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

Phase 4

Completed

Conditions: Sickle Cell Disease (SCD)

Interventions: Drug: crizanlizumab

Registration Number: NCT04662931

Lead Sponsor: Novartis Pharmaceuticals

Brief 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 was 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: 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 was 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 was open label and single armed. 140 patients were treated with crizanlizumab for approximately one year at a dose of 5 mg/kg in addition to receiving standard of care.

The primary objective was to assess frequency, severity and causality of serious adverse events (SAEs) during the treatment period. Secondary objective was to assess overall safety and tolerability of crizanlizumab.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 140

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Crizanlizumab	crizanlizumab	Participants received Crizanlizumab at a dose of 5.0 mg/kg, and standard of care.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Serious Adverse Events (SAEs)	Up to 15 months	Number of participants with treatment emergent SAEs and SAEs grade \>=3. Adverse events were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5. CTCAE ranges severity from Grade 1 through 5 being Grade 1 the lowest severity grade.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events (AEs)	Up to 15 months	Number of participants with treatment emergent AEs, AEs grade \>=3, AEs led to study treatment discontinuation, AEs leading to dose adjustment/interruption, and AEs requiring additional therapy. Adverse events were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Number of Participants With Adverse Events of Special Interest (AESI)	Up to 15 months	The AESIs were designated medical events, infections, infusion-related reaction (IRR), infusion-related reaction new combined and pain events. Pain events are potential infusion-related reactions presenting as pain events (occurred on the day of infusion). IRR (Standard search): Standard search, excluding infusion site-reaction and investigating the most common, nonspecific, potential signs and symptoms indicative of IRRs, and occurring on the day of infusion. IRR (Combined search): Comprised of severe reactions (e.g. bronchospasm, anaphylactic reaction etc.), that occurs any time after infusion (regardless of grade and causality) and pain events on the day of infusion along with the events that are covered under standard search. Designated medical events (DMEs): European Medicines Agency, as well as EEA Member States released a list of DMEs, to identify reports of suspected ADRs that deserve special attention, irrespective of statistical criteria used to prioritize safety reviews.