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

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00129259
• Collaborator: Immune Tolerance Network (ITN) (Other)
• Enrollment: 83
• Locations: 7
• Arms: 2
• Duration (Months): 65.9
• Patients Per Site: 11.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Anti-CD3 monoclonal antibody (a.k.a. hOKT3gamma1 [Ala-Ala],teplizumab, MGA031) is a humanized antibody that is commonly used to prevent organ rejection. The purpose of this study is determine whether anti-CD3 mAb treatment can halt the progression of newly diagnosed type 1 diabetes.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Biological: Anti-CD3 mAb; Other: Diabetes Standard of Care Treatment; Dietary Supplement: Iron supplementation	Phase 2

Detailed Description

Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks insulin-producing beta cells in the pancreas. Without these cells, the body cannot maintain proper blood glucose levels in response to daily activities, such as eating or exercise. Generally, at the time of type 1 diabetes diagnosis, 60% to 85% of the diabetic person's beta cells have already been destroyed. However, between 15% and 40% of these cells remain and are able to produce insulin. Treatment that slows the destruction of additional beta cells may be able to decrease a patient's reliance on insulin and improve their quality of life.

Anti-CD3 mAb is genetically engineered and directed against the CD3 antigen on T cells; this antibody selectively attacks the immune cells responsible for beta cell destruction. In a small exploratory clinical trial, patients with newly diagnosed type 1 diabetes who received a single, 2-week treatment with anti-CD3 mAb had preserved beta cell function and significantly lower insulin requirements than untreated patients for up to two years after therapy. This study will investigate whether a second course of anti-CD3 mAb administered one year after the first administration is able to prolong or improve the effects of the biologic in people who have recently diagnosed type 1 diabetes mellitus.

Participants will be randomly assigned to one of two groups. The Experimental Group will receive anti-CD3 mAb treatment plus Diabetes Standard of Care Treatment; the Active Comparator Group will receive Diabetes Standard of Care Treatment. The Experimental Group will be treated with the antibody for the first 14 days of the study and again one year later. These participants will be admitted to the hospital for the first 5 days of a treatment cycle. Participants who live within 1 hour of the hospital may receive the remainder of a treatment cycle as an outpatient, but those who live farther away will be hospitalized for 14 days. For the first treatment cycle, there will be study visits on the 3 consecutive days after the treatment cycle and at Months 1, 2, 3, 6, 9, and 12. For the second treatment cycle, there will be study visits on the 3 consecutive days after the treatment cycle and at Months 13, 16, 19, 21, and 24.The Active Comparator Group will have 12 study visits over two years.

At study entry, all participants will receive daily iron supplementation, either as ferrous sulfate or a multivitamin with iron. Participants will be followed for up to 2 years to assess their overall diabetes health and to capture laboratory measures of beta cell and immune system function. Medication history and adverse event assessment will occur at all visits. A physical exam, vital signs measurement, and blood collection will occur at most visits. Medical history and urine collection will occur at selected visits.

Study Design

• Study Type: Interventional
• Actual Enrollment: 83 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: The staff at Northwest Lipid Research Laboratory were masked to the treatment assignment since they performed the mixed-meal tolerance test (MMTT) and the HgA1C assays. All study staff including the PI were masked to the results of the MMTT. They were notified of a detectable or undetectable fasting C-peptide result to assess for continuation to the next treatment cycle.
• Primary Purpose: Treatment
• Official Title: Phase II Multiple-Dose Treatment of New Onset Type 1 Diabetes Mellitus With Anti-CD3 mAb
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Anti-CD3 mAb Plus Diabetes Standard of Care Treatment Subjects receive 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 initiated status post treatment randomization.	Biological: Anti-CD3 mAb; Daily 14-day dose escalation course at study entry, with possible second course after 12-month interval; Other Names: mAb hOKT3gamma1(Ala-Ala) teplizumab MGA031 ; Other: Diabetes Standard of Care Treatment; Receipt of 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.; Dietary Supplement: Iron supplementation; Immediately following randomization, all participants regardless of arm allocation begin iron supplementation with either ferrous sulfate or multivitamin with iron.; Other Names: MVI Fer-In-Sol Feosol Fer-Iron Ferolix FeroSul Irospan
Active Comparator: Diabetes Standard of Care Treatment Subjects receive 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 initiated status post treatment randomization.	Other: Diabetes Standard of Care Treatment; Receipt of 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.; Dietary Supplement: Iron supplementation; Immediately following randomization, all participants regardless of arm allocation begin iron supplementation with either ferrous sulfate or multivitamin with iron.; Other Names: MVI Fer-In-Sol Feosol Fer-Iron Ferolix FeroSul Irospan

Outcome Measures

Primary Outcome Measures

1. Change in Mean C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) [Baseline (Pre-treatment), Month 24]

   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.

