An Indian Multi-centric Phase IV Study to Assess the Safety of Crizanlizumab in Sickle Cell Disease Patients

Study Overview
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Brief Summary
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Sickle cell disease (SCD) is a genetic blood disorder. Crizanlizumab has been approved in India and other countries to reduce the frequency of vaso-occlusive crises (VOCs) in patients with SCD aged 16 years and older. The purpose of this local Phase IV study is to evaluate the safety of crizanlizumab specifically in Indian patients with SCD aged 16 years or older with a history of VOC leading to healthcare visit.

Detailed Description
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Sickle cell disease (SCD) is a genetic blood disorder, caused by a mutation in the β-globin gene, which early on progresses into a systemic disease. Vaso-occlusion is a hallmark of SCD and can lead to serious acute and chronic complications. Crizanlizumab has been approved in US, India and other countries to reduce the frequency of vaso-occlusive crises (VOCs) in patients with SCD aged 16 years and older. The purpose of this local Phase IV study is to evaluate the safety of crizanlizumab specifically in Indian patients with SCD aged 16 years or older with a history of VOC leading to healthcare visit. The study is open label and single armed. 140 patients will be treated with crizanlizumab for about one year at a dose of 5 mg/kg in addition to receiving standard of care. The primary objective is to assess frequency, severity and causality of serious adverse events (SAEs) during the treatment period. Secondary objective is to assess overall safety and tolerability of crizanlizumab.

Official Title
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An Indian Multi-centric Phase IV Study to Assess the Safety of Crizanlizumab With or Without Hydroxyurea Therapy in Sickle Cell Disease Patients With Vaso-occlusive Crises.

Conditions
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Sickle Cell Disease (SCD)

Intervention / Treatment
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* Drug: crizanlizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Male or female participant aged 16 years and older Confirmed diagnosis of SCD by hemoglobin electrophoresis or high performance liquid chromatography (HPLC). All SCD genotypes are eligible. History of VOC leading to healthcare visit prior to screening visit Participants must meet the following central laboratory values at the screening visit: Absolute Neutrophil Count ≥1.0 x 109/L Platelet count ≥75 x 109/L Hemoglobin: for adults (Hb) ≥4.0 g/dL and for adolescents (Hb) ≥5.5 g/dL Glomerular filtration rate ≥ 45 mL/min/1.73 m2 using CKD-EPI formula Direct (conjugated) bilirubin < 2.0 x ULN Alanine Aminotransferase (ALT) < 3.0 x ULN ECOG performance status ≤2 for adults and Karnofsky Performance Scale ≥ 50% for adolescents. Exclusion Criteria: Contraindication or hypersensitivity to any drug or metabolites from similar class as study drug. History of severe hypersensitivity reaction to other monoclonal antibodies which in the opinion of the investigator may pose an increased risk of serious infusion reaction. Participant has received crizanlizumab and/or other P-selectin inhibitor prior to the study or plans to receive it during the duration of the study. Concurrent severe and/or uncontrolled medical conditions which, in the opinion of the Investigator, could cause unacceptable safety risks or compromise participation in the study. Any condition which, in the opinion of the investigator, is likely to interfere with the successful collection of the measurements required for the study. Participant has documented immunogenicity to a prior biological drug. Participants who are on active treatment with Voxelotor, other investigational drug or other monoclonal antibody, or intend to initiate the same during the course of the trial. Pregnant females or females who have given birth within the past 90 days prior screening or who are breastfeeding. Women of childbearing potential unless using highly effective methods of contraception during dosing and for 15 weeks after stopping treatment Significant bleeding disorder Active HIV infection Active Hepatitis B infection Positive test for Hepatitis C RNA Malignant disease Active infection or immune deficiency

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crizanlizumab<br>Participants will receive Crizanlizumab at a dose of 5.0 mg/kg. | Drug: crizanlizumab<br>* Crizanlizumab will be taken by IV infusion, at Week 1 Day 1, Week 3 Day 1 and all 4 weeks thereafter.<br>* Other names: SEG101;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with at least one serious adverse event (SAE) with 2-sided 95% confidence interval (CI) | Incidence of serious adverse events (SAEs) | During treatment period - from Week 1 Day 1 (first dose) to safety follow up visit (105 days after Week 51 Day 1, or 105 days after last dose in case of early discontinuation) | 
| Percentage of patients with SAEs of grades >=3 | Severity of serious adverse events (SAEs) | During treatment period - from Week 1 Day 1 (first dose) to safety follow up visit (105 days after Week 51 Day 1, or 105 days after last dose in case of early discontinuation) | 
| Percentage of patients with treatment-related SAEs of all grades | Causality of serious adverse events (SAEs) | During treatment period - from Week 1 Day 1 (first dose) to safety follow up visit (105 days after Week 51 Day 1, or 105 days after last dose in case of early discontinuation) | 
| Percentage of patients with treatment-related SAEs of grades >=3 | Causality of severe serious adverse events (SAEs) | During treatment period - from Week 1 Day 1 (first dose) to safety follow up visit (105 days after Week 51 Day 1, or 105 days after last dose in case of early discontinuation) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with at least one treatment-emergent adverse event (AE)(new or worsening from baseline) | Incidence of treatment-emergent adverse events (AEs) | During treatment period - from Week 1 Day 1 (first dose) to safety follow up visit (105 days after Week 51 Day 1, or 105 days after last dose in case of early discontinuation) | 
| Percentage of patients with AEs of grades >=3 | Severity of adverse events (AEs) | During treatment period - from Week 1 Day 1 (first dose) to safety follow up visit (105 days after Week 51 Day 1, or 105 days after last dose in case of early discontinuation) | 
| Percentage of patients with treatment-related AEs of all grades | Causality of adverse events (AEs) | During treatment period - from Week 1 Day 1 (first dose) to safety follow up visit (105 days after Week 51 Day 1, or 105 days after last dose in case of early discontinuation) | 
| Percentage of patients with treatment-related AEs of grades >=3 | Causality of severe adverse events (AEs) | During treatment period - from Week 1 Day 1 (first dose) to safety follow up visit (105 days after Week 51 Day 1, or 105 days after last dose in case of early discontinuation) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle cell disease, Sickle cell disorder, SCD, Sickle cell anemia, Hemoglobin SC disease, Sickling disorder due to hemoglobin S, Vaso-occlusive crisis, VOC, P-selectin, Crizanlizumab, SEG101