Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

ATG-GCSF in New Onset Type 1 Diabetes (ATG-GCSF)

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: NCT02215200
Recruitment Status : Completed
First Posted : August 13, 2014
Results First Posted : March 2, 2020
Last Update Posted : March 2, 2020
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Center for Research Resources (NCRR)
Juvenile Diabetes Research Foundation
American Diabetes Association
Sanofi
The Leona M. and Harry B. Helmsley Charitable Trust
Amgen
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 1
Interventions Drug: Anti-Thymocyte Globulin (ATG)
Drug: Granulocyte colony stimulating factor (GCSF)
Drug: Placebo (for ATG)
Drug: Placebo (for GCSF)
Enrollment 89
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Anti-Thymocyte Globulin (ATG) and Placebo ATG Plus Granulocyte Colony Stimulating Factor (GCSF) Placebo
Hide Arm/Group Description

Anti-Thymocyte Globulin (ATG)/Placebo: Anti-Thymocyte Globulin (ATG) will be administered at a dose of 2.5mg/kg as two divided IV infusions of 0.5mg/kg and 2mg/kg. First dose (0.5mg/kg) will be infused over a minimum of 12 hours, and the second dose (2mg/kg) over a minimum of 8 hours. The second dose should be given no less than 12 and no more than 24 hours after the previous dose.

Placebo(for GCSF) treatment will begin 6 hours after completion of the ATG. Placebo will be given subcutaneously every 2 weeks for a total of 6 doses

Anti-Thymocyte Globulin (ATG): Thymoglobulin

Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF

Granulocyte colony stimulating factor (GCSF) is supplied in 0.6 mL prefilled syringes for subcutaneous injection. Each syringe contains 6 mg GCSF (based on protein weight), in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), sorbitol (30.0 mg), polysorbate 20 (0.02 mg), and sodium (0.02 mg) in water for injection, U.S. Pharmacopeial Convention (USP). The standard 6mg dose will be given with the exception of subjects who weigh less than 45 kg.

GCSF treatment will begin 6 hours after completion of the ATG / Placebo. GCSF will be given subcutaneously every 2 weeks for a total of 6 doses

Anti-Thymocyte Globulin (ATG): Thymoglobulin

Granulocyte colony stimulating factor (GCSF): Granulocyte colony stimulating factor (GCSF)

Placebo for ATG will be administered by IV infusion in 2 doses. Placebo for GCSF will be administered subcutaneously every 2 weeks for a total of 6 doses

Placebo (for ATG): Normal saline administered by IV infusion to mimic ATG

Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF

Period Title: Overall Study
Started 29 29 31
Completed 29 28 30
Not Completed 0 1 1
Arm/Group Title Anti-Thymocyte Globulin (ATG) and Placebo ATG Plus Granulocyte Colony Stimulating Factor (GCSF) Placebo Total
Hide Arm/Group Description

Anti-Thymocyte Globulin (ATG)/Placebo: Anti-Thymocyte Globulin (ATG) will be administered at a dose of 2.5mg/kg as two divided IV infusions of 0.5mg/kg and 2mg/kg. First dose (0.5mg/kg) will be infused over a minimum of 12 hours, and the second dose (2mg/kg) over a minimum of 8 hours. The second dose should be given no less than 12 and no more than 24 hours after the previous dose.

Placebo(for GCSF) treatment will begin 6 hours after completion of the ATG. Placebo will be given subcutaneously every 2 weeks for a total of 6 doses

Anti-Thymocyte Globulin (ATG): Thymoglobulin

Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF

Granulocyte colony stimulating factor (GCSF) is supplied in 0.6 mL prefilled syringes for subcutaneous injection. Each syringe contains 6 mg GCSF (based on protein weight), in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), sorbitol (30.0 mg), polysorbate 20 (0.02 mg), and sodium (0.02 mg) in water for injection, U.S. Pharmacopeial Convention (USP). The standard 6mg dose will be given with the exception of subjects who weigh less than 45 kg.

