A Phase I, Dose Escalation, Open-label, Multicenter Study of EA5 Injection in Adults With APS and Recurrent Thrombosis

A Phase I, Dose Escalation, Open-label, Multicenter Clinical Study to Evaluate the Safety, Tolerability, Preliminary Efficacy, Pharmacodynamics, and Pharmacokinetics of EA5 Injection in Adult Participants With Antiphospholipid Syndrome (APS) and Recurrent Thrombosis Under Standard-of-Care Background Therapy

This is a Phase I, open-label, dose escalation, multicenter study to evaluate the safety, tolerability, preliminary efficacy, pharmacodynamics (PD), and pharmacokinetics (PK) of EA5 injection in adult participants with Antiphospholipid Syndrome (APS) and recurrent thrombosis who are receiving standard-of-care antithrombotic therapy. Approximately 12 participants will be enrolled. The whole study treatment cycle was 24 weeks. Administration of low-dose EA5: First, administer the loading dose regimen intravenously, then maintain administration subcutaneously every 2 weeks(Q2W). Administration of high-dose EA5: First, administer the loading dose regimen intravenously, then maintain administration subcutaneously every 2 weeks(Q2W).The primary objective is to assess safety and tolerability. Secondary objectives include evaluation of preliminary efficacy, immunogenicity, PK, PD (complement inhibition), and APS-related biomarker changes.

Inclusion Criteria:

1. Participants must be ≥18 years of age at the time of signing the Informed Consent Form (ICF).
2. Participants diagnosed with Antiphospholipid Syndrome (APS) according to the 2023 EULAR/ACR classification criteria, with at least two of the three antiphospholipid antibodies positive: anticardiolipin antibody (aCL), anti-β2-glycoprotein I antibody (anti-β2GPI), and lupus anticoagulant (LA).
3. Experienced ≥2 thrombotic events within the past 5 years under antithrombotic prophylactic therapy, confirmed by objective imaging.
4. Stable antithrombotic treatment regimen for at least 6 months prior to screening (dose adjustment of warfarin to achieve a stable INR is permitted).
5. Vaccination against Neisseria meningitidis (MPV-ACYW) within <3 years prior to initiation of study treatment; OR if not previously vaccinated, receipt of the meningococcal vaccine (MPV-ACYW) at least 14 days prior to the first dose of the investigational product. If the vaccine is administered within 14 days before dosing, antibiotic prophylaxis must be provided until 2 weeks post-vaccination.
6. Vaccination against Streptococcus pneumoniae according to national vaccination recommendations (e.g., Advisory Committee on Immunization Practices [ACIP] guidelines). OR if not previously vaccinated, receipt of the pneumococcal vaccine at least 14 days prior to the first dose of the investigational product. If the vaccine is administered within 14 days before dosing, antibiotic prophylaxis must be provided until 2 weeks post-vaccination.
7. Use of contraception by men and women should be consistent with local regulations regarding contraceptive methods for clinical trial participants.

(1)Male Participants: Male participants must agree to use effective contraception during the treatment period and for at least 6 months after the last dose of the study intervention, and to refrain from donating sperm during this time.

(2)Female Participants: Non-pregnant, non-lactating female participants are eligible to participate if they meet at least one of the following conditions: use of an effective or acceptable contraceptive method during the treatment period and for at least 6 months after the last dose of the study drug.

Capable of understanding the study procedures and methods, willing to sign the ICF, and able to strictly adhere to the clinical study protocol to complete the study.

Exclusion Criteria:

1. History of malignancy within 5 years prior to screening and before administration (except for localized skin basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma in situ that have undergone curative local treatment with no evidence of metastasis in the past 3 years).
2. Thrombosis with other definite etiologies, such as malignancy, hereditary thrombophilia, thrombotic microangiopathy, etc.
3. History of catastrophic antiphospholipid syndrome (i.e., progressive thrombosis in multiple [3 or more] organs occurring within 1 week, involving critical organs such as the brain, kidneys, liver, or heart leading to failure, with pathological confirmation of small vessel thrombosis).
4. Presence of active bleeding or high risk of bleeding, such as gastrointestinal bleeding, intracranial bleeding, respiratory tract bleeding, coagulation disorders, etc.
5. History of major surgery within 1 month prior to screening or requiring major elective surgery during the trial period.
6. History of immunodeficiency, including a positive test for human immunodeficiency virus (HIV) antibody, or having other acquired or congenital immunodeficiency diseases.
7. Comorbid with systemic autoimmune diseases (e.g., systemic lupus erythematosus, systemic sclerosis, etc.).
8. Unresolved meningococcal infection.
9. Positive for hepatitis C virus (HCV) antibody at screening (except for those with a negative HCV RNA result), positive for human immunodeficiency virus (HIV) antibody, positive for anti-Treponema pallidumantibody (TP-Ab) (except for those with a negative RPR or TRUST test), OR positive for hepatitis B virus (HBV) surface antigen (HBsAg) (except for those with an HBV DNA level ≤ 1000 IU/mL).
10. Presence of active infection requiring systemic therapy within 4 weeks prior to the first use of the investigational product (including herpes zoster, active tuberculosis, active Treponema palliduminfection, and fungal infections requiring systemic therapy).
11. Participants with severe hepatic or renal impairment: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 times the upper limit of normal (ULN); total bilirubin ≥ 2 times ULN; serum creatinine ≥ 2.5 times ULN, OR calculated creatinine clearance ≤ 30 mL/min according to the Cockcroft-Gault formula.
12. Receipt of other interventional therapy or participation in another clinical study within 30 days prior to the first use of the investigational product or within 5 half-lives of this investigational product (whichever is longer).
13. Prior use of complement C3 or C5 targeted therapy.
14. History of allergy to any component of EA5, including hypersensitivity to human, humanized, or murine monoclonal antibodies, or known hypersensitivity to any ingredient of the product.
15. Any disease that, in the opinion of the investigator or sponsor, may increase participant risk or confound study outcomes. Including, but not limited to, significant circulatory, respiratory, urinary, endocrine system diseases, etc.
16. Female participants who are pregnant or breastfeeding.
17. Any other condition for which the investigator considers the participant unsuitable to enter this clinical study.