Study of the Safety and Efficacy of OMS906 in Patients With Paroxysmal Nocturnal Hemoglobinuria

A Phase 1b Proof of Concept Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of OMS906 in Patients With Paroxysmal Nocturnal Hemoglobinuria

The purpose of this study is to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH).

Study Overview

• Status: Completed
• Conditions: Paroxysmal Nocturnal Hemoglobinuria
• Intervention / Treatment: Biological: OMS906

Detailed Description

This is a Phase 1b, proof of concept, open-label, uncontrolled study. The primary objective is to assess the safety and tolerability of OMS906 in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH). The study evaluated 3 dosing regimens: (1) 5 mg/kg SC administered every 4 weeks (Q4W), (2) 5 mg/kg IV administered once followed by administration of additional doses of 5 mg/kg IV at the occurrence of protocol-defined subclinical breakthrough hemolysis, and (3) 8 mg/kg IV every 8 weeks (Q8W) on a fixed-dosing (FD) schedule

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Ukraine
  • Kyiv, Ukraine
    • Omeros Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Confirmed diagnosis of PNH by flow cytometry with PNH clone size of >10% RBCs and/or granulocytes.
2. Male or female adults 18 years and older.
3. Competent to provide consent and completed informed consent procedures.
4. Patients who are not receiving complement inhibitor treatment or, alternatively, patients currently treated with eculizumab or ravulizumab with an inadequate response to treatment defined as a Hgb <10.5 g/dL. Patients receiving eculizumab or ravulizumab must be on stable doses for at least 6 months.
5. Hemoglobin level <10.5 g/dL at screening and baseline.
6. Lactate dehydrogenase >1.5 upper limit of normal (ULN) for patients not receiving eculizumab or ravulizumab.
7. Female patients of child-bearing potential (CBP) must have a negative serum test at screening and highly sensitive urine pregnancy test prior to each dose of OMS906.
8. Females must use highly effective birth control to prevent pregnancy during the clinical trial and for 20 weeks (140 days) following their last dose of study drug.
9. Males must use highly effective birth control with a female partner to prevent pregnancy during the clinical trial and for 20 weeks (140 days) following their last dose of study drug.
10. Have received vaccination for Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae (if locally available). Patients who have not received these vaccinations at the time of screening may be vaccinated at any time prior to 2 weeks before the first study drug administration. Patients enrolled in the study at the time of Amendment 02 may receive S. pneumoniae and H. influenzae vaccinations, if not already vaccinated, at their next scheduled visit.

Exclusion Criteria:

1. Treatment with any complement pathway inhibitor except eculizumab or ravulizumab within the 6 months prior to screening.
2. For patients not receiving eculizumab or ravulizumab at the time of screening: receipt of eculizumab within 8 weeks prior to screening or receipt of ravulizumab within 24 weeks prior to screening.
3. History of major organ transplant or hematopoietic stem cell/bone marrow transplant.
4. Reticulocyte count <100,000 /µL, transfusion-free platelet count <30,000/µL or absolute neutrophil count <500 cells/µL at screening.
5. Anemia attributable to any other medical condition apart from PNH.
6. Elevation of liver function tests, defined as total bilirubin >2×ULN, direct bilirubin >1.5xULN, and elevated transaminases, alanine aminotransaminase (ALT) or aspartate transaminase (AST), >2×ULN unless due to PNH related hemolysis.
7. History of any severe hypersensitivity reactions to other monoclonal antibodies or excipients included in the OMS906 preparation.
8. Significant active bacterial, fungal, or viral infection within the 2 weeks of OMS906 drug initiation, including COVID-19 infection.
9. History of primary or secondary immunodeficiency or complement deficiency.
10. Have human immunodeficiency virus, hepatitis B or untreated hepatitis C infection.
11. History of splenectomy.
12. History or prior bacterial meningitis or N. meningitidis infection.
13. Patients on immunosuppressive agents such as but not limited to cyclosporine, mycophenolate mofetil (MMF), tacrolimus, cyclophosphamide, or methotrexate less than 8 weeks prior to first treatment with OMS906 unless on a stable regimen for at least 3 months prior to screening.
14. Patients who require recurrent short courses of systemic corticosteroids (i.e., >4 short courses per year of >2 weeks in duration per course).
15. Pregnant, planning to become pregnant, or nursing female patients.
16. Recent surgery requiring general anesthesia within the 2 weeks prior to screening or expected to have surgery requiring general anesthesia during the treatment periods.
17. History of any clinically significant medical, neurologic, or psychiatric disorder that in the opinion of the investigator would make the patient unsuitable for participation in the study.
18. Treatment with any investigational medicinal product or investigational device within the 30 days (or within 5x its half-life in days, whichever is the longer period) prior to screening or participation in another concurrent clinical trial involving a therapeutic intervention. Participation in observational studies and/or registry studies is permitted.
19. Unable or unwilling to comply with the requirements of the study.

