Drug design, development and therapy · 2025
The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Subcutaneous Administration of a Novel Anti-NGF Monoclonal Antibody (AK115) in Healthy Participants: A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Phase I Clinical Trial.
СтатьяРандомизированное исследованиеКлиническое исследование I фазыНазвание и аннотация: Перевод в очереди
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Zhang Juan, Fan Yu-Xin, Huang Yu, Guan Runfang, Li Ruixia, Long Shuxian, Yang Mei, Yu Binge, Wang Guo Qin, Chen Peng, Gong Xia, Li Baiyong, Xia Michelle, He Jianchang
Аннотация
OBJECTIVE: This study aimed to investigate the safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of a novel anti-nerve growth factor (NGF) monoclonal antibody (mAb) (AK115) in healthy Chinese participants.
METHODS: A randomized, double-blind, placebo-controlled, dose-escalation phase I clinical study was conducted as follows: eligible participants were divided into 6 dose groups, among which 0.5 mg group was administrated with AK115 injection and the remaining 5 groups were randomly assigned to AK115 injection or accompanying placebo at a ratio of 3:1. Adverse events (AEs), PKs, PDs, and anti-drug antibodies (ADAs)/neutralizing antibody were monitored throughout the study.
RESULTS: A total of 42 participants completed the study. Twenty-seven (64.3%) participants occurred treatment emergent AEs (TEAEs), and 2 (4.80%) participants experienced treatment-related TEAEs. The TEAEs among the different dose groups were comparable. No significant differences were observed between the combined AK115 and the placebo group. It was demonstrated that the median Tmax was 4.50-14.0 days, the mean Cmax and AUC0-t of different doses groups were 30.8-5500 ng/mL and 792~181010 Day*ng/mL, respectively. The elimination half-life (t1/2) did not differ among the different dose groups and was calculated to be 7.60-17.7 days. In addition, the total NGF concentration and percentage change from baseline increased with an increase in the AK115 dose. No ADA positivity was detected in the healthy participants.
CONCLUSION: The favorable safety and tolerability of AK115 in healthy Chinese participants, as well as the predictable PK and PD profiles, will provide sufficient support for future dose exploration studies of AK115 in patients with analgesia.
TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (CTR20220431) and the official website of the US Department of Health and Human Services, National Institutes of Health, with Clinical Trials. gov (NCT05286970) on March 2022.
METHODS: A randomized, double-blind, placebo-controlled, dose-escalation phase I clinical study was conducted as follows: eligible participants were divided into 6 dose groups, among which 0.5 mg group was administrated with AK115 injection and the remaining 5 groups were randomly assigned to AK115 injection or accompanying placebo at a ratio of 3:1. Adverse events (AEs), PKs, PDs, and anti-drug antibodies (ADAs)/neutralizing antibody were monitored throughout the study.
RESULTS: A total of 42 participants completed the study. Twenty-seven (64.3%) participants occurred treatment emergent AEs (TEAEs), and 2 (4.80%) participants experienced treatment-related TEAEs. The TEAEs among the different dose groups were comparable. No significant differences were observed between the combined AK115 and the placebo group. It was demonstrated that the median Tmax was 4.50-14.0 days, the mean Cmax and AUC0-t of different doses groups were 30.8-5500 ng/mL and 792~181010 Day*ng/mL, respectively. The elimination half-life (t1/2) did not differ among the different dose groups and was calculated to be 7.60-17.7 days. In addition, the total NGF concentration and percentage change from baseline increased with an increase in the AK115 dose. No ADA positivity was detected in the healthy participants.
CONCLUSION: The favorable safety and tolerability of AK115 in healthy Chinese participants, as well as the predictable PK and PD profiles, will provide sufficient support for future dose exploration studies of AK115 in patients with analgesia.
TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (CTR20220431) and the official website of the US Department of Health and Human Services, National Institutes of Health, with Clinical Trials. gov (NCT05286970) on March 2022.