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Clinical Trial
. 2024 Apr 2;63(4):1058-1067.
doi: 10.1093/rheumatology/kead333.

The COMPARE head-to-head, randomized controlled trial of SEL-212 (pegadricase plus rapamycin-containing nanoparticle, ImmTOR™) versus pegloticase for refractory gout

Herbert S B Baraf  1   2 , Puja P Khanna  3 , Alan J Kivitz  4 , Vibeke Strand  5 , Hyon K Choi  6 , Robert Terkeltaub  7 , Nicola Dalbeth  8 , Wesley DeHaan  9 , Rehan Azeem  9 , Peter G Traber  9 , Robert T Keenan  10   11
Affiliations
Clinical Trial

The COMPARE head-to-head, randomized controlled trial of SEL-212 (pegadricase plus rapamycin-containing nanoparticle, ImmTOR™) versus pegloticase for refractory gout

Herbert S B Baraf et al. Rheumatology (Oxford). .

Abstract

Objectives: Serum urate (SU) lowering with PEGylated uricases in gout can reduce flares and tophi. However, treatment-emergent anti-drug antibodies adversely affect safety and efficacy and the currently approved PEGylated uricase pegloticase requires twice-monthly infusions. Investigational SEL-212 therapy aims to promote uricase-specific tolerance via monthly sequential infusions of a proprietary rapamycin-containing nanoparticle (ImmTOR) and pegadricase.

Methods: COMPARE was a randomized, phase 2, open-label trial of SEL-212 vs pegloticase in adults with refractory gout. SEL-212 [ImmTOR (0.15 mg/kg) and pegadricase (0.2 mg/kg)] was infused monthly or pegloticase (8 mg) twice monthly for 6 months. The primary endpoint was the proportion of participants with SU <6 mg/dl for ≥80% of the time during 3 and 6 months. Secondary outcomes were mean SU, gout flares, number of tender and/or swollen joints and safety.

Results: During months 3 and 6 combined, numerically more participants achieved and maintained a SU <6 mg/dl for ≥80% of the time with SEL-212 vs pegloticase (53.0% vs 46.0%, P = 0.181). The percentage reductions in SU levels were statistically greater during months 3 and 6 with SEL-212 vs pegloticase (-73.79% and -47.96%, P = 0.0161). Reductions in gout flare incidence and number of tender and/or swollen joints were comparable between treatments. There were numerical differences between the most common treatment-related adverse events of interest with SEL-212 and pegloticase: gout flares (60.2% vs 50.6%), infections (25.3% vs 18.4%) and infusion-related reactions (15.7% vs 11.5%), respectively. Stomatitis (and related terms) was experienced by eight participants (9.6%) with SEL-212 and none with pegloticase. Stomatitis, a known event for rapamycin, was associated with ImmTOR only.

Conclusions: SEL-212 efficacy and tolerability were comparable to pegloticase in refractory gout. This was associated with a substantial reduction in treatment burden with SEL-212 due to decreased infusion frequency vs pegloticase.

Clinical trial registration: NCT03905512.

Keywords: SEL-212; gout; nanotechnology; pegadricase; pegloticase; rapamycin; serum urate; uricase.

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Figures

Figure 1.
Figure 1.
Participant disposition
Figure 2.
Figure 2.
Mean percentage change in SU with SEL-212 and pegloticase from baseline (ITT population). D: day; M: month
Figure 3.
Figure 3.
Mean SU levels over time by overall, responder and non-responder populations (ITT population). Data are means and s.d.s.
See this image and copyright information in PMC

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