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| ID | Type | Description | Link |
|---|---|---|---|
| R01DK057846 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
| Juvenile Diabetes Research Foundation | OTHER |
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This is a randomized placebo controlled study to test whether a single 14 course of treatment with the anti-CD3 monoclonal antibody, hOKT3gamma1(Ala-Ala),Teplizumab will prevent the loss of insulin secretory capacity in individuals with Type 1 diabetes of 4 - 12 months duration since diagnosis.
The study design is a double blind placebo controlled trial that will enroll subjects between the ages of 8 - 30 who have had the diagnosis of Type 1 diabetes made 4 - 12 months prior to enrollment. A single 14 course of treatment with mAb hOKT3gamma1(Ala-Ala), Teplizumab will be given. The primary endpoint is the C-peptide response to a mixed meal at 12 months. A total of 60 subjects will be enrolled (30 in the drug treatment and 30 in the placebo groups) at 4 study sites: Yale University,the University of California at San Francisco, Children's Hospital of Philadelphia, and the Barbara Davis Diabetes Center.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | The course of Teplizumab 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. |
|
| 2 | Placebo Comparator | Normal saline infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| mAb hOKT3gamma1(Ala-Ala), Teplizumab | Drug | This is a randomized, two-arm, double blind placebo controlled phase II trial in which 60 participants with recent-onset T1DM are randomized at a 1:1 ratio to receive Teplizumab or placebo over a 14 day treatment period. The course of Teplizumab comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2. |
| Measure | Description | Time Frame |
|---|---|---|
| C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months | 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. | At month 12 post-treatment |
| C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline | 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. | At Baseline (before treatment) |
| Measure | Description | Time Frame |
|---|---|---|
| Hemoglobin A1c | At 12 months post-treatment | |
| Average Insulin Use Over 12 Months | After 12 months post-treatment | |
| Baseline Insulin Use |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kevan C Herold | Yale University | Principal Investigator |
| Jeffrey A Bluestone, PhD | University of California at San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California at San Francisco | San Francisco | California | 94143 | United States | ||
| Barbara Davis Diabetes Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12037148 | Background | 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. doi: 10.1056/NEJMoa012864. | |
| 15919798 | Background | 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. doi: 10.2337/diabetes.54.6.1763. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Teplizumab Infusions (Active) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months | 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. | 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) | Posted | Least Squares Mean | 95% Confidence Interval | pmol/ml | At month 12 post-treatment |
|
The adverse event data was collected throughout the duration of the study which was approximately 6 years.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Drug Related Hypersensitivity | Immune system disorders | MedDRA (10.0) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Discomfort | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kevan Herold, MD | Yale University | 203-785-6507 | kevan.herold@yale.edu |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D001327 | Autoimmune Diseases |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C502540 | teplizumab |
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|
|
| Placebo Arm | Drug |
|
| At baseline (before treatment) |
| Baseline Hemoglobin A1c | At baseline (before treatment) |
| Aurora |
| Colorado |
| 80045 |
| United States |
| Yale University | New Haven | Connecticut | 06520 | United States |
| Children's Hospital of Philadelphia (CHOP) | Philadelphia | Pennsylvania | 10194 | United States |
| 24115337 | Derived | Sherr JL, Ghazi T, Wurtz A, Rink L, Herold KC. Characterization of residual beta cell function in long-standing type 1 diabetes. Diabetes Metab Res Rev. 2014 Feb;30(2):154-62. doi: 10.1002/dmrr.2478. |
| 23423576 | Derived | Lebastchi J, Deng S, Lebastchi AH, Beshar I, Gitelman S, Willi S, Gottlieb P, Akirav EM, Bluestone JA, Herold KC. Immune therapy and beta-cell death in type 1 diabetes. Diabetes. 2013 May;62(5):1676-80. doi: 10.2337/db12-1207. Epub 2013 Feb 19. |
| 23086558 | Derived | Herold KC, Gitelman SE, Willi SM, Gottlieb PA, Waldron-Lynch F, Devine L, Sherr J, Rosenthal SM, Adi S, Jalaludin MY, Michels AW, Dziura J, Bluestone JA. Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial. Diabetologia. 2013 Feb;56(2):391-400. doi: 10.1007/s00125-012-2753-4. Epub 2012 Oct 21. |
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.
