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

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.

• Authors: Herbert S B Baraf, Puja P Khanna, Alan J Kivitz, Vibeke Strand, Hyon K Choi, Robert Terkeltaub, Nicola Dalbeth, Wesley DeHaan, Rehan Azeem, Peter G Traber, Robert T Keenan
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 63 Issue 4 Pg. 1058-1067 (Apr 02 2024) ISSN: 1462-0332 [Electronic] England
• PMID: 37449908 (Publication Type: Randomized Controlled Trial, Journal Article)
• Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Chemical References

• Pegloticase
• Urate Oxidase
• Gout Suppressants
• Uric Acid
• Polyethylene Glycols
• Uricosuric Agents

Topics

• Adult
• Humans
• Gout
• Urate Oxidase (therapeutic use, adverse effects)
• Gout Suppressants (adverse effects)
• Uric Acid
• Treatment Outcome
• Symptom Flare Up
• Polyethylene Glycols (adverse effects)
• Uricosuric Agents (therapeutic use)
• Stomatitis (chemically induced, drug therapy)