Thrombotic MicroangiopathiesPhase 2NCT02222545
Safety and Efficacy Study of OMS721 in Patients With Thrombotic Microangiopathies
A Phase 2 study testing OMS721 in people with Thrombotic Microangiopathies, run by Omeros Corporation at 24 sites in 12 countries.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thrombotic Microangiopathies
- What is being tested?
- OMS721
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 24 sitesin 12 countries
- Study dates
- 2 Nov 2014to 11 Aug 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
24 sites in 12 countries.
24 sites in 12 countries
United States5 sites
Omeros Investigational Site
Duarte, California, 91010
Omeros Investigational Site
Durham, North Carolina, 27710
Omeros Investigational Site
Madison, Wisconsin, 53792
Omeros Investigational Site
New York, New York, 10065
Omeros Investigational Site
Rochester, Minnesota, 55905
Poland4 sites
Omeros Investigational Site
Katowice
Omeros Investigational Site
Krakow
Omeros Investigational Site
Lodz
Omeros Investigational Site
Warsaw
Belgium3 sites
Omeros Investigational Site
Brussels
Omeros Investigational Site
Leuven
Omeros Investigational Site
Liège
Thailand3 sites
Omeros Investigational Site
Ban Pathumwan
Omeros Investigational Site
Bangkok
Omeros Investigational Site
Pathum Thani
Taiwan2 sites
Omeros Investigational Site
Taichung
Omeros Investigational Site
Taipei
About this study
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
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).
Read the 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.
- Conditions
- Thrombotic Microangiopathies
- Being tested
- OMS721
- Keywords
- TMA, aHUS, HSCT-associated TMA, TTP
- Medical subject headings
- Thrombotic Microangiopathies, Atypical Hemolytic Uremic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OMS721Biological
| Study group | Role | What they receive |
|---|---|---|
| OMS721 low dose | Experimental | Administration of OMS721 at a low dose Receives: Biological: OMS721 |
| OMS721 medium dose | Experimental | Administration of OMS721 at a medium dose Receives: Biological: OMS721 |
| OMS721 high dose | Experimental | Administration of OMS721 at a high dose Receives: Biological: OMS721 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: Day 1 to up to 2 years following the first dose of OMS721
Secondary outcomes (15)
Participants With HSCT-TMA Treated With OMS721: 100-day Survival
Number of participants alive from the date of TMA diagnosis
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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
Measured: Pre-dose and up to 204 days post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2014 (estimated)
- Study start2 Nov 2014
- Primary completion30 Jan 2020
- Study completion11 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Thrombotic MicroangiopathiesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Omeros Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02222545
- Sponsor's protocol ID
- OMS721-TMA-001
- Other IDs
- 2014-001032-11, 2014
- Status last verified
- Jan 2024
- First submitted
- 18 Aug 2014
- Last updated
- 28 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Expanded access
- Available
Publications
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.
PubMed 35439028Pugh 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.
PubMed 33783815
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02222545
- Acronym / sponsor ID
- OMS721-TMA-001
- Conditions
- Thrombotic Microangiopathies
- Keywords
- TMA, aHUS, HSCT-associated TMA, TTP
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Omeros CorporationIndustry (pharma, biotech, devices)
- Study start
- 2 Nov 2014 (actual)
- Primary completion
- 30 Jan 2020 (actual)
- Study completion
- 11 Aug 2020 (actual)
- First posted
- 21 Aug 2014 (estimated)
- Results
- Posted 28 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| OMS721 low dose | Experimental | Biological: OMS721Administration of OMS721 at a low dose |
| OMS721 medium dose | Experimental | Biological: OMS721Administration of OMS721 at a medium dose |
| OMS721 high dose | Experimental | Biological: OMS721Administration of OMS721 at a high dose |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (4 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OMS721 | Biological | OMS721 high dose, OMS721 low dose, OMS721 medium dose |
Primary outcome
Assess the Safety and Tolerability of Multiple-dose Administration of OMS721 in Participants With TMA
Time frame: Day 1 to 37 days after end of treatment, approximately up to 31 weeks.
Incidence of treatment-emergent adverse events (AEs): clinically significant changes in vital signs, ECG, and laboratory tests were reported as AEs.
Number of Participants With HSCT-TMA Who Respond to OMS721
Time frame: Day 1 to up to 2 years following the first dose of OMS721
Response defined as: Improvement in TMA laboratory markers of platelet count and lactate dehydrogenase (LDH) and improvement in clinical status
15 secondary outcomes
Participants With HSCT-TMA Treated With OMS721: 100-day Survival
Time frame: Study Day of HSCT-TMA diagnosis to 100 days later
Participants With HSCT-TMA Treated With OMS721: Overall Survival
Time frame: 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
Time frame: Study Day 1 to up to 2 years following first dose of OMS721
Participants With HSCT-TMA Treated With OMS721: Freedom From Platelet Transfusion
Time frame: 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
Time frame: Study Day -14 to 4 weeks following the last RBC transfusion
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Platelet Count
Time frame: Study Day 1 to Day 97, approximately 13 weeks
Participants With HSCT-TMA: Pharmacokinetics (PK) of Multiple-dose Administration of OMS721
Time frame: Pre-dose and up to 204 days post-dose
Participants With HSCT-TMA (ADA)
Time frame: Pre-dose and up to 204 days post-dose
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in LDH
Time frame: Study Day 1 to Day 97, approximately 13 weeks
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Creatine
Time frame: Study Day 1 to Day 97, approximately 13 weeks
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Haptoglobin
Time frame: Study Day 1 to Day 97, approximately 13 weeks
Participants With HSCT-TMA Treated With OMS721: Change From Baseline in Hemoglobin
Time frame: Study Day 1 to Day 97, approximately 13 weeks
Participants With HSCT-TMA: Pharmacokinetics (PK) of Multiple-dose Administration of OMS721
Time frame: Pre-dose and up to 204 days post-dose
Participants With HSCT-TMA: Pharmacokinetics (PK) of Multiple-dose Administration of OMS721
Time frame: Pre-dose and up to 204 days post-dose
Participants With HSCT-TMA: Pharmacodynamics (PD)
Time frame: Pre-dose and up to 204 days post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35439028Khaled 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.
- Derived from this study: PubMed 33783815Pugh 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
24 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing OMS721 in people with Thrombotic Microangiopathies, run by Omeros Corporation at 24 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Poland, Belgium, Thailand, Taiwan and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess the Safety and Tolerability of Multiple-dose Administration of OMS721 in Participants With TMA (time frame: Day 1 to 37 days after end of treatment, approximately up to 31 weeks.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02222545, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2024.