Laura Kooienga, Steven Burke, Amarnath Kathresal, Wenli Luo, Zhihui Yang, Zhiqun Zhang, Rafal Zwiech, German T Hernandez
{"title":"每日一次和每周三次服用伐杜司他治疗透析依赖型慢性肾病贫血患者的安全性和有效性","authors":"Laura Kooienga, Steven Burke, Amarnath Kathresal, Wenli Luo, Zhihui Yang, Zhiqun Zhang, Rafal Zwiech, German T Hernandez","doi":"10.34067/KID.0000000567","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor for treating anemia in chronic kidney disease (CKD). This study investigated safety and efficacy of once-daily and 3-times-weekly dosing in patients with dialysis-dependent (DD)-CKD compared with darbepoetin alfa (DA).</p><p><strong>Methods: </strong>This phase 3b, randomized (1:1:1; vadadustat once-daily [starting dose: 300 or 450 mg], vadadustat 3-times-weekly [starting dose: 600 or 750 mg], DA), open-label, active-controlled, noninferiority trial included conversion (weeks 0-20) and maintenance (weeks 20-52) periods. Primary and secondary efficacy endpoints were mean change in hemoglobin from baseline during the primary (PEP, weeks 20-26) and secondary (SEP, weeks 46-52) evaluation periods. Other endpoints included proportion of patients requiring ESA rescue (hemoglobin <9.5 g/dL or with increases in dose ≥50% or ≥100% in DA group). Safety endpoints included treatment-emergent adverse events (TEAEs) and serious AEs (SAEs).</p><p><strong>Results: </strong>Least squares (LS) mean treatment difference between vadadustat once-daily and DA from baseline to PEP was -0.27 g/dL (95% CI, -0.55 to 0.01); the lower bound met the noninferiority threshold (-0.75 g/dL). The LS mean treatment difference between vadadustat 3-times-weekly and DA from baseline to PEP was -0.53 g/dL (95% CI, -0.80 to -0.25), which did not meet the lower bound noninferiority threshold. The LS mean change from baseline to the SEP between DA and vadadustat once-daily was -0.40 (95% CI, -0.79 to -0.02), and for vadadustat 3-times-weekly was -0.42 (95% CI, -0.81 to -0.02). Proportion of patients who received ESA rescue during weeks 2-52 was higher in the DA group than vadadustat groups. Similar TEAEs and treatment-emergent SAEs were observed across groups.</p><p><strong>Conclusions: </strong>Vadadustat once-daily, but not 3-times-weekly, was noninferior to DA in the correction and maintenance of hemoglobin in patients with DD-CKD converted from an ESA; safety profiles were similar across groups.</p><p><strong>Trial registration: </strong>EudraCT 2019-004851-36/ClinicalTrials.gov identifier: NCT04313153.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Safety and Efficacy of Vadadustat Once-Daily and 3-Times-Weekly in Dialysis-Dependent Chronic Kidney Disease Patients with Anemia.\",\"authors\":\"Laura Kooienga, Steven Burke, Amarnath Kathresal, Wenli Luo, Zhihui Yang, Zhiqun Zhang, Rafal Zwiech, German T Hernandez\",\"doi\":\"10.34067/KID.0000000567\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor for treating anemia in chronic kidney disease (CKD). This study investigated safety and efficacy of once-daily and 3-times-weekly dosing in patients with dialysis-dependent (DD)-CKD compared with darbepoetin alfa (DA).</p><p><strong>Methods: </strong>This phase 3b, randomized (1:1:1; vadadustat once-daily [starting dose: 300 or 450 mg], vadadustat 3-times-weekly [starting dose: 600 or 750 mg], DA), open-label, active-controlled, noninferiority trial included conversion (weeks 0-20) and maintenance (weeks 20-52) periods. Primary and secondary efficacy endpoints were mean change in hemoglobin from baseline during the primary (PEP, weeks 20-26) and secondary (SEP, weeks 46-52) evaluation periods. Other endpoints included proportion of patients requiring ESA rescue (hemoglobin <9.5 g/dL or with increases in dose ≥50% or ≥100% in DA group). Safety endpoints included treatment-emergent adverse events (TEAEs) and serious AEs (SAEs).</p><p><strong>Results: </strong>Least squares (LS) mean treatment difference between vadadustat once-daily and DA from baseline to PEP was -0.27 g/dL (95% CI, -0.55 to 0.01); the lower bound met the noninferiority threshold (-0.75 g/dL). The LS mean treatment difference between vadadustat 3-times-weekly and DA from baseline to PEP was -0.53 g/dL (95% CI, -0.80 to -0.25), which did not meet the lower bound noninferiority threshold. The LS mean change from baseline to the SEP between DA and vadadustat once-daily was -0.40 (95% CI, -0.79 to -0.02), and for vadadustat 3-times-weekly was -0.42 (95% CI, -0.81 to -0.02). Proportion of patients who received ESA rescue during weeks 2-52 was higher in the DA group than vadadustat groups. 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Safety and Efficacy of Vadadustat Once-Daily and 3-Times-Weekly in Dialysis-Dependent Chronic Kidney Disease Patients with Anemia.
Background: Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor for treating anemia in chronic kidney disease (CKD). This study investigated safety and efficacy of once-daily and 3-times-weekly dosing in patients with dialysis-dependent (DD)-CKD compared with darbepoetin alfa (DA).
Methods: This phase 3b, randomized (1:1:1; vadadustat once-daily [starting dose: 300 or 450 mg], vadadustat 3-times-weekly [starting dose: 600 or 750 mg], DA), open-label, active-controlled, noninferiority trial included conversion (weeks 0-20) and maintenance (weeks 20-52) periods. Primary and secondary efficacy endpoints were mean change in hemoglobin from baseline during the primary (PEP, weeks 20-26) and secondary (SEP, weeks 46-52) evaluation periods. Other endpoints included proportion of patients requiring ESA rescue (hemoglobin <9.5 g/dL or with increases in dose ≥50% or ≥100% in DA group). Safety endpoints included treatment-emergent adverse events (TEAEs) and serious AEs (SAEs).
Results: Least squares (LS) mean treatment difference between vadadustat once-daily and DA from baseline to PEP was -0.27 g/dL (95% CI, -0.55 to 0.01); the lower bound met the noninferiority threshold (-0.75 g/dL). The LS mean treatment difference between vadadustat 3-times-weekly and DA from baseline to PEP was -0.53 g/dL (95% CI, -0.80 to -0.25), which did not meet the lower bound noninferiority threshold. The LS mean change from baseline to the SEP between DA and vadadustat once-daily was -0.40 (95% CI, -0.79 to -0.02), and for vadadustat 3-times-weekly was -0.42 (95% CI, -0.81 to -0.02). Proportion of patients who received ESA rescue during weeks 2-52 was higher in the DA group than vadadustat groups. Similar TEAEs and treatment-emergent SAEs were observed across groups.
Conclusions: Vadadustat once-daily, but not 3-times-weekly, was noninferior to DA in the correction and maintenance of hemoglobin in patients with DD-CKD converted from an ESA; safety profiles were similar across groups.
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