Meplazumab in hospitalized adults with severe COVID-19 (DEFLECT): a multicenter, seamless phase 2/3, randomized, third-party double-blind clinical trial

Abstract

Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.

CD147 Sparks Atherosclerosis by Driving M1 Phenotype and Impairing Efferocytosis

“…This finding is consistent with studies showing that the anti-CD147 antibody, meplazumab, eases cytokine storms in patients with COVID-19, as evidenced by decreased levels of 12 cytokines/chemokines in the serum. 18 Moreover, targeting CD147 improves defective efferocytosis during inflammation, preventing the accumulation of secondary necrosis and the formation of a highly inflammatory necrotic core. Notably, the atheroprotective effects of targeting CD147 are dependent on the proinflammatory environment, which may effectively reduce the risk of infection due to its specific effects under proinflammatory conditions.…”

“…[13][14][15][16] Meplazumab, a humanized CD147 antibody, can reduce cytokine levels, viral load, and mortality in patients with COVID-19, with a favorable safety profile. 17,18 Cardiovascular diseases are the most prevalent complications in patients with COVID-19, and their high mortality rates are often attributed to preexisting atherosclerosis. 19 Increasing evidence suggests a substantial increase in CD147 expression in atherosclerosis, closely associated with inflammatory cytokines.…”

“…Considering the crucial role of inflammation in plaque progression, we investigated the inflammatory signatures in vivo. Positron emission tomography imaging revealed enhanced aortic uptake of 18 F-fluorodeoxyglucose in CD147 M-KI ApoE -/mice fed a Western diet for 8 weeks compared with controls (Figure 3A), indicating increased arterial inflammation. RNA-sequencing and gene set enrichment analysis were performed on BMDMs and enrichment of the Th1 (T helper cell) and Th2 cell differentiation pathway was found (Figure 3B).…”

Coombs-Negative Hemolytic Anemia in an Elderly COVID-19 Patient

“…There are ongoing clinical trials on the use of CD147 humanized antibody (meplazumab) in severe COVID-19 infections which could effectively inhibit viral entry and cytokine storm [ 6 ]. It would be interesting to see if this can prevent such complications in future use (Figure 2 ).…”

Therapeutic strategies for COVID-19: progress and lessons learned

“…Meplazumab, a humanized anti-CD147 IgG2 mAb, plus standard care reduced the 29-day mortality and viral loads in a phase II/III study of inpatients with severe COVID-19 (ref. 186 ). In theory, inhibitors targeted at conserved host proteins overcome drug resistance, but their efficacy and safety profiles require evaluation.…”