A Phase 2 Proof of Concept Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of OMS906 in PNH Patients With a Sub-optimal Response to the C5 Inhibitor, Ravulizumab
Overview
- Phase
- Phase 2
- Intervention
- OMS906
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Sponsor
- Omeros Corporation
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- To assess the overall OMS906 administration at 8-week intervals in PNH patients.
- Status
- Completed
- Last Updated
- 7 months ago
Overview
Brief Summary
The purpose of this study is to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of OMS906 for the treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) in patients who have a sub-optimal response to ravulizumab.
Detailed Description
This is a Phase 2, proof of concept, open label study examining two doses of OMS906, 3 mg/kg and 5 mg/kg IV given to PNH patients at 8-week intervals, first in combination with the C5 inhibitor ravulizumab then as monotherapy. The primary objective is to assess overall safety and tolerability of repeat-dose IV OMS906 administration at 8-week intervals in patients with PNH.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Confirmed diagnosis of PNH by flow cytometry with PNH clone size of \> 10% red blood cells (RBCs) and/or granulocytes.
- •Male or female adults 18 years and older.
- •Completed informed consent procedures.
- •In relation to ravulizumab treatment prescribed in accordance with its marketing authorization and summary of product characteristics (SmPC):
- •Must have a sub-optimal response to ravulizumab, defined as a hemoglobin level \< 10.5 g/dL despite treatment measured at screening and confirmed at baseline (Day 1, predose). Ravulizumab treatment will have been maintained at a stable dose for at least 2 doses (4 months) prior to baseline.
- •Female patients of child-bearing potential must have a negative highly sensitive urine pregnancy test at screening and prior to each dose of OMS
- •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. If a female, must be sterile (either surgically or biologically)\* or at least one year postmenopausal\*\*, or have a monogamous partner who is surgically sterile, or have a same sex partner, or if in a heterosexual relationship, must agree to comply with the following contraception guidelines:
- •Practice abstinence (only considered an acceptable method of contraception when it is in line with the patients' usual and preferred lifestyle and the patient agrees to refrain from heterosexual intercourse during the entire period of risk associated with the study treatments, including during the clinical trial and for 20 weeks \[140 days\] following their last dose of study drug), or
- •Use at least 1 of the following medically acceptable methods of birth control:
- •Hormonal methods as follows:
Exclusion Criteria
- •History of major organ transplant or hematopoietic stem cell/marrow transplant.
- •Platelet count \< 30,000/µL or absolute neutrophil count \< 500 cells/µL at Screening.
- •Anemia, as evidenced by hemoglobin \< 10.5 g/dL, attributable to any other medical condition apart from PNH.
- •Elevation of liver function tests, defined as total bilirubin \> 2×ULN, direct bilirubin \> 1.5× upper limit of normal (ULN), and elevated transaminases, alanine aminotransferase (ALT) or aspartate aminotransferase (AST), \> 2×ULN unless due to PNH related hemolysis.
- •History of any severe hypersensitivity reactions to other monoclonal antibodies or excipients included in the OMS906 preparation.
- •Significant active bacterial or viral infection within the 2 weeks prior to Screening, including COVID-19 infection.
- •Immunodeficiency or immunosuppression (including chronic use of immunosuppressive drugs, such as ciclosporin or tacrolimus).
- •History of meningococcal disease and/or has not received vaccination for N. meningitidis.
- •Pregnant, planning to become pregnant, or nursing female patients.
- •Recent surgery requiring general anesthesia within the 2 weeks prior to Screening or expected to have surgery requiring general anesthesia during the Treatment Period.
Arms & Interventions
3 mg/kg IV OMS906 with Ravulizumab IV
Up to 6 doses of 3 mg/kg at 8-week intervals. All patients will receive 3 doses of OMS906 of 3 mg/kg Intravenous (IV) at 8-week intervals. Clinical responders at Week 24 will receive an additional 3 doses of OMS906 only at 8-week intervals at 5 mg/kg (monotherapy). Incomplete responders may receive an additional 3 doses of OMS906 with ravulizumab at 8-week intervals. Non responders will not receive additional OMS906.
Intervention: OMS906
5 mg/kg IV OMS906 with Ravulizumab IV
Up to 6 doses of 5 mg/kg at 8-week intervals. All patients will receive 3 doses of OMS906 of 5 mg/kg Intravenous (IV) at 8-week intervals. Clinical responders at Week 24 will receive an additional 3 doses of OMS906 only at 8-week intervals (monotherapy). Incomplete responders may receive an additional 3 doses of OMS906 with ravulizumab at 8-week intervals. Non responders will not receive additional OMS906.
Intervention: OMS906
Outcomes
Primary Outcomes
To assess the overall OMS906 administration at 8-week intervals in PNH patients.
Time Frame: 56 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 Outcomes
- OMS906 anti-drug antibodies (ADA)(56 weeks)
- Pharmacokinetics (PK) of multiple-dose administration of OMS906(56 weeks)
- Reticulocyte count(56 weeks)
- Transfusion requirements(56 weeks)
- Pharmacodynamics (PD) of multiple-dose administration of OMS906(56 weeks)
- Incidence of patients with hemoglobin increase ≥ 2.0 g/dL from baseline (Response criterion) baseline on adjunctive treatment and sustained during monotherapy.(56 weeks)
- Lactate dehydrogenase (LDH)(56 weeks)