WAVE T1D: low-dose ATG followed by adalimumab or verapamil in new-onset T1D

What is being tested, and why it matters

Almost every immunotherapy trial in new-onset type 1 diabetes (T1D) has asked the same shape of question: does this one drug slow the immune destruction of beta cells? Several now say yes — but the effect fades. WAVE T1D asks the next question, the one the field has been circling for years: can you follow one drug with another and make the benefit stick?¹

The design is a two-step, "induction then maintenance" sequence borrowed from transplant medicine. Everyone first gets a short course of low-dose anti-thymocyte globulin (ATG) — an antibody preparation that thins out and re-tunes the T cells doing the damage. Participants are then randomised to one of two maintenance drugs meant to keep the peace after ATG wears off:¹

• Adalimumab, an antibody that blocks TNF, an inflammatory signal implicated in the autoimmune attack. It is a long-established drug in other autoimmune conditions.
• Extended-release verapamil, an old and inexpensive blood-pressure tablet that is thought to reduce the internal stress that makes beta cells vulnerable — an approach aimed at the target of the attack rather than the attacker.

The two arms come at the problem from opposite directions, which is what makes this trial interesting: it is not just testing whether combination therapy works, but which kind of partner drug is worth pairing with an induction agent.

Who it is for

The trial is for children and young adults aged 9 to 20 who have been diagnosed with stage-3 T1D and can be randomised within six months of diagnosis — the window in which enough beta cells survive to be worth protecting. Entry also requires at least one islet autoantibody, a stimulated C-peptide of at least 0.2 pmol/mL on a mixed-meal tolerance test (proof there is still insulin production to preserve), and a body weight above 30 kg. Anyone who has already received ATG or teplizumab is excluded.¹

How it is designed

WAVE T1D is a randomised phase 1/2 trial planning to enrol 120 participants across 11 US sites — UCSF, the Barbara Davis Center, Yale, the University of Florida, the University of Miami, Indiana, Minnesota, Buffalo, Pittsburgh, Baylor and Seattle Children's. It is sponsored by City of Hope Medical Center with the Jaeb Center for Health Research, and started recruiting on 10 March 2026.¹

The primary endpoint is stimulated C-peptide AUC on a 2-hour mixed-meal tolerance test at week 104 — how much of your own insulin you still make two years in. That is a demanding bar. Many trials read out at 12 months, when almost any immune-modulating drug still looks good; asking the question at 24 months is how you find out whether an effect is durable or merely delayed.¹

What to watch for

This is early-stage work, and the honest framing is: nothing is known yet. There are no results, no interim readouts, and no published data. Primary completion is not expected until April 2030, with full completion around April 2031.¹ A phase 1/2 label also means safety is still an open question — combining an induction agent with ongoing immune suppression carries real risk, and that trade-off is part of what the trial is measuring.

If it works, though, the implication is larger than any of the three drugs involved. It would be evidence that beta-cell preservation should be treated the way transplant rejection and other autoimmune diseases already are — as something you induce, then maintain — rather than as a single course of treatment given once and hoped over.

References

1. City of Hope Medical Center / Jaeb Center for Health Research. WAVE T1D: A Randomized Phase 1/2 Trial of Low Dose ATG With Subsequent Adalimumab or Verapamil in New Onset Type 1 Diabetes (NCT07061574). ClinicalTrials.gov (record checked 2026-07-14). https://clinicaltrials.gov/study/NCT07061574 ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