PubMed:33211076 JSONTXT

{"project":"luoyt2021_800_3","denotations":[{"id":"T1","span":{"begin":34,"end":56},"obj":"CI"},{"id":"T11","span":{"begin":80,"end":91},"obj":"CI"},{"id":"T12","span":{"begin":142,"end":162},"obj":"DP"},{"id":"T13","span":{"begin":229,"end":249},"obj":"DP"},{"id":"T14","span":{"begin":853,"end":873},"obj":"DP"},{"id":"T15","span":{"begin":2866,"end":2886},"obj":"DP"},{"id":"T16","span":{"begin":2819,"end":2823},"obj":"CI"},{"id":"T17","span":{"begin":2604,"end":2608},"obj":"CI"},{"id":"T18","span":{"begin":2459,"end":2463},"obj":"CI"},{"id":"T19","span":{"begin":2018,"end":2022},"obj":"CI"},{"id":"T2","span":{"begin":340,"end":362},"obj":"CI"},{"id":"T20","span":{"begin":1789,"end":1793},"obj":"CI"},{"id":"T21","span":{"begin":1665,"end":1669},"obj":"CI"},{"id":"T22","span":{"begin":1028,"end":1032},"obj":"CI"},{"id":"T23","span":{"begin":544,"end":548},"obj":"CI"},{"id":"T24","span":{"begin":2788,"end":2799},"obj":"CI"},{"id":"T25","span":{"begin":1036,"end":1047},"obj":"CI"},{"id":"T3","span":{"begin":372,"end":376},"obj":"CI"},{"id":"T4","span":{"begin":2643,"end":2654},"obj":"CI"},{"id":"T5","span":{"begin":2468,"end":2479},"obj":"CI"},{"id":"T6","span":{"begin":2051,"end":2062},"obj":"CI"},{"id":"T7","span":{"begin":1828,"end":1839},"obj":"CI"},{"id":"T8","span":{"begin":1676,"end":1687},"obj":"CI"},{"id":"T9","span":{"begin":577,"end":588},"obj":"CI"}],"text":"Efficacy and Safety of a Proposed Ranibizumab Biosimilar Product vs a Reference Ranibizumab Product for Patients With Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial.\nIMPORTANCE: Neovascular age-related macular degeneration is the leading cause of blindness in individuals 50 years or older. The availability of a ranibizumab biosimilar product (SB11) may facilitate access to an effective alternative to this treatment.\nOBJECTIVE: To demonstrate equivalence of efficacy, similar safety, and similar immunogenicity of SB11 compared with the reference ranibizumab.\nDESIGN, SETTING, AND PARTICIPANTS: This randomized, double-masked, parallel-group phase 3 equivalence study was conducted in 75 centers in 9 countries from March 14, 2018, to December 9, 2019, among 705 participants 50 years or older with neovascular age-related macular degeneration with active subfoveal choroidal neovascularization lesions. Analysis was performed on an intent-to-treat basis.\nINTERVENTIONS: Intravitreous injection of SB11 or ranibizumab, 0.5 mg, every 4 weeks through week 48.\nMAIN OUTCOMES AND MEASURES: Preplanned interim analysis after all participants completed the week 24 assessment of primary efficacy end points at week 8 for change from baseline in best-corrected visual acuity (BCVA) and week 4 for central subfield thickness (CST), with predefined equivalence margins for adjusted treatment differences of -3 letters to 3 letters for BCVA and -36 μm to 36 μm for CST.\nRESULTS: Baseline and disease characteristics among 705 randomized participants (403 women [57.2%]; mean [SD] age, 74.1 [8.5] years) were comparable between treatment groups (SB11, 351; ranibizumab, 354). Least-squares mean (SE) changes in BCVA from baseline at week 8 were 6.2 (0.5) letters in the SB11 group vs 7.0 (0.5) letters in the ranibizumab group, with an adjusted treatment difference of -0.8 letter (90% CI, -1.8 to 0.2 letters). Least-squares mean (SE) changes in CST from baseline at week 4 were -108 (5) μm in the SB11 group vs -100 (5) μm in the ranibizumab group, with an adjusted treatment difference of -8 μm (95% CI, -19 to 3 μm). Incidences of treatment-emergent adverse events (231 of 350 [66.0%] vs 237 of 354 [66.9%]), including serious treatment-emergent adverse events (44 of 350 [12.6%] vs 44 of 354 [12.4%]) and treatment-emergent adverse events leading to study drug discontinuation (8 of 350 [2.3%] vs 5 of 354 [1.4%]), were similar in the SB11 and ranibizumab groups. Immunogenicity was low, with a cumulative incidence of antidrug antibodies up to week 24 of 3.0% (10 of 330) in the SB11 group and 3.1% (10 of 327) in the ranibizumab group.\nCONCLUSIONS AND RELEVANCE: These findings of equivalent efficacy and similar safety and immunogenicity profiles compared with ranibizumab support the use of SB11 for patients with neovascular age-related macular degeneration.\nTRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03150589."}

