The COMPARE head-to-head, randomized controlled trial of SEL-212 (pegadricase plus rapamycin-containing nanoparticle, ImmTOR™) versus pegloticase for refractory gout
© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology..
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.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:63 |
---|---|
Enthalten in: |
Rheumatology (Oxford, England) - 63(2024), 4 vom: 02. Apr., Seite 1058-1067 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Baraf, Herbert S B [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 03.04.2024 Date Revised 04.04.2024 published: Print ClinicalTrials.gov: NCT03905512 Citation Status MEDLINE |
---|
doi: |
10.1093/rheumatology/kead333 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM359506488 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM359506488 | ||
003 | DE-627 | ||
005 | 20240404234228.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1093/rheumatology/kead333 |2 doi | |
028 | 5 | 2 | |a pubmed24n1364.xml |
035 | |a (DE-627)NLM359506488 | ||
035 | |a (NLM)37449908 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Baraf, Herbert S B |e verfasserin |4 aut | |
245 | 1 | 4 | |a The COMPARE head-to-head, randomized controlled trial of SEL-212 (pegadricase plus rapamycin-containing nanoparticle, ImmTOR™) versus pegloticase for refractory gout |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 03.04.2024 | ||
500 | |a Date Revised 04.04.2024 | ||
500 | |a published: Print | ||
500 | |a ClinicalTrials.gov: NCT03905512 | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a CLINICAL TRIAL REGISTRATION: NCT03905512 | ||
650 | 4 | |a Randomized Controlled Trial | |
650 | 4 | |a Journal Article | |
650 | 4 | |a SEL-212 | |
650 | 4 | |a gout | |
650 | 4 | |a nanotechnology | |
650 | 4 | |a pegadricase | |
650 | 4 | |a pegloticase | |
650 | 4 | |a rapamycin | |
650 | 4 | |a serum urate | |
650 | 4 | |a uricase | |
650 | 7 | |a Pegloticase |2 NLM | |
650 | 7 | |a R581OT55EA |2 NLM | |
650 | 7 | |a Urate Oxidase |2 NLM | |
650 | 7 | |a EC 1.7.3.3 |2 NLM | |
650 | 7 | |a Gout Suppressants |2 NLM | |
650 | 7 | |a Uric Acid |2 NLM | |
650 | 7 | |a 268B43MJ25 |2 NLM | |
650 | 7 | |a Polyethylene Glycols |2 NLM | |
650 | 7 | |a 3WJQ0SDW1A |2 NLM | |
650 | 7 | |a Uricosuric Agents |2 NLM | |
700 | 1 | |a Khanna, Puja P |e verfasserin |4 aut | |
700 | 1 | |a Kivitz, Alan J |e verfasserin |4 aut | |
700 | 1 | |a Strand, Vibeke |e verfasserin |4 aut | |
700 | 1 | |a Choi, Hyon K |e verfasserin |4 aut | |
700 | 1 | |a Terkeltaub, Robert |e verfasserin |4 aut | |
700 | 1 | |a Dalbeth, Nicola |e verfasserin |4 aut | |
700 | 1 | |a DeHaan, Wesley |e verfasserin |4 aut | |
700 | 1 | |a Azeem, Rehan |e verfasserin |4 aut | |
700 | 1 | |a Traber, Peter G |e verfasserin |4 aut | |
700 | 1 | |a Keenan, Robert T |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Rheumatology (Oxford, England) |d 1999 |g 63(2024), 4 vom: 02. Apr., Seite 1058-1067 |w (DE-627)NLM102581908 |x 1462-0332 |7 nnns |
773 | 1 | 8 | |g volume:63 |g year:2024 |g number:4 |g day:02 |g month:04 |g pages:1058-1067 |
856 | 4 | 0 | |u http://dx.doi.org/10.1093/rheumatology/kead333 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 63 |j 2024 |e 4 |b 02 |c 04 |h 1058-1067 |