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Trial record 28 of 147 for:    visilizumab

Anti-CD3 mAb Treatment of Recent Onset Type 1 Diabetes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00378508
Recruitment Status : Completed
First Posted : September 20, 2006
Results First Posted : October 31, 2012
Last Update Posted : August 2, 2016
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
Yale University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Type 1 Diabetes Mellitus
Interventions Drug: mAb hOKT3gamma1(Ala-Ala), Teplizumab
Drug: Placebo Arm
Enrollment 63
Recruitment Details 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  
Arm/Group Title Saline Infusions (Placebo) Teplizumab Infusion (Active)
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 29 34
Randomized 29 34
Received Intervention/Placebo 28 31
Completed 27 31
Not Completed 2 3
Reason Not Completed
Withdrawal by Subject             1             3
Lost to Follow-up             1             0
Arm/Group Title Saline Infusions (Placebo) Teplizumab Infusions (Active) Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 27 31 58
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 27 participants 31 participants 58 participants
<15 years 20 18 38
>=15 years 7 13 20
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 27 participants 31 participants 58 participants
Female 10 15 25
Male 17 16 33
1.Primary Outcome
Title C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months
Hide Description

C-peptide secretory response was calculated as ln[(Area Under the Curve of the C-peptide from the 240 minute MMTT/240 +1]

For presentation, the C-peptide data were converted to the AUC as pmol/ml. This is adjusted for baseline.

Time Frame At month 12 post-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
This endpoint was compared in the modified intent to treat population which included all subjects with at least one post-randomization mixed meal tolerance test (MMTT)
Arm/Group Title Teplizumab Infusions (Active) Saline Infusions (Placebo)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 31 27
Least Squares Mean (95% Confidence Interval)
Unit of Measure: pmol/ml
0.451
(0.4 to 0.505)
0.371
(0.319 to 0.424)
2.Primary Outcome
Title C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline
Hide Description

C-peptide secretory response was calculated as ln[(Area Under the Curve of the C-peptide from the 240 minute MMTT/240 +1]

For presentation, the C-peptide data were converted to the AUC as pmol/ml. This baseline data was used to adjust for the C-peptide AUC primary endpoint measure at 12 months.

