Trial Outcomes & Findings for Protege Encore Study- Clinical Trial of Teplizumab (MGA031) in Children and Adults With Recent-Onset Type 1 Diabetes Mellitus (NCT NCT00920582)

NCT ID: NCT00920582

Last Updated: 2023-12-20

Results Overview

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

254 participants

Primary outcome timeframe

52 weeks after randomization

Results posted on

2023-12-20

Participant Flow

Participant milestones

Participant milestones
Measure	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	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	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	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
Overall Study STARTED	63	66	63	62
Overall Study COMPLETED	50	60	52	57
Overall Study NOT COMPLETED	13	6	11	5

Reasons for withdrawal

Reasons for withdrawal
Measure	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	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	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	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
Overall Study Lost to Follow-up	5	1	2	0
Overall Study Withdrawal by Subject	5	4	6	3
Overall Study Protocol Violation	1	0	0	0
Overall Study Other	2	1	3	2

Baseline Characteristics

Protege Encore Study- Clinical Trial of Teplizumab (MGA031) in Children and Adults With Recent-Onset Type 1 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Herold Regimen n=63 Participants 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	33.3% Herold Regimen n=66 Participants 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	Curtailed Herold Regimen n=63 Participants 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	Placebo n=62 Participants 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	Total n=254 Participants Total of all reporting groups
Age, Continuous	16.0 years n=5 Participants	16.0 years n=7 Participants	15.0 years n=5 Participants	16.0 years n=4 Participants	16.0 years n=21 Participants
Age, Customized 8-11 years	13 Participants n=5 Participants	12 Participants n=7 Participants	13 Participants n=5 Participants	11 Participants n=4 Participants	49 Participants n=21 Participants
Age, Customized 12-17 years	24 Participants n=5 Participants	29 Participants n=7 Participants	24 Participants n=5 Participants	25 Participants n=4 Participants	102 Participants n=21 Participants
Age, Customized 18-35 years	26 Participants n=5 Participants	25 Participants n=7 Participants	26 Participants n=5 Participants	26 Participants n=4 Participants	103 Participants n=21 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	20 Participants n=7 Participants	17 Participants n=5 Participants	21 Participants n=4 Participants	83 Participants n=21 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	46 Participants n=7 Participants	46 Participants n=5 Participants	41 Participants n=4 Participants	171 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants	6 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	63 Participants n=5 Participants	65 Participants n=7 Participants	62 Participants n=5 Participants	58 Participants n=4 Participants	248 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	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) American Indian or Alaska Native	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) Asian	25 Participants n=5 Participants	26 Participants n=7 Participants	25 Participants n=5 Participants	23 Participants n=4 Participants	99 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	0 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) White	36 Participants n=5 Participants	39 Participants n=7 Participants	35 Participants n=5 Participants	37 Participants n=4 Participants	147 Participants n=21 Participants
Race (NIH/OMB) More than one race	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) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Region of Enrollment Romania	3 participants n=5 Participants	3 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants	10 participants n=21 Participants
Region of Enrollment United States	17 participants n=5 Participants	17 participants n=7 Participants	17 participants n=5 Participants	17 participants n=4 Participants	68 participants n=21 Participants
Region of Enrollment Czechia	4 participants n=5 Participants	5 participants n=7 Participants	6 participants n=5 Participants	5 participants n=4 Participants	20 participants n=21 Participants
Region of Enrollment Ukraine	5 participants n=5 Participants	5 participants n=7 Participants	4 participants n=5 Participants	6 participants n=4 Participants	20 participants n=21 Participants
Region of Enrollment United Kingdom	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Region of Enrollment India	25 participants n=5 Participants	26 participants n=7 Participants	25 participants n=5 Participants	23 participants n=4 Participants	99 participants n=21 Participants
Region of Enrollment Spain	1 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants	7 participants n=21 Participants
Region of Enrollment Belgium	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Region of Enrollment Finland	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Region of Enrollment Poland	3 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants	9 participants n=21 Participants
Region of Enrollment Mexico	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants
Region of Enrollment Israel	3 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants	2 participants n=4 Participants	12 participants n=21 Participants
Region of Enrollment Germany	1 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants	5 participants n=21 Participants

