Dataset Information

Open-label, multicentre, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still's disease.

ABSTRACT:

Objectives

Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disease; its management is largely empirical. This is the first clinical study to determine if interleukin (IL)-18 inhibition, using the recombinant human IL-18 binding protein, tadekinig alfa, is a therapeutic option in AOSD.

Methods

In this phase II, open-label study, patients were ≥18 years with active AOSD plus fever or C reactive protein (CRP) levels ≥10 mg/L despite treatment with prednisone and/or conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Previous biological DMARD treatment was permitted. Patients received tadekinig alfa 80 mg or 160 mg subcutaneously three times per week for 12 weeks; those receiving 80 mg not achieving early predicted response criteria (reduction of ≥50% CRP values from baseline and fever resolution) were up-titrated to 160 mg for a further 12 weeks. The primary endpoint was the occurrence of adverse events (AEs) throughout the study.

Results

Ten patients were assigned to receive 80 mg tadekinig alfa and 13 patients to the 160 mg dose. One hundred and fifty-five treatment-emerging AEs were recorded, and 47 were considered related to the study drug. Most AEs were mild and resolved after drug discontinuation. Three serious AEs occurred, one possibly related to treatment (toxic optic neuropathy). At week 3, 5 of 10 patients receiving 80 mg and 6 of 12 patients receiving 160 mg achieved the predefined response criteria.

Conclusions

Our results indicate that tadekinig alfa appears to have a favourable safety profile and is associated with early signs of efficacy in patients with AOSD.

Trial registration number

NCT02398435.

SUBMITTER: Gabay C

PROVIDER: S-EPMC5965361 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Publications

Open-label, multicentre, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still's disease.

Gabay Cem C Fautrel Bruno B Rech Jürgen J Spertini François F Feist Eugen E Kötter Ina I Hachulla Eric E Morel Jacques J Schaeverbeke Thierry T Hamidou Mohamed A MA Martin Thierry T Hellmich Bernhard B Lamprecht Peter P Schulze-Koops Hendrik H Courvoisier Delphine Sophie DS Sleight Andrew A Schiffrin Eduardo Jorge EJ

Annals of the rheumatic diseases 20180222 6

<h4>Objectives</h4>Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disease; its management is largely empirical. This is the first clinical study to determine if interleukin (IL)-18 inhibition, using the recombinant human IL-18 binding protein, tadekinig alfa, is a therapeutic option in AOSD.<h4>Methods</h4>In this phase II, open-label study, patients were ≥18 years with active AOSD plus fever or C reactive protein (CRP) levels ≥10 mg/L despite treatment with prednisone an ...[more]

PMID: 29472362

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Dataset Information

Open-label, multicentre, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still's disease.

Objectives

Methods

Results

Conclusions

Trial registration number

Publications

Open-label, multicentre, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still's disease.

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