{"project":"Linmchun_800_3","denotations":[{"id":"T10","span":{"begin":1036,"end":1047},"obj":"CI"},{"id":"T11","span":{"begin":1676,"end":1687},"obj":"CI"},{"id":"T12","span":{"begin":1828,"end":1839},"obj":"CI"},{"id":"T13","span":{"begin":2051,"end":2062},"obj":"CI"},{"id":"T14","span":{"begin":2468,"end":2479},"obj":"CI"},{"id":"T15","span":{"begin":2643,"end":2654},"obj":"CI"},{"id":"T16","span":{"begin":2788,"end":2799},"obj":"CI"},{"id":"T17","span":{"begin":544,"end":548},"obj":"CI"},{"id":"T18","span":{"begin":1028,"end":1032},"obj":"CI"},{"id":"T19","span":{"begin":1665,"end":1669},"obj":"CI"},{"id":"T20","span":{"begin":1789,"end":1793},"obj":"CI"},{"id":"T21","span":{"begin":2018,"end":2022},"obj":"CI"},{"id":"T22","span":{"begin":2459,"end":2463},"obj":"CI"},{"id":"T23","span":{"begin":2604,"end":2608},"obj":"CI"},{"id":"T24","span":{"begin":2819,"end":2823},"obj":"CI"},{"id":"T25","span":{"begin":142,"end":162},"obj":"DP"},{"id":"T26","span":{"begin":229,"end":249},"obj":"DP"},{"id":"T27","span":{"begin":853,"end":873},"obj":"DP"},{"id":"T28","span":{"begin":2866,"end":2886},"obj":"DP"},{"id":"T5","span":{"begin":372,"end":376},"obj":"CI"},{"id":"T6","span":{"begin":34,"end":56},"obj":"CI"},{"id":"T7","span":{"begin":80,"end":91},"obj":"CI"},{"id":"T8","span":{"begin":340,"end":362},"obj":"CI"},{"id":"T9","span":{"begin":577,"end":588},"obj":"CI"}],"text":"Efficacy and Safety of a Proposed Ranibizumab Biosimilar Product vs a Reference Ranibizumab Product for Patients With Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial.\nIMPORTANCE: Neovascular age-related macular degeneration is the leading cause of blindness in individuals 50 years or older. The availability of a ranibizumab biosimilar product (SB11) may facilitate access to an effective alternative to this treatment.\nOBJECTIVE: To demonstrate equivalence of efficacy, similar safety, and similar immunogenicity of SB11 compared with the reference ranibizumab.\nDESIGN, SETTING, AND PARTICIPANTS: This randomized, double-masked, parallel-group phase 3 equivalence study was conducted in 75 centers in 9 countries from March 14, 2018, to December 9, 2019, among 705 participants 50 years or older with neovascular age-related macular degeneration with active subfoveal choroidal neovascularization lesions. Analysis was performed on an intent-to-treat basis.\nINTERVENTIONS: Intravitreous injection of SB11 or ranibizumab, 0.5 mg, every 4 weeks through week 48.\nMAIN OUTCOMES AND MEASURES: Preplanned interim analysis after all participants completed the week 24 assessment of primary efficacy end points at week 8 for change from baseline in best-corrected visual acuity (BCVA) and week 4 for central subfield thickness (CST), with predefined equivalence margins for adjusted treatment differences of -3 letters to 3 letters for BCVA and -36 μm to 36 μm for CST.\nRESULTS: Baseline and disease characteristics among 705 randomized participants (403 women [57.2%]; mean [SD] age, 74.1 [8.5] years) were comparable between treatment groups (SB11, 351; ranibizumab, 354). Least-squares mean (SE) changes in BCVA from baseline at week 8 were 6.2 (0.5) letters in the SB11 group vs 7.0 (0.5) letters in the ranibizumab group, with an adjusted treatment difference of -0.8 letter (90% CI, -1.8 to 0.2 letters). Least-squares mean (SE) changes in CST from baseline at week 4 were -108 (5) μm in the SB11 group vs -100 (5) μm in the ranibizumab group, with an adjusted treatment difference of -8 μm (95% CI, -19 to 3 μm). Incidences of treatment-emergent adverse events (231 of 350 [66.0%] vs 237 of 354 [66.9%]), including serious treatment-emergent adverse events (44 of 350 [12.6%] vs 44 of 354 [12.4%]) and treatment-emergent adverse events leading to study drug discontinuation (8 of 350 [2.3%] vs 5 of 354 [1.4%]), were similar in the SB11 and ranibizumab groups. Immunogenicity was low, with a cumulative incidence of antidrug antibodies up to week 24 of 3.0% (10 of 330) in the SB11 group and 3.1% (10 of 327) in the ranibizumab group.\nCONCLUSIONS AND RELEVANCE: These findings of equivalent efficacy and similar safety and immunogenicity profiles compared with ranibizumab support the use of SB11 for patients with neovascular age-related macular degeneration.\nTRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03150589."}