Therapeutic Effects of Batoclimab in Chinese Patients with Generalized Myasthenia Gravis: A Double-Blinded, Randomized, Placebo-Controlled Phase II Study

Chong Yan, Rui-Sheng Duan, Huan Yang, Hai-Feng Li, Zhangyu Zou, Hua Zhang, Hongyu Zhou, Xiao-Li Li, Hao Zhou, Lidong Jiao, Jialin Chen, Jian Yin, Qin Du, Michael Lee, Yu Chen, Xiaoxiang Chen, Chongbo Zhao, Chong Yan, Rui-Sheng Duan, Huan Yang, Hai-Feng Li, Zhangyu Zou, Hua Zhang, Hongyu Zhou, Xiao-Li Li, Hao Zhou, Lidong Jiao, Jialin Chen, Jian Yin, Qin Du, Michael Lee, Yu Chen, Xiaoxiang Chen, Chongbo Zhao

Abstract

Introduction: We investigated the safety and explore potential efficacy of batoclimab administered subcutaneously in Chinese patients with generalized myasthenia gravis (gMG).

Methods: A randomized, double-blinded, placebo-controlled, parallel phase II study was conducted. First, in the double-blinded treatment period, eligible patients received batoclimab (680 mg), batoclimab (340 mg), or placebo on days 1, 8, 15, 22, 29, and 36. In the open-label treatment period, patients received batoclimab (340 mg) on days 50, 64, and 78. In the follow-up period, patients were examined on days 92, 106, and 120. The primary endpoint was Myasthenia Gravis Activities of Daily Living (MG-ADL) score change on day 43 from baseline.

Results: In total, 30 eligible patients were enrolled, with 11, 10, and 9 patients in the batoclimab 680 mg, batoclimab 340 mg, and placebo groups, respectively. MG-ADL score changes from baseline to day 43 were -2.2 ± 0.9, -4.7 ± 0.6, and -4.4 ± 1.0 in the placebo, batoclimab 340 mg, and 680 mg groups, respectively. Similar changes were observed in Quantitative Myasthenia Gravis, Myasthenia Gravis Composite, and 15-item Myasthenia Gravis Quality of Life scores in the placebo, batoclimab 340 mg, and 680 mg groups, respectively. The proportion of patients with clinically significant improvement on day 43 was higher in the batoclimab groups. On day 120, all four scales in the placebo group had more significant improvement compared with the batoclimab groups, with total serum IgG levels reaching a plateau. No death or treatment-emergent adverse events (TEAEs) led to study discontinuation.

Conclusion: Batoclimab is effective and safe in Chinese patients with gMG.

Trial registration: This study was registered at ClinicalTrials.gov (NCT04346888) on 15 April 2020, with the first patient enrolled on 23 July 2020.

Keywords: Batoclimab; Efficacy; Generalized myasthenia gravis; Neonatal Fc receptor; Safety.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Study flow diagram. *The two patients who withdrew in the open-label period received one injection
Fig. 2
Fig. 2
Clinical efficacy. A Changes from baseline to day 43 in Myasthenia Gravis Activities of Daily Living (MG-ADL), Quantitative Myasthenia Gravis (QMG), Myasthenia Gravis Composite (MGC), and revised 15-item Myasthenia Gravis Quality of Life (MG-QoL15r) scores. Values are mean ± standard error, expressed as point reduction from baseline. B Day 43 responder rates for Myasthenia Gravis Activities of Daily Living (MG-ADL) (reduction ≥ 2 points) and Quantitative Myasthenia Gravis (QMG) (reduction ≥ 3 points) scores. The percentage of patients with a clinical improvement of specified value is indicated next to the corresponding bar. Two batoclimab dose groups were combined. C Fast and durable clinical improvement. Patients showing fast clinical improvement by Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores at least 1 week within 2 weeks after the first dose. Patients showing durable response by Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. MG-ADL or QMG improvement from baseline with a magnitude as indicated in the y-axis for 4 or more weeks during the double-blinded treatment period. Two batoclimab dose groups were combined
Fig. 3
Fig. 3
Changes in IgG, total cholesterol, and albumin levels. A Serum total immunoglobulin G (IgG) levels after batoclimab and placebo treatment over the whole study period. Values are mean ± standard error, expressed as the percentage change from baseline in IgG concentration. B Serum total cholesterol levels after batoclimab and placebo treatment over the whole study period. Values are mean ± standard error, expressed as serum total cholesterol concentration. C Serum total albumin levels after batoclimab and placebo treatment over the whole study period. Values are mean ± standard error, expressed as serum albumin concentration

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