Safety and Efficacy Study of OMS721 in Patients With Thrombotic Microangiopathies

Thrombotic Microangiopathies Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02222545
• Other study ID #: OMS721-TMA-001
• Secondary ID: 2014-001032-11
• Status: Completed
• Phase: Phase 2
• Start date: November 2, 2014
• Est. completion date: August 11, 2020

Study information

• Verified date: July 2021
• Source: Omeros Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: August 11, 2020
• Est. primary completion date: January 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Thrombotic Microangiopathies
• Vascular Diseases

Intervention

Biological:
• OMS721

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Omeros Corporation

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Hong Kong,  Italy,  Lithuania,  Malaysia,  New Zealand,  Poland,  Singapore,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Evaluate the following in patients with HSCT-TMA treated with OMS721: 100-day survival	Vital status	Study Day 1 to 100 days later
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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