Pharmacokinetics, Safety, and Immunogenicity of Intravenous and Subcutaneous Single-Dose QX002N Injection in Healthy Subjects: A Randomized, Open, Parallel, Single-Center, Phase I Study

Abstract

Introduction

Interleukin-17A (IL-17A) plays a crucial role in the pathogenesis of ankylosing spondylitis (AS), although not all patients respond to traditional IL-17A antibody treatments. QX002N injection, as a new monoclonal antibody targeting IL-17A, has shown potential in treating AS, offering a new treatment option for patients who do not respond well to existing therapies.

Methods

A randomized, open, parallel, single-center, phase I study was conducted to assess the pharmacokinetics, safety, and immunogenicity of single doses of QX002N injection administered intravenously (IV) or subcutaneously (SC) to healthy Chinese volunteers. Blood samples were collected at specified time intervals, and then serum concentrations of QX002N were analyzed by enzyme-linked immunosorbent assay.

Results

Pharmacokinetic analysis of the drug concentration–time data showed that the mean maximum observed serum QX002N concentration (C_max) was 110 and 33.9 µg/ml, respectively. The average area under the drug concentration–time curves from 0 to the time of the last quantifiable concentration (AUC_last) were 52,656 and 36,269 µg·h/ml, respectively and the average area under the drug concentration–time curves from 0 to infinity (AUC_inf) were 54,867 and 38,194 µg·h/ml, respectively. The absolute bioavailability of QX002N after SC injection was 69.6%.

Conclusions

Immunogenicity was assessed and all the subjects in this study were Anti-drug antibody (ADA)-negative, which means no subjects appeared to develop immunogenicity to QX002N. All the results testify to the safety of QX002N injection, which is satisfactory after IV or SC dosing in healthy subjects.

Trial Registration

www.chinadrugtirals.org.cn, CTR20220430.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40744-024-00683-0.

Key Summary Points

Why carry out this study?

Interleukin-17 (IL-17A) is pivotal in the pathogenesis of ankylosing spondylitis (AS), a chronic inflammatory disease with an appreciable economic burden and unmet medical needs due to limitations in current treatment efficacy.

The study aimed to evaluate the pharmacokinetics, safety, and immunogenicity of QX002N, a novel anti-IL-17A monoclonal antibody, to determine its potential as a therapeutic agent for AS.

What was learned from the study?

QX002N displayed a satisfactory safety profile with no serious adverse events and demonstrated promising pharmacokinetics, including a 69.6% bioavailability after SC administration.

The findings suggest that QX002N is a viable anti-IL-17A antibody for clinical application in AS, warranting further research and consideration for its role in therapeutic protocols.

Introduction

Ankylosing spondylitis (AS) is an immune-mediated chronic inflammatory disease characterized by inflammation of the sacroiliac joints and spinal attachment points. It predominantly affects axial joints, such as the sacroiliac joints and spine, and surrounding tissues like tendons and ligaments. This results in inflammatory back pain, stiffness, limitations in sexual function, and eventual changes in joint structure, leading to new bone formation, joint fusion, and disability [1]. The whole course of the disease is irreversible [2]. Despite a wide range of available treatments including non-steroidal anti-inflammatory drugs (NSAIDs), traditional synthetic disease-modifying anti-rheumatic drugs (DMARDs), glucocorticoids, and biological DMARDs (bDMARDs), many patients experience suboptimal control of symptoms and progression, highlighting substantial unmet medical needs [3]. The limitations in treatment efficacy underscore the necessity for more effective therapeutic options.

In recent years, research findings from animal models, human tissue sample cytokine analysis, whole-genome analysis, and clinical trials of drugs provide strong evidence that the IL-23/IL-17 immune axis is implicated in the pathogenesis of AS [4, 5]. IL-17A plays an important role during the pathophysiological process of AS by promoting the activation of neutrophils, macrophages, epithelial cells, and fibroblasts. Therefore, IL-17A may be an important target for treating AS [6]. Several studies have investigated the fact that IL-17A blockers can specifically bind to IL-17A cytokine, thereby neutralizing the activity of IL-17A to inhibit the inflammatory cascade associated with the IL-17A pathway [7, 8]. Currently developed drugs like secukinumab and ixekizumab, which are both selective high-affinity monoclonal antibodies against human IL-17A, show promising results for the treatment of AS and have been approved for the treatment of AS in the United States [9–12].

