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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04662931

Collaborator

(none)

140

Enrollment

Locations

Arm

37.2

Anticipated Duration (Months)

17.5

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease (SCD)	Drug: crizanlizumab	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

140 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

Actual Study Start Date :

Jul 14, 2021

Anticipated Primary Completion Date :

Aug 20, 2024

Anticipated Study Completion Date :

Aug 20, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Crizanlizumab Participants will receive Crizanlizumab at a dose of 5.0 mg/kg.	Drug: crizanlizumab Crizanlizumab will be taken by IV infusion, at Week 1 Day 1, Week 3 Day 1 and all 4 weeks thereafter. Other Names: SEG101

Arm

Intervention/Treatment

Experimental: Crizanlizumab

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

Drug: crizanlizumab

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

Other Names:

SEG101

Outcome Measures

Primary Outcome Measures

Percentage of patients with at least one serious adverse event (SAE) with 2-sided 95% confidence interval (CI) [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)]
Incidence of serious adverse events (SAEs)
Percentage of patients with SAEs of grades >=3 [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)]
Severity of serious adverse events (SAEs)
Percentage of patients with treatment-related SAEs of all grades [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)]
Causality of serious adverse events (SAEs)
Percentage of patients with treatment-related SAEs of grades >=3 [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)]
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) [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)]
Incidence of treatment-emergent adverse events (AEs)
Percentage of patients with AEs of grades >=3 [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)]
Severity of adverse events (AEs)
Percentage of patients with treatment-related AEs of all grades [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)]
Causality of adverse events (AEs)
Percentage of patients with treatment-related AEs of grades >=3 [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)]
Causality of severe adverse events (AEs)

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Hyderabad	Andhra Pradesh	India	500018
2	Novartis Investigative Site	Raipur	Chhattisgarh	India	492099
3	Novartis Investigative Site	Kozhikode	Kerala	India	673008
4	Novartis Investigative Site	Bhubaneswar	Odisha	India	751003
5	Novartis Investigative Site	Hyderabad	Telangana	India	500082
6	Novartis Investigative Site	Lucknow	Uttar Pradesh	India	226014
7	Novartis Investigative Site	Kolkata	West Bengal	India	700014
8	Novartis Investigative Site	Guwahati		India	781003