study Days 1-4, respectively, and one dose of 273 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab 33.3% Herold Regimen: One third full dose of teplizumab IV for 14 days, repeated at Week 26
OG002	Curtailed Herold Regimen	Subjects received a 6 day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-6, followed by 8 days of IV placebo (Study Days 7-14). Repeat at Week 26 Teplizumab Curtailed Herold Regimen: Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Herold Regimen	14-day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab Herold Regimen: Full dose of teplizumab IV for 14 days, repeated at Week 26	63	7	63	63	63
EG001	33.3% Herold Regimen	Subjects received a 14-day cycle of teplizumab consisting of daily IV doses of 17 µg/m2, 34 µg/m2, 68 µg/m2, and 136 µg/m2 on Study Days 1-4, respectively, and one dose of 273 µg/m2 on each of Study Days 5-14. Repeat at Week 26 Teplizumab 33.3% Herold Regimen: One third full dose of teplizumab IV for 14 days, repeated at Week 26	66	6	66	66	66
EG002	Curtailed Herold Regimen	Subjects received a 6 day cycle of teplizumab consisting of daily IV doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, and 413 µg/m2 on Study Days 1-4, respectively, and one dose of 826 µg/m2 on each of Study Days 5-6, followed by 8 days of IV placebo (Study Days 7-14). Repeat at Week 26 Teplizumab Curtailed Herold Regimen: Full dose of teplizumab IV for 6 days followed by placebo for 8 days, repeated at Week 26	63	8	63	63	63
EG003	Placebo	14-day cycle of placebo consisting of daily IV doses. Repeat at Week 26 Placebo: IV dosing daily for 14 days repeated at Week 26	62	3	62	62	62

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Lymphopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	too few lymphocytes	EG0001 affected63 at risk EG0010 affected66 at risk EG0021 affected63 at risk EG0030 affected62 at risk
Deafness neurosensory	Ear and labyrinth disorders	MedDRA	Systematic Assessment		EG0000 affected63 at risk EG0011 affected66 at risk EG0020 affected63 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment		EG0001 affected63 at risk EG0010 affected66 at risk EG0020 affected63 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA	Systematic Assessment		EG0000 affected63 at risk EG0010 affected66 at risk EG0021 affected63 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment		EG0000 affected63 at risk EG0011 affected66 at risk EG0020 affected63 at risk EG003
Pain	General disorders	MedDRA	Systematic Assessment		EG0000 affected63 at risk EG0011 affected66 at risk EG0020 affected63 at risk EG003
Cytokine release syndrome	Immune system disorders	MedDRA	Systematic Assessment		EG0001 affected63 at risk EG0011 affected66 at risk EG0020 affected63 at risk EG003
Hepatic amoebiasis	Infections and infestations	MedDRA	Systematic Assessment	Entamoeba infection in the liver	EG0000 affected63 at risk EG0010 affected66 at risk EG0021 affected63 at risk EG003
Pyelonephritis	Infections and infestations	MedDRA	Systematic Assessment	kidney infection	EG0001 affected63 at risk EG0010 affected66 at risk EG0020 affected63 at risk EG003
Staphylococcal sepsis	Infections and infestations	MedDRA	Systematic Assessment		EG0000 affected63 at risk EG0010 affected66 at risk EG0021 affected63 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA	Systematic Assessment		EG0001 affected63 at risk EG0010 affected66 at risk EG0020 affected63 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA	Systematic Assessment	stomach flu	EG0000 affected63 at risk EG0010 affected66 at risk EG0020 affected63 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA	Systematic Assessment		EG0001 affected63 at risk EG0011 affected66 at risk EG0020 affected63 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA	Systematic Assessment		EG0001 affected63 at risk EG0011 affected66 at risk EG0020 affected63 at risk EG003
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	too much sugar, not enough insulin	EG0001 affected63 at risk EG0011 affected66 at risk EG0023 affected63 at risk EG003
Hypoglycaemic seizure	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	seizure from low blood sugar	EG0000 affected63 at risk EG0011 affected66 at risk EG0022 affected63 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	too much blood sugar	EG0001 affected63 at risk EG0010 affected66 at risk EG0020 affected63 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	not enough blood sugar	EG0000 affected63 at risk EG0011 affected66 at risk EG0020 affected63 at risk EG003
Hypoglycaemic unconsciousness	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	unconscious due to low blood sugar	EG0001 affected63 at risk EG0010 affected66 at risk EG0020 affected63 at risk EG003
