Safety and Efficacy Study of OMS721 in Patients With Thrombotic Microangiopathies

Phase 2

Completed

• Conditions: Thrombotic Microangiopathies
• Interventions: Biological: OMS721

• Registration Number: NCT02222545
• Lead Sponsor: Omeros Corporation

Brief Summary

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

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 Timeline

• Study First Submitted: 2014-08-18
• Study First Submitted QC: 2014-08-20
• Study First Posted: 2014-08-21
• Study Start: 2014-11-02
• Primary Completion: 2020-01-30
• Study Completion: 2020-08-11
• Results First Submitted: 2023-08-04
• Status Verified: 2024-01
• Results First Submitted QC: 2024-08-22
• Last Update Submitted: 2024-08-22
• Results First Posted: 2024-08-28
• Last Update Posted: 2024-08-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 58

Inclusion Criteria

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

Exclusion Criteria

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
OMS721 medium dose	OMS721	Administration of OMS721 at a medium dose
OMS721 high dose	OMS721	Administration of OMS721 at a high dose
OMS721 low dose	OMS721	Administration of OMS721 at a low dose

Primary Outcome Measures

Name	Time	Method
Number of Participants With HSCT-TMA Who Respond to OMS721	Day 1 to up to 2 years following the first dose of OMS721	Response defined as: Improvement in TMA laboratory markers of platelet count and lactate dehydrogenase (LDH) and improvement in clinical status
Assess the Safety and Tolerability of Multiple-dose Administration of OMS721 in Participants With TMA	Day 1 to 37 days after end of treatment, approximately up to 31 weeks.	Incidence of treatment-emergent adverse events (AEs): clinically significant changes in vital signs, ECG, and laboratory tests were reported as AEs.

Secondary Outcome Measures

Name	Time	Method
Participants With HSCT-TMA Treated With OMS721: Freedom From Platelet Transfusion	Study Day -14 to 4 weeks following the last platelet transfusion	Number of participants with absence of platelet transfusions
Participants With HSCT-TMA Treated With OMS721: Freedom From Red Blood Cell (RBC) Transfusion	Study Day -14 to 4 weeks following the last RBC transfusion	Number of participants with absence of RBC transfusions
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Platelet Count	Study Day 1 to Day 97, approximately 13 weeks	Changes from baseline in Platelet count
Participants With HSCT-TMA Treated With OMS721: 100-day Survival	Study Day of HSCT-TMA diagnosis to 100 days later	Number of participants alive from the date of TMA diagnosis
Participants With HSCT-TMA: Pharmacokinetics (PK) of Multiple-dose Administration of OMS721	Pre-dose and up to 204 days post-dose	PK parameters Concentration of OMS721 that achieves half maximum elimination rate (KM) (ug/mL)
Participants With HSCT-TMA Treated With OMS721: Overall Survival	Study Day of HSCT-TMA diagnosis to up to 2 years following first dose of OMS721	Survival days from the day of TMA diagnosis
Participants With HSCT-TMA Treated With OMS721: Duration of Response	Study Day 1 to up to 2 years following first dose of OMS721	Number of days from the first response date to the first relapse date
Participants With HSCT-TMA (ADA)	Pre-dose and up to 204 days post-dose	Presence of ADA response. Immunogenicity of multiple-dose administration of OMS721 in subjects with TMA
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in LDH	Study Day 1 to Day 97, approximately 13 weeks	Changes from baseline in LDH
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Creatine	Study Day 1 to Day 97, approximately 13 weeks	Changes from baseline in Creatine
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Haptoglobin	Study Day 1 to Day 97, approximately 13 weeks	Changes from baseline in Haptoglobin
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Hemoglobin	Study Day 1 to Day 97, approximately 13 weeks	Changes from baseline in Hemoglobin
Participants With HSCT-TMA: Pharmacodynamics (PD)	Pre-dose and up to 204 days post-dose	PD measure is expressed as percentage inhibition of C4d to assess ex-vivo lectin pathway activation

Trial Locations

Locations (1)

Omeros Investigational Site; 🇹🇭 Pathum Thani, Thailand