Trial Outcomes & Findings for Autoimmunity-blocking Antibody for Tolerance in Recently Diagnosed Type 1 Diabetes (NCT NCT00129259)

Last Updated: 2017-05-22

Results Overview

C-peptide AUC is computed using the trapezoidal rule and dividing by the interval of time from the 4 hour Mixed Meal Tolerance Test (MMTT) where assessments are taken every 30 minutes after initial assessments 15 minutes apart. A higher C-peptide AUC is desirable as detectable C-peptide is a marker for the ability of the pancreas to produce insulin in response to a MMTT. The baseline data was used to adjust for the C-peptide AUC primary endpoint at 24 months. Missing month 24 C-peptide results are imputed using a conservative scenario.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

83 participants

Primary outcome timeframe

Baseline (Pre-treatment), Month 24

Results posted on

2017-05-22

Participant Flow

Seven centers randomized 83 subjects between September 2005 and March 2009. Seventy-seven subjects are in the intent-to-treat (ITT) population. Those not in the ITT population did not have a baseline visit and were not included in the participant flow portion of the results section.

At a screening visit, subjects underwent procedures to establish that all inclusion criteria were met and none of the exclusion criteria were met. All subjects or guardians provided written informed consent at screening.

Participant milestones

Participant milestones
Measure	Anti-CD3 mAb Plus Diabetes Standard of Care Treatment Other name: mAb hOKT3gamma1(Ala-Ala), Teplizumab, MGA031. Subjects received 1.) a 14-day course of anti-CD3 monoclonal antibody (mAb) intravenously (IV) comprised of daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 days of 826 µg/m2 \[Cycle 1\] and, when eligible per protocol, receipt of a second 14-day course after a 12-month interval (at month 13)\[Cycle 2\]. Note: Prior to May 2007, the course of IV daily doses of anti-CD3 mAb were: 57 µg/m2, 115 µg/m2, 230 µg/m2, 460 µg/m2, and 10 days of 919 µg/m2 and, when eligible per protocol, a second course after a 12-month interval (at month 13). 2.) and intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team. Iron supplementation was initiated status post treatment randomization.	Diabetes Standard of Care Treatment Subjects received intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team. Iron supplementation was initiated status post treatment randomization.
Overall Study STARTED	52	25
Overall Study Received All or Part of Cycle 1	52	0
Overall Study Received All or Part of Cycle 2	40	0
Overall Study COMPLETED	49	22
Overall Study NOT COMPLETED	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Anti-CD3 mAb Plus Diabetes Standard of Care Treatment Other name: mAb hOKT3gamma1(Ala-Ala), Teplizumab, MGA031. Subjects received 1.) a 14-day course of anti-CD3 monoclonal antibody (mAb) intravenously (IV) comprised of daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 days of 826 µg/m2 \[Cycle 1\] and, when eligible per protocol, receipt of a second 14-day course after a 12-month interval (at month 13)\[Cycle 2\]. Note: Prior to May 2007, the course of IV daily doses of anti-CD3 mAb were: 57 µg/m2, 115 µg/m2, 230 µg/m2, 460 µg/m2, and 10 days of 919 µg/m2 and, when eligible per protocol, a second course after a 12-month interval (at month 13). 2.) and intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team. Iron supplementation was initiated status post treatment randomization.	Diabetes Standard of Care Treatment Subjects received intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team. Iron supplementation was initiated status post treatment randomization.
Overall Study Lost to Follow-up	1	1
Overall Study Withdrawal by Subject	2	1
Overall Study Only available minimal phone assessments	0	1

Baseline Characteristics

Autoimmunity-blocking Antibody for Tolerance in Recently Diagnosed Type 1 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Anti-CD3 mAb Plus Diabetes Standard of Care Treatment n=52 Participants Other name: mAb hOKT3gamma1(Ala-Ala), Teplizumab, MGA031. Subjects received 1.) a 14-day course of anti-CD3 monoclonal antibody (mAb) intravenously (IV) comprised of daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 days of 826 µg/m2 \[Cycle 1\] and, when eligible per protocol, receipt of a second 14-day course after a 12-month interval (at month 13)\[Cycle 2\]. Note: Prior to May 2007, the course of IV daily doses of anti-CD3 mAb were: 57 µg/m2, 115 µg/m2, 230 µg/m2, 460 µg/m2, and 10 days of 919 µg/m2 and, when eligible per protocol, a second course after a 12-month interval (at month 13). 2.) and intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team.	Diabetes Standard of Care Treatment n=25 Participants Subjects received intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team.	Total n=77 Participants Total of all reporting groups
Age, Continuous	12.7 years STANDARD_DEVIATION 4.9 • n=5 Participants	12.3 years STANDARD_DEVIATION 4.1 • n=7 Participants	12.5 years STANDARD_DEVIATION 4.6 • n=5 Participants
Age, Customized 8-12	34 participants n=5 Participants	15 participants n=7 Participants	49 participants n=5 Participants
Age, Customized 13-17	14 participants n=5 Participants	9 participants n=7 Participants	23 participants n=5 Participants
Age, Customized 18-30	4 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	9 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	16 Participants n=7 Participants	44 Participants n=5 Participants
Region of Enrollment United States	52 participants n=5 Participants	25 participants n=7 Participants	77 participants n=5 Participants
C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline	0.72 pmol/mL STANDARD_DEVIATION 0.29 • n=5 Participants	0.67 pmol/mL STANDARD_DEVIATION 0.28 • n=7 Participants	0.70 pmol/mL STANDARD_DEVIATION 0.29 • n=5 Participants
Hemoglobin A1c at Baseline (Pre-treatment)	7.4 Percentage (%) STANDARD_DEVIATION 0.99 • n=5 Participants	7.7 Percentage (%) STANDARD_DEVIATION 1.23 • n=7 Participants	7.5 Percentage (%) STANDARD_DEVIATION 1.07 • n=5 Participants
Average Total Daily Insulin Dose Per Body Weight at Baseline (Pre-treatment)	0.39 Units of Insulin/kilogram/day (U/kg/day) STANDARD_DEVIATION 0.26 • n=5 Participants	0.39 Units of Insulin/kilogram/day (U/kg/day) STANDARD_DEVIATION 0.17 • n=7 Participants	0.39 Units of Insulin/kilogram/day (U/kg/day) STANDARD_DEVIATION 0.23 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Pre-treatment), Month 24

Population: Intent-to-treat

Outcome measures

Outcome measures
Measure	Anti-CD3 mAb Plus Diabetes Standard of Care Treatment n=52 Participants Other name: mAb hOKT3gamma1(Ala-Ala), Teplizumab, MGA031. Subjects received 1.) a 14-day course of anti-CD3 monoclonal antibody (mAb) intravenously (IV) comprised of daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 days of 826 µg/m2 \[Cycle 1\] and, when eligible per protocol, receipt of a second 14-day course after a 12-month interval (at month 13)\[Cycle 2\]. Note: Prior to May 2007, the course of IV daily doses of anti-CD3 mAb were: 57 µg/m2, 115 µg/m2, 230 µg/m2, 460 µg/m2, and 10 days of 919 µg/m2 and, when eligible per protocol, a second course after a 12-month interval (at month 13). 2.) and intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team.	Diabetes Standard of Care Treatment n=25 Participants Subjects received intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team.
Change in Mean C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT)	-0.28 pmol/mL Interval -0.36 to -0.2	-0.46 pmol/mL Interval -0.57 to -0.35

SECONDARY outcome

Timeframe: Baseline (Pre-treatment), Month 24

Population: Intent-to-treat with available data

Glycosylated hemoglobin (HbA1c) is a measure of the average plasma glucose concentration over prolonged periods of time and measures the level of optimal management of underlying disease. (Normal :\< 5.7%; pre-diabetes: 5.7% -6.4%; diabetes: 6.5% or higher).A decline in HbA1c from baseline to month 24 signifies an improvement in diabetic control. The goal of treatment: to maintain the HgA1c level as close to normal as possible without frequent occurrence of hypoglycemia.

Outcome measures

Outcome measures
Measure	Anti-CD3 mAb Plus Diabetes Standard of Care Treatment n=48 Participants Other name: mAb hOKT3gamma1(Ala-Ala), Teplizumab, MGA031. Subjects received 1.) a 14-day course of anti-CD3 monoclonal antibody (mAb) intravenously (IV) comprised of daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 days of 826 µg/m2 \[Cycle 1\] and, when eligible per protocol, receipt of a second 14-day course after a 12-month interval (at month 13)\[Cycle 2\]. Note: Prior to May 2007, the course of IV daily doses of anti-CD3 mAb were: 57 µg/m2, 115 µg/m2, 230 µg/m2, 460 µg/m2, and 10 days of 919 µg/m2 and, when eligible per protocol, a second course after a 12-month interval (at month 13). 2.) and intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team.	Diabetes Standard of Care Treatment n=21 Participants Subjects received intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team.
Change in HbA1c	0.129 Percentage (%) Standard Deviation 2.032	0.195 Percentage (%) Standard Deviation 1.683

