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Diabetes Mellitus, Type 1Phase 2ATG-GCSFNCT02215200

ATG-GCSF in New Onset Type 1 Diabetes

A Phase 2 study testing Anti-Thymocyte Globulin (ATG) and Granulocyte colony stimulating factor (GCSF) in people with Diabetes Mellitus, Type 1, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 12 to 45 years
Conditions the study is for
Diabetes Mellitus, Type 1
What is being tested?
Anti-Thymocyte Globulin (ATG) and Granulocyte colony stimulating factor (GCSF)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
89 participants
Where
13 sitesUnited States
Study dates
Dec 2014to Aug 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 45 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites

  • Barbara Davis Center

    Aurora, Colorado, 80045

  • University of Florida

    Gainesville, Florida, 32610

  • Indiana University-Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • University of Miami

    Miami, Florida, 33136

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Vanderbilt Eskind Diabetes Clinic

    Nashville, Tennessee, 37232

  • Yale University

    New Haven, Connecticut, 06519

  • Columbia University-Naomi Berrie Diabetes Center

    New York, New York, 10032

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15224

  • University of California - San Francisco

    San Francisco, California, 94158-2549

  • Benaroya Research Institute

    Seattle, Washington, 98101

  • Stanford University

    Stanford, California, 94305

  • University of South Florida Diabetes Center

    Tampa, Florida, 33612

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Anti-Thymocyte Globulin (ATG), Granulocyte colony stimulating factor (GCSF), Placebo (for ATG), Placebo (for GCSF)
Keywords
Type 1 Diabetes TrialNet
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anti-Thymocyte Globulin (ATG)Drug

    Also called Thymoglobulin

    Thymoglobulin

  • Granulocyte colony stimulating factor (GCSF)Drug

    Also called Neulasta

    Granulocyte colony stimulating factor (GCSF)

  • Placebo (for ATG)Drug

    Normal saline administered by IV infusion to mimic ATG

  • Placebo (for GCSF)Drug

    Placebo prepared to mimic 6mg subcutaneous injection of GCSF

Study groups in NCT02215200
Study groupRoleWhat they receive
Anti-Thymocyte Globulin (ATG) and PlaceboExperimentalAnti-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
Receives: Drug: Anti-Thymocyte Globulin (ATG); Drug: Placebo (for GCSF)
ATG plus Granulocyte colony stimulating factor (GCSF)ExperimentalGranulocyte 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
Receives: Drug: Anti-Thymocyte Globulin (ATG); Drug: Granulocyte colony stimulating factor (GCSF)
PlaceboPlacebo comparatorPlacebo 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
Receives: Drug: Placebo (for ATG); Drug: Placebo (for GCSF)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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").

    Measured: -10, 0 15, 30, 60, 90, and 120 minutes post-dose at baseline and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Aug 2014 (estimated)
  2. Study startDec 2014
  3. Primary completionAug 2017
  4. Study completionAug 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
89 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02215200
Sponsor's protocol ID
ATG-GCSF (IND)
Other IDs
Type 1 Diabetes TrialNet, TN19, UC4DK106993, UC4DK117009
Acronym
ATG-GCSF
Status last verified
Feb 2020
First submitted
11 Aug 2014
Last updated
2 Mar 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Data are available at the NIDDK Central Repository

Publications

  • Jacobsen LM, Diggins K, Blanchfield L, McNichols J, Perry DJ, Brant J, Dong X, Bacher R, Gersuk VH, Schatz DA, Atkinson MA, Mathews CE, Haller MJ, Long SA, Linsley PS, Brusko TM. Responders to low-dose ATG induce CD4+ T cell exhaustion in type 1 diabetes. JCI Insight. 2023 Aug 22;8(16):e161812. doi: 10.1172/jci.insight.161812.

    PubMed 37432736

  • Haller MJ, Long SA, Blanchfield JL, Schatz DA, Skyler JS, Krischer JP, Bundy BN, Geyer SM, Warnock MV, Miller JL, Atkinson MA, Becker DJ, Baidal DA, DiMeglio LA, Gitelman SE, Goland R, Gottlieb PA, Herold KC, Marks JB, Moran A, Rodriguez H, Russell WE, Wilson DM, Greenbaum CJ; Type 1 Diabetes TrialNet ATG-GCSF Study Group. Low-Dose Anti-Thymocyte Globulin Preserves C-Peptide, Reduces HbA1c, and Increases Regulatory to Conventional T-Cell Ratios in New-Onset Type 1 Diabetes: Two-Year Clinical Trial Data. Diabetes. 2019 Jun;68(6):1267-1276. doi: 10.2337/db19-0057. Epub 2019 Apr 9.

    PubMed 30967424

  • 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 beta-Cell Function and Improves HbA1c in New-Onset Type 1 Diabetes. Diabetes Care. 2018 Sep;41(9):1917-1925. doi: 10.2337/dc18-0494. Epub 2018 Jul 16.

    PubMed 30012675

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anti-Thymocyte Globulin (ATG) and Granulocyte colony stimulating factor (GCSF) in people with Diabetes Mellitus, Type 1, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 13 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Area Under the Stimulated C-peptide Curve From Baseline to 12 Months. (time frame: -10, 0 15, 30, 60, 90, and 120 minutes post-dose at baseline and 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02215200, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2020.

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