{"title":"SCALA：在进展期多发性硬化症患者中比较皮下注射和静脉注射阿仑妥珠单抗的随机 I 期试验。","authors":"Xavier Montalban, Breogan Rodriguez-Acevedo, Carlos Nos, Mireia Resina, Mireia Forner, Yanzhen Wu, Magdalena Chirieac","doi":"10.1177/17562864241291655","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Alemtuzumab is administered intravenously (IV) for relapsing-remitting multiple sclerosis (RRMS), with limited studies of subcutaneous (SC) treatment.</p><p><strong>Objectives: </strong>We sought to evaluate the pharmacodynamics (PD), pharmacokinetics (PK), and safety profile of SC-administered alemtuzumab in people with progressive multiple sclerosis (PMS).</p><p><strong>Design: </strong>SCALA was a phase I, open-label, randomized, parallel-group study with two 12-month periods and a safety monitoring phase to 60 months.</p><p><strong>Methods: </strong>Of 29 screened participants, 24 were enrolled and randomized 2:1 to two 12 mg/day alemtuzumab treatments (60 and 36 mg total; SC:IV). Key inclusion criteria: ⩾18 years with a PMS diagnosis. Key exclusion criteria included RRMS diagnosis and prior treatment with anti-CD52 antibodies. Primary endpoint: CD3<sup>+</sup> lymphocyte count. Secondary endpoints: PD and PK parameters.</p><p><strong>Results: </strong>Demographics were broadly similar for participants in the SC (16) and IV (8) arms; more participants with primary PMS received SC (44%) versus IV (25%) treatment. After the first course, the mean CD3<sup>+</sup> cell count/µL was reduced at month 1 in both arms (SC: baseline (BL) 1326 to 48 vs IV: BL 1155 to 84). Lymphocyte counts partially repopulated by month 12, with mean CD3<sup>+</sup> cell counts/µL of SC 599 versus IV 528. The mean lymphocyte counts/µL decreased again after the second course at month 13 in both arms (SC: 90 vs IV: 129), with partial repopulation by month 24. Alemtuzumab serum concentrations were lower following SC administration relative to IV, with 32% bioavailability. There were no adverse events leading to permanent treatment discontinuation or death.</p><p><strong>Conclusion: </strong>In SCALA, there were similar patterns of lymphocyte depletion and repopulation for participants receiving SC or IV alemtuzumab. In both arms, alemtuzumab had a manageable safety profile, with no emerging safety concerns. The general stabilization of neurological outcomes observed over 60 months underscores the potential long-term benefits of alemtuzumab treatment.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov identifier: NCT02583594.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864241291655"},"PeriodicalIF":4.7000,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542112/pdf/","citationCount":"0","resultStr":"{\"title\":\"SCALA: a randomized phase I trial comparing subcutaneous and intravenous alemtuzumab in patients with progressive multiple sclerosis.\",\"authors\":\"Xavier Montalban, Breogan Rodriguez-Acevedo, Carlos Nos, Mireia Resina, Mireia Forner, Yanzhen Wu, Magdalena Chirieac\",\"doi\":\"10.1177/17562864241291655\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Alemtuzumab is administered intravenously (IV) for relapsing-remitting multiple sclerosis (RRMS), with limited studies of subcutaneous (SC) treatment.</p><p><strong>Objectives: </strong>We sought to evaluate the pharmacodynamics (PD), pharmacokinetics (PK), and safety profile of SC-administered alemtuzumab in people with progressive multiple sclerosis (PMS).</p><p><strong>Design: </strong>SCALA was a phase I, open-label, randomized, parallel-group study with two 12-month periods and a safety monitoring phase to 60 months.</p><p><strong>Methods: </strong>Of 29 screened participants, 24 were enrolled and randomized 2:1 to two 12 mg/day alemtuzumab treatments (60 and 36 mg total; SC:IV). Key inclusion criteria: ⩾18 years with a PMS diagnosis. Key exclusion criteria included RRMS diagnosis and prior treatment with anti-CD52 antibodies. Primary endpoint: CD3<sup>+</sup> lymphocyte count. Secondary endpoints: PD and PK parameters.