Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Ear, Nose, Throat and Head and Neck Surgery Research Center, Iran University of Medical Sciences, Tehran, Iran.
Front Immunol. 2024 Jul 29;15:1425906. doi: 10.3389/fimmu.2024.1425906. eCollection 2024.
Allergic asthma has a considerable burden on the quality of life. A significant portion of moderate-to-severe allergic asthma patients need omalizumab, an anti-immunoglobulin-E monoclonal antibody, as an add-on therapy. In this phase III clinical trial P043 (Zerafil, CinnaGen, Iran) efficacy, safety, and immunogenicity were compared with Xolair (the originator omalizumab). The primary outcome was the rate of protocol-defined asthma exacerbations.
Exacerbation rates, Asthma Control Test (ACT) results, spirometry measurements, immunogenicity, and safety were evaluated. Each subject received either medication with a dose ranging from 150 to 375 mg based on pre-treatment serum total IgE level (IU/mL) and body weight (kg) every two or four weeks for a duration of 28 weeks.
Exacerbation rates were 0.150 (CI: 0.079-0.220) in the P043 group, and 0.190 (CI: 0.110-0.270) in the omalizumab group (per-protocol). The least squares mean differences of predicted Forced Expiratory Volume in the First second (FEV) were -2.51% (CI: -7.17-2.15, P=0.29) and -3.87% (CI: -8.79-1.04, P=0.12), pre- and post-bronchodilator use. The mean ± SD of ACT scores at the screening and the last visit were 10.62 ± 2.93 and 20.93 ± 4.26 in P043 and 11.09 ± 2.75 and 20.46 ± 5.11 in the omalizumab group. A total of 288 adverse events were reported for the 256 enrolled participants. Among all, "dyspnea" and "headache" were the most reported ones. The overall incidence of adverse events (P=0.62) and serious adverse events (P=0.07) had no significant differences between the two groups. None of the samples were positive for anti-drug antibodies.
P043 was equivalent to omalizumab in the management of asthma in reduction of exacerbations. There was no significant difference in other efficacy and safety parameters.
www.clinicaltrials.gov (NCT05813470) and www.IRCT.ir (IRCT20150303021315N20).
过敏性哮喘对生活质量有相当大的影响。相当一部分中重度过敏性哮喘患者需要奥马珠单抗（一种抗免疫球蛋白 E 单克隆抗体）作为附加治疗。在这项 P043（CinnaGen，伊朗）的 III 期临床试验中，比较了其疗效、安全性和免疫原性与 Xolair（奥马珠单抗原研药）。主要结局为方案规定的哮喘加重率。
评估哮喘加重率、哮喘控制测试（ACT）结果、肺活量测定、免疫原性和安全性。根据治疗前血清总 IgE 水平（IU/mL）和体重（kg），每位受试者每 2 或 4 周接受一次 150 至 375mg 的药物治疗，持续 28 周。
P043 组哮喘加重率为 0.150（CI：0.079-0.220），奥马珠单抗组为 0.190（CI：0.110-0.270）（按方案）。使用支气管扩张剂前后用力肺活量（FEV）的最小二乘均值差异分别为-2.51%（CI：-7.17-2.15，P=0.29）和-3.87%（CI：-8.79-1.04，P=0.12）。P043 组在筛选和最后一次就诊时的 ACT 评分均值±SD 分别为 10.62±2.93 和 20.93±4.26，奥马珠单抗组分别为 11.09±2.75 和 20.46±5.11。在 256 名入组的参与者中，共报告了 288 例不良事件。其中，“呼吸困难”和“头痛”是最常见的不良事件。两组间不良事件的总体发生率（P=0.62）和严重不良事件的发生率（P=0.07）无显著差异。两组均无药物抗体阳性样本。
P043 在减少哮喘加重方面与奥马珠单抗等效。其他疗效和安全性参数无显著差异。
www.clinicaltrials.gov（NCT05813470）和 www.IRCT.ir（IRCT20150303021315N20）。
