Healthy Adult
Conditions
Brief summary
This is a Phase Id, randomised, double-blind, placebo-controlled, multiple-dose, bridging study conducted at a single Phase I clinical research unit in Australia. The study is designed to evaluate the pharmacokinetics, safety, tolerability, and immunogenicity of XKH001 following repeated subcutaneous administration in healthy adult Caucasian participants, and to provide an ethnic-bridging pharmacokinetic comparison with the prior Phase I dataset in Chinese participants, required for XKH001's global development programme.
Detailed description
The study will consist of two cohorts of healthy adult Caucasian participants. Cohort 1 will receive XKH001 300 mg subcutaneously once every 4 weeks (Q4W) on Day 1, Day 29, and Day 57... Cohort 2 will receive XKH001 600 mg subcutaneously Q4W on Day 1, Day 29, and Day 57. Dosing will be initiated sequentially, with Cohort 1 (300 mg) dosed first, followed by Cohort 2 (600 mg). Dosing in Cohort 2 will not commence earlier than 21 days after the first participant in Cohort 1 receives the first dose and may proceed only following joint review of the available Cohort 1 safety data and unanimous agreement by the Sponsor's medical representative, the Medical Monitor, and the Principal Investigator A total of 16 healthy adult Caucasian participants will be enrolled in the study, with 8 participants per cohort. Within each cohort, participants will be randomised in a 3:1 ratio (6 active drug XKH001; 2 placebo) in a double-blind manner. Randomisation will be performed using a cohort-specific block randomisation schedule to maintain allocation concealment and treatment balance within each cohort. Enrolment will not be stratified by sex; however, at least 3 female participants will be enrolled in each cohort to ensure adequate female representation and to ensure that at least 1 female participant receives the investigational drug.
Interventions
DRUGXKH001 Injection
XKH001, developed by Zhejiang Kanova Biopharmaceutical Co., Ltd., is a recombinant anti-IL-25 humanized IgG1 monoclonal antibody (mAb) composed of two identical light chains and two identical heavy chains linked by disulfide bonds. Each light chain consists of 215 amino acids, and each heavy chain consists of 455 amino acids, for a total of 1340 amino acids.
Placebo；
Sponsors
Zhejiang Kanova Biopharmaceutical Co., LTD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy participants who voluntarily provide written informed consent and can comply with all study procedures according to the protocol. 2. Male or female participants of Caucasian ethnicity(both biological parents and all four grandparents of Caucasian origin), 18-65 years of age (inclusive). 3. Body mass index (BMI) between 18.0-32.0 kg/m² (inclusive). 4. Vital signs, physical examination, clinical laboratory tests, and 12-lead electrocardiogram (ECG) within normal limits or considered not clinically significant by the investigator, with QTcF ≤450 ms. 5. No use of prescription or over-the-counter medications within 4 weeks prior to first dosing. 6. Participants must meet the sex- and reproductive-status-specific contraception and gamete-donation requirements specified in Appendix 2. Where contraception is required, the participant must agree to use the protocol-specified established effective contraception from the time of signing the informed consent form until 7 months after the last dose of study drug.
Exclusion criteria
1. Pregnant or breastfeeding women. 2. Any clinically significant disease within 5 years that could affect participation (gastrointestinal, renal, hepatic, pulmonary, neurology, Haematology, endocrine, oncology, metabolic, psychiatric, or cerebrovascular). 3. History of autoimmune disease, known hereditary immunodeficiency, or recurrent infections suggesting immunodeficiency. 4. Active infection requiring hospitalisation or IV antibiotics within 3 months, or clinically symptomatic bacterial, viral, or fungal infection within 4 weeks prior to first dosing. 5. Active or latent tuberculosis infection. 6. HBsAg positive, HCV antibody positive, syphilis antibody positive, or HIV antigen/antibody positive. 7. Live or attenuated vaccine within 4 weeks prior to dosing or planned during trial. 8. Participation in any clinical trial within 3 months or 5 half-lives of the investigational drug (whichever is longer) prior to dosing. 9. History of allergy to the investigational drug, any formulation component, or protein-based drugs. 10. Alcohol consumption \>14 units/week within 6 weeks prior to screening, or alcohol-containing products within 1 day before dosing (1 unit = 8 g or 10 mL of pure alcohol). 11. Drug abuse or illicit substance use within 5 years, or positive urine drug screen(A positive cotinine result alone is not exclusionary). 12. Smoking history (\>5 cigarettes/day) within 3 months prior to screening. 13. Blood donation or loss \>450 mL within 8 weeks, or \>200 mL blood donation or \>300 mL blood loss within 1 month. 14. Unsuitable venous access or intolerance of venipuncture. 15. Prior exposure to any anti-IL-25 therapeutic agent, including XKH001 or any other investigational or approved therapeutic agent targeting IL-25. 16. Any other reason deemed unsuitable by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Outcome 1 | Day 1, Day 29, and Day 57 | Maximum observed serum concentration at steady state (Cmax,ss) |
| Primary Outcome 2 | Day 1, Day 29, and Day 57 | Minimum observed serum concentration at steady state (Cmin,ss) |
| Primary Outcome 3 | Day 1, Day 29, and Day 57 | Average serum concentration at steady state (Cavg,ss) |
| Primary Outcome 4 | Day 1, Day 29, and Day 57 | Area under the serum concentration-time curve from time zero to the last quantifiable concentration at steady state (AUC0-t,ss) |
| Primary Outcome 5 | Day 1, Day 29, and Day 57 | Area under the serum concentration-time curve from time zero to the theoretical infinite time at steady state (AUC0-inf,ss) |
| Primary Outcome 6 | Day 1, Day 29, and Day 57 | Area under the serum concentration-time curve over one dosing interval at steady state (AUCtau) |
| Primary Outcome 7 | Day 1, Day 29, and Day 57 | Time to maximum observed serum concentration at steady state (tmax,ss) |
| Primary Outcome 8 | Day 1, Day 29, and Day 57 | Terminal elimination half-life at steady state (t½,ss) |
| Primary Outcome 9 | Day 1, Day 29, and Day 57 | Mean residence time at steady state (MRTss) |
| Primary Outcome 10 | Day 1, Day 29, and Day 57 | Terminal elimination rate constant (λz,ss) |
| Primary Outcome 11 | Day 1, Day 29, and Day 57 | Percent of extrapolated area under the curve (%AUCex) |
| Primary Outcome 12 | Day 1, Day 29, and Day 57 | Accumulation ratio based on Cmax and AUC (Rac) |
| Primary Outcome 13 | Day 1, Day 29, and Day 57 | Apparent clearance at steady state (CLss/F) |
| Primary Outcome 14 | Day 1, Day 29, and Day 57 | Apparent volume of distribution at steady state (Vz,ss/F) |
| Primary Outcome 15 | first dose administration through Day 169 | Incidence, severity, seriousness, and relationship to study treatment of treatment-emergent adverse events (TEAEs) |
| Primary Outcome 16 | first dose administration through Day 169 | Incidence, severity, seriousness, and relationship to study treatment of treatment-emergent serious adverse events (SAEs) |
| Primary Outcome 17 | first dose administration through Day 169 | Incidence, severity, seriousness, and relationship to study treatment of treatment-emergent adverse drug reactions (ADRs) |
| Primary Outcome 18 | first dose administration through Day 169 | Incidence, severity, seriousness, and relationship to study treatment of treatment-emergent suspected unexpected serious adverse reactions (SUSARs) |
| Primary Outcome 19 | first dose administration through Day 169 | Incidence and severity of local injection-site reactions following subcutaneous administration of XKH001 or placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Outcome 1 | Day 1, Day 29, and Day 57, and during follow-up visits on Day 85, Day 113, and Day 169. | Incidence of anti-drug antibodies (ADA) to XKH001, including neutralising antibody (NAb) status for confirmed ADA-positive samples |
| Secondary Outcome 2 | Day 1, Day 29, and Day 57, and during follow-up visits on Day 85, Day 113, and Day 169. | Prevalence of anti-drug antibodies (ADA) to XKH001, including neutralising antibody (NAb) status for confirmed ADA-positive samples |
| Secondary Outcome 3 | Day 1, Day 29, and Day 57, and during follow-up visits on Day 85, Day 113, and Day 169. | Characterisation of anti-drug antibodies (ADA) to XKH001, including neutralising antibody (NAb) status for confirmed ADA-positive samples |
Countries
Australia
Contacts
CONTACTJiangguo You
CONTACTYaxin Li
Outcome results
None listed