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

Primary Purpose

Sickle Cell Disease (SCD)

Status

Active

Phase

Phase 4

Locations

India

Study Type

Interventional

Intervention

crizanlizumab

About this trial

This is an interventional treatment trial for Sickle Cell Disease (SCD) focused on measuring 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

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Crizanlizumab

Arm Description

Participants will receive Crizanlizumab at a dose of 5.0 mg/kg.

Outcomes

Primary Outcome Measures

Percentage of patients with at least one serious adverse event (SAE) with 2-sided 95% confidence interval (CI)

Incidence of serious adverse events (SAEs)

Percentage of patients with SAEs of grades >=3

Severity of serious adverse events (SAEs)

Percentage of patients with treatment-related SAEs of all grades

Causality of serious adverse events (SAEs)

Percentage of patients with treatment-related SAEs of grades >=3

Causality of severe serious adverse events (SAEs)

Secondary Outcome Measures

Percentage of patients with at least one treatment-emergent adverse event (AE)(new or worsening from baseline)

Incidence of treatment-emergent adverse events (AEs)

Percentage of patients with AEs of grades >=3

Severity of adverse events (AEs)

Percentage of patients with treatment-related AEs of all grades

Causality of adverse events (AEs)

Percentage of patients with treatment-related AEs of grades >=3

Causality of severe adverse events (AEs)

Full Information

NCT ID

NCT04662931

First Posted

November 24, 2020

Last Updated

June 12, 2023

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT04662931

Brief Title

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

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

July 14, 2021 (Actual)

Primary Completion Date

November 28, 2023 (Anticipated)

Study Completion Date

March 3, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

140 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Crizanlizumab

Arm Type

Experimental

Arm Description

Participants will receive Crizanlizumab at a dose of 5.0 mg/kg.

Intervention Type

Drug

Intervention Name(s)

crizanlizumab

Other Intervention Name(s)

SEG101

Intervention Description

Crizanlizumab will be taken by IV infusion, at Week 1 Day 1, Week 3 Day 1 and all 4 weeks thereafter.

Primary Outcome Measure Information:

Title

Percentage of patients with at least one serious adverse event (SAE) with 2-sided 95% confidence interval (CI)

Description

Incidence of serious adverse events (SAEs)

Time Frame

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)

Title

Percentage of patients with SAEs of grades >=3

Description

Severity of serious adverse events (SAEs)

Time Frame

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)

Title

Percentage of patients with treatment-related SAEs of all grades

Description

Causality of serious adverse events (SAEs)

Time Frame

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)

Title

Percentage of patients with treatment-related SAEs of grades >=3

Description

Causality of severe serious adverse events (SAEs)

Time Frame

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 Measure Information:

Title

Percentage of patients with at least one treatment-emergent adverse event (AE)(new or worsening from baseline)

Description

Incidence of treatment-emergent adverse events (AEs)

Time Frame

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)

Title

Percentage of patients with AEs of grades >=3

Description

Severity of adverse events (AEs)

Time Frame

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)

Title

Percentage of patients with treatment-related AEs of all grades

Description

Causality of adverse events (AEs)

Time Frame

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)

Title

Percentage of patients with treatment-related AEs of grades >=3

Description

Causality of severe adverse events (AEs)

Time Frame

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)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

16 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Raipur

State/Province

Chhattisgarh

ZIP/Postal Code

492099

Country

India

Facility Name

Novartis Investigative Site

City

Kozhikode

State/Province

Kerala

ZIP/Postal Code

673008

Country

India

Facility Name

Novartis Investigative Site

City

Bhubaneswar

State/Province

Odisha

ZIP/Postal Code

751003

Country

India

Facility Name

Novartis Investigative Site

City

Hyderabad

State/Province

Telangana

ZIP/Postal Code

500082

Country

India

Facility Name

Novartis Investigative Site

City

Lucknow

State/Province

Uttar Pradesh

ZIP/Postal Code

226014

Country

India

Facility Name

Novartis Investigative Site

City

Kolkata

State/Province

West Bengal

ZIP/Postal Code

700014

Country

India

Facility Name

Novartis Investigative Site

City

Guwahati

ZIP/Postal Code

781003

Country

India

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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

IPD Sharing URL

http://www.clinicalstudydatarequest.com

Learn more about this trial

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

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