Dataset Information

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.

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 (C_max, AUC_0-last, AUC_0-inf) after intravenous infusion increased in an approximately proportional manner as the dose increased from 150 to 2400 mg. The elimination half-life (t_1/2) 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.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC8651971 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

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.

Zhang Qian Q Zhou Renpeng R Yang Jingjing J Dou Changlin C Gan Tianyi T Liu Fujia F Hu Baihui B Song Deyong D Lu Chao C Hu Wei W

Infectious diseases and therapy 20211208 1

<h4>Introduction</h4>We aimed to evaluate the safety, tolerability, pharmacokinetics, and immunogenicity of a single dose of LY-CovMab in Chinese healthy adults.<h4>Methods</h4>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 i ...[more]

PMID: 34878625

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Project description:Ibrexafungerp (code name in China: HS-10366) is a first-in-class and orally active triterpenoid antifungal agent with broad antifungal activity against Candida spp., Aspergillus spp., and other fungal pathogens. It was approved by the U.S. Food and Drug Administration for the treatment of vulvovaginal candidiasis. The study aimed to evaluate the safety, tolerability, and pharmacokinetic (PK) characteristics of oral ibrexafungerp in healthy Chinese adults. A single-center, randomized, double-blind, placebo-controlled single ascending dose (SAD, n = 42), and multiple ascending dose (MAD, n = 28) study was conducted in healthy Chinese subjects from March to October 2022. There were three cohorts in the SAD stage (300, 600, and 1,500 mg) and two cohorts in the MAD stage [450 mg once daily (QD) for 7 days; a loading dose of 750 mg twice daily (BID) for the first 2 days followed by a maintenance dose of 750 mg QD for consecutive 5 days]. Eligible participants in each cohort were randomly assigned in a 6:1 ratio to receive either ibrexafungerp or placebo orally. The primary objectives were to evaluate the safety and tolerability. The secondary objective was to evaluate PK parameters, including Cmax, AUC, and t1/2. A total of 70 healthy Chinese subjects were enrolled in the study. The mean (SD) age was 29.0 (6.32), and 55.7% were male. All treatment-emergent adverse events (TEAEs) were mild or moderate. There were no serious adverse events, and no subjects were discontinued from the study due to TEAEs. All TEAEs were recovered or resolved. The most common TEAEs were diarrhea, abdominal pain, and nausea. In the SAD stage, Cmax, and AUC increased in an approximately dose-proportional manner in the dose range of 300-1,500 mg. The mean t1/2 was within 18.29-21.30 hours. In the MAD stage, an accumulation of exposure (Cmax and AUC) was observed following multiple doses. This phase 1 study demonstrates a favorable safety, tolerability, and PK profile of ibrexafungerp in healthy Chinese subjects.

Dataset Information

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.

Introduction

Methods

Results

Conclusions

Trial registration

Publications

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.

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