Reversing Type 1 Diabetes After it is Established

• Sponsor: University of Florida (Other)
• Overall Status: Completed
• CT.gov ID: NCT01106157
• Collaborator: The Leona M. and Harry B. Helmsley Charitable Trust (Other), Genzyme, a Sanofi Company (Industry)
• Enrollment: 25
• Locations: 3
• Arms: 2
• Actual Duration (Months): 111.5
• Patients Per Site: 8.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: Anti-Thymocyte Globin (ATG); Drug: Placebo; Drug: Pegylated GCSF	Phase 1/Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Reversing Type 1 Diabetes After it is Established: A Pilot Safety and Feasibility Study of Anti-Thymocyte Globulin (Thymoglobulin®)and Pegylated GCSF (Neulasta®) in Established Type 1 Diabetes
• Actual Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Jul 16, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Anti-Thymocyte Globin (ATG); Anti-Thymocyte Globin (ATG) will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2.; Other Names: Thymoglobulin ; Drug: Pegylated GCSF; 6 doses of pegylated GCSF (6mg/dose) will be given subcutaneously every 2 weeks beginning after the ATG infusion.; Other Names: Neulasta
Placebo Comparator: 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	Drug: Placebo; Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes; Other Names: Saline infusion

Outcome Measures

Primary Outcome Measures

1. Change in Metabolic Function Baseline to 12 Months. [Baseline and 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

Secondary Outcome Measures

1. Percent Change in Regulatory T Cells (Treg) Baseline to 12 Months [Change in Baseline to 12 months]

   Change in regulatory T cells (Treg) baseline to 12 months

2. A1c [Change in baseline to 12 months]

   Change in A1c baseline to 12 months

3. Change in Insulin Requirements, Baseline to 12 Months [Change from baseline to 12 months]

   Change in Insulin Requirements, baseline to 12 months

4. Change in Glutamic Acid Decarboxylase Antibodies (GADA) From Baseline to 12 Months [Change from baseline to 12 months]

   Change in Glutamic Acid Decarboxylase Antibodies (GADA) over 12 months

5. Change in Insulin Autoantibodies (IAA) From Baseline to 12 Months [Change from baseline to 12 months]

   Change in Insulin Autoantibodies (IAA) over 12 months

6. Change in Insulinoma Associated 2 Autoantibodies (IA-2A) From Baseline to 12 Months [Change from baseline to 12 months]

   Change in Insulinoma Associated 2 Autoantibodies (IA-2A)

7. Change in Zinc Transporter 8 Autoantibodies (ZnT8A) From Baseline to 12 Months [Change from baseline to 12 months]

   Change in Zinc Transporter 8 Autoantibodies (ZnT8A) over 12 months

8. Percentage of Neutrophils [Change from baseline to 12 months]

   Change in Neutrophil Count over 12 months

9. Change in White Blood Count (WBC) From Baseline to 12 Months [Change from baseline to 12 months]

   Change in WBC over 12 months

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Must be > 12 years < 45

• Must have a diagnosis of T1D of greater than 4 months duration, with an upper limit of 2 years, Now only recruiting for those diagnosed greater than 1 year but less than 2 years.

• Must have at least one diabetes-related autoantibody present (e.g., islet cell autoantigen (ICA), GAD, ZnT8, or islet antigen 2 (IA2) autoantibodies)

• Must have stimulated C-peptide levels ≥ 0.1 pmol/ml (0.3ng/mL) when measured during a mixed meal tolerance test (MMTT), conducted at least 4 months from diagnosis of diabetes, and within 8 weeks of randomization

• Must be EBV PCR negative within two weeks of randomization if EBV seronegative at screening

• Be at least 6 weeks from last live immunization

• Be willing to forgo live vaccines for 3 months following last dose of study drug

• Be willing to comply with intensive diabetes management

• Normal screening values for complete blood count (CBC), renal function and electrolytes (CMP).

Exclusion Criteria:

• Be immunodeficient or have clinically significant chronic lymphopenia: (Leukopenia (< 3,000 leukocytes /μL), neutropenia (<1,500 neutrophils/μL), lymphopenia (<800 lymphocytes/μL), or thrombocytopenia (<125,000 platelets/μL).

• Have a chronic infection at time of randomization

• Have a positive PPD

• Be currently pregnant or lactating, or anticipate getting pregnant within the next two years

• Require use of other immunosuppressive agents

• Have serologic evidence of current or past HIV, Tuberculosis, Hepatitis B or Hepatitis C infection

• Have any complicating medical issues or abnormal clinical laboratory results that interfere with study conduct, or cause increased risk to include pre-existing cardiac disease, chronic obstructive pulmonary disease (COPD), sickle cell disease, neurological, or blood count abnormalities (e.g., lymphopenia, leukopenia, or thrombocytopenia)

• Have a history of malignancies

• Evidence of liver dysfunction with angiotensin sensitivity test (AST) or ALT greater than 3 times the upper limits of normal

