A Study to Evaluate the Safety, PK, and Immunogenicity of Recombinant Human Hyaluronidase in Healthy Subjects

Official title

A Phase I Clinical Study to Evaluate the Safety, Pharmacokinetics, and Immunogenicity of Recombinant Human Hyaluronidase in Healthy Chinese Adult Male Subjects

Overview

The study is being conducted to evaluate the safety, pharmacokinetics, and immunogenicity of recombinant human hyaluronidase in healthy Chinese adult male subjects.

Interventions

• Drug recombinant human hyaluronidase
  HLXTE-HAase02 is a proprietary recombinant human hyaluronidase, with a molecular weight of approximately 49 kDa, is expressed in Chinese Hamster Ovary (CHO) cells and is intended for formulation development.

Primary outcome measures

• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: From enrollment to 21 days after the second dose]
• Incidence of hypersensitivity reactions [Time frame: From enrollment to 21 days after the second dose]
• Incidence of injection site reactions (ISRs) [Time frame: From enrollment to 21 days after the second dose]

Secondary outcome measures (10)

• Area under the concentration-time curve from time zero extrapolated to infinity (AUC0-inf) [Time frame: From enrollment to 21 days after the second dose]
• Area under the concentration-time curve from time zero to to the last measurable concentration (AUC0-t) [Time frame: From enrollment to 21 days after the second dose]
• Maximum serum concentration (Cmax) [Time frame: From enrollment to 21 days after the second dose]
• Time to maximum serum concentration (Tmax) [Time frame: From enrollment to 21 days after the second dose]
• Terminal elimination half-life (T1/2) [Time frame: From enrollment to 21 days after the second dose]
• Terminal elimination rate constant (λz) [Time frame: From enrollment to 21 days after the second dose]
• Extrapolation percentage of AUC (%AUCex) [Time frame: From enrollment to 21 days after the second dose]
• Positive rates of anti-drug antibodies (ADA) and neutralizing antibodies (NAb) [Time frame: From enrollment to 21 days after the second dose]
• Subcutaneous injection rate (mL/min) [Time frame: From enrollment to 21 days after the second dose]
• Mean of triplicate abdominal circumference measurements [Time frame: From enrollment to 21 days after the second dose]

Eligibility criteria

Inclusion criteria

• Healthy male subjects, aged ≥ 18 and ≤ 45 years.
• Body Mass Index (BMI) ≥ 18.0 and ≤ 28.0 kg/m².
• Intact skin at the injection site, with no damage, tattoos, or other markings.
• No significant medical history, or a history of abnormalities that, in the investigator's judgment, will not impact the study.
• Physical examination, vital signs, electrocardiogram (ECG), chest X-ray, and clinical laboratory tests are normal or abnormal without clinical significance (NCS).
• Subjects must agree to use highly effective contraception with their spouse or partner from the time of signing the Informed Consent Form (ICF) until 3 months after the last dose, or the subject is not capable of reproduction. Subjects must also refrain from sperm donation during the study and for 3 months following the last dose of the investigational product.
• Voluntarily signed the Informed Consent Form (ICF) prior to any study procedures, with a full understanding of the study content, procedures, and potential adverse events (AEs); and the ability to comply with the protocol requirements to complete the study.

Exclusion criteria

• History of drug abuse or or substance use, or a positive drug screen; history of long-term heavy alcohol consumption (defined as consuming more than 14 units of alcohol per week within 3 months prior to screening \[1 unit = 360 mL of beer, or 45 mL of spirits with 40% alcohol content, or 150 mL of wine\]) or a positive blood alcohol test; history of long-term heavy alcohol use or positive blood alcohol test; history of long-term heavy smoking (defined as an average of more than 5 cigarettes per day within 3 months prior to screening, or inability to abstain from smoking during the ).
• Cardiac disorders, including but not limited to clinically significant ECG abnormalities during the screening period, QTcF > 450ms, or a history of clinically significant ECG abnormalities.
• History of any clinically severe hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or oncological diseases, or allergic diseases.
• History of upper respiratory tract infection or other acute infections within 7 days prior to the first dose, or systemic use of antibiotics within 7 days.
• Known allergy to recombinant human hyaluronidase for injection or its formulation components; history of severe allergic reactions to any medication (e.g., angioedema); special dietary requirements or inability to comply with the standardized diet provided by the clinical site.
• Use of any prescription drugs, over-the-counter (OTC) medications, or herbal medicines within 4 weeks prior to screening (especially salicylates, cortisone, adrenocorticotropic hormone, estrogens, or antihistamines, except for routine vitamin supplements), or within 5 half-lives of the medication (whichever is longer).
• Vaccination within 1 month prior to administration.
• History of blood donation or blood loss ≥ 400 mL within 3 months prior to the use of the investigational product.
• Participation in any other clinical study and use of investigational/control products within 3 months prior to the investigational product administration.
• Positive for HBsAg, anti-HCV, anti-HIV, or the syphilis spirochete test.
• Sensory-motor disorders or autonomic movement disorders.
• Any condition which, in the investigator's judgment, would make the subject unable to comply with the protocol requirements, instructions, or study restrictions, such as an uncooperative attitude, inability to return for follow-up visits, or inability to complete the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Second Affiliated Hospital of Anhui Medical University — Hefei

Identifiers

NCT: NCT07484893 · HLXTE-HAase02-FIH001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