Secondary Outcome Measures

1. Change in HbA1c [Baseline (Pre-treatment), Month 24]

   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.

2. Change in Average Total Insulin Dose Per Body Weight [Baseline (Pre-treatment), Month 24]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 30 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of type 1 diabetes (according to American Diabetes Association [ADA] criteria) within the 8 weeks prior to study entry

• Weigh at least 25 kg (55 lbs)

• Insulin autoantibodies assessed within 10 days of any insulin use OR anti-glutamic acid decarboxylase (GAD) autoantibodies OR anti-ICA512/IA-2 autoantibodies

• Subjects or guardian(s) willing to provide informed consent

Exclusion Criteria:

• Prior participation in a clinical trial that could potentially affect diabetes condition or immunologic status

• Participation in another investigational clinical trial within the 6 weeks prior to study entry

• Pregnancy or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Diabetes Center at UCSF	San Francisco	California	United States	94143
2	Barbara Davis Center for Childhood Diabetes	Denver	Colorado	United States	80262
3	Yale University	New Haven	Connecticut	United States	06520
4	Medical College of Georgia	Augusta	Georgia	United States	30912
5	Dept. of Medicine, Division of Endocrinology and the Naomi Berrie Diabetes Center/Columbia University	New York	New York	United States	10032
6	Benaroya Research Institute	Seattle	Washington	United States	98108
7	Pacific Northwest Research Institute/University of Washington	Seattle	Washington	United States	98122

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• Immune Tolerance Network (ITN)

Investigators

• Principal Investigator: Kevan Herold, MD, Yale University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)
• Click here for the Immune Tolerance Network (ITN) TrialShare Web site
• Click here for the ITN Website

Publications

• Herold KC, Gitelman SE, Masharani U, Hagopian W, Bisikirska B, Donaldson D, Rother K, Diamond B, Harlan DM, Bluestone JA. A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes. 2005 Jun;54(6):1763-9.
• Herold KC, Hagopian W, Auger JA, Poumian-Ruiz E, Taylor L, Donaldson D, Gitelman SE, Harlan DM, Xu D, Zivin RA, Bluestone JA. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med. 2002 May 30;346(22):1692-8.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00129259
• Other Study ID Numbers: DAIT ITN027AI
• First Posted: Aug 11, 2005
• Last Update Posted: May 22, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): T1D; type 1 diabetes; type 1 diabetes mellitus; juvenile diabetes; autoimmune diabetes; autoimmune; anti-CD3 mAb; mAb hOKT3g1(Ala-Ala); teplizumab
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Iron

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	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.

Arm/Group Title	Anti-CD3 mAb Plus Diabetes Standard of Care Treatment	Diabetes Standard of Care Treatment
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	52	25
Received All or Part of Cycle 1	52	0
Received All or Part of Cycle 2	40	0
COMPLETED	49	22
NOT COMPLETED	3	3

Baseline Characteristics

Arm/Group Title	Anti-CD3 mAb Plus Diabetes Standard of Care Treatment	Diabetes Standard of Care Treatment	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	52	25	77
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.7 (4.9)	12.3 (4.1)	12.5 (4.6)
Age, Customized (participants) [Number]
8-12	34 65.4%	15 60%	49 63.6%
13-17	14 26.9%	9 36%	23 29.9%
18-30	4 7.7%	1 4%	5 6.5%
Sex: Female, Male (Count of Participants)
Female	24 46.2%	9 36%	33 42.9%
Male	28 53.8%	16 64%	44 57.1%
Region of Enrollment (participants) [Number]
United States	52 100%	25 100%	77 100%
C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline (pmol/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pmol/mL]	0.72 (0.29)	0.67 (0.28)	0.70 (0.29)
Hemoglobin A1c at Baseline (Pre-treatment) (Percentage (%)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage (%)]	7.4 (0.99)	7.7 (1.23)	7.5 (1.07)
Average Total Daily Insulin Dose Per Body Weight at Baseline (Pre-treatment) (Units of Insulin/kilogram/day (U/kg/day)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units of Insulin/kilogram/day (U/kg/day)]	0.39 (0.26)	0.39 (0.17)	0.39 (0.23)

