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| ID | Type | Description | Link |
|---|---|---|---|
| IRB201702525 | Other Identifier | University of Florida | |
| 041-2010 | Other Identifier | Univeristy of Florida | |
| OCR16038 | Other Identifier | University of Florida |
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| Name | Class |
|---|---|
| The Leona M. and Harry B. Helmsley Charitable Trust | OTHER |
| Genzyme, a Sanofi Company | INDUSTRY |
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The primary purpose of this study is to determine if giving the combination therapy consisting of Thymoglobulin® (ATG) and Neulasta® (GCSF) to patients with established Type 1 Diabetes (T1D) is safe and secondarily, if the ATG and GCSF will preserve insulin production.
This is a randomized, placebo controlled, phase I/II trial. Potential subjects will be screened via a 4 hour mixed meal tolerance test to assess residual beta cell (C-peptide) function. If the C-peptide level at any time is ≥ 0.1 pmol/ml, and the subject meets the additional inclusion and exclusion criteria, they will be eligible for randomization and enrollment. The study will be randomized 2:1 such that 17 subjects will receive active therapy and 8 will receive placebo. Subjects must receive Thymoglobulin®/ Neulasta® or placebo within 8 weeks of randomization. Thymoglobulin® (2.5mg/kg)/placebo will be given as 0.5 mg/kg IV on day 1 and 2 mg/kg on day 2. Six doses of Neulasta® (6mg/dose)/placebo will be given as standard of care every 2 weeks, with the first dose given prior to discharge after the Thymoglobulin® infusion. Complete metabolic panel (CMP) and complete blood count (CBC) will be done at the screening visit, just prior to study drug initiation, daily during the Thymoglobulin® infusion admission, and at follow up visits. Following discharge, daily phone calls will be made to the subjects during the first 5 days of therapy and weekly thereafter. In addition, weekly phone calls for the month following completion of therapy will be used to document adverse reactions. Thereafter calls will be made every two weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Anti-Thymocyte Globin plus pegylated GCSF | Experimental | Subjects will receive an infusion of Anti-Thymocyte Globin (ATG) followed by 6 doses of pegylated GCSF every 2 weeks for 10 weeks. |
|
| Placebo | Placebo Comparator | Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Anti-Thymocyte Globin (ATG) | Drug | Anti-Thymocyte Globin (ATG) will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Metabolic Function Baseline to 12 Months. | Area Under Curve (AUC) C-peptide production. Subjects underwent a 2 hour mixed meal tolerance test (MMTT) using a 6ml/kg load of boost to stimulate insulin production. Samples were collected at baseline, 10 minutes, 20 minutes, 30 minutes, 60 minutes, 90 minutes, and 120 minutes. AUC was then calculated. Subjects repeated the MMTT at baseline, 3, 6, 9, and 12 months following ATG/GCSF or placebo. The primary outcome for the study was the change over 12 months in AUC C-peptide (1 year - baseline) for those who received ATG/GCSF versus the change in AUC C-peptide (1 year - baseline) for those who received placebo | Baseline and 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in Regulatory T Cells (Treg) Baseline to 12 Months | Change in regulatory T cells (Treg) baseline to 12 months | Change in Baseline to 12 months |
| A1c | Change in A1c baseline to 12 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael J. Haller, MD | University of Florida Pediatric Endocrinology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Francisco | San Francisco | California | 94143-0748 | United States | ||
| Barbara Davis Center for Childhood Diabetes |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19628781 | Background | Parker MJ, Xue S, Alexander JJ, Wasserfall CH, Campbell-Thompson ML, Battaglia M, Gregori S, Mathews CE, Song S, Troutt M, Eisenbeis S, Williams J, Schatz DA, Haller MJ, Atkinson MA. Immune depletion with cellular mobilization imparts immunoregulation and reverses autoimmune diabetes in nonobese diabetic mice. Diabetes. 2009 Oct;58(10):2277-84. doi: 10.2337/db09-0557. Epub 2009 Jul 23. | |
| 25500887 |
| Label | URL |
|---|---|
