Paroxysmal Nocturnal Hemoglobinuria
Conditions
Keywords
PNH
Brief summary
The purpose of this study is to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH).
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
Interventions
BIOLOGICALOMS906
Biological: OMS906
Sponsors
Omeros Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients will receive zaltenibart, administered as subcutaneous (SC) injections or intravenous (IV) infusions
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Assess the Overall Safety and Tolerability of Zaltenibart (OMS906) Administration in PNH patients | 48 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Lactate Dehydrogenase (LDH) change from baseline | 48 weeks | Mean Lactate Dehydrogenase (LDH) change from baseline (Only patients not receiving complement inhibitor treatment) |
| Mean change of hemoglobin (Hgb) | 48 weeks | To assess preliminary efficacy by the effect on hemolysis and anemia measured by hemoglobin (Hgb). |
| Time to subclinical breakthrough hemolysis post-treatment | 48 weeks | Time (in days) to subclinical breakthrough hemolysis during the 5 mg/kg IV on demand period. |
| Mean change from baseline in absolute reticulocyte count | 48 weeks | Individual patient changes from baseline in absolute reticulocyte counts |
| Transfusion requirements | -24 weeks to 48 weeks | Mean change from baseline in transfusion frequency from the 6-month period prior to the first OMS906 dose to the end of the study |
| Transfusion free | Week 4 to Week 48 | Proportion of patients who are transfusion free from Week 4 through the end of the study |
| Proportion of breakthrough hemolysis | 48 weeks | Proportion of patients experiencing breakthrough hemolysis during the 5 mg/kg Q4W SC treatment period. |
| Incidence of patients with hemoglobin increase ≥ 2.0 g/dL from baseline | 48 weeks | Number and % of participants with hemoglobin increase ≥ 2.0 g/dL from baseline |
| Incidence of patients with hemoglobin increase ≥ 12.0 g/dL from baseline | 48 weeks | Number and % of participants with hemoglobin increase ≥ 12.0 g/dL from baseline |
| Pharmacokinetics (PK) of multiple-dose administration of OMS906: Cmax | 48 weeks | Maximum concentration (Cmax) of observed OMS906 plasma concentration by OMS906 dosing regimen. |
| Pharmacokinetics (PK) of multiple-dose administration of OMS906: AUC | 48 weeks | Area under the plasma concentration versus time curve (AUC) |
| Free Mannan-binding lectin-associated Serine protease 3 concentration | 48 weeks | Free MASP-3 serum concentrations by dosing regimen following the first dose and repeated doses |
| Mature Complement Factor Concentration | 48 weeks | Mature Complement Factor D (CFD) concentrations by dosing regimen following the first dose and repeated doses |
| Total Mannan-Binding Lectin-Associated Serine Protease 3 (MASP-3) Concentration | 48 weeks | Total MASP-3 serum concentrations by OMS906 dosing regimen following first dose and repeated doses |
| OMS906 anti-drug antibodies (ADA) | 48 weeks | Number of patients with measurable ADA |
Countries
Ukraine
Contacts
STUDY_DIRECTORSteve Whitaker, MD
Omeros Corporation
Outcome results
None listed