5 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
Ethical issues with the disclosure of surgical trial short-term data
Background:âThis paper describes the distinctions between major surgical and pharmaceutical trials and questions the application of a common ethical paradigm to guide their conduct and reporting. Methods:âSurgical trials differ from other trials in cumulative therapeutic effects, operator dependence, the clinical setting, interdependence of short- and long-term outcomes, and equipoise. A principal tenant of randomized controlled trial management is the maintenance of interim data confidentiality. Its application to complete surgical short-term data is examined across a variety of common clinical trial circumstances that influence data integrity and the reliability of conclusions regarding the benefit-to-risk profile of experimental interventions. Results:âComplete perioperative results describe important treatment ends that cannot influence primary outcomes. These short-term results may inform patient consent, teaching and provide valuable procedural insights to surgeons outside trial precincts. Conclusion:âStructured experimentation standards are necessary. But, the common paradigm applied across all clinical trials and the prohibition on short term data reporting may not serve the achievement of safe and effective advancements in surgery.Randall A. Allardyce, Philip F. Bagshaw, Christopher M. Frampton, Francis A. Frizelle, Peter J. Hewett, Nicholas A Rieger, J. Shona Smith, Michael J. Solomon and Andrew R. L. Stevenso
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Twelveâmonth results of the ADAPT randomized controlled trial: Reproducibility and sustainability of advanced hybrid closedâloop therapy outcomes versus conventional therapy in adults with type 1 diabetes
Funder: Medtronic International Trading SĂ rlAims: To reassess the 6âmonth efficacy and to assess the 12âmonth sustained efficacy of the MiniMedâą 780G advanced hybrid closedâloop automated insulin delivery (AID) system compared to multiple daily injections plus intermittently scanned glucose monitoring (MDI+isCGM) in people with type 1 diabetes not meeting glucose targets. Methods: The ADAPT study was a prospective, multicentre, openâlabel, randomized control trial in people with type 1 diabetes, with a glycated haemoglobin (HbA1c) concentration of at least 8.0% (64 mmol/mol), on MDI+isCGM therapy. After a 6âmonth study phase, participants randomized at baseline to MDI+isCGM switched to AID (SWITCH) while the others continued AID therapy (SUSTAIN) for an additional 6 months. The primary endpoint of this continuation phase was the withinâgroup change in mean HbA1c between 6 and 12 months, with superiority in the SWITCH group and noninferiority in the SUSTAIN group (ClinicalTrials.gov: NCT04235504). Results: A total of 39 SWITCH and 36 SUSTAIN participants entered the continuation phase. In the SWITCH group, HbA1c was significantly decreased by â1.4% (95% confidence interval [CI] â1.7% to â1.1%; P < 0.001) from a mean ± SD of 8.9% ± 0.8% (73.9 ± 8.6 mmol/mol) at 6 months to 7.5% ± 0.6% (58.5 ± 6.9 mmol/mol) at 12 months. Mean HbA1c increased by 0.1% (95% CI â0.05% to +0.25%), from 7.3% ± 0.6% (56.5 ± 6.7 mmol/mol) to 7.4% ± 0.8% (57.7 ± 9.1 mmol/mol) in the SUSTAIN group, meeting noninferiority criteria. Three severe hypoglycaemia events occurred in two SWITCH participants during the continuation phase. Conclusion: ADAPT study phase glycaemic improvements were reproduced and sustained in the continuation phase, supporting the early adoption of AID therapy in people with type 1 diabetes not meeting glucose targets on MDI therapy