| University of Florida Diabetes Center of Excellence | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Anti-Thymocyte Globin Plus Pegylated GCSF | Subjects will receive an infusion of Anti-Thymocyte Globin (ATG) followed by 6 doses of pegylated GCSF every 2 weeks for 10 weeks. Anti-Thymocyte Globin plus pegylated GCSF: Anti-Thymocyte Globin (ATG)will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2, plus 6 doses of pegylated GCSF (6mg/dose) given subcutaneously every 2 weeks beginning after the ATG infusion. |
| FG001 | Placebo | Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner. Placebo: Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Anti-Thymocyte Globin Plus Pegylated GCSF | Subjects will receive an infusion of Anti-Thymocyte Globin (ATG) followed by 6 doses of pegylated GCSF every 2 weeks for 10 weeks. Anti-Thymocyte Globin plus pegylated GCSF: Anti-Thymocyte Globin (ATG)will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2, plus 6 doses of pegylated GCSF (6mg/dose)given subcutaneously every 2 weeks beginning after the ATG infusion |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Change in Metabolic Function Baseline to 12 Months. | Area Under Curve (AUC) C-peptide production. Subjects underwent a 2 hour mixed meal tolerance test (MMTT) using a 6ml/kg load of boost to stimulate insulin production. Samples were collected at baseline, 10 minutes, 20 minutes, 30 minutes, 60 minutes, 90 minutes, and 120 minutes. AUC was then calculated. Subjects repeated the MMTT at baseline, 3, 6, 9, and 12 months following ATG/GCSF or placebo. The primary outcome for the study was the change over 12 months in AUC C-peptide (1 year - baseline) for those who received ATG/GCSF versus the change in AUC C-peptide (1 year - baseline) for those who received placebo | Posted | Mean | Standard Deviation | nmol/L/min | Baseline and 12 months |
|
12 months
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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 | Anti-Thymocyte Globin Plus Pegylated GCSF | Subjects will receive an infusion of Anti-Thymocyte Globin (ATG) followed by 6 doses of pegylated GCSF every 2 weeks for 10 weeks. Anti-Thymocyte Globin plus pegylated GCSF: Anti-Thymocyte Globin (ATG)will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2, plus 6 doses of pegylated GCSF (6mg/dose)given subcutaneously every 2 weeks beginning after the ATG infusion |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphocyte Count Decreased | Immune system disorders | CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Elevated Alk Phos | Endocrine disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michael J Haller | University of Florida | 3522739264 | hallemj@peds.ufl.edu |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| 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 |
|---|---|
| C512542 | thymoglobulin |
| C455861 | pegfilgrastim |
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| Placebo | Drug | Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes |
|
|
| Pegylated GCSF | Drug | 6 doses of pegylated GCSF (6mg/dose) will be given subcutaneously every 2 weeks beginning after the ATG infusion. |
|
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| Change in baseline to 12 months |
| Change in Insulin Requirements, Baseline to 12 Months | Change in Insulin Requirements, baseline to 12 months | Change from baseline to 12 months |
| Change in Glutamic Acid Decarboxylase Antibodies (GADA) From Baseline to 12 Months | Change in Glutamic Acid Decarboxylase Antibodies (GADA) over 12 months | Change from baseline to 12 months |
| Change in Insulin Autoantibodies (IAA) From Baseline to 12 Months | Change in Insulin Autoantibodies (IAA) over 12 months | Change from baseline to 12 months |
| Change in Insulinoma Associated 2 Autoantibodies (IA-2A) From Baseline to 12 Months | Change in Insulinoma Associated 2 Autoantibodies (IA-2A) | Change from baseline to 12 months |
| Change in Zinc Transporter 8 Autoantibodies (ZnT8A) From Baseline to 12 Months | Change in Zinc Transporter 8 Autoantibodies (ZnT8A) over 12 months | Change from baseline to 12 months |
| Percentage of Neutrophils | Change in Neutrophil Count over 12 months | Change from baseline to 12 months |
| Change in White Blood Count (WBC) From Baseline to 12 Months | Change in WBC over 12 months | Change from baseline to 12 months |
| Aurora |
| Colorado |
| 80045-6511 |
| United States |
| University of Florida | Gainesville | Florida | 32610-0296 | United States |
| Derived |