Outcome Measures

1. Primary Outcome

Title	Change in Mean C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT)
Description	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.
Time Frame	Baseline (Pre-treatment), Month 24

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Anti-CD3 mAb Plus Diabetes Standard of Care Treatment	Diabetes Standard of Care Treatment
Arm/Group Description	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.	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.
Measure Participants	52	25
Least Squares Mean (95% Confidence Interval) [pmol/mL]	-0.28	-0.46

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anti-CD3 mAb Plus Diabetes Standard of Care Treatment, Diabetes Standard of Care Treatment
	Comments	Null hypothesis: The mean change from baseline to Month 24 in the 4-hour C-peptide AUC does not differ between treatment groups after adjusting for baseline C-peptide AUC. Alternative hypothesis: The mean change from baseline to Month 24 in the 4-hour C-peptide AUC differs between the treatment groups after adjusting for baseline values.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	ANCOVA
	Comments	P-value for testing treatment effect uses change in ln(AUC+1) as the outcome variable and adjusts for baseline ln(AUC+1).

2. Secondary Outcome

Title	Change in HbA1c
Description	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.
Time Frame	Baseline (Pre-treatment), Month 24

Outcome Measure Data

Analysis Population Description

Intent-to-treat with available data

Arm/Group Title	Anti-CD3 mAb Plus Diabetes Standard of Care Treatment	Diabetes Standard of Care Treatment
Arm/Group Description	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.	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.
Measure Participants	48	21
Mean (Standard Deviation) [Percentage (%)]	0.129 (2.032)	0.195 (1.683)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anti-CD3 mAb Plus Diabetes Standard of Care Treatment, Diabetes Standard of Care Treatment
	Comments	Null hypothesis: The mean change in HbA1c from baseline (pre-treatment) to Month 24 does not differ between treatment groups. Alternative hypothesis: The mean change in HbA1c from baseline to Month 24 differs between treatment groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.697
	Comments
	Method	ANCOVA
	Comments	ANCOVA adjusts for baseline HbA1c.

3. Secondary Outcome

Title	Change in Average Total Insulin Dose Per Body Weight
Description	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.
Time Frame	Baseline (Pre-treatment), Month 24

Outcome Measure Data

Analysis Population Description

Intent-to-treat with available data

Arm/Group Title	Anti-CD3 mAb Plus Diabetes Standard of Care Treatment	Diabetes Standard of Care Treatment
Arm/Group Description	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.	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.
Measure Participants	46	22
Mean (Standard Deviation) [Units of Insulin/kilogram/day (U/kg/day)]	0.23 (0.29)	0.35 (0.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anti-CD3 mAb Plus Diabetes Standard of Care Treatment, Diabetes Standard of Care Treatment
	Comments	Null hypothesis: The mean change from baseline to Month 24 in daily insulin use per kg does not differ between the treatment and control groups. Alternative hypothesis: The mean change from baseline to Month 24 in daily insulin use per kg differs between the treatment and control groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.110
	Comments
	Method	ANCOVA
	Comments	ANCOVA adjusts for baseline daily insulin use per kg

