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

Sickle Cell Disease (SCD) Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04662931
• Other study ID #: CSEG101A2403
• Status: Completed
• Phase: Phase 4
• Start date: July 14, 2021
• Est. completion date: February 14, 2024

Study information

• Verified date: April 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Sickle cell disease (SCD) is a genetic blood disorder. Crizanlizumab is indicated 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.

Description:

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. 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 approximately 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: February 14, 2024
• Est. primary completion date: February 14, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease (SCD)

Intervention

Drug:
• crizanlizumab
Crizanlizumab will be taken by IV infusion, at Week 1 Day 1, Week 3 Day 1, and Day 1 of every 4-weeks cycle until Week 51 Day 1

Locations

Country	Name	City	State
India	Novartis Investigative Site	Bhubaneswar	Odisha
India	Novartis Investigative Site	Guwahati
India	Novartis Investigative Site	Hyderabad	Telangana
India	Novartis Investigative Site	Kolkata	West Bengal
India	Novartis Investigative Site	Kozhikode	Kerala
India	Novartis Investigative Site	Lucknow	Uttar Pradesh
India	Novartis Investigative Site	Raipur	Chhattisgarh

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)