Anti-CD3 mAb Treatment of Recent Onset Type 1 Diabetes

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
Kevan Herold, Yale University
ClinicalTrials.gov Identifier:
NCT00378508
First received: September 18, 2006
Last updated: October 31, 2012
Last verified: October 2012
Results First Received: September 4, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Condition: Type 1 Diabetes Mellitus
Interventions: Drug: mAb hOKT3gamma1(Ala-Ala), Teplizumab
Drug: Placebo Arm

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects were recruited from 4 clinical sites and were eligible if they were between the ages of 8-30 and diagnosed with Type 1 Diabetes for at least 4 months, but not more than 12 months prior to enrollment.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Saline Infusions (Placebo) The course of normal saline infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.
Teplizumab Infusion (Active) The course of teplizumab infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.

Participant Flow:   Overall Study
    Saline Infusions (Placebo)     Teplizumab Infusion (Active)  
STARTED     29     34  
Randomized     29     34  
Received Intervention/Placebo     28     31  
COMPLETED     27     31  
NOT COMPLETED     2     3  
Withdrawal by Subject                 1                 3  
Lost to Follow-up                 1                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Saline Infusions (Placebo) The course of normal saline infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.
Teplizumab Infusions (Active) The course of teplizumab infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.
Total Total of all reporting groups

Baseline Measures
    Saline Infusions (Placebo)     Teplizumab Infusions (Active)     Total  
Number of Participants  
[units: participants]
  27     31     58  
Age, Customized  
[units: participants]
     
<15 years     20     18     38  
>=15 years     7     13     20  
Gender, Customized  
[units: participants]
     
Female     10     15     25  
Male     17     16     33  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months   [ Time Frame: At month 12 post-treatment ]

2.  Primary:   C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline   [ Time Frame: At Baseline (before treatment) ]

3.  Secondary:   Hemoglobin A1c   [ Time Frame: At 12 months post-treatment ]

4.  Secondary:   Average Insulin Use Over 12 Months   [ Time Frame: After 12 months post-treatment ]

5.  Secondary:   Baseline Insulin Use   [ Time Frame: At baseline (before treatment) ]

6.  Secondary:   Baseline Hemoglobin A1c   [ Time Frame: At baseline (before treatment) ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame The adverse event data was collected throughout the duration of the study which was approximately 6 years.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
Saline Infusions (Placebo) The course of a saline infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.
Teplizumab Infusion (Active) The course of teplizumab infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.