| Haller MJ, Gitelman SE, Gottlieb PA, Michels AW, Rosenthal SM, Shuster JJ, Zou B, Brusko TM, Hulme MA, Wasserfall CH, Mathews CE, Atkinson MA, Schatz DA. Anti-thymocyte globulin/G-CSF treatment preserves beta cell function in patients with established type 1 diabetes. J Clin Invest. 2015 Jan;125(1):448-55. doi: 10.1172/JCI78492. Epub 2014 Dec 15. |
| BG001 | Placebo | Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner Placebo: Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| OG001 | Placebo | Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner Placebo: Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes |
|
|
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| Secondary | Percent Change in Regulatory T Cells (Treg) Baseline to 12 Months | Change in regulatory T cells (Treg) baseline to 12 months | Posted | Mean | Standard Deviation | percentage change | Change in Baseline to 12 months |
|
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| Secondary | A1c | Change in A1c baseline to 12 months | Posted | Mean | Standard Deviation | % change | Change in baseline to 12 months |
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| Secondary | Change in Insulin Requirements, Baseline to 12 Months | Change in Insulin Requirements, baseline to 12 months | Insulin use data was not provided by all subjects resulting in sampling for analysis that was smaller than the cohort for the entire study. | Posted | Mean | Standard Deviation | units/kg/day | Change from baseline to 12 months |
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| Secondary | Change in Glutamic Acid Decarboxylase Antibodies (GADA) From Baseline to 12 Months | Change in Glutamic Acid Decarboxylase Antibodies (GADA) over 12 months | Posted | Mean | Standard Deviation | nmol/L | Change from baseline to 12 months |
|
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| Secondary | Change in Insulin Autoantibodies (IAA) From Baseline to 12 Months | Change in Insulin Autoantibodies (IAA) over 12 months | Posted | Mean | Standard Deviation | Units/mL | Change from baseline to 12 months |
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| Secondary | Change in Insulinoma Associated 2 Autoantibodies (IA-2A) From Baseline to 12 Months | Change in Insulinoma Associated 2 Autoantibodies (IA-2A) | Posted | Mean | Standard Deviation | nmol/L | Change from baseline to 12 months |
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| Secondary | Change in Zinc Transporter 8 Autoantibodies (ZnT8A) From Baseline to 12 Months | Change in Zinc Transporter 8 Autoantibodies (ZnT8A) over 12 months | Posted | Mean | Standard Deviation | nmol/L | Change from baseline to 12 months |
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| Secondary | Percentage of Neutrophils | Change in Neutrophil Count over 12 months | Posted | Mean | Standard Deviation | Percentage of neutrophils | Change from baseline to 12 months |
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| Secondary | Change in White Blood Count (WBC) From Baseline to 12 Months | Change in WBC over 12 months | Posted | Mean | Standard Deviation | Change in percentage of WBC | Change from baseline to 12 months |
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|
| 0 |
| 16 |
| 15 |
| 16 |
| 15 |
| 16 |
| EG001 | Placebo | Saline infusion will be given on both Day 1 and Day 2 followed by placebo injection given in identical volumes in identical syringes in the identical subcutaneous manner Placebo: Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes | 0 | 8 | 3 | 8 | 5 | 8 |
| Serum Sickness | Immune system disorders | CTCAE (4.0) | Systematic Assessment |
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| Cytokine Release Syndrome | Immune system disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Back Pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Chills | Immune system disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Fatigue | General disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Headache | General disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Hypoglycemia | Endocrine disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Hyponatremia | Endocrine disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Nausea | General disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Others | General disorders | CTCAE (4.0) | Non-systematic Assessment |
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| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |