Safety and Efficacy Study of OMS721 in Patients With Thrombotic Microangiopathies

• Sponsor: Omeros Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02222545
• Collaborator: (none)
• Enrollment: 58
• Locations: 25
• Arms: 3
• Actual Duration (Months): 69.3
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0

Study Details

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

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

• Study Type: Interventional
• 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: Nov 2, 2014
• Actual Primary Completion Date: Jan 30, 2020
• Actual Study Completion Date: Aug 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

1. Assess the safety and tolerability of multiple-dose administration of OMS721 in subjects with TMA [4 to 24 weeks]

   Incidence of Adverse Events, vital signs, ECG, and clinical laboratory tests

2. Evaluate the response rate to OMS721 in patients with HSCT-TMA [4 to 24 weeks]

   Improvement in TMA laboratory markers of platelet count and lactate dehydrogenase (LDH) and improvement in clinical status

Secondary Outcome Measures

1. Evaluate the following in patients with HSCT-TMA treated with OMS721: 100-day survival [Study Day 1 to 100 days later]

   Vital status

2. Evaluate the following in patients with HSCT-TMA treated with OMS721: Overall survival [Study Day 1 to up to 2 years following first dose of OMS721]

   Vital status

3. Evaluate the following in patients 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

4. Evaluate the following in patients with HSCT-TMA treated with OMS721: Freedom from platelet transfusion [Study Day -14 to 4 weeks following the last platelet transfusion]

   Absence of platelet transfusions

5. Evaluate the following in patients with HSCT-TMA treated with OMS721: Freedom from red blood cell (RBC) transfusion [Study Day -14 to 4 weeks following the last RBC transfusion]

   Absence of RBC transfusions

6. Evaluate the following in patients with HSCT-TMA treated with OMS721: Change from baseline in platelet count, LDH, haptoglobin, hemoglobin (Hgb), creatinine [Study Day 1 to up to 2 years following the first dose of OMS721]

   Platelet count, LDH, haptoglobin, Hgb, creatinine

7. Evaluate the following in patients with HSCT-TMA, aHUS, and TTP: Pharmacokinetics (PK) of multiple-dose administration of OMS721 [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

8. Evaluate the following in patients with HSCT-TMA, aHUS, and TTP: Pharmacodynamics (PD) of multiple-dose administration of OMS721 in subjects with TMA [Pre-dose and up to 204 days post-dose]

   PD measure in inhibition of ex vivo lectin pathway activation

9. Evaluate the following in patients with HSCT-TMA, aHUS, and TTP: Immunogenicity of multiple-dose administration of OMS721 in subjects with TMA [Pre-dose and up to 204 days post-dose]

   Presence of ADA response

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Omeros Investigational Site	Duarte	California	United States	91010
2	Omeros Investigational Site	Rochester	Minnesota	United States	55905
3	Omeros Investigational Site	New York	New York	United States	10065
4	Omeros Investigational Site	Durham	North Carolina	United States	27710
5	Omeros Investigational Site	Madison	Wisconsin	United States	53792
6	Omeros Investigational Site	Brussels		Belgium
7	Omeros Investigational Site	Leuven		Belgium
8	Omeros Investigational Site	Liege		Belgium
9	Omeros Investigational Site	Sofia		Bulgaria
10	Omeros Investigational Site	PokFuLam		Hong Kong
11	Omeros Investigational Site	Sha Tin		Hong Kong
12	Omeros Investigational Site	Bergamo		Italy
13	Omeros Investigational Site	Vilnius		Lithuania
14	Omeros Investigational Site	Selangor		Malaysia
15	Omeros Investigational Site	Christchurch		New Zealand
16	Omeros Investigational Site	Katowice		Poland
17	Omeros Investigational Site	Krakow		Poland
18	Omeros Investigational Site	Warsaw		Poland
19	Omeros Investigational Site	Łódź		Poland
20	Omeros Investigational Site	Singapore		Singapore
21	Omeros Investigational Site	Taichung		Taiwan
22	Omeros Investigational Site	Taipei		Taiwan
23	Omeros Investigational Site	Bangkok		Thailand
24	Omeros Investigational Site	Pathum Thani		Thailand
25	Omeros Investigational Site	Pathumwan		Thailand

Sponsors and Collaborators

• Omeros Corporation

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Omeros Corporation
• ClinicalTrials.gov Identifier: NCT02222545
• Other Study ID Numbers: OMS721-TMA-001; 2014-001032-11
• First Posted: Aug 21, 2014
• Last Update Posted: Jul 6, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by Omeros Corporation: TMA, aHUS, HSCT-associated TMA, TTP
• Additional relevant MeSH terms: Vascular Diseases; Thrombotic Microangiopathies

Study Results

No Results Posted as of Jul 6, 2021