| BG002 | Total | Total of all reporting groups |
| participants |
|
| Sex/Gender, Customized | Number | participants |
|
| 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. |
|
|
| Secondary | Hemoglobin A1c | Posted | Least Squares Mean | 95% Confidence Interval | percentage of hemogloblin A1c | At 12 months post-treatment |
|
|
|
| Secondary | Average Insulin Use Over 12 Months | 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) | Posted | Least Squares Mean | 95% Confidence Interval | U/kg/d | After 12 months post-treatment |
|
|
|
| Primary | C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline | 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. | 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) | Posted | Least Squares Mean | 95% Confidence Interval | pmol/ml | At Baseline (before treatment) |
|
|
|
| Secondary | Baseline Insulin Use | 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) | Posted | Least Squares Mean | 95% Confidence Interval | U/kg/d | At baseline (before treatment) |
|
|
|
| Secondary | Baseline Hemoglobin A1c | Posted | Least Squares Mean | 95% Confidence Interval | percentage of hemoglobin A1c | At baseline (before treatment) |
|
|
|
| 0 |
| 29 |
| 29 |
| 29 |
| EG001 | 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. | 1 | 34 | 25 | 34 |
| Abdominal Pain | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Abdominal Pain (Upper) | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Activated Partial Thromboplastin Time Prolonged | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Alanine Aminotransferase Decreased | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Alanine Aminotransferase Increased | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (10.0) | Systematic Assessment |
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| Aphthous Stomatitis | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
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| Arthropod Bite | Injury, poisoning and procedural complications | MedDRA (10.0) | Systematic Assessment |
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| Aspartate Aminotransferase Increased | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Blood Albumin Decreased | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Blood Alkaline Phosphatase Increased | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| Blood Bicarbonate Decreased | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Blood Calcium Decreased | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| Blood Calcium Increased | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Blood Creatinine Increased | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Blood Potassium Decreased | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Blood Sodium Decreased | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Blood Urea Increased | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| Carbon Dioxide Abnormal | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Cardiac Murmur | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Catheter Related Complication | General disorders | MedDRA (10.0) | Systematic Assessment |
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| Catheter Site Pain | General disorders | MedDRA (10.0) | Systematic Assessment |
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| Catheter Site Rash | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Conjunctivitis | Eye disorders | MedDRA (10.0) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA (10.0) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Cytokine Release Syndrome | Immune system disorders | MedDRA (10.0) | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Dry Skin | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Dysmenorrhea | Reproductive system and breast disorders | MedDRA (10.0) | Systematic Assessment |
|
| Edema Peripheral | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
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| Excoriation | Injury, poisoning and procedural complications | MedDRA (10.0) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Gamma-glutamyltransferase Increased | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Glycosylated Hemoglobin Increased | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Hematuria | Renal and urinary disorders | MedDRA (10.0) | Systematic Assessment |
|
| Hemoglobin Decreased | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | MedDRA (10.0) | Systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | MedDRA (10.0) | Systematic Assessment |
|
| Hypoglycemia | Metabolism and nutrition disorders | MedDRA (10.0) | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | MedDRA (10.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (10.0) | Systematic Assessment |
|
| Influenza Like Illness | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| International Normalized Ratio Increased | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| Ketonuria | Renal and urinary disorders | MedDRA (10.0) | Systematic Assessment |
|
| Laboratory Test Abnormal | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (10.0) | Systematic Assessment |
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| Lipohypertrophy | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Lymphocyte Count Decreased | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Lymphocyte Count Increased | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Lymphopenia | Blood and lymphatic system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Mean Cell Hemoglobin Increased | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| Musculoskeletal Pain | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Neck Pain | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (10.0) | Systematic Assessment |
|
| Nodule | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Oral Pain | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Pain in Extremity | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Pharyngitis Streptococcal | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
|
| Pharyngolaryngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Platelet Count Decreased | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| Protein Total Decreased | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Rash Generalized | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Rash Papular | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Red Blood Cell Count Decreased | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| Rhinitis Allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Skin Disorder | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Skin Exfoliation | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Skin Papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (10.0) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (10.0) | Systematic Assessment |
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| Upper Respiratory Tract Infection | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| White Blood Cell Count Decreased | Investigations | MedDRA (10.0) | Systematic Assessment |
|
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| D007154 | Immune System Diseases |