ATG-GCSF in New Onset Type 1 Diabetes

Diabetes Mellitus, Type 1 Clinical Trial

— ATG-GCSF  

Official title:

Antithymocyte Globulin (ATG) and Pegylated Granulocyte Colony Stimulating Factor (GCSF) in New Onset Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02215200
• Other study ID #: ATG-GCSF (IND)
• Secondary ID: Type 1 Diabetes
• Status: Completed
• Phase: Phase 2
• Start date: December 2014
• Est. completion date: August 2018

Study information

• Verified date: February 2020
• Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a three-arm, 1:1:1 randomized, placebo controlled, double- blinded trial in which at least 28 subjects will receive active Anti-Thymocyte Globulin and Granulocyte colony-stimulating factor (ATG-GCSF), at least 28 subjects will receive ATG alone and at least 28 subjects will receive placebo alone within 100 days from diagnosis of Type 1 Diabetes (T1D).

The primary objective of the study will be to determine the safety and ability of low dose ATG plus GCSF and low dose ATG alone to retain/enhance C-peptide production in new onset T1D patients demonstrating residual beta cell function.

Description:

The primary statistical hypothesis to be assessed in the study is whether the 2 hour area under the curve (change in baseline to 12 months) in residual beta cell function (C-peptide) will differ between those treated with ATG and GCSF or ATG alone as compared with placebo.

The study will also examine the effect of the proposed treatments on surrogate markers for immunologic and metabolic outcomes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 89
• Est. completion date: August 2018
• Est. primary completion date: August 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 45 Years

Eligibility

Inclusion Criteria:

• Must be > 12 years < 46

• Must have a diagnosis of T1D for less than 100 days at randomization

• Willing to provide Informed Consent or have a parent or legal guardian provide informed consent if the subject is <18 years of age

• Positive for at least one islet cell autoantibody; glutamic acid decarboxylase 65 (GAD65A), Insulin micro IAA (mIAA), if obtained within 10 days of the onset of insulin therapy, islet antigen 2 (IA-2A), Islet Cell Antigen (ICA), or zinc transporter 8 (ZnT8A)

• Must have stimulated C-peptide levels = 0.2 pmol/ml measured during a mixed meal tolerance test (MMTT) conducted at least 21 days from diagnosis of diabetes and within one month (37 days) of randomization

• Must be Epstein-Barr virus (EBV PCR) negative within two weeks of randomization if EBV seronegative at screening

• Be at least 6 weeks from last live immunization

• Participants are required to receive killed influenza vaccination at least 2 weeks prior to randomization when vaccine for the current or upcoming flu season is available

• Be willing to forgo vaccines during the treatment period and for 3 months following last dose of study drug

• Be willing to comply with intensive diabetes management

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 (<100,000 platelets/µL).

• Have active signs or symptoms of acute infection at the time of randomization

• Have evidence of prior or current tuberculosis infection as assessed by purified protein derivative (PPD), interferon gamma release assay (IGRA) or by history

• Be currently pregnant or lactating, or anticipate getting pregnant within the two year study period

• Require use of other immunosuppressive agents including chronic use of systemic steroids

• Have evidence of current or past human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection

• Have any complicating medical issues or abnormal clinical laboratory results that may 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

• Have a history of malignancies other than skin

• Evidence of liver dysfunction with aspartate aminotransferase (AST) or alanine transaminase (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 or ongoing use of non-insulin pharmaceuticals that affect glycemic control within prior 7 days of screening

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

• Prior treatment with abatacept or anti-cd3

• Known allergy to GCSF 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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

Drug:
• Anti-Thymocyte Globulin (ATG)
Thymoglobulin
• Granulocyte colony stimulating factor (GCSF)
Granulocyte colony stimulating factor (GCSF)
• Placebo (for ATG)
Normal saline administered by IV infusion to mimic ATG
• Placebo (for GCSF)
Placebo prepared to mimic 6mg subcutaneous injection of GCSF

Locations

Country	Name	City	State
United States	Barbara Davis Center	Aurora	Colorado
United States	University of Florida	Gainesville	Florida
United States	Indiana University-Riley Hospital for Children	Indianapolis	Indiana
United States	University of Miami	Miami	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt Eskind Diabetes Clinic	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Columbia University-Naomi Berrie Diabetes Center	New York	New York
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of California - San Francisco	San Francisco	California
United States	Benaroya Research Institute	Seattle	Washington
United States	Stanford University	Stanford	California
United States	University of South Florida Diabetes Center	Tampa	Florida

Sponsors (9)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	American Diabetes Association, Amgen, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Juvenile Diabetes Research Foundation, National Center for Research Resources (NCRR), National Institute of Allergy and Infectious Diseases (NIAID), Sanofi, The Leona M. and Harry B. Helmsley Charitable Trust

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Area Under the Stimulated C-peptide Curve From Baseline to 12 Months.	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").	-10, 0 15, 30, 60, 90, and 120 minutes post-dose at baseline and 12 months

External Links

•   Type 1 Diabetes TrialNet