Long-Term Safety, Tolerability, and Efficacy Evaluation of OMS906 in Patients with Paroxysmal Nocturnal Hemoglobinuria: An Open-Label Study

The primary objective of this study is to evaluate the **long-term safety** and tolerability of repeat-dose OMS906, administered intravenously at a dosage of 5 mg/kg every 8 weeks, in patients diagnosed with **Paroxysmal Nocturnal Hemoglobinuria (PNH)**. This objective is clinically relevant as it aims to ensure that the treatment is safe for prolonged use, which is crucial for managing a chronic condition like PNH.

Secondary objectives include:

• Assessing long-term efficacy by evaluating the effect on hemolysis and anemia, measured through hemoglobin (Hb) levels, lactate dehydrogenase (LDH), reticulocyte count, and red blood cell (RBC) transfusion burden.
• Assessing the incidence of breakthrough hemolysis.
• Evaluating population pharmacokinetics (PK) and pharmacodynamics (PD).
• Assessing the presence of anti-drug antibodies (ADAs).
• Evaluating the effect of OMS906 on Quality of Life.

The clinical trial involves a total of **22 participants** diagnosed with **Paroxysmal Nocturnal Hemoglobinuria (PNH)**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on their completion of prior OMS906 PNH studies, demonstrating tolerance and an adequate clinical response to the treatment. The trial includes individuals who are part of a vulnerable population, indicating a need for careful monitoring and ethical considerations. Participants are required to maintain current vaccination status for Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae, where applicable. Lifestyle considerations such as the use of highly effective birth control methods are mandated for both male and female participants to prevent pregnancy during and after the trial period. The study aims to assess the long-term safety and tolerability of repeat-dose OMS906 administered intravenously at 8-week intervals.

The clinical trial is designed to evaluate the long-term safety, tolerability, and efficacy of **OMS906** in patients with **Paroxysmal Nocturnal Hemoglobinuria (PNH)**. This is an open-label, Phase IV study involving the administration of OMS906 at a dose of 5 mg/kg via intravenous injection every eight weeks. The trial is expected to span a duration of approximately 104 weeks, with the estimated recruitment start date set for August 1, 2024, and an anticipated end date of December 31, 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as completion of prior OMS906 studies, adequate clinical response, and current vaccination status. Female participants of child-bearing potential must have a negative pregnancy test prior to each dose and adhere to strict contraception guidelines. Male participants are also required to use effective birth control methods. The primary endpoint focuses on safety and tolerability, assessed through adverse events, vital signs, ECGs, and laboratory tests. Secondary endpoints include efficacy measures such as hemoglobin levels and transfusion requirements.

Study visits will occur at regular intervals, including follow-up visits every eight weeks to monitor the participants' response to treatment and any potential adverse effects. The end-of-study visit will conclude the trial, assessing the long-term outcomes of the treatment. Participants are expected to be involved for the entire duration of the trial unless conditions arise that necessitate early termination, such as significant adverse events or withdrawal of consent. The trial's design ensures a comprehensive evaluation of OMS906's impact on PNH, contributing valuable data to the understanding of its long-term use in this patient population.

The clinical trial involves the administration of **OMS906**, an investigational medicinal product developed by Omeros Corporation. **OMS906** is a **solution for injection** intended for the treatment of patients with **Paroxysmal Nocturnal Hemoglobinuria (PNH)**. The active substance, also named **OMS906**, is of biological/biotechnological origin, specifically classified as a protein of other origin. The pharmaceutical form of the product is a solution for injection, and it is administered via the **intravenous route**. The dosing regimen for this trial involves the administration of **OMS906** at a dose of **5 mg/kg**. The treatment is repeated at **8-week intervals** over a maximum treatment period of **104 weeks**. The maximum total dose amount is **70 mg/kg**.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is on evaluating the long-term safety, tolerability, and efficacy of **OMS906** in the specified patient population. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol. The trial is designed to assess the repeat-dose administration of **OMS906** and its impact on patients with PNH, with a primary objective of evaluating safety and tolerability over the long term.

Efficacy in the clinical trial will be assessed through several secondary endpoints. These include the proportion of patients achieving **hemoglobin (Hb)** levels of ≥ 12.0 g/dL, which will be evaluated at 6-month intervals. Additionally, the trial will measure the proportion of patients maintaining an increase in Hb of ≥ 2 g/dL, as achieved in the prior study. The proportion of patients who remain transfusion-free will be assessed at Weeks 48 and 96. Furthermore, the trial will evaluate the proportion of patients experiencing clinical breakthrough hemolysis at Weeks 48 and 96. Changes in mean lactate dehydrogenase (LDH) and reticulocyte counts from baseline, at the start of the long-term extension, and at Weeks 48 and 96 will also be analyzed. Population pharmacokinetic (PK) and pharmacodynamic (PD) parameters of OMS906 will be included in the efficacy assessment. These parameters will be collected and analyzed according to the specified timepoints to determine the long-term efficacy of OMS906 in patients with **Paroxysmal Nocturnal Hemoglobinuria (PNH)**.