Time Frame At Baseline (before treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
This endpoint was compared in the modified intent to treat population which included all subjects with at least one post-randomization mixed meal tolerance test (MMTT)
Arm/Group Title Teplizumab Infusions (Active) Saline Infusions (Placebo)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 31 27
Least Squares Mean (95% Confidence Interval)
Unit of Measure: pmol/ml
0.593
(0.493 to 0.699)
0.554
(0.417 to 0.705)
3.Secondary Outcome
Title Hemoglobin A1c
Hide Description [Not Specified]
Time Frame At 12 months post-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Teplizumab Infusions (Active) Saline Infusions (Placebo)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 31 27
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percentage of hemogloblin A1c
6.85
(6.47 to 7.23)
7.35
(6.87 to 7.83)
4.Secondary Outcome
Title Average Insulin Use Over 12 Months
Hide Description [Not Specified]
Time Frame After 12 months post-treatment
Hide Outcome Measure Data
Hide Analysis Population Description
This endpoint was compared in the modified intent to treat population which included all subjects with at least one post-randomization mixed meal tolerance test (MMTT)
Arm/Group Title Teplizumab Infusions (Active) Saline Infusion (Placebo)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 31 27
Least Squares Mean (95% Confidence Interval)
Unit of Measure: U/kg/d
0.475
(0.428 to 0.521)
0.574
(0.0526 to 0.622)
5.Secondary Outcome
Title Baseline Insulin Use
Hide Description [Not Specified]
Time Frame At baseline (before treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
This endpoint was compared in the modified intent to treat population which included all subjects with at least one post-randomization mixed meal tolerance test (MMTT)
Arm/Group Title Teplizumab Infusions (Active) Saline Infusion (Placebo)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 31 27
Least Squares Mean (95% Confidence Interval)
Unit of Measure: U/kg/d
0.405
(0.354 to 0.456)
0.386
(0.308 to 0.464)
6.Secondary Outcome
Title Baseline Hemoglobin A1c
Hide Description [Not Specified]
Time Frame At baseline (before treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Teplizumab Infusions (Active) Saline Infusions (Placebo)
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 31 27
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percentage of hemoglobin A1c
6.32
(6.04 to 6.60)
7.1
(6.66 to 7.64)
Time Frame The adverse event data was collected throughout the duration of the study which was approximately 6 years.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Saline Infusions (Placebo) Teplizumab Infusion (Active)
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Saline Infusions (Placebo) Teplizumab Infusion (Active)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Saline Infusions (Placebo) Teplizumab Infusion (Active)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/29 (0.00%)   1/34 (2.94%) 
Immune system disorders     
Drug Related Hypersensitivity * 1  0/29 (0.00%)  1/33 (3.03%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (10.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Saline Infusions (Placebo) Teplizumab Infusion (Active)
Affected / at Risk (%) Affected / at Risk (%)
Total   29/29 (100.00%)   25/34 (73.53%) 
Blood and lymphatic system disorders     
Leukopenia  1  9/29 (31.03%)  10/33 (30.30%) 
Lymphopenia  1  10/29 (34.48%)  15/33 (45.45%) 
Neutropenia  1  7/29 (24.14%)  7/33 (21.21%) 
Cardiac disorders     
Tachycardia  1  2/29 (6.90%)  3/34 (8.82%) 
Eye disorders     
Conjunctivitis  1  2/29 (6.90%)  1/34 (2.94%) 
Gastrointestinal disorders     
Abdominal Discomfort  1  2/29 (6.90%)  1/34 (2.94%) 
Abdominal Pain  1  6/29 (20.69%)  3/34 (8.82%) 
Abdominal Pain (Upper)  1  9/29 (31.03%)  2/34 (5.88%) 
Aphthous Stomatitis  1  2/29 (6.90%)  1/34 (2.94%) 
Constipation  1  2/29 (6.90%)  0/34 (0.00%) 
Diarrhea  1  6/29 (20.69%)  3/34 (8.82%) 
Nausea  1  11/29 (37.93%)  14/33 (42.42%) 
Oral Pain  1  3/29 (10.34%)  2/33 (6.06%) 
Vomiting  1  12/29 (41.38%)  6/34 (17.65%) 
General disorders     
Catheter Related Complication  1  3/29 (10.34%)  1/34 (2.94%) 
Catheter Site Pain  1  3/29 (10.34%)  0/34 (0.00%) 
Catheter Site Rash  1  3/29 (10.34%)  1/34 (2.94%) 
Chills  1  1/29 (3.45%)  3/34 (8.82%) 
Edema Peripheral  1  0/29 (0.00%)  3/34 (8.82%) 
Fatigue  1  3/29 (10.34%)  8/34 (23.53%) 
Influenza Like Illness  1  7/29 (24.14%)  4/33 (12.12%) 
Nodule  1  2/29 (6.90%)  0/33 (0.00%) 
Pain  1  2/29 (6.90%)  1/33 (3.03%) 
Pyrexia  1  6/29 (20.69%)  8/34 (23.53%) 
