XKH001 Injection in Healthy Subjects

NCT05991661 | Completed Phase 1 FDA Drug

• 1 other identifier: XKH001-102
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (33)

• 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 Outcomes (6)

• Total IgE;

  From baseline to 24 weeks of follow-up

• EOS count in whole blood;

  From baseline to 24 weeks of follow-up

• NEUT count in whole blood;

  From baseline to 24 weeks of follow-up

• Blood LYM count;

  From baseline to 24 weeks of follow-up

• Levels of IL-25-related cytokines in serum

  From baseline to 24 weeks of follow-up

Other Outcomes (1)

• QT/QTc

  From baseline to 24 weeks of follow-up

Study Arms (2)

XKH001 Injection

ACTIVE COMPARATOR

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

XKH001 Placebo Injection

PLACEBO COMPARATOR

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

Interventions

XKH001 Injection DRUG

100mg/ml，1ml/vial

Also known as: XKH001

XKH001 Injection

XKH001 Placebo Injection DRUG

1ml/vial

Also known as: XKH001 Placebo

XKH001 Placebo Injection

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy subjects who voluntarily sign a written informed consent form (ICF) and are able to complete the study as required by the protocol;
• Male or female subjects aged 18 to 65 years (inclusive);
• Subjects with BMI between 18 and 28 kg/m2 (inclusive);
• Subjects with normal or abnormal but not clinically significant results of vital signs, physical examinations, laboratory tests, 12-lead ECGs and QTcF ≤ 450 ms;
• Subjects who did not use any prescription or over-the-counter medications within two weeks prior to dosing;
• 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.

You may not qualify if:

• Pregnant or lactating women;
• 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.;
• Subjects with history of autoimmune diseases, known family history of inherited immunodeficiency disorders, or recurrent infections suggestive of possible immunodeficiency;
• 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;
• Subjects with a history of active tuberculosis or subjects with active or latent tuberculosis infection at screening;
• 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;
• Subjects who plan to receive live or live attenuated vaccines within 4 weeks prior to dosing or during the study;
• 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;
• 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;
• 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;
• 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;
• Subjects who have a smoking history (\> 5 cigarettes/day) within 3 months prior to screening;
• 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;
• Subjects with obstructed venous access or intolerance to venipuncture;
• Subjects who are considered inappropriate for the study by the investigator.

Sponsors & Collaborators

• Beijing Kanova Biopharmaceutical Co., LTD: lead

Study Sites (1)

The First Hospital of Jilin University Phase I Clinical Research Center

Changchun, Jilin, 130000, China

Location

Related Publications (1)

• Zhang H, Zheng W, Peng R, Wu D, Hu Y, Sun T, Gao L, Liu Y, Guo L, Ding Y, Liu L. First-in-human study on tolerability, pharmacokinetics and pharmacodynamics of single and multiple escalating doses of XKH001, a recombinant humanized monoclonal antibody against IL-25 in healthy Chinese volunteers. Expert Opin Investig Drugs. 2025 Jan-Feb;34(1-2):81-87. doi: 10.1080/13543784.2025.2453162. Epub 2025 Jan 20.

  PMID: 39815604 DERIVED

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Yanhua Ding

  The First Hospital of Jilin University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2023
• First Posted: August 14, 2023
• Study Start: May 12, 2023
• Primary Completion: February 20, 2024
• Study Completion: March 29, 2024
• Last Updated: March 5, 2026

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)