Safety and Efficacy Study of OMS721 in Patients With Thrombotic Microangiopathies

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ClinicalTrials.gov Identifier: NCT02222545

Recruitment Status : Completed

First Posted : August 21, 2014

Last Update Posted : July 6, 2021

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Omeros Corporation

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Thrombotic Microangiopathies	Biological: OMS721	Phase 2

Expanded Access : Omeros Corporation has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	58 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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
Actual Study Start Date :	November 2, 2014
Actual Primary Completion Date :	January 30, 2020
Actual Study Completion Date :	August 11, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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)

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02222545

Locations

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

Sponsors and Collaborators

Omeros Corporation

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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Responsible Party:	Omeros Corporation
ClinicalTrials.gov Identifier:	NCT02222545
Other Study ID Numbers:	OMS721-TMA-001 2014-001032-11 ( EudraCT Number )
First Posted:	August 21, 2014 Key Record Dates
Last Update Posted:	July 6, 2021
Last Verified:	July 2021

Keywords provided by Omeros Corporation:


TMA, aHUS, HSCT-associated TMA, TTP

Additional relevant MeSH terms:

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Vascular Diseases Thrombotic Microangiopathies Cardiovascular Diseases	Thrombocytopenia Blood Platelet Disorders Hematologic Diseases

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