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Trial record 47 of 2791 for:    Type 1 Diabetes

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 : Active, not recruiting
First Posted : August 13, 2014
Last Update Posted : December 25, 2017
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
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.


Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Drug: Anti-Thymocyte Globulin (ATG) Drug: Granulocyte colony stimulating factor (GCSF) Drug: Placebo (for ATG) Drug: Placebo (for GCSF) Phase 2

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 Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Antithymocyte Globulin (ATG) and Pegylated Granulocyte Colony Stimulating Factor (GCSF) in New Onset Type 1 Diabetes
Study Start Date : December 2014
Primary Completion Date : August 2017
Estimated Study Completion Date : October 2018


Arms and Interventions

Arm Intervention/treatment
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

Drug: Anti-Thymocyte Globulin (ATG)
Thymoglobulin
Other Name: Thymoglobulin
Drug: Placebo (for GCSF)
Placebo prepared to mimic 6mg subcutaneous injection of 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

Drug: Anti-Thymocyte Globulin (ATG)
Thymoglobulin
Other Name: Thymoglobulin
Drug: Granulocyte colony stimulating factor (GCSF)
Granulocyte colony stimulating factor (GCSF)
Other Name: Neulasta
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
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


Outcome Measures

Primary Outcome Measures :
  1. 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.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02215200


Locations
United States, California
University of California - San Francisco
San Francisco, California, United States, 94158-2549
Stanford University
Stanford, California, United States, 94305
United States, Colorado
Barbara Davis Center
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06519
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
University of Miami
Miami, Florida, United States, 33136
University of South Florida Diabetes Center
Tampa, Florida, United States, 33612
United States, Indiana
Indiana University-Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
Columbia University-Naomi Berrie Diabetes Center
New York, New York, United States, 10032
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15224
United States, Tennessee
Vanderbilt Eskind Diabetes Clinic
Nashville, Tennessee, United States, 37232
United States, Washington
Benaroya Research Institute
Seattle, Washington, United States, 98101
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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
Principal Investigator: Michael J Haller, M.D. University of Florida
More Information

Additional Information:
Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT02215200     History of Changes
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 Posted: August 13, 2014    Key Record Dates
Last Update Posted: December 25, 2017
Last Verified: December 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Type 1 Diabetes TrialNet

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Thymoglobulin
Lenograstim
Antilymphocyte Serum
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Adjuvants, Immunologic