Clinical Trials

Inclusion Criteria:

• Competent to provide informed consent.
• Voluntarily provide informed consent in accordance with local regulations and governing ethics committee requirements prior to any procedures or evaluations performed specifically for the sole purpose of the study.
• Are age ≥18 at screening (Visit 1).
• Have a diagnosis of one of the following TMAs:
  • As of Amendment 10 of this protocol, enrollment of aHUS subjects is closed. Primary aHUS, diagnosed clinically and having ADAMTS13 activity > 10% in plasma. Subjects are eligible with or without a documented complement mutation or anti-CFH antibody. Subjects are categorized according to their response to plasma therapy (plasma exchange or plasma infusion):
    • Plasma therapy-resistant aHUS subjects must have all of the following:
      • screening platelet count < 150,000/μL despite at least four plasma therapy treatments prior to screening;
      • evidence of microangiopathic hemolysis (presence of schistocytes, serum lactate dehydrogenase (LDH) > upper limit of normal (ULN), haptoglobin < LLN); and 3) serum creatinine > ULN;
      • Chronic plasma therapy-responsive aHUS subjects (plasma therapy-sensitive) must require at least once-per-week plasma therapy for four weeks before first dose of OMS721 with serum creatinine > ULN.
    • As of Amendment 10 of this protocol, enrollment of TTP subjects is closed. TTP defined as having all of the following:
      • Platelet count < 150,000/μL;
      • Evidence of microangiopathic hemolysis (presence of schistocytes, serum LDH > ULN, or haptoglobin < LLN);
      • ADAMTS13 activity ≤ 10% during the current episode of TTP or historically.
    • Persistent HSCT-associated TMA defined as having all of the following at least two weeks following modification or discontinuation of calcineurin inhibitor treatment or at least 30 days after the transplant:
      • Platelet count < 150,000/μL;
      • Evidence of microangiopathic hemolysis (presence of schistocytes, serum LDH > ULN, or haptoglobin < LLN);
      • Renal dysfunction (doubling of serum creatinine from pretransplant).
• No clinically apparent alternative explanation for thrombocytopenia and anemia.
• If sexually active and of childbearing potential, must agree to practice a highly effective method of birth control until the end of the study, defined as one which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence, or vasectomized partner.

Exclusion Criteria:

• Had eculizumab therapy within three months prior to screening.
• Have STEC-HUS.
• Have a positive direct Coombs test.
• Have an active systemic bacterial or fungal infection requiring antimicrobial therapy (prophylactic antimicrobial therapy administered as standard of care is allowed).
• Baseline resting heart rate < 45 beats per minute or > 115 beats per minute.
• Baseline QTcF > 470 milliseconds.
• Have malignant hypertension (diastolic blood pressure > 120 mm Hg with bilateral hemorrhages or “cotton-wool” exudates on funduscopic examination).
• Have a poor prognosis with a life expectancy of less than three months in the opinion of the investigator.
• Are pregnant or lactating.
• Have received treatment with an investigational drug or device within four weeks prior to screening.
• Have abnormal liver function tests defined as ALT or AST > five times ULN.
• Have a positive test for human immunodeficiency virus (HIV) antibodies.
• Are an employee of Omeros, an investigator, a study staff member, or their immediate family member.
• Have a known hypersensitivity to any constituent of the product.
• Presence of any condition that the investigator believes would put the subject at risk.