SECONDARY outcome

Timeframe: Baseline (Pre-treatment), Month 24

Population: Intent-to-treat with available data

This measure is computed using the average amount of exogenous insulin taken per day for the 3 days prior to the visit. The average insulin use is divided by the subject's weight in kilograms (kg). The need for lower dose(s) of prescribed exogenous insulin while maintaining optimal control of a subject's diabetes reflects improved management of the underlying disease.

Outcome measures

Outcome measures
Measure	Anti-CD3 mAb Plus Diabetes Standard of Care Treatment n=46 Participants Other name: mAb hOKT3gamma1(Ala-Ala), Teplizumab, MGA031. Subjects received 1.) a 14-day course of anti-CD3 monoclonal antibody (mAb) intravenously (IV) comprised of daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 days of 826 µg/m2 \[Cycle 1\] and, when eligible per protocol, receipt of a second 14-day course after a 12-month interval (at month 13)\[Cycle 2\]. Note: Prior to May 2007, the course of IV daily doses of anti-CD3 mAb were: 57 µg/m2, 115 µg/m2, 230 µg/m2, 460 µg/m2, and 10 days of 919 µg/m2 and, when eligible per protocol, a second course after a 12-month interval (at month 13). 2.) and intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team.	Diabetes Standard of Care Treatment n=22 Participants Subjects received intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team.
Change in Average Total Insulin Dose Per Body Weight	0.23 Units of Insulin/kilogram/day (U/kg/day) Standard Deviation 0.29	0.35 Units of Insulin/kilogram/day (U/kg/day) Standard Deviation 0.28

Adverse Events

Anti-CD3 mAb Plus Diabetes Standard of Care Treatment

Serious events: 10 serious events

Other events: 52 other events

Deaths: 0 deaths

Diabetes Standard of Care Treatment

Serious events: 1 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Anti-CD3 mAb Plus Diabetes Standard of Care Treatment n=52 participants at risk Other name: mAb hOKT3gamma1(Ala-Ala), Teplizumab, MGA031. Subjects received 1.) a 14-day course of anti-CD3 monoclonal antibody (mAb) intravenously (IV) comprised of daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 days of 826 µg/m2 \[Cycle 1\] and, when eligible per protocol, receipt of a second 14-day course after a 12-month interval (at month 13)\[Cycle 2\]. Note: Prior to May 2007, the course of IV daily doses of anti-CD3 mAb were: 57 µg/m2, 115 µg/m2, 230 µg/m2, 460 µg/m2, and 10 days of 919 µg/m2 and, when eligible per protocol, a second course after a 12-month interval (at month 13). 2.) and intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team.	Diabetes Standard of Care Treatment n=25 participants at risk Subjects received intensive diabetes standard of care treatment/management under the care of a physician: dietary counseling, insulin dosing and multiple consultations during the course of the trial with the clinical diabetes management team.
Immune system disorders Cytokine release syndrome	3.8% 2/52 • Number of events 2 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/25 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Infections and infestations Cellulitis	1.9% 1/52 • Number of events 1 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/25 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Infections and infestations Diarrhoea infectious	1.9% 1/52 • Number of events 1 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/25 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Infections and infestations Infection	1.9% 1/52 • Number of events 1 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/25 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Injury, poisoning and procedural complications Skull fracture	1.9% 1/52 • Number of events 1 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/25 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Injury, poisoning and procedural complications Splenic rupture	1.9% 1/52 • Number of events 1 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/25 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Metabolism and nutrition disorders Diabetic ketoacidosis	1.9% 1/52 • Number of events 1 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/25 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Metabolism and nutrition disorders Hypoglycaemia	3.8% 2/52 • Number of events 2 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	4.0% 1/25 • Number of events 1 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Nervous system disorders Cerebral haemorrhage	1.9% 1/52 • Number of events 1 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	0.00% 0/25 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)
Psychiatric disorders Hallucination	0.00% 0/52 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)	4.0% 1/25 • Number of events 1 • From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study) This study graded the severity of adverse events experienced by the study participant according to criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0 (June 10, 2003)

Other adverse events

Additional Information

Director, Clinical Research Operations Program

DAIT/NIAID

Phone: 301-594-7669

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place