</p><p><strong>Results: </strong>Demographics were broadly similar for participants in the SC (16) and IV (8) arms; more participants with primary PMS received SC (44%) versus IV (25%) treatment. After the first course, the mean CD3<sup>+</sup> cell count/µL was reduced at month 1 in both arms (SC: baseline (BL) 1326 to 48 vs IV: BL 1155 to 84). Lymphocyte counts partially repopulated by month 12, with mean CD3<sup>+</sup> cell counts/µL of SC 599 versus IV 528. The mean lymphocyte counts/µL decreased again after the second course at month 13 in both arms (SC: 90 vs IV: 129), with partial repopulation by month 24. Alemtuzumab serum concentrations were lower following SC administration relative to IV, with 32% bioavailability. There were no adverse events leading to permanent treatment discontinuation or death.</p><p><strong>Conclusion: </strong>In SCALA, there were similar patterns of lymphocyte depletion and repopulation for participants receiving SC or IV alemtuzumab. In both arms, alemtuzumab had a manageable safety profile, with no emerging safety concerns. The general stabilization of neurological outcomes observed over 60 months underscores the potential long-term benefits of alemtuzumab treatment.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov identifier: NCT02583594.</p>\",\"PeriodicalId\":22980,\"journal\":{\"name\":\"Therapeutic Advances in Neurological Disorders\",\"volume\":\"17 \",\"pages\":\"17562864241291655\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2024-11-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542112/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Advances in Neurological Disorders\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17562864241291655\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Neurological Disorders","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17562864241291655","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
SCALA: a randomized phase I trial comparing subcutaneous and intravenous alemtuzumab in patients with progressive multiple sclerosis.
Background: Alemtuzumab is administered intravenously (IV) for relapsing-remitting multiple sclerosis (RRMS), with limited studies of subcutaneous (SC) treatment.
Objectives: We sought to evaluate the pharmacodynamics (PD), pharmacokinetics (PK), and safety profile of SC-administered alemtuzumab in people with progressive multiple sclerosis (PMS).
Design: SCALA was a phase I, open-label, randomized, parallel-group study with two 12-month periods and a safety monitoring phase to 60 months.
Methods: Of 29 screened participants, 24 were enrolled and randomized 2:1 to two 12 mg/day alemtuzumab treatments (60 and 36 mg total; SC:IV). Key inclusion criteria: ⩾18 years with a PMS diagnosis. Key exclusion criteria included RRMS diagnosis and prior treatment with anti-CD52 antibodies. Primary endpoint: CD3+ lymphocyte count. Secondary endpoints: PD and PK parameters.
Results: Demographics were broadly similar for participants in the SC (16) and IV (8) arms; more participants with primary PMS received SC (44%) versus IV (25%) treatment. After the first course, the mean CD3+ cell count/µL was reduced at month 1 in both arms (SC: baseline (BL) 1326 to 48 vs IV: BL 1155 to 84). Lymphocyte counts partially repopulated by month 12, with mean CD3+ cell counts/µL of SC 599 versus IV 528. The mean lymphocyte counts/µL decreased again after the second course at month 13 in both arms (SC: 90 vs IV: 129), with partial repopulation by month 24. Alemtuzumab serum concentrations were lower following SC administration relative to IV, with 32% bioavailability. There were no adverse events leading to permanent treatment discontinuation or death.
Conclusion: In SCALA, there were similar patterns of lymphocyte depletion and repopulation for participants receiving SC or IV alemtuzumab. In both arms, alemtuzumab had a manageable safety profile, with no emerging safety concerns. The general stabilization of neurological outcomes observed over 60 months underscores the potential long-term benefits of alemtuzumab treatment.
期刊介绍：
Therapeutic Advances in Neurological Disorders is a peer-reviewed, open access journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies across all areas of neurology. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in neurology, providing a forum in print and online for publishing the highest quality articles in this area.
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