Rituximab-pvvr followed by abatacept in new-onset T1D (TrialNet T1D RELAY / TN25)
What this study tests
A TrialNet Phase 2 trial testing whether a short course of the B-cell-depleting antibody rituximab-pvvr, followed by the co-stimulation blocker abatacept, preserves the body's own insulin production better than rituximab-pvvr alone in people aged 8-45 newly diagnosed with type 1 diabetes. Enrollment of 74 is complete; the trial is ongoing with no results yet.
Editorial review: .
Registry checked: 2026-09-17. Registry’s own update: 2026-09-01.
Most recent recorded citation date: 2009-11-26. Only explicit date metadata is included; an undated citation may be newer. This does not mean every claim was reviewed on that date.
Trial status, labels and access can change between reviews. How we review the evidence · How to read the evidence
Evidence at a glance
- Who can enter the study?
- For people newly diagnosed with type 1 diabetes within the past ~100 days who still make some of their own insulin (stimulated C-peptide >=0.2 pmol/mL) and carry at least one islet autoantibody. Body weight must be at least 20 kg. Excludes significant immune deficiency, active or chronic infection (including TB, HIV, hepatitis B/C), prior immunosuppressive or trial immunotherapy, pregnancy, and malignancy; participants must be up to date on vaccines and willing to use intensive diabetes management and wear a CGM periodically. Registered eligibility ↗Enrollment criteria describe who may enter. They do not establish who was analyzed or the denominator for a reported result.
- Reported benefit and results
- No results summary is available in this record. This is not a finding of benefit, and it does not establish whether results exist elsewhere.Read the result sources and their limitations →
- Important harms
- Read the reported results, safety discussion and original sources. A separate harms summary is not available; this does not establish safety.
- Research access and approval
- Study regions: United States, Australia. A trial listing does not establish product approval or current recruitment at a particular site. Check the study’s current entry requirements.
- What remains uncertain?
- Read the full discussion and original sources for study limitations. Planned endpoints and completion dates are not results.
Research status alone does not establish approval, clinical benefit or local availability.
Australian sites in the registry
- Queensland Children's Hospital, South Brisbane, Queensland — Site status not reported
- Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria — Site status not reported
Overall recruitment does not imply availability at every site. Confirm eligibility and local recruitment with the study team.
Primary endpoints
- C-peptide response (area under the curve) to a 2-hour mixed-meal tolerance test at 24 months post-enrollment, comparing rituximab-pvvr + abatacept versus rituximab-pvvr + placebo
The full picture
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
Sources
- [1]Type 1 Diabetes TrialNet. Rituximab-pvvr / Abatacept Newly Diagnosed Study (T1D RELAY). *TrialNet.org* (accessed 2026) · Open-source community
Type 1 Diabetes TrialNet. Rituximab-pvvr / Abatacept Newly Diagnosed Study (T1D RELAY). TrialNet.org (accessed 2026).
- [2]Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. · Peer-reviewed study · 2009-11-26
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.
- [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 · Peer-reviewed study
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.
- [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) · Trial registry
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).