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Clinical Trial
. 2022 Jan 18;20(1):13.
doi: 10.1186/s12916-021-02208-w.

PCSK9 inhibitor recaticimab for hypercholesterolemia on stable statin dose: a randomized, double-blind, placebo-controlled phase 1b/2 study

Mingtong Xu #  1 , Xiaoxue Zhu #  2 , Junyan Wu  3 , Yuling Zhang  4 , Dong Zhao  5 , Xuhong Wang  5 , Yanhua Ding  2 , Yu Cao  6 , Chengqian Li  7 , Wei Hu  8 , Jianlong Sheng  9 , Zhu Luo  10 , Zeqi Zheng  11 , Jinfang Hu  12 , Jianying Liu  13 , Xiaoyang Zhou  14 , Aizong Shen  15 , Xiaomei Ding  16 , Yongdong Zhang  17 , Yonggang Zhao  18 , Yijing Li  19 , Sheng Zhong  19 , Shimin An  19 , Jianjun Zou  19 , Li Yan  20
Affiliations
Clinical Trial

PCSK9 inhibitor recaticimab for hypercholesterolemia on stable statin dose: a randomized, double-blind, placebo-controlled phase 1b/2 study

Mingtong Xu et al. BMC Med. .

Abstract

Background: Recaticimab (SHR-1209, a humanized monoclonal antibody against PCSK9) showed robust LDL-C reduction in healthy volunteers. This study aimed to further assess the efficacy and safety of recaticimab in patients with hypercholesterolemia.

Methods: In this randomized, double-blind, placebo-controlled phase 1b/2 trial, patients receiving stable dose of atorvastatin with an LDL-C level of 2.6 mmol/L or higher were randomized in a ratio of 5:1 to subcutaneous injections of recaticimab or placebo at different doses and schedules. Patients were recruited in the order of 75 mg every 4 weeks (75Q4W), 150Q8W, 300Q12W, 150Q4W, 300Q8W, and 450Q12W. The primary endpoint was percentage change in LDL-C from the baseline to end of treatment (i.e., at week 16 for Q4W and Q8W schedule and at week 24 for Q12W schedule).

Results: A total of 91 patients were enrolled and received recaticimab and 19 received placebo. The dose of background atorvastatin in all 110 patients was 10 or 20 mg/day. The main baseline LDL-C ranged from 3.360 to 3.759 mmol/L. The least-squares mean percentage reductions in LDL-C from baseline to end of treatment relative to placebo for recaticimab groups at different doses and schedules ranged from -48.37 to -59.51%. No serious treatment-emergent adverse events (TEAEs) occurred. The most common TEAEs included upper respiratory tract infection, increased alanine aminotransferase, increased blood glucose, and increased gamma-glutamyltransferase.

Conclusion: Recaticimab as add-on to moderate-intensity statin therapy significantly and substantially reduced the LDL-C level with an infrequent administration schedule (even given once every 12 weeks), compared with placebo.

Trial registration: ClinicalTrials.gov , number NCT03944109.

Keywords: Hypercholesterolemia; Infrequent administration; PCSK9; Recaticimab.

PubMed Disclaimer

Conflict of interest statement

YL, SZ, SA, and JZ reported being employed at Jiangsu Hengrui Pharmaceuticals. No other disclosures were reported.

Figures

Fig. 1
Fig. 1
Study flow. *2, 2, 2, 4, 4, and 4 patients were assigned to receive placebo at a dose and frequency of 75 mg Q4W, 150 mg Q4W, 150 mg Q8W, 300 mg Q8W, 300 mg Q12W, and 450 mg Q12W, respectively
Fig. 2
Fig. 2
Percentage change in LDL-C during treatment. Mean percentage changes (standard error) in LDL-C from baseline to end of treatment (i.e., at week 16 for patients receiving treatment Q4W and Q8W and at week 24 for patients receiving treatment Q12W) are shown. LDL-C low-density lipoprotein cholesterol
See this image and copyright information in PMC

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