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

Study Overview
=================
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, fixed-dose study. The primary objective is to assess safety and tolerability of OMS906 in patients with PNH. Patients will receive 5 mg/kg OMS906 administered as subcutaneous (SC) injections at 4-week intervals.

Official Title
-----------------
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

Conditions
-----------------
Paroxysmal Nocturnal Hemoglobinuria

Intervention / Treatment
-----------------
* Drug: OMS906 study drug


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Confirmed diagnosis of PNH by flow cytometry with PNH clone size of >10% RBCs and/or granulocytes. Male or female adults 18 years and older. Completed informed consent procedures. 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. Hemoglobin level <10.5 g/dL at screening and baseline. Lactate dehydrogenase >1.5 upper limit of normal (ULN) for patients not receiving eculizumab or ravulizumab. 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. 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. 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. Have received vaccination for Neisseria meningitidis. Patients who have not received this vaccination at the time of screening may be vaccinated at any time prior to 2 weeks before the first study drug administration. Exclusion Criteria: Treatment with any complement pathway inhibitor except eculizumab or ravulizumab within the 6 months prior to screening. 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. History of major organ transplant or hematopoietic stem cell/bone marrow transplant. Reticulocyte count <100,000 /µL, transfusion-free platelet count <30,000/µL or absolute neutrophil count <500 cells/µL at screening. Anemia attributable to any other medical condition apart from PNH. 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. History of any severe hypersensitivity reactions to other monoclonal antibodies or excipients included in the OMS906 preparation. Significant active bacterial, fungal, or viral infection within the 2 weeks of OMS906 drug initiation, including COVID-19 infection. History of primary or secondary immunodeficiency or complement deficiency. Have human immunodeficiency virus, hepatitis B or untreated hepatitis C infection. History of splenectomy. History or prior bacterial meningitis or N. meningitidis infection. 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. Patients who require recurrent short courses of systemic corticosteroids (i.e., >4 short courses per year of >2 weeks in duration per course). 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. 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. 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. Unable or unwilling to comply with the requirements of the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OMS906 study drug<br>OMS906 study drug repeat-dose 5 mg/kg SC administration at 4-week intervals | Drug: OMS906 study drug<br>* OMS906 study drug dose repeat-dose 5mg/kg SC administration at 4-week intervals<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess overall safety and tolerability of repeat-dose OMS906 5 mg/kg SC administration at 4-week intervals in patients with PNH. | Number of participants with treatment-emergent adverse events assessed by CTCAE v5.0 and changes in laboratory measures, ECGs and physical examination. | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess preliminary efficacy by the effect on hemolysis and anemia measured by hemoglobin (Hgb). | To assess preliminary efficacy by the effect on hemolysis and anemia measured by hemoglobin (Hgb). | 48 weeks | 
| To assess preliminary efficacy by the effect on hemolysis and anemia measured by Lactate dehydrogenase (LDH). | To assess preliminary efficacy by the effect on hemolysis and anemia measured by Lactate dehydrogenase (LDH). | 48 weeks | 
| To assess preliminary efficacy by the effect on hemolysis and anemia measured by red blood cell (RBC) transfusion burden. | To assess preliminary efficacy by the effect on hemolysis and anemia measured by red blood cell (RBC) transfusion burden. | 48 weeks | 
| To assess preliminary efficacy measured by PK, PD, and ADA. | Pharmacokinetics (PK) of multiple-dose administration of OMS906. PK parameters including maximum concentration, area under the time-concentration curve, and terminal half-life. Pharmacodynamics (PD) of multiple-dose administration of OMS906. PD parameters including change from baseline in mature complement factor D (FD) and alternative pathway (AP) activation (ex vivo rabbit RBC lysis). Presence of anti-drug antibodies (ADA) in serum will be measured. | 48 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PNH