Efficacy and safety of QL0911 in adult patients with chronic primary immune thrombocytopenia: A multicenter, randomized, double-blind, placebo-controlled, phase III trial

• Published in: Journal of translational internal medicine 2023-12, Vol.11 (4), p.423-432
• Main Authors: Zhou, Hu, Han, Shouqing, Jin, Jie, Huang, Ruibin, Guo, Xinhong, Shen, Xuliang, Wang, Binghua, Wang, Xin, Yao, Hongxia, Du, Xin, Huang, Meijuan, Ran, Xuehong, Wang, Wei, Yang, Tonghua, Zhang, Feng, Zheng, Changcheng, Zuo, Xuelan, Fu, Rong, Gao, Da, Ge, Zheng, Han, Ying, Li, Yujie, Kang, Xiaoyan, Shi, Yan, Hou, Ming
• Format: Article
• Language: English
• Subjects: Adults; biosimilar; Bone marrow; Clinical trials; Drug dosages; efficacy; FDA approval; Original; Peptides; platelet response; primary immune thrombocytopenia; safety; Steroids; Thrombocytopenia; thrombopoietin receptor agonist; Toxicity
• ISSN: 2224-4018; 2450-131X; 2224-4018
• DOI: 10.2478/jtim-2023-0106

NOABSTRACTQL0911, a recombinant human thrombopoietin mimetic peptide-Fc fusion protein, is a romiplostim (Nplate®) biosimilar used to treat primary immune thrombocytopenia (ITP). This phase III study aimed to assess the efficacy and safety of QL0911 in adult patients with chronic primary ITP over a 24-week treatment period.We conducted a double-blind, placebo-controlled, phase III study in patients diagnosed with primary ITP for at least 12 months who had received at least one first-line ITP treatment with no response or recurrence after treatment, or who relapsed after splenectomy at 44 sites in China. Patients were randomly allocated (2:1 ratio) to QL0911 or placebo injection subcutaneously once weekly at an initial dose of 1 μg/kg for 24 weeks. The doses were adjusted to maintain the target platelet counts from 50 × 109/L to 200 × 109/L. Patients and investigators were blinded to the assignment. The primary endpoints were the proportion of patients who achieved a durable platelet response at week 24 (platelet count, ≥ 50 × 109/L during 6 of the last 8 weeks of treatment) and safety. The study was registered at ClinicalTrials.gov (NCT05621330).Between October 2019 and December 2021, 216 patients were randomly assigned (QL0911,144; placebo,72). A durable platelet response was achieved by significantly more patients in the QL0911 group (61.8%, 95% CI: 53.3-69.8; P < 0.0001) than in the placebo group (0%). The mean duration of platelet responses was 15.9 (SE: 0.43) weeks with QL0911, and 1.9 (SE:0.26) week with placebo. Consistent results were achieved in subgroup analyses categorized by baseline splenectomy status (yes/no), concomitant ITP treatment (yes/no), and baseline platelet count (≤ 10 × 109/L, > 10 × 109/L, ≤ 20 × 109/L, > 20 × 109/L, and < 30 × 109/L). The incidence of TEAEs was comparable between the QL0911 and the placebo groups (91.7% and 88.9%, respectively). The most common adverse events overall were ecchymosis (28.5% for QL0911 vs. 37.5% for placebo), upper respiratory tract infections respiratory tract infections (31.9% for QL0911 vs. 27.8% for placebo), and gingival bleeding (17.4% for QL0911 vs. 26.4% for placebo).QL0911 was well-tolerated and increased and maintained platelet counts in adults with ITP. QL0911, a biosimilar to romiplostim (Nplate®), may be a novel treatment option for patients with ITP who have failed or relapsed from first-line treatment in China. Ongoing studies will provide further data on long-term efficacy and safet