• Evidence of renal dysfunction with creatinine greater than 1.5 times the upper limit of normal

• Vaccination with a live virus within the last 6 weeks

• Current use of non-insulin pharmaceuticals that affect glycemic control

• Active participation in another T1D treatment study in the previous 30 days

• Known allergy to G-CSF or ATG

• Prior treatment with ATG or known allergy to rabbit derived products

• Any condition that in the investigator's opinion, may adversely affect study participation or may compromise the study results

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94143-0748
2	Barbara Davis Center for Childhood Diabetes	Aurora	Colorado	United States	80045-6511
3	University of Florida	Gainesville	Florida	United States	32610-0296

Sponsors and Collaborators

• University of Florida
• The Leona M. and Harry B. Helmsley Charitable Trust
• Genzyme, a Sanofi Company

Investigators

• Principal Investigator: Michael J. Haller, MD, University of Florida Pediatric Endocrinology

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Florida Diabetes Center of Excellence

Publications

• 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.

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT01106157
• Other Study ID Numbers: UF-ATG-GCSF001; IRB201702525; 041-2010; OCR16038
• First Posted: Apr 19, 2010
• Last Update Posted: Aug 5, 2019
• Last Verified: Jul 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Florida: Autoimmune, Diabetes Mellitus, Glucose Metabolism
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Thymoglobulin

Study Results

Participant Flow

Arm/Group Title	Anti-Thymocyte Globin Plus Pegylated GCSF	Placebo
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	17	8
COMPLETED	16	8
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Anti-Thymocyte Globin Plus Pegylated GCSF	Placebo	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	17	8	25
Age (Count of Participants)
<=18 years	5 29.4%	5 62.5%	10 40%
Between 18 and 65 years	12 70.6%	3 37.5%	15 60%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	23.64 (10)	23.55 (10.6)	23.61 (10.0)
Sex: Female, Male (Count of Participants)
Female	5 29.4%	3 37.5%	8 32%
Male	12 70.6%	5 62.5%	17 68%
Region of Enrollment (participants) [Number]
United States	17 100%	8 100%	25 100%

Outcome Measures

1. Primary Outcome

Title	Change in Metabolic Function Baseline to 12 Months.
Description	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
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anti-Thymocyte Globin Plus Pegylated GCSF	Placebo
Arm/Group Description	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	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
Measure Participants	16	8
Mean (Standard Deviation) [nmol/L/min]	0.74 (0.47)	0.43 (0.32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anti-Thymocyte Globin Plus Pegylated GCSF, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.017
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.277
	Confidence Interval	(2-Sided) 95%; 0.001 to 0.552
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.134
	Estimation Comments

2. Secondary Outcome

Title	Percent Change in Regulatory T Cells (Treg) Baseline to 12 Months
Description	Change in regulatory T cells (Treg) baseline to 12 months
Time Frame	Change in Baseline to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anti-Thymocyte Globin Plus Pegylated GCSF	Placebo
Arm/Group Description	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	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
Measure Participants	16	8
Mean (Standard Deviation) [percentage change]	-0.46 (0.36)	0 (.036)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anti-Thymocyte Globin Plus Pegylated GCSF, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.30 to 0.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.104
	Estimation Comments

3. Secondary Outcome

Title	A1c
Description	Change in A1c baseline to 12 months
Time Frame	Change in baseline to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anti-Thymocyte Globin Plus Pegylated GCSF	Placebo
Arm/Group Description	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	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
Measure Participants	16	8
Mean (Standard Deviation) [% change]	0.47 (1.88)	0.98 (0.79)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anti-Thymocyte Globin Plus Pegylated GCSF, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.37
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.51
	Confidence Interval	(2-Sided) 95%; -1.64 to 0.63
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.70
	Estimation Comments

4. Secondary Outcome

Title	Change in Insulin Requirements, Baseline to 12 Months
Description	Change in Insulin Requirements, baseline to 12 months
Time Frame	Change from baseline to 12 months

Outcome Measure Data

Analysis Population Description

Insulin use data was not provided by all subjects resulting in sampling for analysis that was smaller than the cohort for the entire study.

Arm/Group Title	Anti-Thymocyte Globin Plus Pegylated GCSF	Placebo
Arm/Group Description	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	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
Measure Participants	14	5
Mean (Standard Deviation) [units/kg/day]	-0.03 (0.4)	0.08 (0.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anti-Thymocyte Globin Plus Pegylated GCSF, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.69
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.064
	Confidence Interval	(2-Sided) 95%; -0.40 to 0.27
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments

5. Secondary Outcome

Title	Change in Glutamic Acid Decarboxylase Antibodies (GADA) From Baseline to 12 Months
Description	Change in Glutamic Acid Decarboxylase Antibodies (GADA) over 12 months
Time Frame	Change from baseline to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anti-Thymocyte Globin Plus Pegylated GCSF	Placebo
Arm/Group Description	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	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
Measure Participants	16	8
Mean (Standard Deviation) [nmol/L]	-17.75 (225.81)	-29.5 (38.96)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anti-Thymocyte Globin Plus Pegylated GCSF, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.89
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	11.75
	Confidence Interval	(2-Sided) 95%; -156.8 to 180.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 81.3
	Estimation Comments

