A Randomized Phase 1/2 Trial of Low Dose Anti-thymocyte Globulin (ATG) With Subsequent Adalimumab or Verapamil in New Onset Type 1 Diabetes

NCT07061574 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 24745
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 11

Brief Summary

This multi-center randomized controlled trial will assess the safety and efficacy of ATG followed by either adalimumab or verapamil in preserving insulin secretion 2 years from randomization in persons aged 9 to \<21 with recent-onset stage 3 T1D.

Conditions

Type 1 Diabetes; New Onset

Keywords

ATG, Verapamil, Adalimumab

Outcome Measures

Primary Outcomes (1)

• Stimulated C-peptide AUC

  The primary outcome is the C-peptide in response to a 2-hour MMTT at week 104. This is measured as the area under the stimulated C-peptide curve (AUC). AUC is computed using a trapezoidal rule, which is a weighted sum of the C-peptide values over 120 minutes.

  Week 104

Secondary Outcomes (6)

• Severe Adverse Events

  week13, week 26, week 52, week 78, and week 104

• Adverse Events

  Week 104

• Severe Hypoglycemia

  Week 104

• Diabetic ketoacidosis (DKA)

  Week 104

• Number of Participants with CD4 count <500 mm3

  Week 104

Study Arms (3)

ATG + Placebo

PLACEBO COMPARATOR

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). This group will receive Verapamil (Oral) placebo or Adalimumab (injectable) placebo.

Drug: Anti-thymocyte globulin (ATG)

ATG + Verapamil

EXPERIMENTAL

Low dose ATG (0.5 mg/kg Day 1 then 2 mg/kg Day 2). From the 6-week visit until the 156-week visit, daily oral administration at 60, 120, 240 or 360 mg based on weight and ECG findings.

Drug: verapamil extended-release capsule

ATG + Adalimumab

EXPERIMENTAL

Low dose ATG (0.5 mg/kg Day 1 then 2 mg/kg Day 2). From the 6-week visit until the 156-week visit, Participants will receive a 40 mg dose injection every other week.

Drug: Adalimumab

Interventions

Anti-thymocyte globulin (ATG) DRUG

ATG (brand name Thymoglobulin) a polyclonal T cell antibody preparation. The first dose (0.5 mg/kg) will be infused on day 0, during a period of 6 hours. The second dose (2 mg/kg) will be given on day 1, over a period of 4 to 6 hours.

Also known as: Thymoglobulin

ATG + Placebo

Adalimumab DRUG

40 mg administered subcutaneously every other week beginning 6 weeks after the last dose of ATG until the 156-week visit.

Also known as: Simlandi

ATG + Adalimumab

verapamil extended-release capsule DRUG

Daily oral (pill) administration at 60, 120, 240 or 360 mg based on weight and ECG findings.

ATG + Verapamil

Eligibility Criteria

• Age: 9 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Recent-onset stage 3 T1D diagnosed by standard ADA criteria, with the ability to be randomized within 6 months from the date of T1D diagnosis and within 37 days of Screening Visit.
• At least one positive T1D auto-antibody.
• If clearly positive (≥20% above local lab's ULN) at screening, repeat antibody testing for central lab is not required.
• Insulin auto-antibodies are only considered if exogenous insulin use is \<10 days when blood is drawn.
• Must have stimulated C-peptide levels ≥0.2 pmol/mL measured during MMTT conducted prior to randomization.
• Age 9 to \<21 years at the time of randomization.
• Body weight \>30kg.
• BMI \<95th percentile for age and gender.
• Willing to comply with intensive diabetes management.
• Female participants with childbearing potential are not currently pregnant, are willing to avoid pregnancy and breastfeeding, and to undergo pregnancy testing prior to MMTTs for the duration of the study.
• Women of childbearing potential (WOCBP) must use an acceptable form of birth control. Acceptable forms include oral/injection contraceptives, transdermal contraceptives, diaphragm, intrauterine devices, condoms with spermicide, documented surgical sterilization of either the participant or their partner or abstinence.
• Male participants with potential to father children must be willing to use abstinence or adequate contraceptive methods for the duration of the study.
• Males must agree to be sexually abstinent or use a condom and agree not to donate sperm for the treatment period and for a minimum of 1 spermatogenesis cycle (90 days after last dose of study drug) after last treatment.
• Willing to provide informed consent and child assent as applicable.
• Sufficient cognitive ability, per investigator judgment, to provide informed consent for study participation on an IRB approved consent form.

You may not qualify if:

• Prior treatment with ATG or known allergy to ATG or rabbit-derived products.
• Local lab draw at screening:
• Immunodeficient or have clinically significant chronic lymphopenia: Leukopenia (\<3,000 leukocytes /μL), neutropenia (\<1,500 neutrophils/μL), lymphopenia (\<800 lymphocytes/μL).
• Thrombocytopenia (\<100,000 platelets/μL) or anemia (hemoglobin \< 10g/dL).
• Leukocytosis (\>14,000/mL)
• Infections:
• Ongoing infection or had recently had a major infection requiring hospitalization or intravenous antibiotics.within 30 days prior to randomization.
• Have active signs or symptoms of acute infection at the time of randomization.
• Have evidence of prior or current tuberculosis infection as assessed interferon gamma release assay (QuantiFERON), or a positive test for latent tuberculosis.
• Have evidence of current or past HIV or Hepatitis B or current Hepatitis C infection.
• History of serious bacterial, viral, fungal, or other opportunistic infections.
• Have active signs or symptoms of CMV or EBV compatible illness lasting more than 7 days within 30 days of randomization.
• Have positive CMV and/or EBV PCR test within 30 days prior to randomization.
• Have positive COVID-19 self-antigen test within 3 days of randomization.
• History of underlying cardiac disease (ex. left ventricular dysfunction, hypertrophic cardiomyopathy), certain arrhythmias (e.g. AV block, accessory pathway such as Wolff- Parkinson-White or Lown-Ganong-Levine syndromes) or abnormal ECG (unless cleared by cardiology).

Sponsors & Collaborators

• City of Hope Medical Center: lead
• Jaeb Center for Health Research: collaborator

Study Sites (11)

UCSF

San Francisco, California, 94143, United States

NOT YET RECRUITING

Barbara Davis Center for Diabetes University of Colorado Anschutz

Aurora, Colorado, 80045, United States

NOT YET RECRUITING

Yale University

New Haven, Connecticut, 06511, United States

NOT YET RECRUITING

University of Florida

Gainesville, Florida, 32610, United States

NOT YET RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Indiana University

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

University of Buffalo

Buffalo, New York, 14203, United States

RECRUITING

University of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

NOT YET RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Antilymphocyte Serum; thymoglobulin; Adalimumab

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; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal

Study Officials

• Alberto Pugliese, MD

  City of Hope Medical Center

  STUDY CHAIR

Central Study Contacts

Robert Henderson, MS

CONTACT

813-975-8690; rhenderson@jaeb.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participants will be randomized 2:2:1:1 using blocked randomization to ATG + Adalimumab, ATG + Verapamil, ATG + injectable placebo, ATG + oral placebo.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multi-center, randomized, double blind, placebo-controlled phase 1/2 clinical trial

Study Record Dates

• First Submitted: July 2, 2025
• First Posted: July 11, 2025
• Study Start: March 10, 2026
• Primary Completion (Estimated): April 15, 2030
• Study Completion (Estimated): April 15, 2031
• Last Updated: May 5, 2026

Record last verified: 2026-05

Locations

US (11)