Clinical trial NCT05991661: XKH001 Injection in Healthy Subjects
Official title: A Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Phase Ib Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of XKH001 Injection in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Asthma
Lead sponsor: Zhejiang Kanova Biopharmaceutical Co., LTD
Sponsor class: INDUSTRY
First posted: 2023-08-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: This study is a randomized, double-blind, placebo-controlled, multiple ascending dose (MAD) clinical study. The primary objective is to evaluate the safety, tolerability, and PK of multiple SC doses of XKH001 in healthy subjects.

Detailed description: A total of 5 cohorts are planned, with 8 subjects (6 on XKH001 and 2 on placebo) in each cohort. The dosing schedule for the first 3 cohorts is as follows:

Cohort Dosing Regimen

1. 100 mg Q4W (D1, D29, D57)
2. 300 mg Q4W (D1, D29, D57)
3. 600 mg Q4W (D1, D29, D57) After completion of a 6-week safety observation (D1\~D43) in the previous cohort, the safety data will be reviewed (blinded) by the investigator and the Sponsor to assess the safety and tolerability of the investigational product. If the dose regimen for the previous cohort is confirmed to be safe and tolerable, dose escalation will continue to the next cohort.

The Sponsor will discuss with the investigator to decide whether to conduct the 4th to 5th cohorts (e.g., 600 mg Q14D, and the specific dose regimen will be determined at that time) no later than the completion of the safety assessment for Cohort 3.

Healthy subjects will be screened within 7 days prior to the first dose and successfully screened subjects will be assigned to the currently ongoing cohort and randomized to receive XKH001 or placebo. Subjects will be admitted to the study site the day before each scheduled dose (D-1, or D28, or D56), complete necessary pre-dose safety assessments, receive SC injection of XKH001 or placebo on D1, or D29, or D57, respectively, and continue to undergo regular safety assessment procedures and other blood sampling (PK, PD, and ADA) after dosing.

Subjects will also undergo comprehensive safety assessments on D15, D43, D71, D85, D113, D141 and D169, including AEs/serious adverse events (SAEs), vital signs, physical examinations, laboratory tests (hematology, blood chemistry, coagulation, urinalysis), 12-lead ECG, etc. Safety data as of D43 will be used by the Sponsor and investigator to assess the safety and tolerability of the investigational product.

If a subject discontinues treatment prematurely, the "Early Withdrawal" visit and all procedures will be performed as on D169.

Eligibility criteria: Inclusion Criteria:

1. Healthy subjects who voluntarily sign a written informed consent form (ICF) and are able to complete the study as required by the protocol;
2. Male or female subjects aged 18 to 65 years (inclusive);
3. Subjects with BMI between 18 and 28 kg/m2 (inclusive);
4. Subjects with normal or abnormal but not clinically significant results of vital signs, physical examinations, laboratory tests, 12-lead ECGs and QTcF ≤ 450 ms;
5. Subjects who did not use any prescription or over-the-counter medications within two weeks prior to dosing;
6. Subjects who agree to have no child-bearing plans and to voluntarily take effective contraception measures during the study and within 6 months after the end of the study.

Exclusion Criteria:

1. Pregnant or lactating women;
2. Subjects with clinically significant diseases that may affect the subject's participation in this study within 5 years as judged by the investigator: including but not limited to gastrointestinal, renal, liver, lung, neurological, blood, endocrine, tumor, metabolic, psychiatric or cardio-cerebrovascular diseases, etc.;
3. Subjects with history of autoimmune diseases, known family history of inherited immunodeficiency disorders, or recurrent infections suggestive of possible immunodeficiency;
4. Subjects with active infections requiring hospitalization or IV antibiotic treatment within 3 months prior to dosing, or bacterial, viral and fungal infections with clinical symptoms within 1 week;
5. Subjects with a history of active tuberculosis or subjects with active or latent tuberculosis infection at screening;
6. Subjects with positive HBsAg in 5 items of hepatitis B serology (if HBsAg is negative, HBcAb is positive, and HBsAb is negative, HBV DNA quantitative test is required to be performed \[the subject will be excluded if the test result is positive\]), positive hepatitis C antibody, treponema pallidum antibody, HIV antigen/antibody;
7. Subjects who plan to receive live or live attenuated vaccines within 4 weeks prior to dosing or during the study;
8. Subjects who have participated in clinical studies of any drug or device within 3 months or 5 half-lives of the investigational product (whichever is longer) prior to dosing;
9. Subjects who are allergic to the investigational product or any component of the formulation of the investigational product or have a history of allergy to protein drugs;
10. Subjects who have consumed more than 14 units of alcohol per week (1 unit of alcohol = 360 mL of beer or 45 mL of spirits containing 40% alcohol or 150 mL of wine) within 6 weeks prior to screening or have taken alcoholic products 1 day before dosing;
11. Subjects who have a history of abuse of other drugs within 5 years prior to screening, or who have a positive urine drug screen result;
12. Subjects who have a smoking history (\> 5 cigarettes/day) within 3 months prior to screening;
13. Subjects who have blood donation or blood loss of more than 450 mL within 8 weeks prior to screening, or blood donation of more than 200 mL or blood loss of more than 300 mL within 1 month;
14. Subjects with obstructed venous access or intolerance to venipuncture;
15. Subjects who are considered inappropriate for the study by the investigator.

Primary outcomes:
measure: Incidence of adverse events (AEs) and serious adverse events (SAEs);
timeFrame: From baseline to 24 weeks of follow-up
measure: laboratory tests 1
timeFrame: From baseline to 24 weeks of follow-up
measure: laboratory tests 2
timeFrame: From baseline to 24 weeks of follow-up
measure: laboratory tests 3
timeFrame: From baseline to 24 weeks of follow-up
measure: laboratory tests 4
timeFrame: From baseline to 24 weeks of follow-up
measure: laboratory tests 5
timeFrame: From baseline to 24 weeks of follow-up
measure: laboratory tests 6
timeFrame: From baseline to 24 weeks of follow-up
measure: laboratory tests 7
timeFrame: From baseline to 24 weeks of follow-up
measure: laboratory tests 8
timeFrame: From baseline to 24 weeks of follow-up
measure: observation of injection site
timeFrame: 2 h (± 30 min) post-dose and 4 h (± 30 min) post-dose
measure: Vital signs
timeFrame: From baseline to 24 weeks of follow-up
measure: Hematology
timeFrame: From baseline to 24 weeks of follow-up
measure: Blood chemistry
timeFrame: From baseline to 24 weeks of follow-up
measure: Hematology includes: activated partial thromboplastin time (APTT), international normalized ratio (INR), and prothrombin time (PT).
timeFrame: From baseline to 24 weeks of follow-up
measure: Three items of thyroid function
timeFrame: From baseline to 24 weeks of follow-up
measure: Urinalysis
timeFrame: From baseline to 24 weeks of follow-up
measure: 12-lead ECGs
timeFrame: From baseline to 24 weeks of follow-up
measure: Infectious disease
timeFrame: From baseline to 24 weeks of follow-up
measure: Anteroposterior chest X-ray
timeFrame: From baseline to 24 weeks of follow-up
measure: PK Cmax
timeFrame: From baseline to 24 weeks of follow-up
measure: PK Cmin
timeFrame: From baseline to 24 weeks of follow-up
measure: PK Cavg
timeFrame: From baseline to 24 weeks of follow-up
measure: PK AUC0-inf
timeFrame: From baseline to 24 weeks of follow-up
measure: PK AUC0-t
timeFrame: From baseline to 24 weeks of follow-up
measure: PK Tmax
timeFrame: From baseline to 24 weeks of follow-up
measure: PK t1/2
timeFrame: From baseline to 24 weeks of follow-up
measure: PK AUCtau
timeFrame: From baseline to 24 weeks of follow-up
measure: PK %AUCex
timeFrame: From baseline to 24 weeks of follow-up
measure: PK λz
timeFrame: From baseline to 24 weeks of follow-up
measure: PK Rac
timeFrame: From baseline to 24 weeks of follow-up
measure: PK Vz
timeFrame: From baseline to 24 weeks of follow-up
measure: PK CL
timeFrame: From baseline to 24 weeks of follow-up
measure: PK MRT
timeFrame: From baseline to 24 weeks of follow-up
Secondary outcomes:
measure: Total IgE;
timeFrame: From baseline to 24 weeks of follow-up
measure: EOS count in whole blood;
timeFrame: From baseline to 24 weeks of follow-up
measure: NEUT count in whole blood;
timeFrame: From baseline to 24 weeks of follow-up
measure: Blood LYM count;
timeFrame: From baseline to 24 weeks of follow-up
measure: Levels of IL-25-related cytokines in serum
timeFrame: From baseline to 24 weeks of follow-up
measure: ADA
timeFrame: From baseline to 24 weeks of follow-up
Other outcomes:
measure: QT/QTc
timeFrame: From baseline to 24 weeks of follow-up
Locations:
Study officials:
affiliation: The First Hospital of Jilin University
name: Yanhua Ding
role: PRINCIPAL_INVESTIGATOR
References: