The purpose of this study is to assess the safety, efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of OMS721 in patients with thrombotic microangiopathies (TMA).
This is a Phase 2, uncontrolled, 3-stage, ascending-dose-escalation study in patients with 1 of 3 forms of TMA: atypical hemolytic uremic syndrome (aHUS), thrombotic thrombocytopenia (TTP), and hematopoietic stem cell transplant - associated TMA (HSCT-associated TMA). In Stage 1 of the study, OMS721 was administered to 3 cohorts, with dose escalation by cohort to identify the optimal dosing regimen. In Stage 2, the dose selected in the first stage was administered to expanded cohorts of patients with distinct etiologies (aHUS alone in 1 cohort and TTP or HSCT-TMA in the other cohort). Patients completing Stage 2 were eligible for continued treatment in Stage 3 if they tolerated OMS721 treatment and derived clinical benefit. Enrollment in the study has been completed.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
58
Omeros Investigational Site
Duarte, California, United States
Assess the Safety and Tolerability of Multiple-dose Administration of OMS721 in Participants With TMA
Incidence of treatment-emergent adverse events (AEs): clinically significant changes in vital signs, ECG, and laboratory tests were reported as AEs.
Time frame: Day 1 to 37 days after end of treatment, approximately up to 31 weeks.
Number of Participants With HSCT-TMA Who Respond to OMS721
Response defined as: Improvement in TMA laboratory markers of platelet count and lactate dehydrogenase (LDH) and improvement in clinical status
Time frame: Day 1 to up to 2 years following the first dose of OMS721
Participants With HSCT-TMA Treated With OMS721: 100-day Survival
Number of participants alive from the date of TMA diagnosis
Time frame: Study Day of HSCT-TMA diagnosis to 100 days later
Participants With HSCT-TMA Treated With OMS721: Overall Survival
Survival days from the day of TMA diagnosis
Time frame: Study Day of HSCT-TMA diagnosis to up to 2 years following first dose of OMS721
Participants With HSCT-TMA Treated With OMS721: Duration of Response
Number of days from the first response date to the first relapse date
Time frame: Study Day 1 to up to 2 years following first dose of OMS721
Participants With HSCT-TMA Treated With OMS721: Freedom From Platelet Transfusion
Number of participants with absence of platelet transfusions
Time frame: Study Day -14 to 4 weeks following the last platelet transfusion
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Omeros Investigational Site
Rochester, Minnesota, United States
Omeros Investigational Site
New York, New York, United States
Omeros Investigational Site
Durham, North Carolina, United States
Omeros Investigational Site
Madison, Wisconsin, United States
Omeros Investigational Site
Brussels, Belgium
Omeros Investigational Site
Leuven, Belgium
Omeros Investigational Site
Liège, Belgium
Omeros Investigational Site
Sofia, Bulgaria
Omeros Investigational Site
Shatin, Hong Kong
...and 14 more locations
Participants With HSCT-TMA Treated With OMS721: Freedom From Red Blood Cell (RBC) Transfusion
Number of participants with absence of RBC transfusions
Time frame: Study Day -14 to 4 weeks following the last RBC transfusion
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Platelet Count
Changes from baseline in Platelet count
Time frame: Study Day 1 to Day 97, approximately 13 weeks
Participants With HSCT-TMA: Pharmacokinetics (PK) of Multiple-dose Administration of OMS721
PK parameters including clearance rate
Time frame: Pre-dose and up to 204 days post-dose
Participants With HSCT-TMA (ADA)
Presence of ADA response. Immunogenicity of multiple-dose administration of OMS721 in subjects with TMA
Time frame: Pre-dose and up to 204 days post-dose
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in LDH
Changes from baseline in LDH
Time frame: Study Day 1 to Day 97, approximately 13 weeks
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Creatine
Changes from baseline in Creatine
Time frame: Study Day 1 to Day 97, approximately 13 weeks
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Haptoglobin
Changes from baseline in Haptoglobin
Time frame: Study Day 1 to Day 97, approximately 13 weeks
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Hemoglobin
Changes from baseline in Hemoglobin
Time frame: Study Day 1 to Day 97, approximately 13 weeks
Participants With HSCT-TMA: Pharmacokinetics (PK) of Multiple-dose Administration of OMS721
PK parameters Apparent volume of the central compartment (V1)
Time frame: Pre-dose and up to 204 days post-dose
Participants With HSCT-TMA: Pharmacokinetics (PK) of Multiple-dose Administration of OMS721
PK parameters Concentration of OMS721 that achieves half maximum elimination rate (KM) (ug/mL)
Time frame: Pre-dose and up to 204 days post-dose
Participants With HSCT-TMA: Pharmacodynamics (PD)
PD measure is expressed as percentage inhibition of C4d to assess ex-vivo lectin pathway activation
Time frame: Pre-dose and up to 204 days post-dose