GCSF treatment will begin 6 hours after completion of the ATG / Placebo. GCSF will be given subcutaneously every 2 weeks for a total of 6 doses

Anti-Thymocyte Globulin (ATG): Thymoglobulin

Granulocyte colony stimulating factor (GCSF): Granulocyte colony stimulating factor (GCSF)

Placebo for ATG will be administered by IV infusion in 2 doses. Placebo for GCSF will be administered subcutaneously every 2 weeks for a total of 6 doses

Placebo (for ATG): Normal saline administered by IV infusion to mimic ATG

Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF

Total of all reporting groups
Overall Number of Baseline Participants 29 29 31 89
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 29 participants 29 participants 31 participants 89 participants
17.2  (5) 18.1  (6.9) 16.9  (4.6) 17.4  (5.56)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 29 participants 31 participants 89 participants
Female
13
  44.8%
12
  41.4%
14
  45.2%
39
  43.8%
Male
16
  55.2%
17
  58.6%
17
  54.8%
50
  56.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 29 participants 31 participants 89 participants
Hispanic or Latino
1
   3.4%
2
   6.9%
1
   3.2%
4
   4.5%
Not Hispanic or Latino
28
  96.6%
27
  93.1%
30
  96.8%
85
  95.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 29 participants 31 participants 89 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   3.4%
0
   0.0%
2
   6.5%
3
   3.4%
White
28
  96.6%
29
 100.0%
29
  93.5%
86
  96.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 29 participants 29 participants 31 participants 89 participants
29 29 31 89
1.Primary Outcome
Title Change in Area Under the Stimulated C-peptide Curve From Baseline to 12 Months.
Hide Description The C-peptide 2 hour area under the curve (AUC) mean is calculated at baseline and 12 months and measured in nmol/L. The calculation for the concentration of c-peptide is a weighted average of the 6 timed measurements of c-peptide in nano-moles/Liter. We try to distinguish this calculation from the AUC by referring to it as the "AUC mean" and may be expressed algebraically as the AUC/(120 min.); thus, the units are the same as the y-axis").
Time Frame -10, 0 15, 30, 60, 90, and 120 minutes post-dose at baseline and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anti-Thymocyte Globulin (ATG) and Placebo ATG Plus Granulocyte Colony Stimulating Factor (GCSF) Placebo
Hide Arm/Group Description:

Anti-Thymocyte Globulin (ATG)/Placebo: Anti-Thymocyte Globulin (ATG) will be administered at a dose of 2.5mg/kg as two divided IV infusions of 0.5mg/kg and 2mg/kg. First dose (0.5mg/kg) will be infused over a minimum of 12 hours, and the second dose (2mg/kg) over a minimum of 8 hours. The second dose should be given no less than 12 and no more than 24 hours after the previous dose.

Placebo(for GCSF) treatment will begin 6 hours after completion of the ATG. Placebo will be given subcutaneously every 2 weeks for a total of 6 doses

Anti-Thymocyte Globulin (ATG): Thymoglobulin

Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF

Granulocyte colony stimulating factor (GCSF) is supplied in 0.6 mL prefilled syringes for subcutaneous injection. Each syringe contains 6 mg GCSF (based on protein weight), in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), sorbitol (30.0 mg), polysorbate 20 (0.02 mg), and sodium (0.02 mg) in water for injection, U.S. Pharmacopeial Convention (USP). The standard 6mg dose will be given with the exception of subjects who weigh less than 45 kg.

GCSF treatment will begin 6 hours after completion of the ATG / Placebo. GCSF will be given subcutaneously every 2 weeks for a total of 6 doses

Anti-Thymocyte Globulin (ATG): Thymoglobulin

Granulocyte colony stimulating factor (GCSF): Granulocyte colony stimulating factor (GCSF)

Placebo for ATG will be administered by IV infusion in 2 doses. Placebo for GCSF will be administered subcutaneously every 2 weeks for a total of 6 doses

Placebo (for ATG): Normal saline administered by IV infusion to mimic ATG

Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF

Overall Number of Participants Analyzed 29 28 30
Mean (95% Confidence Interval)
Unit of Measure: nmol/L
0.528
(0.435 to 0.627)
0.646
(0.547 to 0.750)
0.406
(0.324 to 0.494)
Time Frame Adverse events were collected over 1 year.
Adverse Event Reporting Description Adverse events were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
 
Arm/Group Title Anti-Thymocyte Globulin (ATG) and Placebo ATG Plus Granulocyte Colony Stimulating Factor (GCSF) Placebo
Hide Arm/Group Description

Anti-Thymocyte Globulin (ATG)/Placebo: Anti-Thymocyte Globulin (ATG) will be administered at a dose of 2.5mg/kg as two divided IV infusions of 0.5mg/kg and 2mg/kg. First dose (0.5mg/kg) will be infused over a minimum of 12 hours, and the second dose (2mg/kg) over a minimum of 8 hours. The second dose should be given no less than 12 and no more than 24 hours after the previous dose.

Placebo(for GCSF) treatment will begin 6 hours after completion of the ATG. Placebo will be given subcutaneously every 2 weeks for a total of 6 doses

Anti-Thymocyte Globulin (ATG): Thymoglobulin

Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF

Granulocyte colony stimulating factor (GCSF) is supplied in 0.6 mL prefilled syringes for subcutaneous injection. Each syringe contains 6 mg GCSF (based on protein weight), in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), sorbitol (30.0 mg), polysorbate 20 (0.02 mg), and sodium (0.02 mg) in water for injection, U.S. Pharmacopeial Convention (USP). The standard 6mg dose will be given with the exception of subjects who weigh less than 45 kg.

GCSF treatment will begin 6 hours after completion of the ATG / Placebo. GCSF will be given subcutaneously every 2 weeks for a total of 6 doses

Anti-Thymocyte Globulin (ATG): Thymoglobulin

Granulocyte colony stimulating factor (GCSF): Granulocyte colony stimulating factor (GCSF)

Placebo for ATG will be administered by IV infusion in 2 doses. Placebo for GCSF will be administered subcutaneously every 2 weeks for a total of 6 doses

Placebo (for ATG): Normal saline administered by IV infusion to mimic ATG

Placebo (for GCSF): Placebo prepared to mimic 6mg subcutaneous injection of GCSF

All-Cause Mortality
Anti-Thymocyte Globulin (ATG) and Placebo ATG Plus Granulocyte Colony Stimulating Factor (GCSF) Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/29 (0.00%)      0/29 (0.00%)      0/31 (0.00%)    
Hide Serious Adverse Events
Anti-Thymocyte Globulin (ATG) and Placebo ATG Plus Granulocyte Colony Stimulating Factor (GCSF) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   28/29 (96.55%)      29/29 (100.00%)      8/31 (25.81%)    
Blood and lymphatic system disorders       
CD4 lymphocyte decrease or other   18/29 (62.07%)  24 17/29 (58.62%)  23 0/31 (0.00%)  0
Blood and lymphatic system disorder   0/29 (0.00%)  0 1/29 (3.45%)  1 0/31 (0.00%)  0
Endocrine disorders       
Endocrine Disorders   0/29 (0.00%)  0 0/29 (0.00%)  0 1/31 (3.23%)  5
Gastrointestinal disorders       
Gastrointestinal Disorders *  1/29 (3.45%)  1 0/29 (0.00%)  0 0/31 (0.00%)  0
General disorders       
General Disorders and administration *  2/29 (6.90%)  4 1/29 (3.45%)  1 1/31 (3.23%)  1
Immune system disorders       
All immune system disorders   12/29 (41.38%)  14 15/29 (51.72%)  15 0/31 (0.00%)  0
Infections and infestations       
Infections and infestations   0/29 (0.00%)  0 0/29 (0.00%)  0 1/31 (3.23%)  1
Injury, poisoning and procedural complications       
Injury, poisoning, and procedural complications *  1/29 (3.45%)  2 1/29 (3.45%)  1 1/31 (3.23%)  1
Metabolism and nutrition disorders       
Metabolism and nutrition disorders *  2/29 (6.90%)  3 0/29 (0.00%)  0 2/31 (6.45%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Neoplasms: benign, malignant, and unspecified *  0/29 (0.00%)  0 1/29 (3.45%)  1 0/31 (0.00%)  0
Nervous system disorders       
Nervous system disorders *  1/29 (3.45%)  1 1/29 (3.45%)  1 1/31 (3.23%)  1
Psychiatric disorders       
Psychiatric Disorders *  1/29 (3.45%)  3 0/29 (0.00%)  0 0/31 (0.00%)  0
Surgical and medical procedures       
Surgical and medical procedures *  0/29 (0.00%)  0 0/29 (0.00%)  0 1/31 (3.23%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Anti-Thymocyte Globulin (ATG) and Placebo ATG Plus Granulocyte Colony Stimulating Factor (GCSF) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   28/29 (96.55%)      29/29 (100.00%)      31/31 (100.00%)    
Blood and lymphatic system disorders       
CD4 lymphocyte decrease or other   21/29 (72.41%)  42 22/29 (75.86%)  43 3/31 (9.68%)  4
Blood and lymphatic system disorder   1/29 (3.45%)  1 1/29 (3.45%)  1 2/31 (6.45%)  2
Cardiac disorders       
Cardiac Disorders *  1/29 (3.45%)  1 0/29 (0.00%)  0 0/31 (0.00%)  0
Ear and labyrinth disorders       
Ear and labyrinth disorders *  1/29 (3.45%)  1 0/29 (0.00%)  0 0/31 (0.00%)  0
Endocrine disorders       
Endocrine Disorders *  1/29 (3.45%)  1 1/29 (3.45%)  1 3/31 (9.68%)  7
Gastrointestinal disorders       
Gastrointestinal Disorders *  5/29 (17.24%)  7 3/29 (10.34%)  5 6/31 (19.35%)  6
General disorders       
General Disorders and administration *  7/29 (24.14%)  16 8/29 (27.59%)  18 1/31 (3.23%)  1
Immune system disorders       
All Immune system disorders   21/29 (72.41%)  33 23/29 (79.31%)  38 0/31 (0.00%)  0
Infections and infestations       
Infections and infestations *  9/29 (31.03%)  14 7/29 (24.14%)  9 9/31 (29.03%)  16
Injury, poisoning and procedural complications       
Injury, poisoning, and procedural complications *  1/29 (3.45%)  4 2/29 (6.90%)  2 5/31 (16.13%)  5
Metabolism and nutrition disorders       
Metabolism and nutrition disorders *  4/29 (13.79%)  7 2/29 (6.90%)  4 4/31 (12.90%)  4
Musculoskeletal and connective tissue disorders       
Musculoskeletal and connective tissue *  10/29 (34.48%)  14 3/29 (10.34%)  3 5/31 (16.13%)  6
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Neoplasms: benign, malignant, and unspecified *  0/29 (0.00%)  0 1/29 (3.45%)  1 1/31 (3.23%)  1
Nervous system disorders       
Nervous system disorders *  4/29 (13.79%)  4 4/29 (13.79%)  11 2/31 (6.45%)  5
Psychiatric disorders       
Psychiatric Disorders *  2/29 (6.90%)  7 1/29 (3.45%)  1 0/31 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Respiratory, thoracic, and mediastinal *  2/29 (6.90%)  2 2/29 (6.90%)  3 1/31 (3.23%)  1
Skin and subcutaneous tissue disorders       
Skin and subcutaneous tissue disorder *  5/29 (17.24%)  6 7/29 (24.14%)  10 4/31 (12.90%)  7
Surgical and medical procedures       
Surgical and medical procedures *  1/29 (3.45%)  1 0/29 (0.00%)  0 1/31 (3.23%)  1
Vascular disorders       
Vascular Disorders *  0/29 (0.00%)  0 2/29 (6.90%)  2 1/31 (3.23%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Carla Greenbaum, MD
Organization: Benaroya Research Institute
Phone: 1-800-425-8361
EMail: cjgreen@benaroyaresearch.org
Layout table for additonal information
Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT02215200    
Other Study ID Numbers: ATG-GCSF (IND)
Type 1 Diabetes TrialNet ( Other Identifier: Type 1 Diabetes TrialNet )
TN19 ( Other Identifier: Type 1 Diabetes TrialNet )
UC4DK106993 ( U.S. NIH Grant/Contract )
UC4DK117009 ( U.S. NIH Grant/Contract )
First Submitted: August 11, 2014
First Posted: August 13, 2014
Results First Submitted: May 30, 2019
Results First Posted: March 2, 2020
Last Update Posted: March 2, 2020