6. Secondary Outcome

Title	Change in Insulin Autoantibodies (IAA) From Baseline to 12 Months
Description	Change in Insulin Autoantibodies (IAA) over 12 months
Time Frame	Change from baseline to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anti-Thymocyte Globin Plus Pegylated GCSF	Placebo
Arm/Group Description	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	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
Measure Participants	16	8
Mean (Standard Deviation) [Units/mL]	0.12 (0.5)	-0.15 (0.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anti-Thymocyte Globin Plus Pegylated GCSF, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.28
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.70
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.21
	Estimation Comments

7. Secondary Outcome

Title	Change in Insulinoma Associated 2 Autoantibodies (IA-2A) From Baseline to 12 Months
Description	Change in Insulinoma Associated 2 Autoantibodies (IA-2A)
Time Frame	Change from baseline to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anti-Thymocyte Globin Plus Pegylated GCSF	Placebo
Arm/Group Description	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	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
Measure Participants	16	8
Mean (Standard Deviation) [nmol/L]	-21.63 (50.3)	2.5 (31.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anti-Thymocyte Globin Plus Pegylated GCSF, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-24.13
	Confidence Interval	(2-Sided) 95%; -64.8 to 16.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 19.61
	Estimation Comments

8. Secondary Outcome

Title	Change in Zinc Transporter 8 Autoantibodies (ZnT8A) From Baseline to 12 Months
Description	Change in Zinc Transporter 8 Autoantibodies (ZnT8A) over 12 months
Time Frame	Change from baseline to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anti-Thymocyte Globin Plus Pegylated GCSF	Placebo
Arm/Group Description	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	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
Measure Participants	16	8
Mean (Standard Deviation) [nmol/L]	-0.07 (0.17)	-0.10 (0.32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anti-Thymocyte Globin Plus Pegylated GCSF, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.79
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.037
	Confidence Interval	(2-Sided) 95%; -0.18 to 0.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

9. Secondary Outcome

Title	Percentage of Neutrophils
Description	Change in Neutrophil Count over 12 months
Time Frame	Change from baseline to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anti-Thymocyte Globin Plus Pegylated GCSF	Placebo
Arm/Group Description	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	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
Measure Participants	16	8
Mean (Standard Deviation) [Percentage of neutrophils]	0.21 (0.69)	0.44 (1.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Anti-Thymocyte Globin Plus Pegylated GCSF, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.163
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-7.67
	Confidence Interval	(2-Sided) 95%; -18.7 to 3.35
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.33
	Estimation Comments

10. Secondary Outcome

Title	Change in White Blood Count (WBC) From Baseline to 12 Months
Description	Change in WBC over 12 months
Time Frame	Change from baseline to 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anti-Thymocyte Globin Plus Pegylated GCSF	Placebo
Arm/Group Description	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	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
Measure Participants	16	8
Mean (Standard Deviation) [Change in percentage of WBC]	-0.51 (0.81)	0.4 (1.25)

Adverse Events

Time Frame	12 months
Arm/Group Title	Anti-Thymocyte Globin Plus Pegylated GCSF		Placebo
Arm/Group Description	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		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
All Cause Mortality
	Anti-Thymocyte Globin Plus Pegylated GCSF		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/8 (0%)
Serious Adverse Events
	Anti-Thymocyte Globin Plus Pegylated GCSF		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/16 (93.8%)		3/8 (37.5%)
Immune system disorders
Lymphocyte Count Decreased	15/16 (93.8%)	15	3/8 (37.5%)	5
Serum Sickness	13/16 (81.3%)	13	0/8 (0%)	0
Cytokine Release Syndrome	14/16 (87.5%)	14	0/8 (0%)	0
Other (Not Including Serious) Adverse Events
	Anti-Thymocyte Globin Plus Pegylated GCSF		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/16 (93.8%)		5/8 (62.5%)
Blood and lymphatic system disorders
Anemia	6/16 (37.5%)	6	3/8 (37.5%)	3
Endocrine disorders
Elevated Alk Phos	7/16 (43.8%)	7	0/8 (0%)	0
Hypoglycemia	12/16 (75%)	12	5/8 (62.5%)	5
Hyponatremia	3/16 (18.8%)	5	2/8 (25%)	4
General disorders
Fatigue	6/16 (37.5%)	6	3/8 (37.5%)	3
Headache	13/16 (81.3%)	13	4/8 (50%)	4
Nausea	5/16 (31.3%)	8	0/8 (0%)	0
Others	15/16 (93.8%)	84	5/8 (62.5%)	41
Immune system disorders
Chills	6/16 (37.5%)	6	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	9/16 (56.3%)	9	0/8 (0%)	0
Back Pain	9/16 (56.3%)	9	0/8 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.