Rituximab-pvvr followed by abatacept in new-onset T1D (TrialNet T1D RELAY / TN25)

What is being tested, and why it matters

In type 1 diabetes (T1D), the immune system destroys the insulin-making beta cells in the pancreas. Most newly diagnosed people still have some surviving beta cells, and protecting that remaining insulin production makes blood sugar easier to control and lowers the risk of complications. This TrialNet study — known publicly as T1D RELAY (protocol TN25) — asks whether combining two different immune therapies, given one after the other, protects insulin production better than one therapy alone.¹

The idea rests on two earlier TrialNet trials that each worked, but only partly. A four-dose course of rituximab (which clears the immune system's antibody-producing B cells) preserved the body's own insulin output at one year compared with placebo.² Separately, abatacept (which dampens T cells by blocking a "co-stimulation" signal they need to attack) slowed the decline in insulin production over two years, delaying the loss of beta-cell function by roughly 9-10 months.³ Because the two drugs hit different arms of the immune attack, researchers reasoned that depleting B cells first and then blocking T-cell activation might extend the benefit of both.¹

Who it is for

The trial enrolled people aged 8 to 45 who were diagnosed with T1D within about the previous 100 days, still produced measurable insulin (stimulated C-peptide of at least 0.2 pmol/mL), and tested positive for at least one islet autoantibody.⁴ People with immune deficiency, active or chronic infections (including TB, HIV, or hepatitis), prior immunosuppressive treatment, pregnancy, or a history of cancer were excluded.⁴

How it is designed

T1D RELAY is a Phase 2, randomized, triple-blind, placebo-controlled trial that enrolled 74 participants across roughly 18 sites in the United States and Australia.⁴ Everyone first receives the same four weekly intravenous infusions of rituximab-pvvr (375 mg/m2). Then, starting at month 4, participants are randomly assigned to add weekly subcutaneous abatacept or matching placebo injections, continuing for 20 months (to month 24).⁴ The main outcome is the C-peptide response to a 2-hour mixed-meal tolerance test at 24 months — C-peptide is a direct marker of how much insulin the body still makes.⁴ Secondary measures include insulin use, HbA1c, CGM time-in-range, severe low blood sugar, and immune markers.¹

Results and what is next

No results have been reported yet. The trial is active and no longer recruiting; enrollment is complete and participants are being followed.⁴ The primary completion is estimated for 2027, with full completion around 2029.⁴ If the combination preserves more insulin than rituximab alone, it would support sequenced, mechanism-complementary immunotherapy as a strategy to protect beta cells early after diagnosis.¹

References

1. Type 1 Diabetes TrialNet. Rituximab-pvvr / Abatacept Newly Diagnosed Study (T1D RELAY). TrialNet.org (accessed 2026). https://www.trialnet.org/our-research/newly-diagnosed-t1d/t1d-relay ↩ ↩² ↩³ ↩⁴

2. Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H, et al. Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. N Engl J Med (2009);361(22):2143-52. https://doi.org/10.1056/NEJMoa0904452 ↩

3. Orban T, Bundy B, Becker DJ, et al. Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. Lancet (2011);378(9789):412-9. https://doi.org/10.1016/S0140-6736%2811%2960886-6 ↩

4. U.S. National Library of Medicine. Rituximab-pvvr and Abatacept vs Rituximab-pvvr Alone in New Onset Type 1 Diabetes (NCT03929601). ClinicalTrials.gov (accessed 2026). https://clinicaltrials.gov/study/NCT03929601 ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