Mental disorder	Psychiatric disorders	MedDRA	Systematic Assessment		EG0001 affected63 at risk EG0010 affected66 at risk EG0020 affected63 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Lymphopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	too few lymphocytes	EG00026 affected63 at risk EG00121 affected66 at risk EG00225 affected63 at risk EG0036 affected62 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	too few white blood cells	EG00011 affected63 at risk EG00112 affected66 at risk EG00211 affected63 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	too few blood neutrophils	EG0007 affected63 at risk EG0018 affected66 at risk EG0025 affected63 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA	Systematic Assessment	too few red blood cells	EG0001 affected63 at risk EG0012 affected66 at risk EG0024 affected63 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment		EG0006 affected63 at risk EG0015 affected66 at risk EG0024 affected63 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment		EG0003 affected63 at risk EG0013 affected66 at risk EG0029 affected63 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA	Systematic Assessment		EG0003 affected63 at risk EG0011 affected66 at risk EG0025 affected63 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment		EG0001 affected63 at risk EG0013 affected66 at risk EG0024 affected63 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment		EG0002 affected63 at risk EG0010 affected66 at risk EG0024 affected63 at risk EG003
Pyrexia	General disorders	MedDRA	Systematic Assessment	fever	EG00014 affected63 at risk EG00112 affected66 at risk EG00220 affected63 at risk EG003
Chills	General disorders	MedDRA	Systematic Assessment		EG0005 affected63 at risk EG0012 affected66 at risk EG0025 affected63 at risk EG003
Epstein-Barr viraemia	Infections and infestations	MedDRA	Systematic Assessment	Epstein-Barr Virus infection	EG00013 affected63 at risk EG0015 affected66 at risk EG0026 affected63 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	sore throat	EG0003 affected63 at risk EG0018 affected66 at risk EG0028 affected63 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment		EG0003 affected63 at risk EG0015 affected66 at risk EG0026 affected63 at risk EG003
Pharyngitis	Infections and infestations	MedDRA	Systematic Assessment	sore throat	EG0003 affected63 at risk EG0011 affected66 at risk EG0022 affected63 at risk EG003
Blood bicarbonate decreased	Investigations	MedDRA	Systematic Assessment		EG00031 affected63 at risk EG00138 affected66 at risk EG00227 affected63 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA	Systematic Assessment		EG00035 affected63 at risk EG00132 affected66 at risk EG00233 affected63 at risk EG003
White blood cell count decreased	Investigations	MedDRA	Systematic Assessment		EG00039 affected63 at risk EG00128 affected66 at risk EG00229 affected63 at risk EG003
Haemoglobin decreased	Investigations	MedDRA	Systematic Assessment		EG00023 affected63 at risk EG00120 affected66 at risk EG00222 affected63 at risk EG003
Neutrophil count decreased	Investigations	MedDRA	Systematic Assessment		EG00023 affected63 at risk EG00116 affected66 at risk EG00223 affected63 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA	Systematic Assessment		EG00020 affected63 at risk EG00115 affected66 at risk EG00222 affected63 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA	Systematic Assessment		EG00020 affected63 at risk EG00114 affected66 at risk EG00219 affected63 at risk EG003
Blood potassium increased	Investigations	MedDRA	Systematic Assessment		EG00016 affected63 at risk EG00112 affected66 at risk EG00214 affected63 at risk EG003
Blood sodium decreased	Investigations	MedDRA	Systematic Assessment		EG0009 affected63 at risk EG00117 affected66 at risk EG00214 affected63 at risk EG003
Blood calcium decreased	Investigations	MedDRA	Systematic Assessment		EG00020 affected63 at risk EG00113 affected66 at risk EG0028 affected63 at risk EG003
Platelet count decreased	Investigations	MedDRA	Systematic Assessment		EG00019 affected63 at risk EG00113 affected66 at risk EG00211 affected63 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA	Systematic Assessment		EG00011 affected63 at risk EG00112 affected66 at risk EG00212 affected63 at risk EG003
Blood calcium increased	Investigations	MedDRA	Systematic Assessment		EG0006 affected63 at risk EG0015 affected66 at risk EG0027 affected63 at risk EG003
Blood bilirubin increased	Investigations	MedDRA	Systematic Assessment		EG0007 affected63 at risk EG0019 affected66 at risk EG0023 affected63 at risk EG003
Epstein-Barr virus antibody positive	Investigations	MedDRA	Systematic Assessment		EG0006 affected63 at risk EG0016 affected66 at risk EG0024 affected63 at risk EG003
