A Phase Ib, Multicenter, Open-Label Study of Multiple-Dose EA5 in Adults With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Exclusion Criteria21

• History of allogeneic bone marrow transplantation.
• History of Neisseria meningitidisinfection within 6 months prior to screening and before the first dose.
• Known or suspected immunodeficiency (e.g., history of frequent or recurrent infections).
• Known or suspected hereditary complement deficiency.
• Evidence of active tuberculosis (TB) within 6 months prior to screening, or a history of active TB without having completed an appropriate, documented course of treatment; OR chest X-ray (posteroanterior and lateral) or CT scan findings during the 3 months prior to screening or during the screening period that suggest the presence of active TB infection.
• History of major surgery (Grade 3 or 4 surgery) within 3 months prior to the first dose.
• Presence of an autoimmune disease, OR use of systemic immunosuppressive/immunomodulatory agents (including, but not limited to, methotrexate, cyclosporine, mycophenolate, tacrolimus, penicillamine, sulfasalazine, hydroxychloroquine, azathioprine, cyclophosphamide) for the treatment of inflammatory diseases within 12 weeks or 5 half-lives (whichever is longer) prior to screening.
• Active systemic bacterial, viral, or fungal infection within 14 days prior to the first dose; OR requirement for hospitalization or intravenous antibiotic therapy for an infection between 28 days prior to screening and the first dose; OR requirement for oral antibiotic therapy for an infection between 14 days prior to screening and the first dose.
• Occurrence of fever (≥38°C) within 7 days prior to the first drug administration.
• Administration of any live-attenuated vaccine within 1 month prior to the first dose.
• History of malignancy within 5 years prior to screening and before the first dose, with the following exceptions: patients with any malignancy that has been treated with curative intent and who have been disease-free and off treatment for \>5 years prior to the first dose may be enrolled. Patients with a history of basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situof the cervix that has been cured with no evidence of recurrence at any time prior to the first dose may be enrolled. Patients with a history of low-grade, early-stage prostate cancer (Gleason score ≤6, Stage 1 or 2) not requiring treatment at any time prior to the first dose may be enrolled.
• History of allergy to any component of EA5, including a history of hypersensitivity to human, humanized, or murine monoclonal antibodies, or known hypersensitivity to any excipient of the product.
• Any contraindication to receiving the meningococcal vaccination and/or antibiotic prophylaxis (e.g., beta-lactam antibiotics, ciprofloxacin) as required by the study protocol.
• Participation in another interventional therapeutic clinical trial involving an investigational drug or receipt of any experimental therapy within 3 months (or within 5 half-lives of the investigational agent, whichever is longer) prior to screening.
• History of drug abuse within 12 months prior to screening, as judged by the investigator.
• Alcohol abuse, or regular alcohol consumption exceeding 14 units per week within 6 months prior to screening (1 unit of alcohol ≈ 360 mL of beer, or 45 mL of 40% spirits, or 150 mL of wine).
• Splenectomy performed within ≤6 months prior to screening.
• 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).
• History of or ongoing cryoglobulinemia at the time of screening.
• History of myelodysplastic syndromes (MDS), with a Revised International Prognostic Scoring System (IPSS-R) risk category of Intermediate, High, or Very High.
• Any other condition that, in the opinion of the investigator, renders the subject unsuitable for participation in the trial.