A Randomized, Double-Blind, Placebo-Controlled, First-in-Human Clinical Trial to Assess Safety, Tolerability, and Pharmacokinetics of LY-CovMab, a Potent Human Neutralizing Antibody Against SARS-CoV-2

Qian Zhang, Renpeng Zhou, Jingjing Yang, Changlin Dou, Tianyi Gan, Fujia Liu, Baihui Hu, Deyong Song, Chao Lu, Wei Hu, Qian Zhang, Renpeng Zhou, Jingjing Yang, Changlin Dou, Tianyi Gan, Fujia Liu, Baihui Hu, Deyong Song, Chao Lu, Wei Hu

Abstract

Introduction: We aimed to evaluate the safety, tolerability, pharmacokinetics, and immunogenicity of a single dose of LY-CovMab in Chinese healthy adults.

Methods: We conducted a phase 1, randomized, dose-escalation, placebo-controlled trial in 42 volunteers, 18-45 years of age, and 40 out of 42 received a single dose of LY-CovMab or placebo with LY-CovMab at a dose of 30 mg, 150 mg, 600 mg, 1200 mg, and 2400 mg. There were ten subjects in each group receiving LY-CovMab or placebo in a 4:1 ratio with the exception that the 30 mg group had two subjects both receiving LY-CovMab.

Results: Among the 42 randomized participants, 40 received an injection with 32 administered LY-CovMab and 8 administered placebo. A total of 18 drug-related treatment-emergent adverse events (TEAEs) were reported in 12 subjects (30.0%), including protein urine present (25%, 10/40) and blood creatinine increased (7.5%, 3/40). The incidence of drug-related TEAE in each dosage group was as follows: 150 mg (28.6%, 2/7), 600 mg (25%, 2/8), 1200 mg (14.3%, 1/7), 2400 mg (50%, 4/8), and placebo (37.5%, 3/8). All drug-related TEAEs were grade 1, and most of them were recovering/resolving or recovered/resolved without taking action. The serum exposure of LY-CovMab (Cmax, AUC0-last, AUC0-inf) after intravenous infusion increased in an approximately proportional manner as the dose increased from 150 to 2400 mg. The elimination half-life (t1/2) value did not differ among different dose cohorts and was estimated to be around 28.5 days.

Conclusions: A single dose of LY-CovMab was shown to be safe and well tolerated in Chinese healthy adults. The pharmacokinetic (PK) profiles of LY-CovMab in healthy adults showed typical monoclonal antibody distribution and elimination characteristics. LY-CovMab demonstrated dose proportionality.

Trial registration: ClinicalTrial.gov Identifier NCT04973735.

Keywords: COVID-19; Immunogenicity; LY-CovMab; Monoclonal neutralizing antibody; Pharmacokinetics; SARS-CoV-2; Safety.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Study design and flow diagram. Note: (1) Full analysis set (FAS) was defined as subjects who were randomized. (2) Safety set (SS) was defined as subjects who were randomized and received at least one dose of study drug. (3) Pharmacokinetics concentration set (PKCS) was defined as subjects who received at least one dose of study drug and had at least one evaluable serum concentration. (4) Pharmacokinetics parameter set (PKPS) was defined as subjects who received at least one dose of study drug and had sufficient serum concentration data to obtain at least one PK parameter and had no major protocol deviations that affected the evaluation of PK parameters. (5) Immunogenicity analysis set (IAS) was defined as subjects who received at least one dose of study drug and had at least one evaluable data point of immunogenicity after administration
Fig.2
Fig.2
Mean (± standard deviation [SD]) of LY-CovMab serum concentration–time profiles in healthy participants following single-dose intravenous infusions at 150 mg, 600 mg, 1200 mg, and 2400 mg: a linear scale and b semi-log scale

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Source: PubMed

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