PRIMARY outcome

Timeframe: 52 weeks after randomization

Outcome measures

Outcome measures
Measure	Herold Regimen n=63 Participants 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	33.3% Herold Regimen n=66 Participants 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	Curtailed Herold Regimen n=63 Participants 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	Placebo n=62 Participants 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
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%.	8 Participants	8 Participants	9 Participants	6 Participants

PRIMARY outcome

Timeframe: 52 weeks after randomization

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

Outcome measures

Outcome measures
Measure	Herold Regimen n=54 Participants 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	33.3% Herold Regimen n=59 Participants 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	Curtailed Herold Regimen n=54 Participants 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	Placebo n=58 Participants 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
Mean Change From Baseline in HbA1c Between Teplizumab and Placebo	0.01 percent HbA1c Standard Deviation 1.803	-0.02 percent HbA1c Standard Deviation 2.169	0.35 percent HbA1c Standard Deviation 25.12	0.03 percent HbA1c Standard Deviation 2.566

SECONDARY outcome

Timeframe: 52 weeks after randomization

Outcome measures

Outcome measures
Measure	Herold Regimen n=29 Participants 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	33.3% Herold Regimen n=30 Participants 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	Curtailed Herold Regimen n=27 Participants 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	Placebo n=26 Participants 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
The Change in Beta-cell Function as Measured by C-peptide Secretory Response Following a Mixed Meal	0.04 nmol/L Standard Deviation 0.276	-0.05 nmol/L Standard Deviation 0.456	0.04 nmol/L Standard Deviation 0.287	-0.04 nmol/L Standard Deviation 0.419

SECONDARY outcome

Timeframe: 104 weeks after randomization

Population: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Throughout the study up to 2 years

Population: 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.

Number of hypoglycemic events by type per participant

Outcome measures

Outcome measures
Measure	Herold Regimen n=63 Participants 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	33.3% Herold Regimen n=66 Participants 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	Curtailed Herold Regimen n=63 Participants 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	Placebo n=62 Participants 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
Mean Number of Total, Major, Minor and Nocturnal Hypoglycemia Events Total (any)	13.7 events Standard Deviation 22.35	15.9 events Standard Deviation 22.90	18.9 events Standard Deviation 41.42	15.5 events Standard Deviation 22.70
Mean Number of Total, Major, Minor and Nocturnal Hypoglycemia Events Minor hypoglycemia	4.1 events Standard Deviation 6.97	4.4 events Standard Deviation 6.38	5.4 events Standard Deviation 12.11	4.7 events Standard Deviation 10.45
Mean Number of Total, Major, Minor and Nocturnal Hypoglycemia Events Major hypoglycemia	10.0 events Standard Deviation 0.13	0.1 events Standard Deviation 0.42	0.0 events Standard Deviation 0.18	0.0 events Standard Deviation 0.13
Mean Number of Total, Major, Minor and Nocturnal Hypoglycemia Events Nocturnal hypoglycemia	2.0 events Standard Deviation 3.17	2.1 events Standard Deviation 5.54	1.4 events Standard Deviation 2.46	1.6 events Standard Deviation 3.33

SECONDARY outcome

Timeframe: 52 weeks after randomization

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 104 weeks after randomization

Outcome measures

Outcome measures
Measure	Herold Regimen n=14 Participants 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	33.3% Herold Regimen n=13 Participants 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	Curtailed Herold Regimen n=15 Participants 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	Placebo n=17 Participants 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
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%.	1 Participants	2 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 52 weeks after randomization

Outcome measures

Outcome measures
Measure	Herold Regimen n=63 Participants 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	33.3% Herold Regimen n=66 Participants 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	Curtailed Herold Regimen n=63 Participants 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	Placebo n=62 Participants 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
The Proportion of Subjects Who Have Both a Total Daily Insulin Dose < 0.5 U/Kg/Day and Hemoglobin A1c (HbA1c) Level < 7.0%	13 Participants	10 Participants	12 Participants	7 Participants