Adverse Events

Time Frame	From the initiation of study treatment through month 24 visit (i.e., throughout the duration of the study)
Adverse Event Reporting Description	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)
Arm/Group Title	Anti-CD3 mAb Plus Diabetes Standard of Care Treatment		Diabetes Standard of Care Treatment
Arm/Group Description	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.		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.
All Cause Mortality
	Anti-CD3 mAb Plus Diabetes Standard of Care Treatment		Diabetes Standard of Care Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Anti-CD3 mAb Plus Diabetes Standard of Care Treatment		Diabetes Standard of Care Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/52 (19.2%)		1/25 (4%)
Immune system disorders
Cytokine release syndrome	2/52 (3.8%)	2	0/25 (0%)	0
Infections and infestations
Cellulitis	1/52 (1.9%)	1	0/25 (0%)	0
Diarrhoea infectious	1/52 (1.9%)	1	0/25 (0%)	0
Infection	1/52 (1.9%)	1	0/25 (0%)	0
Injury, poisoning and procedural complications
Skull fracture	1/52 (1.9%)	1	0/25 (0%)	0
Splenic rupture	1/52 (1.9%)	1	0/25 (0%)	0
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/52 (1.9%)	1	0/25 (0%)	0
Hypoglycaemia	2/52 (3.8%)	2	1/25 (4%)	1
Nervous system disorders
Cerebral haemorrhage	1/52 (1.9%)	1	0/25 (0%)	0
Psychiatric disorders
Hallucination	0/52 (0%)	0	1/25 (4%)	1
Other (Not Including Serious) Adverse Events
	Anti-CD3 mAb Plus Diabetes Standard of Care Treatment		Diabetes Standard of Care Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	52/52 (100%)		23/25 (92%)
Blood and lymphatic system disorders
Anaemia	3/52 (5.8%)	3	0/25 (0%)	0
Leukopenia	12/52 (23.1%)	24	0/25 (0%)	0
Lymphadenopathy	4/52 (7.7%)	4	0/25 (0%)	0
Lymphopenia	22/52 (42.3%)	41	0/25 (0%)	0
Neutropenia	9/52 (17.3%)	15	0/25 (0%)	0
Thrombocytopenia	5/52 (9.6%)	5	0/25 (0%)	0
Endocrine disorders
Goitre	3/52 (5.8%)	3	1/25 (4%)	1
Hypothyroidism	0/52 (0%)	0	2/25 (8%)	2
Gastrointestinal disorders
Abdominal pain	16/52 (30.8%)	20	0/25 (0%)	0
Abdominal pain upper	9/52 (17.3%)	12	6/25 (24%)	6
Constipation	5/52 (9.6%)	6	0/25 (0%)	0
Diarrhoea	4/52 (7.7%)	4	1/25 (4%)	1
Nausea	25/52 (48.1%)	43	5/25 (20%)	6
Vomiting	19/52 (36.5%)	34	3/25 (12%)	4
General disorders
Catheter site rash	7/52 (13.5%)	7	0/25 (0%)	0
Chills	5/52 (9.6%)	5	1/25 (4%)	1
Fatigue	7/52 (13.5%)	9	1/25 (4%)	1
Infusion site pain	6/52 (11.5%)	6	1/25 (4%)	1
Malaise	3/52 (5.8%)	3	2/25 (8%)	2
Pyrexia	20/52 (38.5%)	27	5/25 (20%)	5
Hepatobiliary disorders
Hyperbilirubinaemia	3/52 (5.8%)	4	1/25 (4%)	1
Immune system disorders
Cytokine release syndrome	5/52 (9.6%)	6	0/25 (0%)	0
Seasonal allergy	3/52 (5.8%)	3	1/25 (4%)	1
Infections and infestations
Acne pustular	5/52 (9.6%)	6	3/25 (12%)	3
Bronchitis	3/52 (5.8%)	3	4/25 (16%)	4
Conjunctivitis infective	3/52 (5.8%)	4	1/25 (4%)	1
Diarrhoea infectious	6/52 (11.5%)	6	2/25 (8%)	2
Ear infection	4/52 (7.7%)	4	1/25 (4%)	1
Gastroenteritis	3/52 (5.8%)	3	1/25 (4%)	1
