Safety and Efficacy Study of OMS721 in Patients With Thrombotic Microangiopathies

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

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).

Study Overview

• Status: Completed
• Conditions: Thrombotic Microangiopathies
• Intervention / Treatment: Biological: OMS721

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 Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Omeros Investigational Site
  • Leuven, Belgium
    • Omeros Investigational Site
  • Liege, Belgium
    • Omeros Investigational Site
• Bulgaria
  • Sofia, Bulgaria
    • Omeros Investigational Site
• Hong Kong
  • Sha Tin, Hong Kong
    • Omeros Investigational Site
• Italy
  • Bergamo, Italy
    • Omeros Investigational Site
• Lithuania
  • Vilnius, Lithuania
    • Omeros Investigational Site
• Malaysia
  • Selangan, Malaysia
    • Omeros Investigational Site
• New Zealand
  • Christchurch, New Zealand
    • Omeros Investigational Site
• Poland
  • Katowice, Poland
    • Omeros Investigational Site
  • Krakow, Poland
    • Omeros Investigational Site
  • Warsaw, Poland
    • Omeros Investigational Site
  • Łódź, Poland
    • Omeros Investigational Site
• Singapore
  • Singapore, Singapore
    • Omeros Investigational Site
• Taiwan
  • Taichung, Taiwan
    • Omeros Investigational Site
  • Taipei, Taiwan
    • Omeros Investigational Site
• Thailand
  • Ban Pathumwan, Thailand
    • Omeros Investigational Site
  • Bangkok, Thailand
    • Omeros Investigational Site
  • Pathum Thani, Thailand
    • Omeros Investigational Site
• United States
  • California
    • Duarte, California, United States, 91010
      • Omeros Investigational Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Omeros Investigational Site
  • New York
    • New York, New York, United States, 10065
      • Omeros Investigational Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Omeros Investigational Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Omeros Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OMS721 low dose; Administration of OMS721 at a low dose	Biological: OMS721
Experimental: OMS721 medium dose; Administration of OMS721 at a medium dose	Biological: OMS721
Experimental: OMS721 high dose; Administration of OMS721 at a high dose	Biological: OMS721

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	Day 1 to up to 2 years following the first dose of OMS721

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants With HSCT-TMA Treated With OMS721: 100-day Survival	Number of participants alive from the date of TMA diagnosis	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	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	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	Study Day -14 to 4 weeks following the last platelet transfusion
Participants With HSCT-TMA Treated With OMS721: Freedom From Red Blood Cell (RBC) Transfusion	Number of participants with absence of RBC transfusions	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	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	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	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	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	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	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	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)	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)	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	Pre-dose and up to 204 days post-dose

Collaborators and Investigators

• Sponsor: Omeros Corporation

Publications and helpful links

General Publications

• Pugh D, O'Sullivan ED, Duthie FA, Masson P, Kavanagh D. Interventions for atypical haemolytic uraemic syndrome. Cochrane Database Syst Rev. 2021 Mar 23;3(3):CD012862. doi: 10.1002/14651858.CD012862.pub2.
• Khaled SK, Claes K, Goh YT, Kwong YL, Leung N, Mendrek W, Nakamura R, Sathar J, Ng E, Nangia N, Whitaker S, Rambaldi A; OMS721-TMA-001 Study Group Members. Narsoplimab, a Mannan-Binding Lectin-Associated Serine Protease-2 Inhibitor, for the Treatment of Adult Hematopoietic Stem-Cell Transplantation-Associated Thrombotic Microangiopathy. J Clin Oncol. 2022 Aug 1;40(22):2447-2457. doi: 10.1200/JCO.21.02389. Epub 2022 Apr 19.

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2014
• Primary Completion (Actual): January 30, 2020
• Study Completion (Actual): August 11, 2020

Study Registration Dates

• First Submitted: August 18, 2014
• First Submitted That Met QC Criteria: August 20, 2014
• First Posted (Estimated): August 21, 2014

Study Record Updates

• Last Update Posted (Actual): August 28, 2024
• Last Update Submitted That Met QC Criteria: August 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: TMA, aHUS, HSCT-associated TMA, TTP
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Hematologic Diseases; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Vascular Diseases; Thrombotic Microangiopathies
• Other Study ID Numbers: OMS721-TMA-001; 2014-001032-11 (EudraCT Number)