Phase IV, Open-label, Multi-center Rollover Study of Crizanlizumab in Patients with Sickle Cell Disease Post-Novartis-Sponsored Study Completion

The primary objective of this study is to provide continued access to **crizanlizumab** for patients with **sickle cell disease** (SCD) who are currently receiving this treatment as part of a Novartis-sponsored study. This is clinically relevant as it ensures the ongoing management of SCD symptoms in patients who have previously benefited from crizanlizumab, potentially improving their quality of life and reducing disease-related complications.

Secondary objectives include assessing the overall safety of crizanlizumab in patients with SCD. This evaluation is crucial for understanding the long-term safety profile of the treatment, ensuring that any adverse effects are identified and managed appropriately, thereby safeguarding patient health during extended use.

The clinical trial involves a total of **59 participants** diagnosed with **sickle cell disease**. The study population includes both male and female subjects, encompassing a broad age range from children to adults. Participants were selected based on their current enrollment and benefit from a Novartis-sponsored study receiving crizanlizumab. The trial includes individuals who have demonstrated compliance with the planned visit schedule in the parent study and have shown willingness and ability to adhere to future visit schedules. The trial population is characterized by a vulnerable group, indicating special considerations in their selection and management. Specific lifestyle factors such as diet, physical activity, or habits are not detailed in the available data.

The clinical trial is designed as an open-label, multi-center, Phase IV rollover study for patients with **sickle cell disease** who have completed a prior Novartis-sponsored study involving **crizanlizumab**. The primary objective is to allow continued access to crizanlizumab for patients who are currently benefiting from the treatment. The trial is expected to run from June 10, 2021, to October 27, 2031. Participants will be involved in the study for a maximum treatment period of 120 weeks, receiving crizanlizumab as a **concentrate for solution for infusion** administered via intravenous use. The study will not include a control group, and there is no blinding involved.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as written informed consent and compliance with previous study protocols. Follow-up visits will be scheduled to monitor the frequency, severity, and causality of treatment-emergent adverse events. The end-of-study visit will conclude the participant's involvement, assessing overall treatment outcomes and any long-term effects. Participants may be terminated early from the study if they fail to comply with visit schedules or if the investigator deems it necessary for safety reasons. The trial does not specify primary endpoints but focuses on secondary endpoints related to adverse events. The study is not classified as low intervention, and it is not an orphan drug trial.

The clinical trial involves the administration of **crizanlizumab**, marketed under the product name SEG101, which is a **concentrate for solution for infusion**. This experimental medication is developed by Novartis Pharma AG and is intended for **intravenous use**. The active substance, crizanlizumab, is a humanized monoclonal antibody targeting P-selectin, classified under the origin of "Protein - Other." The dosage is calculated based on body weight, with a maximum daily dose of 7.5 mg/kg. The treatment period is capped at 120 days. The administration schedule and participant compliance are closely monitored to ensure adherence to the dosing regimen.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial is designed to provide continued access to crizanlizumab for patients with sickle cell disease who have completed a prior Novartis-sponsored study. The focus is on maintaining the therapeutic regimen established in previous studies, ensuring that participants receive the intended therapeutic benefits of crizanlizumab without the introduction of additional treatments.

Efficacy in this clinical trial will be assessed through the evaluation of secondary endpoints, specifically focusing on the **frequency, severity, and causality of treatment emergent adverse events**. These parameters will be systematically collected and analyzed to determine the impact of the investigational product, crizanlizumab, on patients with Sickle Cell Disease (SCD) who have completed a prior Novartis-sponsored study. The trial is designed as an open-label, multi-center, Phase IV rollover study, allowing continued access to crizanlizumab for eligible patients. The assessment of adverse events will be conducted throughout the trial duration, with data collection aligned with the planned visit schedules. The analysis will involve a comprehensive review of adverse event reports to ascertain their relationship to the treatment, thereby providing insights into the safety profile of crizanlizumab in this patient population.