Safety and Efficacy Study of OMS721 in Patients With Atypical Hemolytic Uremic Syndrome (aHUS)

A Phase 3 Study to Evaluate the Safety and Efficacy of OMS721 for the Treatment of Atypical Hemolytic Uremic Syndrome (aHUS) in Adults and Adolescents

The purpose of this study is to evaluate the platelet count change from baseline and safety of OMS721 (narsoplimab) in adults and adolescents with atypical hemolytic uremic syndrome (aHUS). The study will also evaluate pharmacokinetics (PK), pharmacodynamics (PD), and anti-drug antibody response (ADA).

Study Overview

• Status: Terminated
• Conditions: Thrombotic Microangiopathies; Atypical Hemolytic Uremic Syndrome
• Intervention / Treatment: Biological: OMS721 (narsoplimab)

Detailed Description

This is a Phase 3, uncontrolled, open-label study to evaluate the effect of OMS721 in subjects with aHUS. The primary outcome to be measured is platelet count change from baseline. The secondary outcomes to be measured are other efficacy measures, safety, PK, PD, and immunogenicity (i.e., presence of anti-drug antibody [ADA] response. Subjects with plasma therapy-resistant aHUS and plasma therapy-responsive aHUS will be eligible. The efficacy endpoints, including the primary efficacy endpoint, may not be relevant for plasma therapy-responsive subjects because these subjects may enter the study with normal markers of aHUS activity due to successful treatment with plasma therapy. Therefore, efficacy analyses will be performed separately in the plasma therapy-resistant and plasma therapy responsive subjects. The principal efficacy analyses will be the analyses in the plasma therapy resistant cohort and efficacy analyses of the plasma therapy-responsive cohort will be supportive. Safety analyses will be conducted in all subjects.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Lithuania
  • Vilnius, Lithuania
    • Omeros Investigational Site
• Poland
  • Lodz, Poland
    • Omeros Investigational Site
• Taiwan
  • New Taipei City, Taiwan
    • Omeros Investigational Site
• United States
  • Illinois
    • Chicago, Illinois, United States, 60643
      • Omeros Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Are age >= 12 years old at screening (Visit 1).

2. Have a primary aHUS, diagnosed clinically, and have ADAMTS13 activity > 5% in plasma. Participants are eligible with or without a documented complement mutation or anti-CFH antibody. Participants are categorized according to their response to plasma therapy (plasma exchange or plasma infusion):

   • Plasma therapy-resistant aHUS participants must have all of the following:

     • Screening platelet count < 150,000/μL despite at least four plasma therapy treatments in a 7-day period prior to screening

     • Evidence of microangiopathic hemolysis (at least one of:

       1. presence of schistocytes,
       2. serum LDH > 1.5 times upper limit of normal (ULN), and
       3. haptoglobin < LLN)
     • Serum creatinine > ULN

   • Plasma therapy-responsive aHUS participants must have all of the following:

     • Have a documented history of requiring plasma therapy to prevent aHUS exacerbation defined as all of the following:

       • decrease in platelet count > 25% when plasma therapy frequency has been decreased (including discontinuation of plasma therapy)
       • LDH > 1.5 times ULN when plasma therapy frequency has been decreased (including discontinuation of plasma therapy)
   • Have received plasma therapy at least once every 2 weeks at an unchanged frequency for at least 8 weeks before first dose of OMS721
3. If sexually active and of childbearing potential, must agree to practice a highly effective method of birth control until the end of the study, defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence or vasectomized partner.
4. Do not have access to eculizumab treatment, have not derived therapeutic benefit from eculizumab treatment, or have not been able to tolerate eculizumab treatment.

Exclusion Criteria:

1. Have STEC-HUS.
2. Have a positive direct Coombs test.
3. Have a history of hematopoietic stem cell transplant.
4. Have HUS from an identified drug.
5. History of vitamin B12 deficiency-related HUS.
6. History of Systemic Lupus Erythematosus.
7. History of antiphospholipid syndrome.
8. Active cancer or history of cancer (except non-melanoma skin cancers) within 5 years of screening.
9. Have been on hemodialysis or peritoneal dialysis for ≥ 12 weeks.
10. Have an active systemic bacterial or fungal infection requiring systemic antimicrobial therapy (prophylactic antimicrobial therapy administered as standard of care is allowed).
11. Baseline resting heart rate < 45 beats per minute or > 115 beats per minute.
12. Baseline QTcF > 470 milliseconds.
13. Have malignant hypertension (diastolic blood pressure [BP] > 120 mm Hg with bilateral hemorrhages or "cotton-wool" exudates on funduscopic examination).
14. Have a poor prognosis with a life expectancy of less than three months in the opinion of the Investigator.
15. Are pregnant or lactating.
16. Have received treatment with an investigational drug or device within four weeks of the screening visit.
17. Have abnormal liver function tests defined as ALT or AST > five times ULN.
18. Have HIV infection.
19. History of cirrhosis of the liver.
20. Are an employee of Omeros, an Investigator, a study staff member, or their immediate family member.
21. Have a known hypersensitivity to any constituent of the product.
22. Presence of any condition that the Investigator believes would put the subject at risk or confound the interpretation of the data.
23. Have previously completed treatment in an OMS721study.
24. Have received intravenous immunoglobulin (IVIG) treatment within 8 weeks of screening visit.
25. Have received rituximab within 24 weeks of screening visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OMS721 (narsoplimab); Administration of OMS721 (narsoplimab)	Biological: OMS721 (narsoplimab); Intravenous loading dose followed by daily subcutaneous injections; Other Names: narsoplimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet Count (10^9 Platelets/L) Change From Baseline at Week 26	The primary outcome to be measured is platelet count change from baseline.	Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety as Measured by Incidences of Adverse Events, Vital Signs, ECG, and Clinical Laboratory Tests	Assessment of safety of OMS721 (narsoplimab) in participants with aHUS by incidence of Adverse Events, clinically significant vital sign abnormalities, ECG abnormalities, and clinical laboratory test abnormalities	Pre-dose and up to 771 days post-dose
Thrombotic Microangiopathies (TMA) Response	Complete TMA response defined as normalization of platelet count, normalization of serum lactate dehydrogenase (LDH), and > 25% decrease in serum creatinine by at least 2 consecutive measures over at least 4 consecutive weeks, within the initial 26-week period	26 weeks
TMA Event-free Status	No decrease in platelet count of > 25% from baseline, no plasma exchange or plasma infusion, and no initiation of new dialysis over at least 12 consecutive weeks, within the initial 26-week period	26 weeks
Increase in Estimated Glomerular Filtration Rate (eGFR)	Increase of greater than 15 ml/min/1.73 m2 in eGFR calculated by the modification of diet in renal disease (MDRD) Equation	26 weeks
Hematological Normalization	Normalization of platelet count and normalization of serum LDH by 2 consecutive measurements over at least 4 weeks, within the initial 26-week period	26 weeks
TMA Remission	Platelet count greater than or equal to 150,000/μL on at least 2 consecutive measures over at least 2 consecutive weeks, within the initial 26-week period	26 weeks
Incidence of Antidrug Antibodies (ADA)	Incidences of ADA in participants with aHUS, administered OMS721 (narsoplimab)	771 days post-dose
Change From Baseline in Serum Creatinine (mg/dL)	Assessment of subject's change from baseline in serum creatinine.	26 weeks
Change From Baseline in Serum LDH (U/L)	Assessment of subject's change from baseline in serum LDH	26 weeks
Change From Baseline in Haptoglobin (mg/dL)	Assessment of subject's change from baseline in haptoglobin	26 weeks
Pharmacokinetics (PK): Trough Plasma Concentration, Lower Limit of Quantification (LLOQ)	Pharmacokinetics (PK): Trough plasma concentration, lower limit of quantification (LLOQ)	Days 1-4; Treatment Maintenance (103 weeks): 17 visits; Rescue Therapy (RT) (if occurs): RT Days 1-4; Follow-Up at Day 771
Pharmacokinetics (PK): Maximum Plasma Concentrations (Cmax)	Pharmacokinetics (PK): Maximum plasma concentrations (Cmax)	Days 1-4; Treatment Maintenance (103 weeks): 17 visits; Rescue Therapy (if occurs): RT Days 1-4; Follow-Up at Day 771
Pharmacokinetics (PK): Area Under Time-concentration Curve (AUC)	Pharmacokinetics (PK): Area under time-concentration curve (AUC)	Days 1-4; Treatment Maintenance (103 weeks): 17 visits; Rescue Therapy (if occurs): RT Days 1-4; Follow-Up at Day 771
Pharmacodynamics (PD): Inhibition of C3 Activity (%)	Pharmacodynamics (PD): Inhibition of C3 activity	Days 1-4; Treatment Maintenance (103 weeks): 17 visits; Rescue Therapy (if occurs): RT Days 1-4; Follow-Up at Day 771
Pharmacodynamics (PD): Inhibition of C4 Activity (%)	Pharmacodynamics (PD): Inhibition of C4 activity	Days 1-4; Treatment Maintenance (103 weeks): 17 visits; Rescue Therapy (if occurs): RT Days 1-4; Follow-Up at Day 771

Collaborators and Investigators

• Sponsor: Omeros Corporation
• Investigators: Study Director: Eckhard Leifke, M.D., Omeros Corporation

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2018
• Primary Completion (Actual): February 2, 2021
• Study Completion (Actual): February 2, 2021

Study Registration Dates

• First Submitted: April 17, 2017
• First Submitted That Met QC Criteria: June 28, 2017
• First Posted (Actual): July 2, 2017

Study Record Updates

• Last Update Posted (Estimated): December 10, 2025
• Last Update Submitted That Met QC Criteria: November 25, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: aHUS; TMA
• Additional Relevant MeSH Terms: Urogenital Diseases; Cytopenia; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Hematologic Diseases; Anemia, Hemolytic; Anemia; Blood Platelet Disorders; Thrombocytopenia; Uremia; Hemic and Lymphatic Diseases; Hemolytic-Uremic Syndrome; Thrombotic Microangiopathies; Atypical Hemolytic Uremic Syndrome; narsoplimab
• Other Study ID Numbers: OMS721-HUS-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No