Clinical trial NCT02222545: Safety and Efficacy Study of OMS721 in Patients With Thrombotic Microangiopathies
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Thrombotic Microangiopathies
Keywords: TMA, aHUS, HSCT-associated TMA, TTP
Lead sponsor: Omeros Corporation
Sponsor class: INDUSTRY
First posted: 2014-08-21
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Assess the Safety and Tolerability of Multiple-dose Administration of OMS721 in Participants With TMA
timeFrame: Day 1 to 37 days after end of treatment, approximately up to 31 weeks.
measure: Number of Participants With HSCT-TMA Who Respond to OMS721
timeFrame: Day 1 to up to 2 years following the first dose of OMS721
Secondary outcomes:
measure: Participants With HSCT-TMA Treated With OMS721: 100-day Survival
timeFrame: Study Day of HSCT-TMA diagnosis to 100 days later
measure: Participants With HSCT-TMA Treated With OMS721: Overall Survival
timeFrame: Study Day of HSCT-TMA diagnosis to up to 2 years following first dose of OMS721
measure: Participants With HSCT-TMA Treated With OMS721: Duration of Response
timeFrame: Study Day 1 to up to 2 years following first dose of OMS721
measure: Participants With HSCT-TMA Treated With OMS721: Freedom From Platelet Transfusion
timeFrame: Study Day -14 to 4 weeks following the last platelet transfusion
measure: Participants With HSCT-TMA Treated With OMS721: Freedom From Red Blood Cell (RBC) Transfusion
timeFrame: Study Day -14 to 4 weeks following the last RBC transfusion
measure: Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Platelet Count
timeFrame: Study Day 1 to Day 97, approximately 13 weeks
measure: Participants With HSCT-TMA: Pharmacokinetics (PK) of Multiple-dose Administration of OMS721
timeFrame: Pre-dose and up to 204 days post-dose
measure: Participants With HSCT-TMA (ADA)
timeFrame: Pre-dose and up to 204 days post-dose
measure: Participants With HSCT-TMA Treated With OMS721: Change From Baseline in LDH
timeFrame: Study Day 1 to Day 97, approximately 13 weeks
measure: Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Creatine
timeFrame: Study Day 1 to Day 97, approximately 13 weeks
measure: Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Haptoglobin
timeFrame: Study Day 1 to Day 97, approximately 13 weeks
measure: Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Hemoglobin
timeFrame: Study Day 1 to Day 97, approximately 13 weeks
measure: Participants With HSCT-TMA: Pharmacokinetics (PK) of Multiple-dose Administration of OMS721
timeFrame: Pre-dose and up to 204 days post-dose
measure: Participants With HSCT-TMA: Pharmacokinetics (PK) of Multiple-dose Administration of OMS721
timeFrame: Pre-dose and up to 204 days post-dose
measure: Participants With HSCT-TMA: Pharmacodynamics (PD)
timeFrame: Pre-dose and up to 204 days post-dose
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Omeros Investigational Site
state: California
city: Rochester
country: United States
facility: Omeros Investigational Site
state: Minnesota
city: New York
country: United States
facility: Omeros Investigational Site
state: New York
city: Durham
country: United States
facility: Omeros Investigational Site
state: North Carolina
city: Madison
country: United States
facility: Omeros Investigational Site
state: Wisconsin
city: Brussels
country: Belgium
facility: Omeros Investigational Site
city: Leuven
country: Belgium
facility: Omeros Investigational Site
city: Liege
country: Belgium
facility: Omeros Investigational Site
city: Sofia
country: Bulgaria
facility: Omeros Investigational Site
city: Sha Tin
country: Hong Kong
facility: Omeros Investigational Site
city: Bergamo
country: Italy
facility: Omeros Investigational Site
city: Vilnius
country: Lithuania
facility: Omeros Investigational Site
city: Selangan
country: Malaysia
facility: Omeros Investigational Site
city: Christchurch
country: New Zealand
facility: Omeros Investigational Site
city: Katowice
country: Poland
facility: Omeros Investigational Site
city: Krakow
country: Poland
facility: Omeros Investigational Site
city: Warsaw
country: Poland
facility: Omeros Investigational Site
city: Łódź
country: Poland
facility: Omeros Investigational Site
city: Singapore
country: Singapore
facility: Omeros Investigational Site
city: Taichung
country: Taiwan
facility: Omeros Investigational Site
city: Taipei
country: Taiwan
facility: Omeros Investigational Site
city: Ban Pathumwan
country: Thailand
facility: Omeros Investigational Site
city: Bangkok
country: Thailand
facility: Omeros Investigational Site
city: Pathum Thani
country: Thailand
facility: Omeros Investigational Site
Study officials:
References:
citation: 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.
citation: 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.