Reversing Type 1 Diabetes After it is Established

NCT01106157 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: UF-ATG-GCSF001IRB201702525041-2010OCR16038
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 3

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.

Conditions

Diabetes Mellitus, Type 1

Keywords

Autoimmune, Diabetes Mellitus, Glucose Metabolism

Outcome Measures

Primary Outcomes (1)

• Change in Metabolic Function Baseline to 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

  Baseline and 12 months

Secondary Outcomes (9)

• Percent Change in Regulatory T Cells (Treg) Baseline to 12 Months

  Change in Baseline to 12 months

• A1c

  Change in baseline to 12 months

• Change in Insulin Requirements, Baseline to 12 Months

  Change from baseline to 12 months

• Change in Glutamic Acid Decarboxylase Antibodies (GADA) From Baseline to 12 Months

  Change from baseline to 12 months

• Change in Insulin Autoantibodies (IAA) From Baseline to 12 Months

  Change from baseline to 12 months

Study Arms (2)

Anti-Thymocyte Globin plus pegylated GCSF

EXPERIMENTAL

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); Drug: Pegylated GCSF

Placebo

PLACEBO COMPARATOR

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

Interventions

Anti-Thymocyte Globin (ATG) DRUG

Anti-Thymocyte Globin (ATG) will be given as 0.5/mg/kg on day 1 and 2mg/kg on day 2.

Also known as: Thymoglobulin

Anti-Thymocyte Globin plus pegylated GCSF

Placebo DRUG

Saline infusions will be given on Day 1 and Day 2 followed by placebo injections given in identical volumes in identical syringes

Also known as: Saline infusion

Placebo

Pegylated GCSF DRUG

6 doses of pegylated GCSF (6mg/dose) will be given subcutaneously every 2 weeks beginning after the ATG infusion.

Also known as: Neulasta

Anti-Thymocyte Globin plus pegylated GCSF

Eligibility Criteria

• Age: 12 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (3)

University of California, San Francisco

San Francisco, California, 94143-0748, United States

Location

Barbara Davis Center for Childhood Diabetes

Aurora, Colorado, 80045-6511, United States

Location

University of Florida

Gainesville, Florida, 32610-0296, United States

Location

Related Publications (2)

• 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.

  PMID: 19628781 BACKGROUND

• Haller MJ, Gitelman SE, Gottlieb PA, Michels AW, Rosenthal SM, Shuster JJ, Zou B, Brusko TM, Hulme MA, Wasserfall CH, Mathews CE, Atkinson MA, Schatz DA. Anti-thymocyte globulin/G-CSF treatment preserves beta cell function in patients with established type 1 diabetes. J Clin Invest. 2015 Jan;125(1):448-55. doi: 10.1172/JCI78492. Epub 2014 Dec 15.

  PMID: 25500887 DERIVED

Related Links

• University of Florida Diabetes Center of Excellence

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Interventions

thymoglobulin; pegfilgrastim

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Michael J Haller
• Organization: University of Florida

hallemj@peds.ufl.edu

3522739264

Study Officials

• Michael J. Haller, MD

  University of Florida Pediatric Endocrinology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2010
• First Posted: April 19, 2010
• Study Start: April 1, 2010
• Primary Completion: January 1, 2015
• Study Completion: July 16, 2019
• Last Updated: August 5, 2019
• Results First Posted: January 20, 2016

Record last verified: 2019-07

Locations

US (3)