Immune system disorders     
Cytokine Release Syndrome  1  2/29 (6.90%)  1/34 (2.94%) 
Infections and infestations     
Nasopharyngitis  1  4/29 (13.79%)  2/33 (6.06%) 
Pharyngitis Streptococcal  1  0/29 (0.00%)  2/33 (6.06%) 
Upper Respiratory Tract Infection  1  7/29 (24.14%)  10/34 (29.41%) 
Injury, poisoning and procedural complications     
Arthropod Bite  1  2/29 (6.90%)  1/34 (2.94%) 
Contusion  1  1/29 (3.45%)  4/34 (11.76%) 
Excoriation  1  4/29 (13.79%)  2/34 (5.88%) 
Investigations     
Activated Partial Thromboplastin Time Prolonged  1  3/29 (10.34%)  4/34 (11.76%) 
Alanine Aminotransferase Decreased  1  0/29 (0.00%)  2/34 (5.88%) 
Alanine Aminotransferase Increased  1  5/29 (17.24%)  5/34 (14.71%) 
Aspartate Aminotransferase Increased  1  5/29 (17.24%)  4/34 (11.76%) 
Blood Albumin Decreased  1  7/29 (24.14%)  7/34 (20.59%) 
Blood Alkaline Phosphatase Increased  1  3/29 (10.34%)  3/34 (8.82%) 
Blood Bicarbonate Decreased  1  3/29 (10.34%)  1/34 (2.94%) 
Blood Calcium Decreased  1  1/29 (3.45%)  3/34 (8.82%) 
Blood Calcium Increased  1  2/29 (6.90%)  0/34 (0.00%) 
Blood Creatinine Increased  1  4/29 (13.79%)  2/34 (5.88%) 
Blood Potassium Decreased  1  0/29 (0.00%)  2/34 (5.88%) 
Blood Sodium Decreased  1  4/29 (13.79%)  2/34 (5.88%) 
Blood Urea Increased  1  2/29 (6.90%)  0/34 (0.00%) 
Carbon Dioxide Abnormal  1  2/29 (6.90%)  0/34 (0.00%) 
Cardiac Murmur  1  0/29 (0.00%)  2/34 (5.88%) 
Gamma-glutamyltransferase Increased  1  2/29 (6.90%)  1/34 (2.94%) 
Glycosylated Hemoglobin Increased  1  2/29 (6.90%)  3/34 (8.82%) 
Hemoglobin Decreased  1  7/29 (24.14%)  10/34 (29.41%) 
International Normalized Ratio Increased  1  4/29 (13.79%)  2/33 (6.06%) 
Laboratory Test Abnormal  1  3/29 (10.34%)  1/33 (3.03%) 
Lymphocyte Count Decreased  1  0/29 (0.00%)  5/33 (15.15%) 
Lymphocyte Count Increased  1  2/29 (6.90%)  0/33 (0.00%) 
Mean Cell Hemoglobin Increased  1  2/29 (6.90%)  0/33 (0.00%) 
Platelet Count Decreased  1  1/29 (3.45%)  6/33 (18.18%) 
Protein Total Decreased  1  3/29 (10.34%)  1/34 (2.94%) 
Red Blood Cell Count Decreased  1  2/29 (6.90%)  0/34 (0.00%) 
White Blood Cell Count Decreased  1  0/29 (0.00%)  3/34 (8.82%) 
Metabolism and nutrition disorders     
Hyperglycemia  1  2/29 (6.90%)  2/34 (5.88%) 
Hypocalcemia  1  3/29 (10.34%)  3/34 (8.82%) 
Hypoglycemia  1  3/29 (10.34%)  6/34 (17.65%) 
Hyponatremia  1  2/29 (6.90%)  0/34 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  4/29 (13.79%)  3/34 (8.82%) 
Musculoskeletal Pain  1  0/29 (0.00%)  3/33 (9.09%) 
Myalgia  1  2/29 (6.90%)  0/33 (0.00%) 
Neck Pain  1  2/29 (6.90%)  0/33 (0.00%) 
Pain in Extremity  1  4/29 (13.79%)  5/33 (15.15%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Skin Papilloma  1  2/29 (6.90%)  1/34 (2.94%) 
Nervous system disorders     
Dizziness  1  5/29 (17.24%)  4/34 (11.76%) 
Headache  1  20/29 (68.97%)  15/34 (44.12%) 
Psychiatric disorders     
Anxiety  1  10/29 (34.48%)  11/34 (32.35%) 
Renal and urinary disorders     
Hematuria  1  2/29 (6.90%)  0/34 (0.00%) 
Ketonuria  1  3/29 (10.34%)  0/33 (0.00%) 
Reproductive system and breast disorders     
Dysmenorrhea  1  0/29 (0.00%)  2/34 (5.88%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  4/29 (13.79%)  4/34 (11.76%) 
Nasal Congestion  1  2/29 (6.90%)  5/33 (15.15%) 
Pharyngolaryngeal Pain  1  6/29 (20.69%)  6/33 (18.18%) 
Rhinitis Allergic  1  5/29 (17.24%)  2/34 (5.88%) 
Skin and subcutaneous tissue disorders     
Acne  1  1/29 (3.45%)  2/34 (5.88%) 
Dry Skin  1  1/29 (3.45%)  4/34 (11.76%) 
Erythema  1  2/29 (6.90%)  1/34 (2.94%) 
Lipohypertrophy  1  1/29 (3.45%)  3/33 (9.09%) 
Petechiae  1  2/29 (6.90%)  0/33 (0.00%) 
Pruritus  1  9/29 (31.03%)  11/34 (32.35%) 
Rash  1  16/29 (55.17%)  18/34 (52.94%) 
Rash Generalized  1  0/29 (0.00%)  4/34 (11.76%) 
Rash Papular  1  2/29 (6.90%)  3/34 (8.82%) 
Skin Disorder  1  0/29 (0.00%)  2/34 (5.88%) 
Skin Exfoliation  1  4/29 (13.79%)  6/34 (17.65%) 
Urticaria  1  2/29 (6.90%)  2/34 (5.88%) 
Vascular disorders     
Hypotension  1  3/29 (10.34%)  2/34 (5.88%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.0)
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Kevan Herold, MD
Organization: Yale University
Phone: 203-785-6507
EMail: Kevan.Herold@yale.edu
Layout table for additonal information
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT00378508     History of Changes
Other Study ID Numbers: Delay-Study 5
R01DK057846 ( U.S. NIH Grant/Contract )
First Submitted: September 18, 2006
First Posted: September 20, 2006
Results First Submitted: September 4, 2012
Results First Posted: October 31, 2012
Last Update Posted: August 2, 2016