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

NCT: NCT07061574 · Status: RECRUITING · Phase: Phase 2 · Sponsor: City of Hope Medical Center · Started: 2026-03-30 · Est. Completion: 2031-04-15

Official 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.

Study Design

Interventions

Primary Outcomes

Secondary Outcomes

Eligibility Criteria

Key Inclusion Criteria:

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.
* Able to read and understand English or Spanish (both participant and legally authorized representative, if applicable).
* Must be fully vaccinated for age.
* Must have been vaccinated for flu (if currently in flu season).
* Must be willing to not receive live vaccines throughout the treatment period.
* Must be willing to not use any non-insulin glucose-lowering agents such as GLP-1 agonists (including for weight loss indication), symlin, DPP-4 inhibitors, SGLT-2 inhibitors, biguanides, sulfonylureas) for the duration of study treatment. Participants are required to go off these drugs at least 30 days prior to screening.

Key Exclusion Criteria:

* 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).
* Blood pressure (either systolic or diastolic) \<5th percentile for age, gender, and height on two out of three measurements.
* Pulse \<2nd percentile for age and gender on two out of three measurements.
* History of vasovagal syncopal episodes related to hypotension.
* History of malignancies other than of skin.
* Use of medications likely to interfere with study results:
* Any immunomodulators, including systemic steroids or participation in prior research study in which a potential participant received an immunomodulatory agent (may participate if received placebo only).
* Current or previous use of Teplizumab.
* Ongoing use of medications known to influence glycemia or glucose tolerance. Only topical steroids are allowed.
* Need to use of any of the following medications during the study: beta blocker, seizure medication (carbamazepine, phenobarbital, phenytoin), other antihypertensive medications, HMG-CoA reductase inhibitors

Trial Locations

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