Other Adverse Events
    Saline Infusions (Placebo)     Teplizumab Infusion (Active)  
Total, other (not including serious) adverse events      
# participants affected / at risk     29/29     25/34  
Blood and lymphatic system disorders      
Leukopenia † 1    
# participants affected / at risk     9/29 (31.03%)     10/33 (30.30%)  
Lymphopenia † 1    
# participants affected / at risk     10/29 (34.48%)     15/33 (45.45%)  
Neutropenia † 1    
# participants affected / at risk     7/29 (24.14%)     7/33 (21.21%)  
Cardiac disorders      
Tachycardia † 1    
# participants affected / at risk     2/29 (6.90%)     3/34 (8.82%)  
Eye disorders      
Conjunctivitis † 1    
# participants affected / at risk     2/29 (6.90%)     1/34 (2.94%)  
Gastrointestinal disorders      
Abdominal Discomfort † 1    
# participants affected / at risk     2/29 (6.90%)     1/34 (2.94%)  
Abdominal Pain † 1    
# participants affected / at risk     6/29 (20.69%)     3/34 (8.82%)  
Abdominal Pain (Upper) † 1    
# participants affected / at risk     9/29 (31.03%)     2/34 (5.88%)  
Aphthous Stomatitis † 1    
# participants affected / at risk     2/29 (6.90%)     1/34 (2.94%)  
Constipation † 1    
# participants affected / at risk     2/29 (6.90%)     0/34 (0.00%)  
Diarrhea † 1    
# participants affected / at risk     6/29 (20.69%)     3/34 (8.82%)  
Nausea † 1    
# participants affected / at risk     11/29 (37.93%)     14/33 (42.42%)  
Oral Pain † 1    
# participants affected / at risk     3/29 (10.34%)     2/33 (6.06%)  
Vomiting † 1    
# participants affected / at risk     12/29 (41.38%)     6/34 (17.65%)  
General disorders      
Catheter Related Complication † 1    
# participants affected / at risk     3/29 (10.34%)     1/34 (2.94%)  
Catheter Site Pain † 1    
# participants affected / at risk     3/29 (10.34%)     0/34 (0.00%)  
Catheter Site Rash † 1    
# participants affected / at risk     3/29 (10.34%)     1/34 (2.94%)  
Chills † 1    
# participants affected / at risk     1/29 (3.45%)     3/34 (8.82%)  
Edema Peripheral † 1    
# participants affected / at risk     0/29 (0.00%)     3/34 (8.82%)  
Fatigue † 1    
# participants affected / at risk     3/29 (10.34%)     8/34 (23.53%)  
Influenza Like Illness † 1    
# participants affected / at risk     7/29 (24.14%)     4/33 (12.12%)  
Nodule † 1    
# participants affected / at risk     2/29 (6.90%)     0/33 (0.00%)  
Pain † 1    
# participants affected / at risk     2/29 (6.90%)     1/33 (3.03%)  
Pyrexia † 1    
# participants affected / at risk     6/29 (20.69%)     8/34 (23.53%)  
Immune system disorders      
Cytokine Release Syndrome † 1    
# participants affected / at risk     2/29 (6.90%)     1/34 (2.94%)  
Infections and infestations      
Nasopharyngitis † 1    
# participants affected / at risk     4/29 (13.79%)     2/33 (6.06%)  
Pharyngitis Streptococcal † 1    
# participants affected / at risk     0/29 (0.00%)     2/33 (6.06%)  
Upper Respiratory Tract Infection † 1    
# participants affected / at risk     7/29 (24.14%)     10/34 (29.41%)  
Injury, poisoning and procedural complications      
Arthropod Bite † 1    
# participants affected / at risk     2/29 (6.90%)     1/34 (2.94%)  
Contusion † 1    
# participants affected / at risk     1/29 (3.45%)     4/34 (11.76%)  
Excoriation † 1    
# participants affected / at risk     4/29 (13.79%)     2/34 (5.88%)  
Investigations      
Activated Partial Thromboplastin Time Prolonged † 1    
# participants affected / at risk     3/29 (10.34%)     4/34 (11.76%)  
Alanine Aminotransferase Decreased † 1    
# participants affected / at risk     0/29 (0.00%)     2/34 (5.88%)  
Alanine Aminotransferase Increased † 1    
# participants affected / at risk     5/29 (17.24%)     5/34 (14.71%)  
Aspartate Aminotransferase Increased † 1    
# participants affected / at risk     5/29 (17.24%)     4/34 (11.76%)  
Blood Albumin Decreased † 1    
# participants affected / at risk     7/29 (24.14%)     7/34 (20.59%)  
Blood Alkaline Phosphatase Increased † 1    
# participants affected / at risk     3/29 (10.34%)     3/34 (8.82%)  
Blood Bicarbonate Decreased † 1    
# participants affected / at risk     3/29 (10.34%)     1/34 (2.94%)  
Blood Calcium Decreased † 1    
# participants affected / at risk     1/29 (3.45%)     3/34 (8.82%)  
Blood Calcium Increased † 1    
# participants affected / at risk     2/29 (6.90%)     0/34 (0.00%)  
Blood Creatinine Increased † 1    
# participants affected / at risk     4/29 (13.79%)     2/34 (5.88%)  
Blood Potassium Decreased † 1    
# participants affected / at risk     0/29 (0.00%)     2/34 (5.88%)  
Blood Sodium Decreased † 1    
# participants affected / at risk     4/29 (13.79%)     2/34 (5.88%)  
Blood Urea Increased † 1    
# participants affected / at risk     2/29 (6.90%)     0/34 (0.00%)  
Carbon Dioxide Abnormal † 1    
# participants affected / at risk     2/29 (6.90%)     0/34 (0.00%)  
Cardiac Murmur † 1    
# participants affected / at risk     0/29 (0.00%)     2/34 (5.88%)  
Gamma-glutamyltransferase Increased † 1    
# participants affected / at risk     2/29 (6.90%)     1/34 (2.94%)  
Glycosylated Hemoglobin Increased † 1    
