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

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.

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease (SCD)
• Intervention / Treatment: Drug: crizanlizumab

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.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Assam
    • Guwahati, Assam, India, 781003
      • Novartis Investigative Site
  • Chhattisgarh
    • Raipur, Chhattisgarh, India, 492099
      • Novartis Investigative Site
  • Kerala
    • Kozhikode, Kerala, India, 673008
      • Novartis Investigative Site
  • Odisha
    • Bhubaneswar, Odisha, India, 751003
      • Novartis Investigative Site
  • Telangana
    • Hyderabad, Telangana, India, 500082
      • Novartis Investigative Site
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226014
      • Novartis Investigative Site
  • West Bengal
    • Kolkata, West Bengal, India, 700014
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Crizanlizumab; Participants received Crizanlizumab at a dose of 5.0 mg/kg, and standard of care.	Drug: crizanlizumab; Crizanlizumab 5.0 mg/kg i.v. initial dose on Week 1 Day 1, second dose on Week 3 Day 1. Subsequently, Day 1 of every 4 weeks until Week 51, in addition of standard of care.; Other Names: SEG101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Serious Adverse Events (SAEs)	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.	Up to 15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (AEs)	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.	Up to 15 months
Number of Participants With Adverse Events of Special Interest (AESI)	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.	Up to 15 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2021
• Primary Completion (Actual): February 14, 2024
• Study Completion (Actual): February 14, 2024

Study Registration Dates

• First Submitted: November 24, 2020
• First Submitted That Met QC Criteria: December 9, 2020
• First Posted (Actual): December 10, 2020

Study Record Updates

• Last Update Posted (Estimated): September 26, 2025
• Last Update Submitted That Met QC Criteria: September 24, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: SCD; P-selectin; SEG101; Sickle cell disease; VOC; Sickle cell disorder; Sickle cell anemia; Hemoglobin SC disease; Sickling disorder due to hemoglobin S; Vaso-occlusive crisis; Crizanlizumab
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Hemoglobin SC Disease; Vaso-Occlusive Crises; crizanlizumab
• Other Study ID Numbers: CSEG101A2403; 2020-003625-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No