Precision Administration of Anti-thymocyte Globulin With or Without Verapamil

NCT06455319 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IRB202400422
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

T cell directed therapy, anti-thymocyte globulin (ATG), in low doses, has been shown to lower HbA1c and preserve endogenous insulin production (measured by C-peptide) in individuals with recently diagnosed type 1 diabetes (T1D). However, not all individuals who received ATG responded to the therapy (i.e., non-responders). Additionally, use of ATG alone does not address inherent beta cell stress. A calcium channel blocker, verapamil, has demonstrated C-peptide preservation in newly diagnosed T1D. Investigators will identify those mostly likely to respond to ATG using an ex vivo predictive biomarker of response to ATG. In addition, Investigators will use sequential therapies to increase efficacy (ATG followed by verapamil) and explore synergistic mechanisms. This will be assessing with in depth immunophenotyping and quantify biomarkers of beta cell stress, cell death, and abnormal prohormone processing. Finally, novel clinical trial endpoints will be assessed for their ability to predict treatment efficacy earlier than the standard endpoint at 1 year.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (2)

• AUC C-peptide between ATG and placebo values

  mean difference between ATG and placebo values of the 2-hr mixed meal tolerance test (MMTT)-stimulated area under the curve (AUC) C-peptide at 12 months

  12 Months

• Change in 2-hr MMTT AUC C-peptide

  mean difference between the change in 2-hr MMTT stimulated AUC C-peptide

  6 months

Secondary Outcomes (1)

• Immune and beta cell mechanistic analyses

  6, 12, 18, 24 months

Study Arms (3)

Anti-thymocyte globulin (ATG) intravenous infusion

EXPERIMENTAL

ATG (brand name Thymoglobulin) a polyclonal T cell antibody preparation. It will be given at low doses (0.5 mg/kg Day 1 then 2 mg/kg Day 2).

Drug: Anti-thymocyte globulin (ATG)

Placebo-ATG

PLACEBO COMPARATOR

Saline placebo

Drug: Placebo

verapamil extended release capsule

EXPERIMENTAL

Open label administration at 120, 240 or 360 mg daily based on weight and ECG findings

Drug: verapamil extended release capsule

Interventions

Anti-thymocyte globulin (ATG) DRUG

ATG (brand name Thymoglobulin) a polyclonal T cell antibody preparation. It will be given at low doses (0.5 mg/kg Day 1 then 2 mg/kg Day 2).

Also known as: Thymoglobulin

Anti-thymocyte globulin (ATG) intravenous infusion

verapamil extended release capsule DRUG

Open label administration at 120, 240 or 360 mg daily based on weight and ECG findings

Also known as: Calan, Isoptin

verapamil extended release capsule

Placebo DRUG

I.V. Saline

Placebo-ATG

Eligibility Criteria

• Age: 6 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Must be \>= 6 years \<= 35
• 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; GAD65A, mIAA, if obtained within 10 days of the onset of insulin therapy, IA-2A, ICA, or ZnT8A
• Must have stimulated C-peptide levels of 0.2 pmol/ml measured during a mixed meal tolerance test (MMTT) conducted at least 21 days from diagnosis of diabetes. Randomization should occur within one month (37 days) of the MMTT.
• Subjects who are EBV seronegative at screening must be EBV PCR negative within 30 days of randomization and may not have had signs or symptoms of an EBV compatible illness lasting longer than 7 days within 30 days of randomization
• 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 live vaccines during the treatment period and for 3 months following last dose of study drug
• Be willing to comply with intensive diabetes management

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 (\<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 PPD, interferon gamma release assay 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 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, COPD, sickle cell disease, neurological, or blood count abnormalities
• Have a history of malignancies other than skin
• Evidence of liver dysfunction with 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 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 any investigational agent to delay beta cell loss in T1D
• Known allergy to ATG or Verapamil

Sponsors & Collaborators

• University of Florida: lead
• University of Colorado, Denver: collaborator
• University of Miami: collaborator

Study Sites (2)

Barbara Davis Center for Diabetes

Aurora, Colorado, 80045, United States

RECRUITING

University of Florida

Gainesville, Florida, 32610, United States

RECRUITING

Related Publications (4)

• 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.

  PMID: 30012675 RESULT

• Foster TP, Jacobsen LM, Bruggeman B, Salmon C, Hosford J, Chen A, Cintron M, Mathews CE, Wasserfall C, Brusko MA, Brusko TM, Atkinson MA, Schatz DA, Haller MJ. Low-Dose Antithymocyte Globulin: A Pragmatic Approach to Treating Stage 2 Type 1 Diabetes. Diabetes Care. 2024 Feb 1;47(2):285-289. doi: 10.2337/dc23-1750.

  PMID: 38117469 RESULT

• Lin A, Mack JA, Bruggeman B, Jacobsen LM, Posgai AL, Wasserfall CH, Brusko TM, Atkinson MA, Gitelman SE, Gottlieb PA, Gurka MJ, Mathews CE, Schatz DA, Haller MJ. Low-Dose ATG/GCSF in Established Type 1 Diabetes: A Five-Year Follow-up Report. Diabetes. 2021 May;70(5):1123-1129. doi: 10.2337/db20-1103. Epub 2021 Feb 25.

  PMID: 33632742 RESULT

• Ovalle F, Grimes T, Xu G, Patel AJ, Grayson TB, Thielen LA, Li P, Shalev A. Verapamil and beta cell function in adults with recent-onset type 1 diabetes. Nat Med. 2018 Aug;24(8):1108-1112. doi: 10.1038/s41591-018-0089-4. Epub 2018 Jul 9.

  PMID: 29988125 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Antilymphocyte Serum; thymoglobulin; Verapamil

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Laura M Jacobsen, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer L Hosford, MPH

CONTACT

352-294-5760; jennifer.hosford@peds.ufl.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: ATG (brand name Thymoglobulin) a polyclonal T cell antibody preparation. It will be given at low doses (0.5 mg/kg Day 1 then 2 mg/kg Day 2). Verapamil extended release capsule will be given via open label administration at 120, 240 or 360 mg daily based on weight and echocardiogram (ECG) findings

Study Record Dates

• First Submitted: June 3, 2024
• First Posted: June 12, 2024
• Study Start: November 12, 2025
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): August 1, 2030
• Last Updated: November 26, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)