Blood phosphorus increased	Investigations	MedDRA	Systematic Assessment		EG0005 affected63 at risk EG0016 affected66 at risk EG0026 affected63 at risk EG003
Blood albumin decreased	Investigations	MedDRA	Systematic Assessment		EG0006 affected63 at risk EG0013 affected66 at risk EG0025 affected63 at risk EG003
Blood creatinine increased	Investigations	MedDRA	Systematic Assessment		EG0004 affected63 at risk EG0014 affected66 at risk EG0025 affected63 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA	Systematic Assessment		EG0004 affected63 at risk EG0012 affected66 at risk EG0027 affected63 at risk EG003
Blood sodium increased	Investigations	MedDRA	Systematic Assessment		EG0006 affected63 at risk EG0014 affected66 at risk EG0021 affected63 at risk EG003
Eosinophil count increased	Investigations	MedDRA	Systematic Assessment		EG0003 affected63 at risk EG0013 affected66 at risk EG0024 affected63 at risk EG003
Blood chloride decreased	Investigations	MedDRA	Systematic Assessment		EG0004 affected63 at risk EG0013 affected66 at risk EG0022 affected63 at risk EG003
Blood potassium decreased	Investigations	MedDRA	Systematic Assessment		EG0005 affected63 at risk EG0012 affected66 at risk EG0023 affected63 at risk EG003
Blood bicarbonate increased	Investigations	MedDRA	Systematic Assessment		EG0002 affected63 at risk EG0014 affected66 at risk EG0023 affected63 at risk EG003
Red blood cell count decreased	Investigations	MedDRA	Systematic Assessment		EG0005 affected63 at risk EG0011 affected66 at risk EG0022 affected63 at risk EG003
Bilirubin conjugated increased	Investigations	MedDRA	Systematic Assessment		EG0005 affected63 at risk EG0013 affected66 at risk EG0020 affected63 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	not enough sodium in the bloodstream	EG0008 affected63 at risk EG0016 affected66 at risk EG00210 affected63 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	not enough calcium in the bloodstream	EG0009 affected63 at risk EG0017 affected66 at risk EG0027 affected63 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	too much potassium in the bloodstream	EG0005 affected63 at risk EG0018 affected66 at risk EG0028 affected63 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	not enough sugar in the bloodstream	EG0004 affected63 at risk EG0012 affected66 at risk EG0026 affected63 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	not enough albumin in the bloodstream	EG0005 affected63 at risk EG0011 affected66 at risk EG0023 affected63 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	too much calcium in the bloodstream	EG0000 affected63 at risk EG0012 affected66 at risk EG0025 affected63 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	muscle pain	EG0005 affected63 at risk EG0011 affected66 at risk EG0025 affected63 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment		EG0004 affected63 at risk EG0010 affected66 at risk EG0021 affected63 at risk EG003
Headache	Nervous system disorders	MedDRA	Systematic Assessment		EG00014 affected63 at risk EG00111 affected66 at risk EG00215 affected63 at risk EG003
Depression	Psychiatric disorders	MedDRA	Systematic Assessment		EG0004 affected63 at risk EG0011 affected66 at risk EG0020 affected63 at risk EG003
proteinuria	Renal and urinary disorders	MedDRA	Systematic Assessment	protein in the urine	EG0004 affected63 at risk EG0017 affected66 at risk EG0023 affected63 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	mouth and throat pain	EG0003 affected63 at risk EG0016 affected66 at risk EG0025 affected63 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment		EG0002 affected63 at risk EG0013 affected66 at risk EG0024 affected63 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment		EG00011 affected63 at risk EG0019 affected66 at risk EG0029 affected63 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment		EG0009 affected63 at risk EG0018 affected66 at risk EG0025 affected63 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment		EG0007 affected63 at risk EG0014 affected66 at risk EG0024 affected63 at risk EG003
Rash papular	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment		EG0004 affected63 at risk EG0017 affected66 at risk EG0023 affected63 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment		EG0006 affected63 at risk EG0011 affected66 at risk EG0023 affected63 at risk EG003
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment		EG0004 affected63 at risk EG0012 affected66 at risk EG0021 affected63 at risk EG003
urticaria	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	itchy rash	EG0004 affected63 at risk EG0011 affected66 at risk EG0021 affected63 at risk EG003
Fatigue	General disorders	MedDRA	Systematic Assessment		EG0001 affected63 at risk EG0013 affected66 at risk EG0025 affected63 at risk EG003

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases