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Abstract Background SCT510 is a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF), which is intended as a candidate biosimilar of bevacizumab that is approved for various metastatic cancers.Please confirm change in wording to match definition for VEGF belowYes. Objective This study aimed to compare the pharmacokinetics profiles, safety, and immunogenicity of SCT510 to bevacizumab (Avastin®) in healthy Chinese males. Methods This was a single-center, double-blind, parallel-group phase I study. A total of 84 participants were randomly assigned (1:1) to receive a single 3 mg/kg infusion of either SCT510 or bevacizumab and followed up for 99 days. Primary endpoints were area under the serum concentration–time curve from time 0 extrapolated to infinity (AUC0–∞), area under the serum concentration–time curve from time 0 to last quantifiable concentration (AUC0–t), and the maximum observed concentration (Cmax). Secondary endpoints included safety and immunogenicity.Kindly check and confirm the edit made in the article title.Yes. Results A total of 82 subjects completed the study. Geometric means ratios (GMR) for AUC0–∞, AUC0–t, and Cmax were 0.88, 0.89, and 0.97, respectively, for SCT510 versus bevacizumab (USA). The 90% confidence intervals for GMRs of AUC0–∞, AUC0–t, and Cmax were all within the prespecified criteria (80–125%). No adverse events (AEs) led to study termination, and no serious adverse events (SAEs) were reported. None of the anti-drug antibodies (ADAs) identified were found to be neutralizing antibodies (NAbs), and only one subject from the SCT510 group tested positive for the ADA at the day 99 visit. Conclusion This study demonstrated that the pharmacokinetics, safety, and immunogenicity of SCT510 were equivalent to bevacizumab (Avastin®). As a proposed biosimilar drug to bevacizumab, SCT510 was well tolerated in healthy Chinese males. Clinical Trials Registration NCT05113511.

SHR-1222, a novel humanized monoclonal antibody targeting sclerostin, has been shown to induce bone formation and decrease bone resorption at a single dose ranging 50–400 mg in our previous phase 1 trial. This study was a randomized, double-blind, placebo-controlled, dose-escalation phase 1 trial, which further investigated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of multiple ascending doses of SHR-1222 in women with postmenopausal osteoporosis (POP). A total of 105 women with POP were enrolled and randomly assigned. Twenty-one received placebo and eighty-four received SHR-1222 sequentially (100 mg QM, n=4; 200 or 300 mg QM, n=20; and 400 or 600 mg Q2M, n=20). The most common adverse events included increased blood parathyroid hormone, increased low-density lipoprotein, increased blood alkaline phosphatase, increased blood cholesterol, back pain, and arthralgia, the majority of which were mild in severity without noticeable safety concerns. Serum SHR-1222 exposure (Cmax,ss and AUC0-tau,ss) increased in a greater than dose-proportional manner. Following multiple doses of SHR-1222, the bone formation markers (terminal propeptide of type I procollagen, bone-specific alkaline phosphatase, and osteocalcin) increased in a dose-dependent manner, whereas the bone resorption marker (β-C-telopeptide) was downregulated. Accordingly, BMD gains in the lumbar spine, total hip, and femoral neck were observed. The maximum BMD increase from baseline at the lumbar spine was detected in the 300 mg QM cohort (14.6% vs. 0.6% in the placebo group on day 169). Six (6/83; 7.2%) subjects developed anti-SHR-1222 antibodies with no discernible effects on PKs, PDs, and safety. Thus, multiple doses of SHR-1222 showed an acceptable safety profile and dose-dependent plasma exposure in women with POP, and could improve their BMD rapidly and prominently by promoting bone formation and inhibiting bone resorption. These findings further support SHR-1222 as a potential alternative agent for the treatment of POP.

SHR-1222, a novel humanized monoclonal antibody targeting sclerostin, has been shown to induce bone formation and decrease bone resorption at a single dose ranging 50-400 mg in our previous phase 1 trial. This study was a randomized, double-blind, placebo-controlled, dose-escalation phase 1 trial, which further investigated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of multiple ascending doses of SHR-1222 in women with postmenopausal osteoporosis (POP). A total of 105 women with POP were enrolled and randomly assigned. Twenty-one received placebo and eighty-four received SHR-1222 sequentially (100 mg QM, n=4; 200 or 300 mg QM, n=20; and 400 or 600 mg Q2M, n=20). The most common adverse events included increased blood parathyroid hormone, increased low-density lipoprotein, increased blood alkaline phosphatase, increased blood cholesterol, back pain, and arthralgia, the majority of which were mild in severity without noticeable safety concerns. Serum SHR-1222 exposure (Cmax,ss and AUC0-tau,ss) increased in a greater than dose-proportional manner. Following multiple doses of SHR-1222, the bone formation markers (terminal propeptide of type I procollagen, bonespecific alkaline phosphatase, and osteocalcin) increased in a dosedependent manner, whereas the bone resorption marker (b-C-telopeptide) was downregulated. Accordingly, BMD gains in the lumbar spine, total hip, and femoral neck were observed. The maximum BMD increase from baseline at the lumbar spine was detected in the 300 mg QM cohort (14.6% vs. 0.6% in the placebo group on day 169). Six (6/83; 7.2%) subjects developed anti-SHR- 1222 antibodies with no discernible effects on PKs, PDs, and safety. Thus, multiple doses of SHR-1222 showed an acceptable safety profile and dosedependent plasma exposure in women with POP, and could improve their BMD rapidly and prominently by promoting bone formation and inhibiting bone resorption. These findings further support SHR-1222 as a potential alternative agent for the treatment of POP. [ABSTRACT FROM AUTHOR]

Uncontrolled hemorrhage remains the leading cause of trauma-related death. The QuikClot is the most popular hemostatic device; however, it also shows severe security hidden dangers. This study aimed to evaluate the efficacy and safety of the selfdeveloped Zeolite Dressing in a rabbit model of hemorrhagic groin injury. A complex hemorrhagic groin injury model was prepared in the right femoral artery of 96 rabbits by lacerating at a half depth and a subsequent 30-second spontaneous hemorrhage, and security was evaluated at the appointed time (1 and 3 weeks after operation). Experimental rabbits were randomly divided into four groups (12 males and 12 females in each group), including sham-operated control group without vascular injury (Con), standard gauze dressing (SD) group, QuikClot (QC) group and Zeolite Dressing (ZD) group. Vascular suture operation and postoperative debridement were thoroughly performed after hemostasis. The results showed that bleeding times of QC and ZD groups were significantly shorter than that of SD group (p<0.001), and there was nonsignificant difference between QC and ZD groups. Similarly, total blood loss was significantly reduced after the intervention of QC or ZD compared with SD group (p<0.001). No obvious toxic reaction was recorded 3 weeks after the treatment in both ZD and QC groups. A high wound temperature (maximum temperature was 96.6±27.9°C) and the "cooked meat like" pathological changes in the skin and muscle were only found in QC group. In conclusion, Zeolite Dressing exhibited a commensurate power to stop bleeding with higher safety compared with QuikClot, indicating that it is a practicable alternative for treating severe hemorrhage. [ABSTRACT FROM AUTHOR]