Gastroenteritis viral	7/52 (13.5%)	7	1/25 (4%)	1
Influenza	10/52 (19.2%)	11	5/25 (20%)	8
Nasopharyngitis	3/52 (5.8%)	3	1/25 (4%)	1
Pharyngitis	11/52 (21.2%)	14	3/25 (12%)	6
Pharyngitis streptococcal	1/52 (1.9%)	1	2/25 (8%)	2
Rhinitis	5/52 (9.6%)	6	1/25 (4%)	2
Sinusitis	5/52 (9.6%)	5	3/25 (12%)	6
Skin papilloma	9/52 (17.3%)	10	2/25 (8%)	2
Tinea infection	0/52 (0%)	0	2/25 (8%)	2
Upper respiratory tract infection	32/52 (61.5%)	80	14/25 (56%)	23
Viral infection	3/52 (5.8%)	4	0/25 (0%)	0
Injury, poisoning and procedural complications
Contusion	5/52 (9.6%)	5	0/25 (0%)	0
Excoriation	8/52 (15.4%)	12	0/25 (0%)	0
Joint sprain	3/52 (5.8%)	4	0/25 (0%)	0
Investigations
Alanine aminotransferase increased	3/52 (5.8%)	3	0/25 (0%)	0
Aspartate aminotransferase increased	3/52 (5.8%)	3	0/25 (0%)	0
CD4 lymphocytes decreased	5/52 (9.6%)	5	0/25 (0%)	0
Glycosylated haemoglobin increased	5/52 (9.6%)	6	8/25 (32%)	8
Haematocrit decreased	4/52 (7.7%)	6	0/25 (0%)	0
Haemoglobin decreased	7/52 (13.5%)	10	1/25 (4%)	1
Lymphocyte count decreased	3/52 (5.8%)	4	0/25 (0%)	0
Platelet count decreased	4/52 (7.7%)	5	0/25 (0%)	0
White blood cell count decreased	3/52 (5.8%)	3	0/25 (0%)	0
Metabolism and nutrition disorders
Hyperglycaemia	4/52 (7.7%)	6	1/25 (4%)	1
Hypoglycaemia	21/52 (40.4%)	26	6/25 (24%)	7
Musculoskeletal and connective tissue disorders
Arthralgia	10/52 (19.2%)	12	0/25 (0%)	0
Back pain	4/52 (7.7%)	7	0/25 (0%)	0
Musculoskeletal pain	2/52 (3.8%)	2	2/25 (8%)	2
Myalgia	2/52 (3.8%)	2	2/25 (8%)	2
Pain in extremity	7/52 (13.5%)	12	0/25 (0%)	0
Nervous system disorders
Dizziness	8/52 (15.4%)	9	1/25 (4%)	1
Headache	30/52 (57.7%)	81	10/25 (40%)	26
Tremor	5/52 (9.6%)	7	1/25 (4%)	1
Psychiatric disorders
Anxiety	11/52 (21.2%)	26	0/25 (0%)	0
Renal and urinary disorders
Ketonuria	3/52 (5.8%)	3	3/25 (12%)	3
Reproductive system and breast disorders
Dysmenorrhoea	3/52 (5.8%)	3	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
Cough	17/52 (32.7%)	22	3/25 (12%)	4
Epistaxis	3/52 (5.8%)	5	0/25 (0%)	0
Nasal congestion	8/52 (15.4%)	8	5/25 (20%)	6
Oropharyngeal pain	12/52 (23.1%)	19	1/25 (4%)	1
Rhinitis allergic	7/52 (13.5%)	10	0/25 (0%)	0
Rhinorrhoea	3/52 (5.8%)	3	1/25 (4%)	1
Tonsillar hypertrophy	3/52 (5.8%)	3	0/25 (0%)	0
Upper respiratory tract congestion	3/52 (5.8%)	3	4/25 (16%)	6
Skin and subcutaneous tissue disorders
Acne	5/52 (9.6%)	5	1/25 (4%)	1
Dermatitis contact	5/52 (9.6%)	6	0/25 (0%)	0
Dry skin	8/52 (15.4%)	8	1/25 (4%)	1
Eczema	3/52 (5.8%)	5	0/25 (0%)	0
Erythema	8/52 (15.4%)	11	0/25 (0%)	0
Lipohypertrophy	2/52 (3.8%)	3	3/25 (12%)	4
Pruritus	15/52 (28.8%)	25	1/25 (4%)	1
Rash	41/52 (78.8%)	91	2/25 (8%)	2
Rash generalised	7/52 (13.5%)	7	0/25 (0%)	0
Rash papular	3/52 (5.8%)	3	0/25 (0%)	0
Rash pruritic	3/52 (5.8%)	3	0/25 (0%)	0
Skin exfoliation	10/52 (19.2%)	12	0/25 (0%)	0
Vascular disorders
Hypotension	12/52 (23.1%)	18	0/25 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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