RESET T1D: rezpegaldesleukin (NKTR-358), a Treg-selective IL-2, in new-onset T1D
A TrialNet phase-2 trial of rezpegaldesleukin, a PEGylated form of interleukin-2 engineered to preferentially wake up the immune system's regulatory T cells rather than the destructive ones. Sixty-six people diagnosed with type 1 diabetes within the last 100 days get an injection every 14 days for 26 weeks, to see whether the beta cells they still have can be protected. It is the first registered trial of this drug in type 1 diabetes, and it tests the field's main answer to plain low-dose IL-2's weakness — a Treg boost that fades within days and needs near-continuous dosing.
Primary endpoints
- Mean area under the stimulated C-peptide curve over a 2-hour mixed-meal tolerance test at 12 months
Results so far
No results yet. The trial started on 14 May 2026 and runs to an estimated completion of 25 May 2028.
The full picture
Low-dose interleukin-2 has a good idea and a bad problem. The idea: give tiny doses of IL-2 and you selectively expand regulatory T cells (Tregs), the immune system's own brakes, without arming the effector T cells that destroy beta cells. The problem: the effect fades within days, so plain low-dose IL-2 needs near-daily or every-third-day injections, and no trial has yet shown a lasting tolerance reset after dosing stops.
RESET T1D is the first registered trial in type 1 diabetes of an engineered answer to that problem. Rezpegaldesleukin (NKTR-358) is a PEGylated IL-2 conjugate, designed to bias the molecule toward the Treg receptor and to stay in the body long enough to be dosed once every two weeks rather than several times a week. The drug has been studied elsewhere — in atopic dermatitis, alopecia areata, psoriasis, lupus and ulcerative colitis — but never before in T1D.1
Design
TrialNet is randomising 66 people 2:1 to rezpegaldesleukin or placebo, triple-masked. Treatment is 12 micrograms/kg subcutaneously every 14 days for 26 weeks, with follow-up out to 12 months. To enrol you must be within 100 days of a type 1 diagnosis, have at least one islet autoantibody, and still have measurable insulin production — a stimulated C-peptide of at least 0.2 pmol/mL on a mixed-meal test done at least 21 days after diagnosis.1
The primary endpoint is the classic beta-cell-preservation measure: mean C-peptide area-under-the-curve across a 2-hour mixed-meal tolerance test at 12 months. That is the same yardstick teplizumab was judged on, which makes the result directly comparable to the rest of the new-onset immunotherapy field.
Who can actually join today
The registry lists ages 8-45, but the protocol enrols in age steps, and the younger bands are not open yet. The first ~18 participants must be adults aged 18-45. Only after the TrialNet data and safety monitoring board — consulting the drug developer's safety group — reviews those adults favourably do ages 12-17 open. Ages 8-11 open only after a further favourable review of 17 more participants (at least nine of them aged 12-17) through their 6-month visit. If either review is unfavourable, the trial finishes enrolling at whatever age threshold it has reached, and children may never be eligible.1 If you are reading this for a child, the honest answer today is: not yet, and possibly not at all.
There are ten sites: nine US centres are recruiting (Barbara Davis Center, University of Florida, University of Miami, Joslin, Columbia, University of Pittsburgh, Vanderbilt, University of Utah and Benaroya). The one Canadian site, the University of British Columbia in Vancouver, is listed but not yet recruiting.1
What to watch for
Two things will decide whether this matters. First, whether a fortnightly injection produces a Treg expansion that is not just bigger but sustained — plain low-dose IL-2's Treg boost collapses between doses, and that is the leading explanation for why its metabolic benefit has only ever shown up in a subgroup of strong responders. Second, whether that Treg expansion translates into preserved C-peptide at all. Immunology surrogates have repeatedly outrun clinical benefit in this field, and a trial of 66 people is sized to detect a signal, not to settle the question.
Note also who is not on the registry record. Nektar Therapeutics developed rezpegaldesleukin and its safety group is consulted for the protocol's age-escalation reviews, but the registry lists NIDDK as the sole sponsor with no collaborator.1 This is an academic trial of an industry drug, not an industry registration programme — a positive result here would be a starting gun, not a filing.
Estimated completion is 25 May 2028, so the first meaningful readout is roughly two years away.1