Clinical trial NCT04662931: An Indian Multi-centric Phase IV Study to Assess the Safety of Crizanlizumab in Sickle Cell Disease Patients
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Sickle Cell Disease (SCD)
Keywords: 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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-12-10
Enrollment: 140
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Treatment Emergent Serious Adverse Events (SAEs)
timeFrame: Up to 15 months
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (AEs)
timeFrame: Up to 15 months
measure: Number of Participants With Adverse Events of Special Interest (AESI)
timeFrame: Up to 15 months
Other outcomes:
Locations:
city: Guwahati
country: India
facility: Novartis Investigative Site
state: Assam
city: Raipur
country: India
facility: Novartis Investigative Site
state: Chhattisgarh
city: Kozhikode
country: India
facility: Novartis Investigative Site
state: Kerala
city: Bhubaneswar
country: India
facility: Novartis Investigative Site
state: Odisha
city: Hyderabad
country: India
facility: Novartis Investigative Site
state: Telangana
city: Lucknow
country: India
facility: Novartis Investigative Site
state: Uttar Pradesh
city: Kolkata
country: India
facility: Novartis Investigative Site
state: West Bengal
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: