Safety and Efficacy Study of OMS721 in Patients With Thrombotic Microangiopathies


About this study

This is a Phase 2, uncontrolled, three-stage, ascending-dose-escalation study in subjects with one of three forms of TMA: atypical hemolytic uremic syndrome (aHUS), thrombotic thrombocytopenic purpura (TTP), or hematopoietic stem cell transplant (HSCT)-associated TMA. In the first stage, OMS721 will be administered to escalating dose cohorts of three subjects per cohort to identify the optimal dosing regimen. After enrollment and treatment of each cohort there will be a safety review to determine whether dose escalation should proceed. In the second stage, the dose selected in the first stage will be administered to expanded cohorts of 40 subjects per cohort with distinct etiologies (aHUS alone in one cohort and TTP or HSCT-TMA in the other cohort). Subjects completing the second stage may be eligible for continued treatment in the third stage if they have tolerated OMS721 treatment and derived clinical benefit. OMS721 is to be used in conjunction with standard of care treatments. Standard of care treatments are not to be delayed or withheld from subjects entering this study. These treatments should be initiated according to local standard of care. For example, plasma exchange should not be delayed or withheld from subjects suspected of having TTP while waiting for confirmatory ADAMTS13 laboratory results and potential initiation of OMS721 treatment. Subjects who have failed a treatment, e.g., subjects with plasma-therapy resistant aHUS, do not require continued treatment with the failed therapy.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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.






Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

Nelson Leung, M.D.

Closed for enrollment

More information


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