# participants affected / at risk     2/29 (6.90%)     3/34 (8.82%)  
Hemoglobin Decreased † 1    
# participants affected / at risk     7/29 (24.14%)     10/34 (29.41%)  
International Normalized Ratio Increased † 1    
# participants affected / at risk     4/29 (13.79%)     2/33 (6.06%)  
Laboratory Test Abnormal † 1    
# participants affected / at risk     3/29 (10.34%)     1/33 (3.03%)  
Lymphocyte Count Decreased † 1    
# participants affected / at risk     0/29 (0.00%)     5/33 (15.15%)  
Lymphocyte Count Increased † 1    
# participants affected / at risk     2/29 (6.90%)     0/33 (0.00%)  
Mean Cell Hemoglobin Increased † 1    
# participants affected / at risk     2/29 (6.90%)     0/33 (0.00%)  
Platelet Count Decreased † 1    
# participants affected / at risk     1/29 (3.45%)     6/33 (18.18%)  
Protein Total Decreased † 1    
# participants affected / at risk     3/29 (10.34%)     1/34 (2.94%)  
Red Blood Cell Count Decreased † 1    
# participants affected / at risk     2/29 (6.90%)     0/34 (0.00%)  
White Blood Cell Count Decreased † 1    
# participants affected / at risk     0/29 (0.00%)     3/34 (8.82%)  
Metabolism and nutrition disorders      
Hyperglycemia † 1    
# participants affected / at risk     2/29 (6.90%)     2/34 (5.88%)  
Hypocalcemia † 1    
# participants affected / at risk     3/29 (10.34%)     3/34 (8.82%)  
Hypoglycemia † 1    
# participants affected / at risk     3/29 (10.34%)     6/34 (17.65%)  
Hyponatremia † 1    
# participants affected / at risk     2/29 (6.90%)     0/34 (0.00%)  
Musculoskeletal and connective tissue disorders      
Arthralgia † 1    
# participants affected / at risk     4/29 (13.79%)     3/34 (8.82%)  
Musculoskeletal Pain † 1    
# participants affected / at risk     0/29 (0.00%)     3/33 (9.09%)  
Myalgia † 1    
# participants affected / at risk     2/29 (6.90%)     0/33 (0.00%)  
Neck Pain † 1    
# participants affected / at risk     2/29 (6.90%)     0/33 (0.00%)  
Pain in Extremity † 1    
# participants affected / at risk     4/29 (13.79%)     5/33 (15.15%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Skin Papilloma † 1    
# participants affected / at risk     2/29 (6.90%)     1/34 (2.94%)  
Nervous system disorders      
Dizziness † 1    
# participants affected / at risk     5/29 (17.24%)     4/34 (11.76%)  
Headache † 1    
# participants affected / at risk     20/29 (68.97%)     15/34 (44.12%)  
Psychiatric disorders      
Anxiety † 1    
# participants affected / at risk     10/29 (34.48%)     11/34 (32.35%)  
Renal and urinary disorders      
Hematuria † 1    
# participants affected / at risk     2/29 (6.90%)     0/34 (0.00%)  
Ketonuria † 1    
# participants affected / at risk     3/29 (10.34%)     0/33 (0.00%)  
Reproductive system and breast disorders      
Dysmenorrhea † 1    
# participants affected / at risk     0/29 (0.00%)     2/34 (5.88%)  
Respiratory, thoracic and mediastinal disorders      
Cough † 1    
# participants affected / at risk     4/29 (13.79%)     4/34 (11.76%)  
Nasal Congestion † 1    
# participants affected / at risk     2/29 (6.90%)     5/33 (15.15%)  
Pharyngolaryngeal Pain † 1    
# participants affected / at risk     6/29 (20.69%)     6/33 (18.18%)  
Rhinitis Allergic † 1    
# participants affected / at risk     5/29 (17.24%)     2/34 (5.88%)  
Skin and subcutaneous tissue disorders      
Acne † 1    
# participants affected / at risk     1/29 (3.45%)     2/34 (5.88%)  
Dry Skin † 1    
# participants affected / at risk     1/29 (3.45%)     4/34 (11.76%)  
Erythema † 1    
# participants affected / at risk     2/29 (6.90%)     1/34 (2.94%)  
Lipohypertrophy † 1    
# participants affected / at risk     1/29 (3.45%)     3/33 (9.09%)  
Petechiae † 1    
# participants affected / at risk     2/29 (6.90%)     0/33 (0.00%)  
Pruritus † 1    
# participants affected / at risk     9/29 (31.03%)     11/34 (32.35%)  
Rash † 1    
# participants affected / at risk     16/29 (55.17%)     18/34 (52.94%)  
Rash Generalized † 1    
# participants affected / at risk     0/29 (0.00%)     4/34 (11.76%)  
Rash Papular † 1    
# participants affected / at risk     2/29 (6.90%)     3/34 (8.82%)  
Skin Disorder † 1    
# participants affected / at risk     0/29 (0.00%)     2/34 (5.88%)  
Skin Exfoliation † 1    
# participants affected / at risk     4/29 (13.79%)     6/34 (17.65%)  
Urticaria † 1    
# participants affected / at risk     2/29 (6.90%)     2/34 (5.88%)  
Vascular disorders      
Hypotension † 1    
# participants affected / at risk     3/29 (10.34%)     2/34 (5.88%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (10.0)



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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Kevan Herold, MD
Organization: Yale University
phone: 203-785-6507
e-mail: Kevan.Herold@yale.edu


Publications:
Publications automatically indexed to this study:

Responsible Party: Kevan Herold, Yale University
ClinicalTrials.gov Identifier: NCT00378508     History of Changes
Other Study ID Numbers: Delay-Study 5, R01DK57846
Study First Received: September 18, 2006
Results First Received: September 4, 2012
Last Updated: October 31, 2012
Health Authority: United States: Food and Drug Administration