SECONDARY outcome

Timeframe: 104 weeks after randomization

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

Outcome measures

Outcome measures
Measure	Herold Regimen n=15 Participants 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	33.3% Herold Regimen n=14 Participants 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	Curtailed Herold Regimen n=15 Participants 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	Placebo n=21 Participants 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
The Mean HbA1c Change From Baseline	1.05 percent glycosylated hemoglobin Standard Deviation 2.344	1.11 percent glycosylated hemoglobin Standard Deviation 2.494	0.71 percent glycosylated hemoglobin Standard Deviation 3.740	1.21 percent glycosylated hemoglobin Standard Deviation 2.857

SECONDARY outcome

Timeframe: throughout the study, up to 104 weeks

Outcome measures

Outcome measures
Measure	Herold Regimen n=63 Participants 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	33.3% Herold Regimen n=66 Participants 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	Curtailed Herold Regimen n=63 Participants 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	Placebo n=62 Participants 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
Number of Participants With Adverse Events	63 Participants	66 Participants	63 Participants	62 Participants

SECONDARY outcome

Timeframe: throughout the study, up to 104 weeks

Outcome measures

Outcome measures
Measure	Herold Regimen n=63 Participants 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	33.3% Herold Regimen n=66 Participants 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	Curtailed Herold Regimen n=63 Participants 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	Placebo n=62 Participants 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
Number of Participants With Serious Adverse Events	7 Participants	6 Participants	8 Participants	3 Participants

Adverse Events

Herold Regimen

Serious events: 7 serious events

Other events: 63 other events

Deaths: 0 deaths

33.3% Herold Regimen

Serious events: 6 serious events

Other events: 66 other events

Deaths: 0 deaths

Curtailed Herold Regimen

Serious events: 8 serious events

Other events: 63 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 62 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Sharon Rowland

Provention Bio, Inc.

Phone: 443-987-0797

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Herold Regimen n=63 participants at risk 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	33.3% Herold Regimen n=66 participants at risk 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	Curtailed Herold Regimen n=63 participants at risk 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	Placebo n=62 participants at risk 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
Blood and lymphatic system disorders Lymphopenia	1.6% 1/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	1.6% 1/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.
Ear and labyrinth disorders Deafness neurosensory	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	1.5% 1/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.
Gastrointestinal disorders Abdominal pain	1.6% 1/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.
Gastrointestinal disorders Gastritis	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	1.6% 1/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.
Gastrointestinal disorders Nausea	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	1.5% 1/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.
General disorders Pain	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	1.5% 1/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.
Immune system disorders Cytokine release syndrome	1.6% 1/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	1.5% 1/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.
Infections and infestations Hepatic amoebiasis	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	1.6% 1/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.
Infections and infestations Pyelonephritis	1.6% 1/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.
Infections and infestations Staphylococcal sepsis	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	1.6% 1/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.
Infections and infestations Urinary tract infection	1.6% 1/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.
Infections and infestations Gastroenteritis	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	1.6% 1/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.
Investigations Alanine aminotransferase increased	1.6% 1/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	1.5% 1/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.
Investigations Aspartate aminotransferase increased	1.6% 1/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	1.5% 1/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.
Metabolism and nutrition disorders Diabetic ketoacidosis	1.6% 1/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	1.5% 1/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	4.8% 3/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.
Metabolism and nutrition disorders Hypoglycaemic seizure	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	1.5% 1/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	3.2% 2/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.
Metabolism and nutrition disorders Hyperglycaemia	1.6% 1/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	3.2% 2/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	1.5% 1/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.
Metabolism and nutrition disorders Hypoglycaemic unconsciousness	1.6% 1/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.
Psychiatric disorders Mental disorder	1.6% 1/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/66 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/63 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.	0.00% 0/62 • Throughout the study, up to 2 years All AEs and SAEs were reported from Day 0 to Day 364. Only treatment-related non-serious AEs, and all SAEs were reported after Day 364.