Safety and pharmacokinetics of IBI112, an IL-23 monoclonal antibody, in Chinese healthy volunteers: a first-in-human phase 1 study

ABSTRACT

Background

Interleukin (IL) 23p19 monoclonal antibodies were efficacious and safe in the treatment of psoriasis. A first-in-human (FIH) study was conducted to evaluate the safety, tolerability, pharmacokinetics (PK) and immunogenicity of IBI112, a novel IL-23p19 monoclonal antibody.

Methods

In this FIH, randomized, double-blind, placebo-controlled, single-ascending-dose study, a subcutaneous (SC, 5–600 mg) or intravenous (IV, 100 and 600 mg) or placebo was administered to eligible healthy subjects. Safety was assessed by physical examinations, vital signs, laboratory tests, and electrocardiograms. Furthermore, non-compartment analysis and population PK modeling were conducted to characterize PK, and model-based simulation was applied to justify dose selection for psoriasis patients.

Results

A total of 46 subjects were enrolled, with 35 receiving IBI112 and 11 receiving placebo. No serious adverse events (SAEs) and no clinically significant adverse events were identified. After a single SC of IBI112, the median T_max was 4–10.5 days, and the half-life (t_1/2) ranged from 21.8 to 35.8 days. IBI112 exposures (C_max and AUC_inf) approached dose proportionality across 5–300 mg range.

Conclusion

IBI112 was well tolerated and safe at SC or IV dose up to 600 mg and showed a linear PK characteristics at SC dose from 5 to 300 mg.

Clinical trial registration

ClinicalTrial.gov NCT04511624

KEYWORDS:

• IBI112
• anti-interleukin-23
• First-in-human
• Pharmacokinetics
• Safety

Declaration of interest

Weijuan Du, Chenghang Cai and Qingyang Ma are employees of Innovent Biologics, Inc. Jinjie He, Haijing Yang, Jingjing Wang, Nanyang Li, Jicheng Yu, Xiaojie Wu, Jufang Wu, Yuancheng Chen, Guoying Cao, and Jing Zhangare employees of Huashan Hospital Fudan University. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One peer reviewer has received research, speaking and/or consulting support from Eli Lilly and Company, GlaxoSmithKline/Stiefel, AbbVie, Janssen, Alovtech, vTv Therapeutics, Bristol-Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, Sun Pharma, Almirall, Galderma, Leo Pharma, Mylan, Celgene, Ortho Dermatology, Menlo, Merck & Co, Qurient, Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Teladoc, BMS, Ono, Micreos, Eurofins, Informa, UpToDate and the National Psoriasis Foundation. They are founder and part owner of Causa Research and holds stock in Sensal Health.

Peer reviewers in this manuscript have no other relevant financial relationships or otherwise to disclose.

Authors’ contributions

All authors contributed to the research conception and design. Jing Zhang and Guoying Cao are the principal investigators of the Phase I clinical study, who are responsible for the whole study management and data collection. Haijing Yang, Jufang Wu, and Nanyang Li are the study physicians of the study and are responsible for the safety evaluation of IBI112 in healthy subjects. Jicheng Yu, Xiaojie Wu, and Jinjie He are contributed to the drug and sample management. Weijuan Du and Chenghang Cai designed the research and analyzed the data. Jinjie He, Weijuan Du, and Qingyang Ma wrote the manuscript. All authors critically reviewed the manuscript and approved it for submission.

Acknowledgments

The authors thank all the subjects, their families, and all investigators and study site staff who are involved in this study.

Availability of data and material

The data of this study are not openly available due to sensitivity issues.

Code availability

The Monolixmodel code is available in the https://mlxtran.lixoft.com/model-libraries/library-of-pk-models/.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13543784.2023.2230122

Additional information

Funding

This manuscript was funded by Innovent Biologics, Inc., Clinical Research Plan of SHDC (SHDC2022CRW004) and National Science and Technology Major Projects for “Major New Drugs Innovation and Development” (2017ZX09304005).