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Trial record 2 of 15 for:    trialnet type 1

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

This study is ongoing, but not recruiting participants.
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)
ClinicalTrials.gov Identifier:
NCT02215200
First received: August 11, 2014
Last updated: July 8, 2016
Last verified: July 2016
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Antithymocyte Globulin (ATG) and Pegylated Granulocyte Colony Stimulating Factor (GCSF) in New Onset Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 84
Study Start Date: December 2014
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   12 Years to 45 Years   (Child, Adult)
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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  TN19 
Study First Received: August 11, 2014
Last Updated: July 8, 2016
Health Authority: United States: Data and Safety Monitoring Board
United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

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

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

ClinicalTrials.gov processed this record on December 07, 2016