A Phase Ia Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Doses of EA5 in Healthy Adult Subjects

A Single-Center, Double-Blind, Placebo-Controlled, Dose-Escalating Phase Ia Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Characteristics of EA5 in a Single Dose in Adult Healthy Subjects

This is a single-center, double-blind, placebo-controlled, dose-escalating Phase Ia clinical study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of a single dose of EA5 in healthy adult subjects.

The study plans to enroll up to 28 subjects. Its primary purpose is to conduct a preliminary assessment of the exposure, safety, and pharmacokinetic profile of EA5 in humans, thereby informing the confirmation or adjustment of the formal trial design. The trial is structured into a pilot phase and a formal phase, encompassing a total of five planned dose cohorts: the pilot trial involves two dose groups (90 mg and 180 mg), each with 2 subjects receiving the active drug; the formal trial consists of three dose groups (360 mg, 720 mg, and 1440 mg), where participants are randomized in a 3:1 ratio (6 subjects receiving the active drug EA5 and 2 subjects receiving placebo per cohort), administered via intravenous (IV) infusion.A 57-day observation period was performed for safety, pharmacokinetic, and pharmacodynamic assessments after study drug administration. Antidrug antibody (ADA) levels were monitored in study participants for the duration of the 57-day follow-up period.

Inclusion Criteria:

• Healthy subjects aged 18 to 55 years (inclusive), regardless of gender.
• Body weight ≥50 kg (male) or ≥45 kg (female), and a body mass index (BMI) between 18 and 28 kg/m² (inclusive).
• Must have received the meningococcal polysaccharide vaccine MenACWY (containing serogroups A, C, W, and Y) at least two weeks prior to dosing.
• Subjects must be able to communicate effectively with the investigator and are expected to comply with the study procedures as defined in the protocol.
• Subjects must be in good general health, as judged by the investigator based on medical history, physical examination, vital signs, electrocardiogram (ECG), chest X-ray, abdominal ultrasound, and laboratory test results.
• Male subjects agree to use effective contraception (vasectomy, abstinence, or condom) from screening until 6 months after the final study intervention. Female subjects must have a negative blood pregnancy test at screening and baseline. Throughout the study and for 6 months thereafter, all subjects and their partners (if of childbearing potential) must use highly effective non-pharmacological contraception.
• Subjects must provide written informed consent voluntarily before any study-specific procedures are performed.
• Systolic and diastolic blood pressure must be within the normal range, or exhibit abnormalities deemed clinically insignificant by the investigator.

Exclusion Criteria:

• History of severe drug allergy; or a clear history of allergy and/or known allergy to the investigational product or any of its excipients, which in the opinion of the investigator, renders the subject unsuitable for participation in the study.
• Prior history of splenectomy.
• History of pulmonary tuberculosis.
• Congenital or acquired complement deficiency (e.g., hypocomplementemia).
• Any contraindication to antibiotic prophylaxis (e.g., beta-lactam antibiotics, ciprofloxacin) for meningococcal infection
• Positive test for hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody, treponemal antibody (TP-Ab), or hepatitis B virus (HBV) surface antigen (HBsAg) at screening
• Presence of symptoms or a significant history of any major disease, including but not limited to cardiac, hepatic, renal, other acute or chronic gastrointestinal or respiratory diseases; hematological, endocrine, neurological, psychiatric disorders; or any other disease or physiological condition that could interfere with the interpretation of the study results.
• Participation in any clinical trial involving an investigational drug or medical device within 3 months prior to screening, or within 5 half-lives of the previous investigational drug prior to screening (whichever is longer)
• Blood loss or donation > 400 mL within 3 months prior to screening, or > 200 mL within 4 weeks prior to screening, or intention to donate blood during the study period
• Average cigarette smoking of ≥5 cigarettes per day within 3 months prior to the study
• Alcohol abuse or regular alcohol consumption exceeding 14 units per week within 6 months prior to screening (1 unit ≈ 360 mL beer, 45 mL 40% spirits, or 150 mL wine), or a positive alcohol breath test at screening.
• History of drug abuse or a positive urine drug screen at screening
• Undergone surgery or received blood or blood product transfusion within 1 month prior to screening。
• Administration of any live or live-attenuated vaccine within 1 month prior to the first dose。
• Use of any prescription drugs, over-the-counter medications, herbal medicines, or vitamins within 14 days or 5 half-lives (whichever is longer) prior to screening。
• Presence of any active infection (viral, bacterial, or fungal), including herpes zoster or herpes simplex, within 14 days prior to dosing.
• History of fever (≥38°C) within 7 days prior to the first dose.
• Female subjects who are pregnant or lactating, or who have engaged in unprotected sexual intercourse within 14 days prior to the study.
• Inability to complete the study for any other reason, or considered by the investigator to be unsuitable for inclusion.