4 research outputs found
Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis
ObjectiveADAPT+ assessed the long-term safety, tolerability, and efficacy of efgartigimod in adult participants with generalized myasthenia gravis (gMG).MethodsADAPT+ was an open-label, single-arm, multicenter, up to 3-year extension of the pivotal phase 3 ADAPT study. Efgartigimod was administered in treatment cycles of 4 intravenous infusions (one 10âmg/kg infusion per week). Initiation of subsequent treatment cycles was individualized based on clinical evaluation. Safety endpoints included incidence and severity of adverse events. Efficacy endpoints assessed disease severity using Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores.ResultsAs of January 2022, 151 participants had rolled over to ADAPT+ and 145 had received â„1 dose of efgartigimod, of whom, 111 (76.6%) were AChR-Ab+ and 34 (23.4%) were AChR-Abâ. Mean study duration (treatment plus follow-up) was 548âdays, and participants received up to 17 treatment cycles, corresponding to 217.6 participant-years of exposure. In the overall population, 123 (84.8%) participants reported â„1 treatment-emergent adverse event; most frequent were headache (36 [24.8%]), COVID-19 (22 [15.2%]), and nasopharyngitis (20 [13.8%]). Clinically meaningful improvement (CMI) in mean MG-ADL and QMG scores was seen as early as 1âweek following the first infusion across multiple cycles in AChR-Ab+ and AChR-Abâ participants. Maximal MG-ADL and QMG improvements aligned with onset and magnitude of total IgG and AChR-Ab reductions. For AChR-Ab+ participants at any time point in each of the first 10 treatment cycles, more than 90% had a maximum reduction of â„2 points (CMI) in MG-ADL total score; across the 7âcycles in which QMG was measured, 69.4% to 91.3% of participants demonstrated a maximum reduction of â„3 points (CMI) in QMG total score. Many participants demonstrated improvements well beyond CMI thresholds. In AChR-Ab+ participants with â„1 year of combined follow-up between ADAPT and ADAPT+, mean number of annualized cycles was 4.7 per year (median [range] 5.0 [0.5â7.6]).ConclusionResults of ADAPT+ corroborate the substantial clinical improvements seen with efgartigimod in ADAPT and support its long-term safety, tolerability, and efficacy, as well as an individualized dosing regimen for treatment of gMG.Clinical trial registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT03770403, NCT03770403
Long-term safety, tolerability, and efficacy of efgartigimod (ADAPT+): interim results from a phase 3 open-label extension study in participants with generalized myasthenia gravis
Objective ADAPT+ assessed the long-term safety, tolerability, and efficacy of efgartigimod in adult participants with generalized myasthenia gravis (gMG). Methods ADAPT+ was an open-label, single-arm, multicenter, up to 3-year extension of the pivotal phase 3 ADAPT study. Efgartigimod was administered in treatment cycles of 4 intravenous infusions (one 10 mg/kg infusion per week). Initiation of subsequent treatment cycles was individualized based on clinical evaluation. Safety endpoints included incidence and severity of adverse events. Efficacy endpoints assessed disease severity using Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. Results As of January 2022, 151 participants had rolled over to ADAPT+ and 145 had received â„1 dose of efgartigimod, of whom, 111 (76.6%) were AChR-Ab+ and 34 (23.4%) were AChR-Abâ. Mean study duration (treatment plus follow-up) was 548 days, and participants received up to 17 treatment cycles, corresponding to 217.6 participant-years of exposure. In the overall population, 123 (84.8%) participants reported â„1 treatment-emergent adverse event; most frequent were headache (36 [24.8%]), COVID-19 (22 [15.2%]), and nasopharyngitis (20 [13.8%]). Clinically meaningful improvement (CMI) in mean MG-ADL and QMG scores was seen as early as 1 week following the first infusion across multiple cycles in AChR-Ab+ and AChR-Abâ participants. Maximal MG-ADL and QMG improvements aligned with onset and magnitude of total IgG and AChR-Ab reductions. For AChR-Ab+ participants at any time point in each of the first 10 treatment cycles, more than 90% had a maximum reduction of â„2 points (CMI) in MG-ADL total score; across the 7 cycles in which QMG was measured, 69.4% to 91.3% of participants demonstrated a maximum reduction of â„3 points (CMI) in QMG total score. Many participants demonstrated improvements well beyond CMI thresholds. In AChR-Ab+ participants with â„1 year of combined follow-up between ADAPT and ADAPT+, mean number of annualized cycles was 4.7 per year (median [range] 5.0 [0.5â7.6]). Conclusion Results of ADAPT+ corroborate the substantial clinical improvements seen with efgartigimod in ADAPT and support its long-term safety, tolerability, and efficacy, as well as an individualized dosing regimen for treatment of gMG. Clinical trial registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT03770403, NCT03770403
Similar Pharmacokinetics of the Adalimumab (HumiraÂź) Biosimilar BI 695501 Whether Administered Via Subcutaneous Autoinjector or Prefilled Syringe (VOLTAIREÂź-AI and VOLTAIREÂź-TAI): Phase 1, Randomised, Open-label, Parallel-group Trials
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LTA4H inhibitor LYS006: Clinical PK/PD and safety in a randomized phase I clinical trial
Abstract LYS006 is a novel, highly potent and selective, newâgeneration leukotriene A4 hydrolase (LTA4H) inhibitor in clinical development for the treatment of neutrophilâdriven inflammatory diseases. We describe the complex pharmacokinetic to pharmacodynamic (PD) relationship in blood, plasma, and skin of LYS006âtreated nonclinical species and healthy human participants. In a randomized first in human study, participants were exposed to single ascending doses up to 100âmg and multiple ascending doses up to 80âmg b.i.d.. LYS006 showed rapid absorption, overall dose proportional plasma exposure and nonlinear blood to plasma distribution caused by saturable target binding. The compound efficiently inhibited LTB4 production in human blood and skin blister cells, leading to greater than 90% predose target inhibition from day 1 after treatment initiation at doses of 20âmg b.i.d. and above. Slow reâdistribution from target expressing cells resulted in a long terminal halfâlife and a longâlasting PD effect in ex vivo stimulated blood and skin cells despite low plasma exposures. LYS006 was wellâtolerated and demonstrated a favorable safety profile up to highest doses tested, without any doseâlimiting toxicity. This supported further clinical development in phase II studies in predominantly neutrophilâdriven inflammatory conditions, such as hidradenitis suppurativa, inflammatory acne, and ulcerative colitis