Abstract
Introduction
We evaluated the pharmacokinetics (PK), safety, and efficacy of ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, in Chinese patients with moderate-to-severe psoriasis.
Methods
In this phase 1, multicenter, open-label study, adults (≥ 18 years) diagnosed with moderate-to-severe plaque psoriasis for ≥ 6 months involving ≥ 10% of their body surface area received ixekizumab 80 mg by subcutaneous injection and were observed for 20 weeks (single-dose phase) and then an initial dose of 160 mg followed by randomization (1:1) to 80 mg ixekizumab every 2 weeks (IXE Q2W) or every 4 weeks (IXE Q4W) for an 8-week treatment period (multiple-dose phase).
Results
The median time to maximum observed ixekizumab concentrations occurred 2–4 days after dosing and the geometric mean half-life was 15–16 days, after single (n = 12) and multiple (n = 29) doses. Approximately linear pharmacokinetics were observed between the 80 and 160 mg single doses. Steady-state systemic exposure to ixekizumab during a dosing interval was similar with the IXE Q2W and IXE Q4W regimens, with estimates of 224 µg·day/mL and 213 µg·day/mL for the area under the concentration–time curve from time 0 to 14 days post-dose and 0 to 28 days post-dose, respectively. Safety was consistent with the established safety profile of ixekizumab. At week 12 after multiple doses, the proportions of patients achieving a 75% or 90% improvement in Psoriasis Area and Severity Index score were 100% and 86% for IXE Q2W, respectively, and 93% and 80% for IXE Q4W, respectively. A Static Physician’s Global Assessment score of 0 or 1 was achieved in 100% and 87% with IXE Q2W and IXE Q4W, respectively.
Conclusions
The PK of ixekizumab in Chinese patients with moderate-to-severe plaque psoriasis was comparable to findings in global populations. After IXE Q2W or IXE Q4W for 12 weeks, clinically relevant treatment responses and an acceptable safety profile were observed.
Trial Registration
Clinicaltrials.gov (NCT03073213).
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Acknowledgements
Funding
This study was sponsored by Eli Lilly and Company. Eli Lilly and Company was involved in the study design, data collection, data analysis, and preparation of the manuscript. The study sponsor paid the Rapid Service Fee.
Medical Writing and/or Editorial Assistance
The authors would like to thank all study participants and Hongying Li for statistical review of the manuscript. Medical writing assistance was provided by ProScribe, Rudehealth and Zipei Xiao from Eli Lilly and Company. This manuscript complied with international guidelines for Good Publication Practice (GPP3).
Author Contributions
All authors participated in the interpretation of study results, and in the drafting, critical revision, and approval of the final version of the manuscript. Feng Wang, Kimberley Jackson, and Fan Yang were involved in designing the study. Min Zheng, Xiang Chen, and Jie Zheng were study investigators. Min Zheng, Xiang Chen, Jisu Chen, and Jie Zheng were involved in data collection. Fan Yang, HongYing Li and Kimberley Jackson were involved in the statistical and pharmacokinetic analyses. YiHui Wang, ZiPei Xiao and Christopher Payne were involved in the data analyses and explanation, respectively.
Prior Presentation
Summaries of the results from this study have been presented as a poster at the American Academy of Dermatology - 78th Annual Meeting and also as an oral presentation at the Chinese Society of Dermatology - 26th Annual Meeting.
Disclosures
Min Zheng, Xiang Chen, Jisu Chen, and Jie Zheng have been investigators for Eli Lilly and Company. Feng Wang, Kimberley Jackson, Fan Yang, Christopher Payne, HongYing Li, YiHui Wang and ZiPei Xiao are employees and shareholders of Eli Lilly and Company.
Compliance with Ethics Guidelines
The study protocol was approved by Ethics Review Boards at each study center (Ruijin Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine Medical Ethics Committee, No. 272, South Chongqing Road, Shanghai, 200025; Xiangya Hospital of Central South University Medical, Ethics Committee, No. 87 Xiangya Road, Changsha, 410008, China; Second Affiliated Hospital of Zhejiang University School of Medicine Ethics Committee, No. 88 Jiefang Road, Hangzhou, 310009, China) and the study was carried out in accordance with the Declaration of Helsinki of 1964 and its later amendments. Patients provided written informed consent before inclusion.
Data Availability
Lilly provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the US and EU and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once data are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, blank or annotated case report forms, will be provided in a secure data sharing environment. For details on submitting a request, see the instructions provided at https://www.vivli.org.
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Zheng, M., Chen, X., Wang, F. et al. Pharmacokinetics, Safety, and Efficacy of Ixekizumab in Chinese Patients with Moderate-to-Severe Plaque Psoriasis: A Phase 1, Single- and Multiple-Dose Study. Adv Ther 40, 3804–3816 (2023). https://doi.org/10.1007/s12325-023-02575-1
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DOI: https://doi.org/10.1007/s12325-023-02575-1