Safety and Efficacy Study of OMS721 in Patients With Thrombotic Microangiopathies

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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A Phase 2, Uncontrolled, Three-Stage, Dose-Escalation Cohort Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Clinical Activity of OMS721 in Adults With Thrombotic Microangiopathies

Conditions
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Thrombotic Microangiopathies

Intervention / Treatment
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* Biological: OMS721


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are at least age 18 at screening (Visit 1) Have a diagnosis of primary aHUS, persistent HSCT-associated TMA or TTP No clinically apparent alternative explanation for thrombocytopenia and anemia 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OMS721 low dose<br>Administration of OMS721 at a low dose | Biological: OMS721<br> <br> |
| Experimental: OMS721 medium dose<br>Administration of OMS721 at a medium dose | Biological: OMS721<br> <br> |
| Experimental: OMS721 high dose<br>Administration of OMS721 at a high dose | Biological: OMS721<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the safety and tolerability of multiple-dose administration of OMS721 in subjects with TMA | Incidence of Adverse Events, vital signs, ECG, and clinical laboratory tests | 4 to 24 weeks | 
| Evaluate the response rate to OMS721 in patients with HSCT-TMA | Improvement in TMA laboratory markers of platelet count and lactate dehydrogenase (LDH) and improvement in clinical status | 4 to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the following in patients with HSCT-TMA treated with OMS721: 100-day survival | Vital status | Study Day 1 to 100 days later | 
| Evaluate the following in patients with HSCT-TMA treated with OMS721: Overall survival | Vital status | Study Day 1 to up to 2 years following first dose of OMS721 | 
| Evaluate the following in patients with HSCT-TMA treated with OMS721: Duration of response | Number of days from the first response date to the first relapse date | Study Day 1 to up to 2 years following first dose of OMS721 | 
| Evaluate the following in patients with HSCT-TMA treated with OMS721: Freedom from platelet transfusion | Absence of platelet transfusions | Study Day -14 to 4 weeks following the last platelet transfusion | 
| Evaluate the following in patients with HSCT-TMA treated with OMS721: Freedom from red blood cell (RBC) transfusion | Absence of RBC transfusions | Study Day -14 to 4 weeks following the last RBC transfusion | 
| Evaluate the following in patients with HSCT-TMA treated with OMS721: Change from baseline in platelet count, LDH, haptoglobin, hemoglobin (Hgb), creatinine | Platelet count, LDH, haptoglobin, Hgb, creatinine | Study Day 1 to up to 2 years following the first dose of OMS721 | 
| Evaluate the following in patients with HSCT-TMA, aHUS, and TTP: Pharmacokinetics (PK) of multiple-dose administration of OMS721 | PK parameters including maximum concentration, time to maximum concentration, elimination half-life, area under time-concentration curve, clearance, and volume of distribution | Pre-dose and up to 204 days post-dose | 
| Evaluate the following in patients with HSCT-TMA, aHUS, and TTP: Pharmacodynamics (PD) of multiple-dose administration of OMS721 in subjects with TMA | PD measure in inhibition of ex vivo lectin pathway activation | Pre-dose and up to 204 days post-dose | 
| Evaluate the following in patients with HSCT-TMA, aHUS, and TTP: Immunogenicity of multiple-dose administration of OMS721 in subjects with TMA | Presence of ADA response | Pre-dose and up to 204 days post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TMA, aHUS, HSCT-associated TMA, TTP