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Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial.

ABSTRACT: Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG₂ monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood C_max and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

SUBMITTER: Bian H

PROVIDER: S-EPMC8127508 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial.

Bian Huijie H Zheng Zhao-Hui ZH Wei Ding D Wen Aidong A Zhang Zheng Z Lian Jian-Qi JQ Kang Wen-Zhen WZ Hao Chun-Qiu CQ Wang Jing J Xie Rong-Hua RH Dong Ke K Xia Jie-Lai JL Miao Jin-Lin JL Kang Wen W Li Guoquan G Zhang Di D Zhang Mingru M Sun Xiu-Xuan XX Ding Likun L Zhang Kui K Jia Junfeng J Ding Jin J Li Zhiqin Z Jia Yanyan Y Liu Lin-Na LN Zhang Zhe Z Gao Zhao-Wei ZW Du Hong H Yao Na N Wang Qing Q Wang Ke K Geng Jie-Jie JJ Wang Bin B Guo Ting T Chen Ruo R Zhu Yu-Meng YM Wang Li-Juan LJ He Qian Q Yao Rui-Rui RR Shi Ying Y Yang Xiang-Min XM Zhou Jian-Sheng JS Ma Yi-Nan YN Wang Ya-Tao YT Liang Xue X Huo Fei F Wang Zhe Z Zhang Yang Y Yang Xu X Zhang Ye Y Gao Lu-Hua LH Wang Ling L Chen Xiao-Chun XC Tang Hao H Liu Shuang-Shuang SS Wang Qing-Yi QY Chen Zhi-Nan ZN Zhu Ping P

Signal transduction and targeted therapy 20210517 1

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG<sub>2</sub> monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate th ...[more]

PMID: 34001849

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Project description:IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is an enveloped, single-stranded RNA virus. Favipiravir is an orally administrable antiviral drug whose mechanism of action is to selectively inhibit RNA-dependent RNA polymerase. A preliminary trial in COVID-19 patients reported significant improvements across a multitude of clinical parameters, but these findings have not been confirmed in an adequate well-controlled trial. We conducted a randomized, single-blind, placebo-controlled Phase III trial assessing the efficacy and safety of favipiravir in patients with moderate pneumonia not requiring oxygen therapy.MethodsCOVID-19 patients with moderate pneumonia (SpO2 ≥ 94%) within 10 days of onset of fever (temperature ≥ 37.5 °C) were assigned to receive either placebo or favipiravir (1800 mg twice a day on Day 1, followed by 800 mg twice a day for up to 13 days) in a ratio of 1:2. An adaptive design was used to re-estimate the sample size. The primary endpoint was a composite outcome defined as the time to improvement in temperature, oxygen saturation levels (SpO2), and findings on chest imaging, and recovery to SARS-CoV-2-negative. This endpoint was re-examined by the Central Committee under blinded conditions.ResultsA total of 156 patients were randomized. The median time of the primary endpoint was 11.9 days in the favipiravir group and 14.7 days in the placebo group, with a significant difference (p = 0.0136). Favipiravir-treated patients with known risk factors such as obesity or coexisting conditions provided better effects. Furthermore, patients with early-onset in the favipiravir group showed higher odds ratio. No deaths were documented. Although adverse events in the favipiravir group were predominantly transient, the incidence was significantly higher.ConclusionsThe results suggested favipiravir may be one of options for moderate COVID-19 pneumonia treatment. However, the risk of adverse events, including hyperuricemia, should be carefully considered.Trial registrationClinicaltrials.jp number: JapicCTI-205238.

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Project description:IntroductionVidofludimus calcium has shown anti-inflammatory effects in clinical trials of autoimmune diseases and recently demonstrated antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We performed a double-blind, randomized, placebo-controlled, phase 2 trial to evaluate the safety and efficacy of vidofludimus calcium in patients hospitalized for coronavirus disease 2019 (COVID-19) in Europe and the USA.MethodsPatients aged 18 years or older who positive for COVID-19 were randomized (1:1) to receive placebo or 45 mg vidofludimus calcium for 14 days with both groups receiving standard-of-care treatment. The primary endpoint was the need for invasive ventilation after 28 days (ClinicalTrials.gov NCT04379271; EudraCT 2020-001264-28).ResultsBetween June 12, 2020 and December 10, 2020, a total of 223 were randomized to receive either placebo (n = 112) or vidofludimus calcium (n = 111); three patients withdrew consent and were not treated. Eight (9%) patients in the placebo group and 12 (11%) patients in the vidofludimus calcium group needed invasive ventilation during the 28-day study period, which was lower than the assumed rate of 40%. Time to clinical improvement was shorter by approximately 1 day in the vidofludimus calcium group (15.0 days [90% CI 14.8-15.9]) compared to the placebo group (15.9 days [90% CI 14.9-19.9]). This effect was greatest in patients who initiated therapy within 9 days of symptom onset (3.8 days shorter in the vidofludimus calcium group). Higher trough concentrations of vidofludimus calcium were associated with quicker time to clinical recovery. The rate and timing of appearance of anti-SARS-CoV-2 antibodies were not different between groups. Serious adverse events occurred in 4 (4%) patients in the placebo group and 2 (2%) patients in the vidofludimus calcium group; treatment-emergent adverse events of increased severity related to COVID-19 occurred in 13 (12%) patients in the placebo group and 8 (7%) patients in the vidofludimus calcium group. Overall mortality was low (2%).ConclusionsThese findings support vidofludimus calcium being safe and well tolerated in patients with COVID-19.

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Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial.

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Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial.

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