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: OMS906 study drug administration in three phases; 5 mg/kg SC administered every 4 weeks (Q4W),; 5 mg/kg IV administered once followed by administration of additional doses of 5 mg/kg IV at the occurrence of protocol-defined subclinical breakthrough hemolysis, and 3.) 8 mg/kg IV every 8 weeks (Q8W) on a fixed-dosing (FD) schedule	Biological: OMS906; Biological: OMS906; Other Names: zaltenibart

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Assess the Overall Safety and Tolerability of Zaltenibart (OMS906) Administration in PNH patients	Number and % of participants with Treatment-emergent Adverse Events (TEAEs) as assessed by CTCAE v5.0, including abnormalities in laboratory measures, ECGs and physical examinations.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Lactate Dehydrogenase (LDH) change from baseline	Mean Lactate Dehydrogenase (LDH) change from baseline (Only patients not receiving complement inhibitor treatment)	48 weeks
Mean change of hemoglobin (Hgb)	To assess preliminary efficacy by the effect on hemolysis and anemia measured by hemoglobin (Hgb).	48 weeks
Time to subclinical breakthrough hemolysis post-treatment	Time (in days) to subclinical breakthrough hemolysis during the 5 mg/kg IV on demand period.	48 weeks
Mean change from baseline in absolute reticulocyte count	Individual patient changes from baseline in absolute reticulocyte counts	48 weeks
Transfusion requirements	Mean change from baseline in transfusion frequency from the 6-month period prior to the first OMS906 dose to the end of the study	-24 weeks to 48 weeks
Transfusion free	Proportion of patients who are transfusion free from Week 4 through the end of the study	Week 4 to Week 48
Proportion of breakthrough hemolysis	Proportion of patients experiencing breakthrough hemolysis during the 5 mg/kg Q4W SC treatment period.	48 weeks
Proportion of breakthrough hemolysis	Proportion of patients experiencing breakthrough hemolysis during the 8 mg/kg Q4W IV treatment period	48 weeks
Incidence of patients with hemoglobin increase ≥ 2.0 g/dL from baseline	Number and % of participants with hemoglobin increase ≥ 2.0 g/dL from baseline	48 weeks
Incidence of patients with hemoglobin increase ≥ 12.0 g/dL from baseline	Number and % of participants with hemoglobin increase ≥ 12.0 g/dL from baseline	48 weeks
Pharmacokinetics (PK) of multiple-dose administration of OMS906: Cmax	Maximum concentration (Cmax) of observed OMS906 plasma concentration by OMS906 dosing regimen.	48 weeks
Pharmacokinetics (PK) of multiple-dose administration of OMS906: AUC	Area under the plasma concentration versus time curve (AUC)	48 weeks
Free Mannan-binding lectin-associated Serine protease 3 concentration	Free MASP-3 serum concentrations by dosing regimen following the first dose and repeated doses	48 weeks
Mature Complement Factor Concentration	Mature Complement Factor D (CFD) concentrations by dosing regimen following the first dose and repeated doses	48 weeks
Total Mannan-Binding Lectin-Associated Serine Protease 3 (MASP-3) Concentration	Total MASP-3 serum concentrations by OMS906 dosing regimen following first dose and repeated doses	48 weeks
OMS906 anti-drug antibodies (ADA)	Number of patients with measurable ADA	48 weeks

Collaborators and Investigators

• Sponsor: Omeros Corporation
• Investigators: Study Director: Steve Whitaker, MD, Omeros Corporation

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2022
• Primary Completion (Actual): November 3, 2025
• Study Completion (Actual): November 3, 2025

Study Registration Dates

• First Submitted: May 4, 2023
• First Submitted That Met QC Criteria: May 25, 2023
• First Posted (Actual): June 5, 2023

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: PNH
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Anemia, Hemolytic; Anemia; Myelodysplastic Syndromes; Hemic and Lymphatic Diseases; Hemoglobinuria, Paroxysmal
• Other Study ID Numbers: OMS906-PNH-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
• product manufactured in and exported from the U.S.: Yes