Three forms of thrombotic microangiopathies (TMA): - atypical hemolytic uremic syndrome (aHUS) - hematopoietic stem cell transplant (HSCT)-associated TMA - thrombotic thrombocytopenic purpura (TTP) MedDRA version: 18.0 Level: PT Classification code 10043645 Term: Thrombotic microangiopathy System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Product Code: OMS721
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: not yet available
Current Sponsor code: OMS721
Other descriptive name: OMS721 100 mg/ml Injection s
Sponsors
Omeros Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Competent to provide informed consent. 2. Voluntarily provide informed consent in accordance with regulations and governing ethics committee requirements prior to any procedures or evaluations performed specifically for the sole purpose of the study. 3. Are age =18 at screening (Visit 1). 4. Have a diagnosis of TMA in accordance with one of the following three categories: • Primary aHUS, diagnosed clinically and having ADAMTS13 activity >10% in plasma. Patients are eligible with or without a documented complement mutation or anti-CFH antibody. Patients are categorized according to their response to plasma therapy (plasma exchange or plasma infusion): o Plasma therapy-resistant aHUS patients must have all of the following: 1) screening platelet count upper limit of normal (ULN), or haptoglobin ULN. o Chronic plasma therapy-responsive aHUS patients (plasma therapy-sensitive) must require at least once-per-week plasma therapy for four weeks before first dose of OMS721 with serum creatinine >ULN. • TTP defined as having all of the following: o Platelet count ULN, or haptoglobin ULN, or haptoglobin =65 years) yes F.1.3.1 Number of subjects for this age range 19
Exclusion criteria
Exclusion criteria: Subjects will be excluded from the study for any of the following reasons: 1. Had eculizumab therapy within three months prior to screening. 2. Have STEC-HUS. 3. Have a positive direct Coombs test. 4. Have an active systemic bacterial or fungal infection requiring antimicrobial therapy (prophylactic antimicrobial therapy administered as standard of care is allowed). 5. Baseline resting heart rate 115 beats per minute. 6. Baseline QTcF > 470 milliseconds. 7. Have malignant hypertension (diastolic blood pressure [BP] > 120 mm Hg with bilateral hemorrhages or “cotton-wool” exudates on funduscopic examination). 8. Have a poor prognosis with a life expectancy of less than three months in the opinion of the investigator. 9. Are pregnant or lactating. 10. Have received treatment with an investigational drug or device within four weeks prior to screening. 11. Have abnormal liver function tests defined as ALT or AST > five times ULN. 12. Have a positive test for human immunodeficiency virus (HIV) antibodies. 13. Are an employee of Omeros, an investigator, a study staff member, or their immediate family member. 14. Have a known hypersensitivity to any constituent of the product. 15. Presence of any condition that the Investigator believes would put the subject at risk.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The co-primary objectives of this study are to: • Assess the safety and tolerability of multiple-dose administration of OMS721 in subjects with TMA • Evaluate the clinical activity of multiple-dose administration of OMS721 in subjects with TMA;Secondary Objective: • Determine the pharmacokinetics (PK) of multiple-dose administration of OMS721 in subjects with TMA • Determine the pharmacodynamics (PD) of multiple-dose administration of OMS721 in subjects with TMA • Determine the immunogenicity of multiple-dose administration of OMS721 in subjects with TMA;Primary end point(s): • Safety as assessed by AEs, vital signs, ECG and clinical laboratory tests • Clinical activity as assessed by platelet count;Timepoint(s) of evaluation of this end point: from baseline across all evaluations/visits | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: pre-dose, 5 min, 2 hours, 24 hours, 48 hours, 72 hours;Secondary end point(s): • TMA clinical activity o Serum LDH o Serum haptoglobin o Hemoglobin o Serum creatinine o TMA-related symptoms o Need for plasma therapy (plasma exchange or plasma infusion) o Need for dialysis • PK parameters including maximum concentration (Cmax), time to maximum concentration (Tmax), elimination half-life (t½), area under time-concentration curve (AUC), clearance (CL), and volume of distribution (Vz) • PD measure of inhibition of ex vivo lectin pathway activation • Presence of ADA response | — |
Countries
Belarus, Belgium, Bulgaria, Germany, Hong Kong, Italy, Lithuania, Malaysia, New Zealand, Poland, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactProject Manager
PSI CRO AG
Outcome results
None listed