Phase I of XKH001Injection in Healthy Adults

NCT05128409 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: XKH001-101
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

XKH001is a recombinant humanized monoclonal IgG1 antibody for subcutaneous injection. XKH001 specifically blocks interleukin-25 from binding to its receptors. To evaluate the safety, tolerability, pharmacokinetics (PK) of single ascending doses of XKH001 injection following subcutaneous administration

Conditions

Healthy Adults

Outcome Measures

Primary Outcomes (18)

• Incidence of adverse events (AEs）

  Incidence of adverse events (AEs）

  from admission to discharge, up to 8 weeks

• Incidence of serious adverse events (SAEs)

  Incidence of serious adverse events (SAEs)

  from admission to discharge, up to 8 weeks

• AEs leading to termination of dose escalation

  AEs leading to termination of dose escalation

  from admission to discharge, up to 8 weeks

• Reported values and changes from baseline in clinical laboratory investigations (hematology）

  Hematology test will include hematocrit, hemoglobin, red blood cell count, platelet count, white blood cell and neutrophil count, lymphocytes, monocytes, eosinophils, platelet and basophils.

  from admission to discharge, up to 8 weeks

• Reported values and changes from baseline in clinical laboratory investigations (serum chemistry）

  Chemistry including sodium, potassium, chloride, creatinine, urea, blood glucose (baseline should check fasting blood glucose), serum albumin, calcium, magnesium, AST, ALT, ALP, LDH , total bilirubin, troponin, lipase and amylase will be tested.

  from admission to discharge, up to 8 weeks

• Reported values and changes from baseline in clinical laboratory investigations （ urinalysis)

  A Urinalysis testing for color/appearance, pH, specific gravity, glucose, protein, ketones, blood and bilirubin . Microscopic analysis (for casts, crystals, epithelial cells, bacteria, RBCs, and WBCs) should be performed if any abnormalities are detected. Urine cotinine test Urine drug tests include cocaine, methamphetamines, amphetamines, barbiturates, opiates, benzodiazepines, cotinine and cannabinoids. Women must have negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test at screening and urine pregnancy test prior to administration of study drug on Day -1.

  from admission to discharge, up to 8 weeks

• Reported values and changes from baseline in clinical laboratory investigations ( coagulation)

  International normalized ratio (INR) or Prothrombin time (PT) and partial thromboplastin time (PTT)

  from admission to discharge, up to 8 weeks

• vital signs (respiratory rate)

  respiratory rate

  from admission to discharge, up to 8 weeks

• vital signs (body temperature）

  body temperature

  from admission to discharge, up to 8 weeks

• vital signs (supine blood pressure)

  supine blood pressure

  from admission to discharge, up to 8 weeks

• vital signs (pulse)

  pulse

  from admission to discharge, up to 8 weeks

• 12-lead electrocardiograms (ECGs)

  12-lead electrocardiograms (ECGs)

  from admission to discharge, up to 8 weeks

• maximum serum concentration of XKH001

  maximum serum concentration of XKH001

  from admission to discharge, up to 8 weeks

• time to reach maximum serum concentration of XKH001

  time to reach maximum serum concentration of XKH001

  from admission to discharge, up to 8 weeks

• area under the serum concentration versus time curve from time zero to time t of XKH001

  area under the serum concentration versus time curve from time zero to time t of XKH001

  from admission to discharge, up to 8 weeks

• systemic clearance of XKH001

  systemic clearance of XKH001

  from admission to discharge, up to 8 weeks

• volume of distribution of XKH001

  volume of distribution of XKH001

  from admission to discharge, up to 8 weeks

• terminal half-life of XKH001

  terminal half-life of XKH001

  from admission to discharge, up to 8 weeks

Secondary Outcomes (1)

• To evaluate the immunogenicity of XKH001

  from admission to discharge, up to 8 weeks

Other Outcomes (2)

• To explore pharmacodynamic biomarkers including serum IgE level

  from admission to discharge, up to 8 weeks

• To explore pharmacodynamic biomarkers including blood eosinophil counts.

  from admission to discharge, up to 8 weeks

Study Arms (2)

XKH001 Injection

ACTIVE COMPARATOR

XKH001 Injection,hypodermic injection，single dose，5 dose cohorts: 0.5 mg/kg, 1.67 mg/kg, 3.34 mg/kg, 5.0 mg/kg and 10.0 mg/kg.

Drug: XKH001 Injection

XKH001 Placebo Injection

PLACEBO COMPARATOR

XKH001 Placebo Injection,hypodermic injection，single dose，4 dose cohorts: 1.67 mg/kg, 3.34 mg/kg, 5.0 mg/kg and 10.0 mg/kg.

