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

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ClinicalTrials.gov Identifier: NCT02215200
Recruitment Status : Active, not recruiting
First Posted : August 13, 2014
Last Update Posted : December 26, 2017
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)

Tracking Information
First Submitted Date  ICMJE August 11, 2014
First Posted Date  ICMJE August 13, 2014
Last Update Posted Date December 26, 2017
Study Start Date  ICMJE December 2014
Actual Primary Completion Date August 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 11, 2014)
Measure of area under the stimulated C-peptide curve over the first 2 hours of a mixed meal glucose tolerance test conducted at the one-year visit. [ Time Frame: 12 months ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02215200 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ATG-GCSF in New Onset Type 1 Diabetes
Official Title  ICMJE Antithymocyte Globulin (ATG) and Pegylated Granulocyte Colony Stimulating Factor (GCSF) in New Onset Type 1 Diabetes
Brief 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.

Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Diabetes Mellitus, Type 1
Intervention  ICMJE
  • Drug: Anti-Thymocyte Globulin (ATG)
    Thymoglobulin
    Other Name: Thymoglobulin
  • Drug: Granulocyte colony stimulating factor (GCSF)
    Granulocyte colony stimulating factor (GCSF)
    Other Name: Neulasta
  • Drug: Placebo (for ATG)
    Normal saline administered by IV infusion to mimic ATG
  • Drug: Placebo (for GCSF)
    Placebo prepared to mimic 6mg subcutaneous injection of GCSF
Study Arms  ICMJE
  • Experimental: Anti-Thymocyte Globulin (ATG) and Placebo

    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

    Interventions:
    • Drug: Anti-Thymocyte Globulin (ATG)
    • Drug: Placebo (for GCSF)
  • Experimental: ATG plus Granulocyte colony stimulating factor (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

    Interventions:
    • Drug: Anti-Thymocyte Globulin (ATG)
    • Drug: Granulocyte colony stimulating factor (GCSF)
  • Placebo Comparator: Placebo
    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
    Interventions:
    • Drug: Placebo (for ATG)
    • Drug: Placebo (for GCSF)
Publications * Haller MJ, Schatz DA, Skyler JS, Krischer JP, Bundy BN, Miller JL, Atkinson MA, Becker DJ, Baidal D, DiMeglio LA, Gitelman SE, Goland R, Gottlieb PA, Herold KC, Marks JB, Moran A, Rodriguez H, Russell W, Wilson DM, Greenbaum CJ; Type 1 Diabetes TrialNet ATG-GCSF Study Group. Low-Dose Anti-Thymocyte Globulin (ATG) Preserves β-Cell Function and Improves HbA(1c) in New-Onset Type 1 Diabetes. Diabetes Care. 2018 Sep;41(9):1917-1925. doi: 10.2337/dc18-0494. Epub 2018 Jul 16.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: August 11, 2014)
84
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2018
Actual Primary Completion Date August 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 45 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02215200
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study Sponsor  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators  ICMJE
  • 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
Investigators  ICMJE
Principal Investigator: Michael J Haller, M.D. University of Florida
PRS Account National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Verification Date December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP