XKH001 Injection in Healthy Subjects

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Asthma
• Intervention / Treatment: Drug: XKH001 Injection; Drug: XKH001 Placebo Injection

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jianguo You, MHA; Phone Number: 010-82176552; Email: jianguo.you@kanovabiopharma.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: XKH001 Injection; Cohort 1: 100 mg Q4W (D1, D29, D57) 6subjects Cohort 2: 300 mg Q4W (D1, D29, D57) 6subjects Cohort 3: 600 mg Q4W (D1, D29, D57) 6subjects The Sponsor will discuss with the investigator to decide whether to conduct the 4th to 5th cohorts (e.g., 600 mg Q14D, 600 mg Q8W, and the specific dose regimen will be determined at that time) no later than the completion of the safety assessment for Cohort 3.	Drug: XKH001 Injection; 100mg/ml，1ml/vial; Other Names: XKH001
Placebo Comparator: XKH001 Placebo Injection; Cohort 1: 100 mg Q4W (D1, D29, D57) 6subjects Cohort 2: 300 mg Q4W (D1, D29, D57) 6subjects Cohort 3: 600 mg Q4W (D1, D29, D57) 6subjects The Sponsor will discuss with the investigator to decide whether to conduct the 4th to 5th cohorts (e.g., 600 mg Q14D, 600 mg Q8W, and the specific dose regimen will be determined at that time) no later than the completion of the safety assessment for Cohort 3.	Drug: XKH001 Placebo Injection; 1ml/vial; Other Names: XKH001 Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AEs) and serious adverse events (SAEs);	Incidence of adverse events (AEs) and serious adverse events (SAEs);	From baseline to 24 weeks of follow-up
laboratory tests 1	general condition	From baseline to 24 weeks of follow-up
laboratory tests 2	skin and mucosa	From baseline to 24 weeks of follow-up
laboratory tests 3	lymph nodes	From baseline to 24 weeks of follow-up
laboratory tests 4	head	From baseline to 24 weeks of follow-up
laboratory tests 5	neck	From baseline to 24 weeks of follow-up
laboratory tests 6	chest	From baseline to 24 weeks of follow-up
laboratory tests 7	abdomen	From baseline to 24 weeks of follow-up
laboratory tests 8	spine/extremities	From baseline to 24 weeks of follow-up
observation of injection site	The specific time of observation of injection site reactions is 2 h (± 30 min) post-dose and 4 h (± 30 min) post-dose.	2 h (± 30 min) post-dose and 4 h (± 30 min) post-dose
Vital signs	Vital signs include temperature, pulse, and blood pressure. Vital signs will be measured within 60 min before dosing, 2 h (± 30 min), 4 h (± 30 min) after dosing on each dosing day (D1, or D29, or D57); at other visits, vital signs should be measured once.	From baseline to 24 weeks of follow-up
Hematology	Hematology should include hemoglobin, red blood cell (RBC) count, mean corpuscular hemoglobin, mean corpuscular volume, platelet count, white blood cell (WBC) count, and absolute and percentage of NEUT, LYM, and EOS.	From baseline to 24 weeks of follow-up
Blood chemistry	Blood chemistry should include fasting glucose, total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, total protein, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase, total bilirubin, direct bilirubin, indirect bilirubin, gamma-glutamyl transpeptidase, creatinine, urea, sodium, potassium, calcium, inorganic phosphorus, chloride, serum lipase, and serum amylase.	From baseline to 24 weeks of follow-up
Hematology includes: activated partial thromboplastin time (APTT), international normalized ratio (INR), and prothrombin time (PT).	Hematology includes: activated partial thromboplastin time (APTT), international normalized ratio (INR), and prothrombin time (PT).	From baseline to 24 weeks of follow-up
Three items of thyroid function	Three items of thyroid function should include: FT3, FT4 and TSH.	From baseline to 24 weeks of follow-up
Urinalysis	Urinalysis should include specific gravity, potential of hydrogen (pH), glucose, bilirubin, urobilinogen, protein, ketones, and occult blood.	From baseline to 24 weeks of follow-up
12-lead ECGs	12-lead ECGs will be performed at screening, 60 min (± 10 min), 30 min (± 10 min), 15 min (± 10 min) pre-dose on D1, 4 h (± 30 min) post-dose on D1, 4 h (± 30 min) post-dose on D15, D28, and D29, 4 h (± 30 min) post-dose on D43, D56, and D57, and on D58 (approximately 24 h), D59 (approximately 48 h), D61 (approximately 96 h), D64 (approximately 168 h), D71 (approximately 336 h), D85 (approximately 672 h), D113 (approximately 1344 h), D141 (approximately 2016 h), and D169 (approximately 2688 h); before dosing on D1, 3 ECGs should be obtained each time, with an interval of 1-2 min. ECGs from D58 to D169 should be completed within 10 min before PK blood sampling at the current visit for 3 consecutive times, with an interval of approximately 1-2 min.	From baseline to 24 weeks of follow-up
Infectious disease	Infectious disease testing should include 5 items of hepatitis B serology (hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B e antigen, hepatitis B e antibody, hepatitis B core antibody), hepatitis C antibody, treponema pallidum antibody, and HIV antigen/antibody. If the subject is negative for HBsAg, positive for HBcAb, and negative for HBsAb, HBV DNA testing is also required.	From baseline to 24 weeks of follow-up
Anteroposterior chest X-ray	Anteroposterior chest X-ray obtained within 3 months before screening is acceptable, and abdominal color ultrasonography obtained within 1 month before screening is acceptable.	From baseline to 24 weeks of follow-up
PK Cmax	Cmax,ss（Maximum observed concentration）	From baseline to 24 weeks of follow-up
PK Cmin	Cmin,ss（Minimum observed concentration）	From baseline to 24 weeks of follow-up
PK Cavg	Cavg,ss（Mean observed concentration）	From baseline to 24 weeks of follow-up
PK AUC0-inf	AUC0-inf,ss（Area under the serum concentration-time curve from zero to infinity）	From baseline to 24 weeks of follow-up
PK AUC0-t	AUC0-t,ss（Area under the serum concentration-time curve from zero to t）	From baseline to 24 weeks of follow-up
PK Tmax	Tmax,ss（Time of observed）	From baseline to 24 weeks of follow-up
PK t1/2	t1/2,ss（Terminal half-life）	From baseline to 24 weeks of follow-up
PK AUCtau	area under the serum concentration-time curve at steady state (AUCtau)	From baseline to 24 weeks of follow-up
PK %AUCex	percentage of extrapolated area under the serum concentration-time curve from zero to infinity at steady state (%AUCex)	From baseline to 24 weeks of follow-up
PK λz	elimination rate constant of serum concentration in the terminal phase (λz,ss)	From baseline to 24 weeks of follow-up
PK Rac	drug accumulation ratio (Rac)	From baseline to 24 weeks of follow-up
PK Vz	volume of distribution at steady state (Vz,ss/F)	From baseline to 24 weeks of follow-up
PK CL	clearance at steady state (CLss/F)	From baseline to 24 weeks of follow-up
PK MRT	mean residence time (MRT)	From baseline to 24 weeks of follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total IgE;	Total Immunoglobulin E（IgE）;	From baseline to 24 weeks of follow-up
EOS count in whole blood;	Eosinophil（EOS） count in whole blood;	From baseline to 24 weeks of follow-up
NEUT count in whole blood;	Neutrophil（NEUT） count in whole blood;	From baseline to 24 weeks of follow-up
Blood LYM count;	Blood Lymphocyte(LYM) count;	From baseline to 24 weeks of follow-up
Levels of IL-25-related cytokines in serum	Levels of IL-25-related cytokines in serum (multiple cytokine panel includes: IL-25, TARC, IL-8, MIP1β, Eotaxin, CXCL1 (KC/GROα), Eotaxin-3);	From baseline to 24 weeks of follow-up
ADA	Incidence of anti-drug antibodies (ADAs).	From baseline to 24 weeks of follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
QT/QTc	Relationship between multiple-dose serum concentrations and QTcF	From baseline to 24 weeks of follow-up

Collaborators and Investigators

• Sponsor: Beijing Kanova Biopharmaceutical Co., LTD
• Investigators: Principal Investigator: Yanhua Ding, The First Hospital of Jilin University

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: July 24, 2023
• First Submitted That Met QC Criteria: August 7, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Estimated): November 3, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: XKH001-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No