However, the differences in the efficacy of different individuals and the adverse reactions of some patients to existing IL-17A inhibitors led us to develop a novel high-affinity humanized IgG1 monoclonal antibody QX002N [13, 14]. QX002N specifically binds to IL-17A, blocking the interaction of IL-17AA and IL-17AF with the IL-17RA receptor. This action inhibits IL-17AA and IL-17AF-mediated signaling, subsequently reducing the secretion of chemokines and inflammatory cytokines such as CXCL-1, IL-6, and IL-8 by target cells [15, 16]. Previous studies have demonstrated that QX002N has superior binding affinity to IL-17A compared to secukinumab, suggesting enhanced inhibition capabilities. Additionally, QX002N exhibits equivalent affinity to ixekizumab, indicating that it is at least as effective in binding IL-17A, with potential for improved clinical outcomes [17].

The initial phase Ia dose-escalation study conducted in healthy volunteers revealed that QX002N was safe and well tolerated across a dose range of 10–320 mg, with drug exposure increasing proportionally with the dose. According to the literature, the bioavailability of secukinumab is about 55–77% after subcutaneous injection, and the absolute bioavailability of ixekizumab is about 60–81% [11, 12]. The selected dose of 240 mg for future studies was based on achieving an optimal balance between bioavailability, safety, and therapeutic effect, which is expected to mirror or surpass the bioavailability of similar treatments, such as secukinumab and ixekizumab [17].

This study aims to further evaluate the pharmacokinetic characteristics, safety, and immunogenicity of QX002N and to compare the absolute bioavailability of subcutaneous injection with intravenous infusion in healthy subjects. These insights will establish a foundational understanding necessary for advancing QX002N into later-stage clinical trials for AS (Trial registration: www.chinadrugtrials.org.cn, CTR20220430).

Methods

Study Population

Chinese volunteers, aged 18–50 years, with body mass index (BMI) values of 18–28.0 kg/m², body weight ≥ 45 kg (female) and ≥ 50 kg (male), were eligible to participate in the study (Table 1). After comprehensive examination, including vital signs, physical examination, laboratory examination, 12-lead electrocardiogram, abdominal color ultrasound and chest radiograph, all subjects were judged to be healthy. The key exclusion criteria included: prior use of IL-17 monoclonal medications; severe hypersensitivity to drugs; significant engagement in smoking, alcohol, or drug misuse; a background of sexually transmitted diseases, tuberculosis; recent blood loss exceeding 400 ml; being a female subject currently pregnant or breastfeeding. For details of the study protocol, see the Supplementary Materials.

Table 1.

Demographic characteristics of the study

Item	QX002N 240 mg SC group	QX002N 240 mg IV group
Sex (n (%))
Male	9 (75.0%)	10 (83.3%)
Female	3 (25.0%)	2 (16.7%)
Race (n (%))
Han	11 (91.7%)	11 (91.7%)
Others	1 (8.3%)	1 (8.3%)
Age (years) [mean (SD)]	30.5 (7.98)	34.5 (9.44)
Height (cm) [mean (SD)]	169.13 (7.840)	164.54 (5.719)
Body weight (kg) [mean (SD)]	69.82 (11.495)	64.53 (9.070)
BMI (kg/m2) [mean (SD)]	24.35 (3.260)	23.89 (3.503)

IV intravenous infusion, SC subcutaneous injection, SD standard deviation, BMI body mass index

Study Design

We conducted a randomized, open, parallel, single-dose, single-center, phase I clinical study. In this study, QX002N injection is supplied as a sterile single-use injection containing 100 mg (1 ml) per vial. Subjects were screened 2–30 days prior to the administration of the study drug. Twenty-four healthy subjects were randomly assigned to SC group or IV group in a 1:1 ratio, with 12 cases in each group, and admitted to the clinical trial center on D-1. Subjects received a single SC or IV inject of 240 mg of QX002N on D1. During the observation period, safety assessment, PK blood collection, or anti-drug antibody (ADA) blood collection were performed. All subjects were discharged at D6 and they were required to return to the clinical trial center for follow-up at D8, D11, D15, D22, D29, D43, D57, D71, D85, D106, and D127. Safety assessment, PK blood collection, or ADA blood collection were performed at each site until to the end of D127.

This study was carried out in Shulan (Hangzhou) Hospital and conducted in accordance with the Good Practice for Quality Management of Clinical Trials (GCP), the current Declaration of Helsinki (2013), relevant regulations, and Ethics Committee reviews. The protocol, informed consent, and amendments were approved by the ethical Review Committee of Shulan (Hangzhou) Hospital (2021–26). All subjects signed written informed consent forms before participating.

Investigational Product Administration

Subjects were admitted to the phase I drug clinical trial unit at baseline (D-1) and left on D6, during which they were fed a uniform diet. Food was not allowed to be provided at least 8 h before drug administration. Subjects received the investigational drug on an empty stomach on D1. During the administration of the drug, subjects were prohibited from drinking water for 1 h before and after dosing. After the dosing was completed, subjects were allowed to consume a standardized breakfast approximately 1 h later. During the first hour after administration, subjects should remain in a lying position and limit their movement away from the bed. After 1 h of post-dose, subjects can resume normal indoor activities but should avoid excessive physical activity or prolonged bed rest. Throughout the entire observation period of the study, subjects must refrain from consuming tea, coffee, or other caffeinated beverages, as well as abstain from smoking.

There are two administration methods in this experiment. In the SC group, subjects received a single dose of 240 mg of QX002N in a volume of 2.4 ml with subcutaneous injection. In the IV group, subjects received a single dose of 240 mg of QX002N in a volume of 2.4 ml with intravenous drip administration, and the infusion time is at least 1 h to avoid rapid intravenous bolus. After administration, subjects should be observed for possible infusion-related reactions.

Pharmacokinetic Assessment

To characterize the PK profile of QX002N injection after drug administration, approximately 4 ml of blood samples were collected from subjects following the collection time points in each dose group: 0 h (within 60 min before dosing) and 1 h after the start of dosing (immediately after dosing, IV only), 2 h (IV only), 4 h, 8 h, 12 h, 24 h (day 2), 48 h (day 3), 72 h (day 4), D5 (96 h), D6 (120 h), D8 (168 h), D11 (240 h), D15 (336 h), D22 (504 h), D29 (672 h), D43 (1008 h), D57 (1344 h), D71 (1680 h), D85 (2016 h), D106 (2520 h) and D127 (3024 h). There were 20 blood collection points in the SC group, and a total of 80 ml of whole blood was collected. There were 22 blood collection points in the IV group, and a total of 88 ml of whole blood was collected.

The serum QX002N concentration data at different time points were measured to calculate the PK parameters with PhoenixTM WinNonlin software (version 8.2, Certara Inc., Princeton, NJ, USA) using non-compartmental analysis (NCA) method, including: Maximum concentration (C_max); Area under the curve from time zero to the time of the last quantifiable concentration (AUC_last); Area under the curve from time zero to infinity (AUC_inf); Time to reach C_max (T_max); Terminal elimination half-life (t_1/2); Terminal elimination rate constant (K_el); Volume of distribution (V_z); Apparent volume of distribution (V_z/F); Clearance/apparent clearance (CL, CL/F); Percentage of the area under the curve that is extrapolated from the last time point to infinity (AUC_{_%Extrap}); Mean residence time from time zero to the time of the last quantifiable concentration (MRT_last); Absolute bioavailability (F_abs). In this analysis, the PK parameters of QX002N in different dose groups were statistically summarized.

Immunogenicity Assessment

Intravenous blood samples of about 4 ml were collected in each dose group at the following time points: 0 h (within 60 min before administration) and D29 (672 h), D57 (1344 h), D85 (2016 h), D127 (3024 h) after administration. A total of five blood sampling points were used to detect anti-drug antibodies (ADA).

The analysis of immunological data was based on the immunogenicity analysis population and included changes in levels of ADA. Neutralizing antibody (NAb) testing is necessary when ADA is positive, antibody associated AE is produced, or PK values are significantly abnormal.

Safety Assessments

In the Ia clinical trial of QX002N injection, two adverse events (AEs) were observed, including hypertriglyceridemia, urinary tract infection, upper respiratory tract infection, elevated blood bilirubin, increased aspartate aminotransferase levels, reduced white blood cell and neutrophil counts, hyperuricemia, hyperkalemia, hematuria, proteinuria, and hyperglycemia. As a result, high-risk individuals are excluded from this protocol, and clear criteria for subject withdrawal and trial termination are specified. Risk management measures are diligently implemented, and AEs are closely monitored throughout the trial.

The safety analysis is based on the safety analysis population (SS). The study classified AEs based on the Chinese version of the International Medical Dictionary of Terms (MedDRA) version 25.1 coding system utilized by the pharmacy administration. AEs were sorted by the quantity of occurrences, frequency, and the total number of instances based on the coded System Organ Classification (SOC) and Preferred Terminology (PT), respectively.

For any adverse event (AE) or serious adverse event (SAE) that occurred during the clinical study, the AE name, clinical features, severity, occurrence time and end time, treatment method and outcome, and correlation with the study drug should be recorded. Assessment was made by vital signs, physical examination, laboratory tests (blood routine, blood biochemistry, urine routine, coagulation routine), 12-lead electrocardiogram, injection site reactions, infusion-related reactions, and other safety checks (pregnancy).

Statistical Analysis

Randomized analysis population: All subjects who were randomized into the group.

Safety analysis population (SS): All subjects who received the investigational drug and had at least one safety assessment. Subjects were grouped according to the actual investigational drug for safety analysis.

Pharmacokinetic concentration analysis population (PKCS): All participants who received randomization, used the study drug, and had at least one observable PK concentration constituted the pharmacokinetic concentration analysis population for this study.

Pharmacokinetic parameter analysis population (PKPS): All subjects who received randomization, used the study drug, and had at least one accurate calculation of PK parameters constituted the pharmacokinetic parameter analysis population of the study.

Immunogenicity analysis population: All subjects who received randomization, used study drugs, and had post-administration immunogenicity evaluation data constituted the immunogenicity analysis population of this study.

General analysis: Descriptive statistical work was performed using SAS® (version 9.4, SAS Institute Inc., Cary, NC, USA) software and R (version 4.0.5, R Core Team (2021), R Foundation for Statistical Computing, Vienna, Austria) software. Data processing, descriptive statistical analysis, and mapping were performed using Phoenix™ WinNonlin software (version 8.2, Certara Inc., Princeton, NJ, USA) for non-compartmental analysis (NCA).

For continuous variables (except PK parameters), descriptive statistics include the arithmetic mean, standard deviation, median, quartile (Q1, Q3), minimum, and maximum. For subtype variables, descriptive statistics include the number of subjects and percentage (retain 1 decimal place). For PK parameters, descriptive statistics include the number of non-missing observations, the mean (arithmetic mean, geometric mean), standard deviation, coefficient of variation (CV%, including arithmetic CV%, geometric CV%), median, Q1, Q3, minimum, and maximum. For time-related parameters, such as T_max, only the median, maximum, and minimum values are reported.

Pharmacokinetic analysis: Based on PKCS, the blood concentration data of QX002N were tabulated and descriptive statistics were summarized according to the treatment group and sampling time specified in the protocol.

Immunogenicity analysis: Analysis of immunological data was based on an immunogenicity analysis population.

Bioanalytical Methods

Serum QX002N concentration was determined using a proven quantitative assay based on enzyme-linked immunosorbent assay. All biological samples were analyzed in acceptable batches. The anti-QX002N antibody in human serum was detected by a methodologically validated electrochemical luminescence method. All biological samples were analyzed in acceptable batches.

Results

Study Subjects

A total of 72 subjects were screened in this study, and a total of 24 subjects including 19 male subjects (79.2%) and five female subjects (20.8%) were enrolled (see Fig. 1). All 24 subjects completed the experiment, and no study termination occurred. Twenty-two (91.7%) of the subjects were Han, and the remaining two (8.3%) were ethnic minorities, of which one is Manchu and one is Dong. The demographics and baseline characteristics analysis of the subjects are shown in Table 1. Demographic characteristics were generally similar between each group [18].

Fig. 1.

Flow chart of subject disposition. N number of samples, IV intravenous infusion, SC subcutaneous injection

Pharmacokinetics and Immunogenicity

In this study, a total of 487 serum concentration measurements were obtained from 24 healthy subjects. The mean serum concentration–time curve (linear and semi-logarithmic coordinates) of healthy subjects after a single intravenous or subcutaneous infusion of 240 mg QX002N is shown in Fig. 2. After a single dose, the mean serum concentration of QX002N in group IV decreased gradually. The mean serum concentration of QX002N in SC group was firstly increased and then decreased. In Fig. 1, the end elimination phase curves of group IV and group SC were roughly parallel, indicating that the end elimination rates of QX002N were similar under the two administration routes.

Fig. 2.

Mean serum concentration–time profiles following intravenous (IV) or subcutaneous (SC) injection of 240 mg of QX002N. The error bars indicate the standard deviations (SD) (up: linear coordinates; down: semi-logarithmic coordinates). IV intravenous infusion, SC subcutaneous injection

In this study, 24 subjects treated with QX002N were included in PK analysis, and the summary results of PK parameters in each group are shown in Table 2. After a single intravenous infusion or subcutaneous injection of 240 mg QX002N, exposure to QX002N was tested. As measured, the mean C_max was 110 and 33.9 µg/ml, respectively; the average AUC_last were 52,656 and 36,269 µg·h/ml, respectively; the average AUC_inf were 54,867 and 38,194 µg·h/ml, respectively. The CV% of C_max and AUC in group IV was 14.9–19.3%, and the CV% of C_max and AUC in group SC was 30.1–33.8%. By comparing the two sets of data, the results showed that compared to intravenous infusion, C_max, AUC_last, and AUC_inf of QX002N after subcutaneous injection is lower and more interindividual with moderate variability. This is mainly due to the significant differences in the absorption rate and extent of absorption of QX002N after subcutaneous injection among the subjects.

Table 2.

Summary of pharmacokinetic concentration set data

PK parameter	n	SC group (N = 12)	n	IV group (N = 12)	n
Cmax (µg/ml)	12	110 ± 16.3 (14.9%)	11a	33.9 ± 10.2 (30.1%)	12
Tmax (h)	12	4.00 (1.00, 24.00)	11a	239.65 (120.00, 674.55)	12
AUClast (µg·h/ml)	12	52,656 ± 9119 (17.3%)	11a	36,269 ± 11,427 (31.5%)	12
Tlast (h)	12	3047.73 (3023.25, 3242.67)	12	3048.07 (3023.37, 3407.17)	12
AUCinf (µg·h/ml)	12	54,867 ± 10,590 (19.3%)	11a	38,194 ± 12,918 (33.8%)	12
CL (ml/h)	12	4.53 ± 0.931 (20.5%)	0	NA	0
Vz (ml)	12	3978 ± 505 (12.7%)	0	NA	0
CL/F (ml/h)	0	NA	11a	6.97 ± 2.46 (35.3%)	12
Vz/F (ml)	0	NA	11a	6265 ± 1619 (25.8%)	12
t1/2 (h)	12	626 ± 129 (20.6%)	12	644 ± 121 (18.8%)	12
MRTlast (h)	12	771 ± 94.0 (12.2%)	11a	901 ± 116 (12.9%)	12
Fabs (%)	0	NA	12	69.6	12

C_max maximum concentration, T_max time to reach C_max, AUC_last area under the curve from time zero to the time of the last quantifiable concentration, T_last the last quantifiable concentration time, AUC_inf area under the curve from time zero to infinity, CL total clearance, V_z volume of distribution, CL/F apparent clearance, V_z/F apparent volume of distribution, t_1/2 terminal elimination half-life, MRT_last mean residence time from time zero to the time of the last quantifiable concentration, F_abs absolute bioavailability, NA not applicable, IV intravenous infusion, SC subcutaneous injection, h hours, N number of samples, n number of samples included in descriptive statistics

^aDue to the epidemic, 1004 subject in SC group failed to visit the center at D22, and the PK blood samples could not be collected. The missing blood drug concentration may be C_max, so their C_max, T_max, AUC_last, MRT_last, AUC_inf, CL/F and V_z/F may not be calculated accurately and are not included in descriptive statistics

The absolute bioavailability of QX002N by subcutaneous injection was 69.6%. According to the data, the absolute bioavailability of secukinumab by subcutaneous injection was about 55–77% [19]. Based on population pharmacokinetic analysis, the absolute bioavailability of another target drug, ixekizumab, was about 60–81% by subcutaneous injection [20]. It is shown that the absolute bioavailability of QX002N by subcutaneous injection is quite satisfying and the absorption degree of QX002N by subcutaneous injection is similar to that of the same target drug. The median T_max was 4.00 h by intravenous infusion, indicating rapid absorption. However, the median T_max was 239.65 h by subcutaneous infusion, which means that the absorption of QX002N was slow after subcutaneous injection. The mean t_1/2 after a single intravenous infusion or subcutaneous injection of QX002N was 626 and 644 h (about 26 and 27 days), respectively, which demonstrated the slow elimination from blood following administration, and the MRT_last was 771 h and 901 h respectively, suggesting that QX002N was eliminated slowly under both routes. The average CL and CL/F were 4.53 and 6.97 ml/h, respectively. The average Vz and Vz/F were 3978 and 6265 ml, respectively.

The sensitivity analysis was also measured and the results were shown in Table 2. It is shown that the absolute bioavailability of QX002N for subcutaneous injection was 69.6%. The absorption of QX002N after a single subcutaneous injection in healthy subjects was slow, with a median T_max of about 10 days. The mean t_1/2 of QX002N was similar after a single intravenous infusion and subcutaneous injection at 626 and 644 h, respectively.

The immunogenicity of biological drugs is a major concern for their clinical application, because of the effects on PK and PD of drugs. A total of 24 subjects were included in the immunogenicity analysis. ADA was negative at all sampling points in all subjects in this study.

Safety

In this study, adverse events (AEs) were typical with no deaths or serious symptom recruiting healthy subjects. Fifteen of the 24 subjects had 27 adverse events (AE), with an incidence of 62.5% (15/24). Among them, there was one subject from the IV group with elevated blood triglycerides, four subjects from the SC group with elevated blood triglycerides, decreased neutrophil count, and decreased white blood cell count. The remaining 20 AE were grade 1 AEs. All AEs were untreated and resolved on their own. The incidence of AE on group SC and IV was 91.7% (11/12, 21 cases) and 33.3% (4/12, six cases), respectively.

The incidence of adverse drug reaction (ADR) in the SC group was 50% (6/12, ten cases), and no ADR occurred in IV group. The incidence of ten ADR cases in the SC group was from high to low according to SOC: 25.0% (3/12) for all kinds of examinations; systemic disease and various reactions at the administration site were 16.7% (2/12); diseases of heart organs, infections and infective diseases, skin and subcutaneous tissue diseases, blood and lymphatic system diseases were 8.3% (1/12). According to the classification of PT, there was one case (8.3%, 1/12) of all AE, which were: decreased neutrophil count, elevated body temperature, urine protein detection, elevated blood triglyceride, hypoesthesia at injection site, chest discomfort, palpitation, upper respiratory infection, rash, and lymphadenopathy. Two of the ADR cases were grade II with decreased neutrophil count and elevated blood triglycerides, and the rest were grade I.

No adverse reactions occurred at the injection site except one patient in the SC group. No infusion-related reactions occurred in group IV. No subjects died during the study period, and no subjects withdrew from the trial early due to AE, suggesting that the possibility of ADAs is very low after drug administration.

The study on QX002N injection showed that it was well tolerated and safe, with no serious adverse events or discontinuations (TEAEs).

Discussion

In a phase I study targeting ankylosing spondylitis (AS), we conducted a detailed examination of the pharmacokinetics and safety of a single 240-mg dose of QX002N, administered both intravenously and subcutaneously. Notably, after subcutaneous administration, the median time to reach maximum plasma concentration (T_max) extended to approximately 10 days, indicating prolonged release and absorption. This suggests the possibility of reducing dosing frequency, thereby enhancing convenience and acceptability for patients. Additionally, with half-lives of about 626 h (26 days) for intravenous administration and 644 h (27 days) for subcutaneous administration, the slow clearance of the drug from the body supports potential monthly dosing schedules, which could significantly improve patient compliance and quality of life. These pharmacokinetic findings affirm that subcutaneous injection offers comparable efficacy to intravenous delivery, underscoring its feasibility for long-term disease management. Moreover, both administration routes were well tolerated, establishing the safety of the subcutaneous method and reinforcing its clinical utility. QX002N’s extended half-life and potential to reduce side effects distinctly differentiate it from existing therapies and highlight its suitability for managing AS, where maintaining consistent treatment adherence poses significant challenges.

The absolute bioavailability of QX002N post-subcutaneous injection (69.6%) compares favorably with that reported for secukinumab and ixekizumab [11, 12]. This high bioavailability indicates that QX002N can achieve effective therapeutic levels with potentially reduced dosing frequency compared to these established competitors. Moreover, the pharmacodynamic properties of QX002N, which demonstrate higher binding affinity and potent inhibition of IL-17A, provide a theoretical basis for improved clinical efficacy and patient outcomes compared to existing IL-17A inhibitors [17].

The negative ADA results provide preliminary favorable evidence for the safety and efficacy of QX002N, but these findings need to be confirmed through more extensive clinical studies and continued monitoring for potential immune responses.

This study’s limitations are that current subject group, consisting only of healthy, young Chinese adults, may not adequately represent the diverse global population of patients with AS, especially those with more severe conditions or who are older. Future studies should therefore include multi-dose, long-term research across varied ethnic backgrounds and disease severities. Moreover, directly comparing QX002N with secukinumab and ixekizumab will help determine its relative efficacy and safety profiles [21, 22]. Phase II and III clinical trials are also necessary to fully assess QX002N’s effects and safety across different patient groups, providing a solid scientific basis for its eventual clinical deployment.

In conclusion, the development of QX002N represents a promising advancement in the treatment of ankylosing spondylitis. Its superior pharmacokinetic properties, enhanced binding and neutralization of IL-17A, and favorable safety profile position it as a potentially more effective option for patients with AS. The continued evaluation of QX002N in phase II and beyond will be crucial in determining its ultimate role in clinical practice and its potential to improve the standard of care for patients with AS.

Conclusions

The phase I clinical trial results demonstrate that the novel IL-17A inhibitor QX002N exhibits favorable pharmacokinetics and safety profiles in healthy volunteers, providing scientific support for its further development in the treatment of ankylosing spondylitis. These findings support the continued evaluation of QX002N as a potential therapy to enhance patient compliance and treatment efficacy.

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contributions

Zhen-Wei Shen, Kai-Qi Wu, Min Fang, and Gui-Ling Chen designed the study. Zhen-Wei Shen, Kai-Qi Wu, Ting-Han Jin, and Tong Guo were responsible for data acquisition. Zhen-Wei Shen, Ting-Han Jin, Jie Zhao, and Qi Jiang contributed to the data analysis and interpretation. Zhen-Wei Shen, Jie Zhao, and Gui-Ling Chen drafted the manuscript.

Funding

This work was supported by Jiangsu Qyuns Therapeutics Co., Ltd. The publication costs, including the journal’s Rapid Service Fee, will be covered by Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University.

Data Availability

The individual participant data that underlie the results reported in this article will be shared after de-identification (text, tables, figures, and appendices). Study protocol will be available. Individual participant data will be available beginning 3 months and ending 1 year after publication. Supporting clinical documents, including study protocol, statistical analysis plan, and the informed consent form, will be available immediately following publication for at least 1 year. Researchers who provide a scientifically sound proposal will be allowed access to individual participant data. Proposals should be directed to gl.chen@zju.edu.cn. These proposals will be reviewed and approved by the funder, investigator, and collaborators on the basis of scientific merit. To gain access, data requesters will need to sign a data access agreement.

Declarations

Conflict of Interest

Zhen-Wei Shen, Kai-Qi Wu, Ting-Han Jin, Jie Zhao, Qi Jiang, Tong Guo, Min Fang, and Gui-Ling Chen have nothing to disclose.

Ethical Approval

The protocol, informed consent, and amendments were approved by the ethical Review Committee of Shulan (Hangzhou) Hospital(2021–26). All subjects signed written informed consent forms before participating. This study was conducted in accordance with the Good Practice for Quality Management of Clinical Trials (GCP), the current Declaration of Helsinki (2013), relevant regulations, and Ethics Committee reviews.