Drug: XKH001Placebo Injection

Interventions

XKH001 Injection DRUG

0.5mg/kg: 3Subjects,1Sentinel Participants 1.67mg/kg: 6Subjects, ,1Sentinel Participants 3.34mg/kg: 6Subjects,1Sentinel Participants 5.0mg/kg: 6Subjects, ,1Sentinel Participants 10.0mg/kg: 6Subjects,1Sentinel Participants

Also known as: XKH001

XKH001 Injection

XKH001Placebo Injection DRUG

1.67mg/kg: 2Subjects,1Sentinel Participants 3.34mg/kg: 2Subjects,1Sentinel Participants 5.0mg/kg: 2Subjects,1Sentinel Participants 10.0mg/kg: 2Subjects, 1Sentinel Participants

Also known as: XKH001Placebo

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:

• Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures.
• Healthy male and female subjects, 18-65 years of age (inclusive).
• Body Mass Index (BMI) between 18 and 32.0 kg/m2.
• Generally, in good health, with no history of chronic or serious cardiovascular, hepatic, renal, respiratory, blood and lymphatic system, endocrine, immune, mental, neurological, psychiatric, gastrointestinal and allergic diseases.
• Vital signs, physical examination, clinical laboratory tests (CBC with differential, urinalysis, blood biochemistry, coagulation, pregnancy test (females), urine drug test and lipid panel , etc.), and 12-lead ECG should be within normal reference range or abnormal not clinically significant at screening and Admission (Day -1). For eligibility purposes, abnormal laboratory or vital signs results may be repeated once if abnormal result is observed at the initial reading. Moreover, Blood pressure must be within 90/50-140/90 mm/Hg. Respiratory rate must be within 12-18/minutes. Pulse must be within 60- 100/minute and the oral temperature must be \< 99.0 oF.
• No prescription or non-prescription drug within 14 days prior to the study drug administration and throughout the study.
• Women of non-childbearing potential defined as being surgically sterile (bilateral oophorectomy and hysterectomy) or menopause confirmed by FSH and Estradiol levels in accordance with local laboratory reference ranges.
• Women of childbearing potential who are not pregnant or breast-feeding must consent to use acceptable contraception (Section 5.3) during the study and for an additional 30 days after the administration of study drug.
• Men with a partner of childbearing potential must consent to use acceptable contraception (Section 5.3) during the study and for an additional 90 days after the administration of study drug.

You may not qualify if:

• Pregnant or breastfeeding woman.
• Within 5 years prior to the study, subjects with history of cardiovascular,respiratory, kidney, liver, metabolism, endocrine, gastrointestinal, blood, nerve, skin and mental illness, cancer or other major disease that in the judgement of the Investigator might put the subject at risk on this study.
• History of autoimmune disease.
• Known history or family history of hereditary immunodeficiency; History of recurrent infection suggestive of immune deficiency.
• Positive test at screening for human immunodeficiency virus antibody (HIV1/HIV2), hepatitis C antibody or hepatitis B virus surface antigen (HBsAg) or hepatitis B core antibody (HBcAb), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing.
• Significant infections requiring hospitalization or intravenous antibiotics or as judged by the investigator within 3 months prior to dosing. Symptomatic viral, bacterial (including upper respiratory infection), or fungal (including cutaneous) infection within 1 week prior to dosing.
• Received live or attenuated vaccines within 6 weeks prior to dosing, or plan to be vaccinated with live or attenuated vaccines during the study or within 6 weeks after dosing.
• Received any experimental drugs or devices or have participated in a clinical study within 60 days prior to admission.
• Allergy to study drug or components of its formulation or history of a Grade 3-4 allergic reaction to treatment with another protein product.
• Abuse on alcohol, cannabis- derived products or other drugs.
• Positive urine drug test (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, cotinine and opiates) at screening and admission.
• Smoking or use of other nicotine-containing products (snuff, chewing tobacco, cigars, pipes or nicotinereplacement products such as nicotine chewing gum and nicotine plasters) within 3 months prior to admission, or negative cotinine test at screening period and Day -1,or during the trial.
• Donated or lost ≥ 450 mL of blood or received blood transfusion or blood products within 8 weeks prior to admission or donated ≥200 mL of blood (blood components) or had blood loss (≥300 mL) within 1 month prior to admission.
• Poor venous access or inability to tolerate venipuncture.
• Any condition that the investigator or primary physician believes may not be appropriate for participating the study.

Sponsors & Collaborators

• Beijing Kanova Biopharmaceutical Co., LTD: lead

Study Sites (1)

The First Hospital of Jilin University Phase I Clinical Research Center

Changchun, 130000, China

Location

Study Officials

• Yanhua Ding, MD

  The First Hospital of Jilin University Phase I Clinical Research Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 5 dose cohorts: 0.5, 1.67, 3.34, 5.0 and 10.0 mg/kg. Three subjects will be enrolled in 0.5 mg/kg cohort (Cohort 1). All subjects in Cohort 1 will receive open-label XKH001. Eight subjects will be enrolled in the remaining dose cohorts (Cohort 2-5) and randomized to XKH001or placebo after baseline evaluations are completed. Subjects will be admitted to the clinical research center the day before the administration of study drug (Day -1) For the study treatment of Cohort 2-5, the Investigator and other clinical center staff will be blinded. Any off-site staff who are unblinded will have no contact with the study participants. Two sentinel participants (randomized in a 1:1 ratio) will be dosed 48 hours prior to dosing the remainders of Cohort 2-5 (n=6, randomized in a 5:1 ratio).

Study Record Dates

• First Submitted: October 13, 2021
• First Posted: November 22, 2021
• Study Start: March 7, 2023
• Primary Completion: October 1, 2024
• Study Completion: December 1, 2024
• Last Updated: April 12, 2023

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)