CRIZANLIZUMAB for Sickle cell disease

Inclusion criteria

• {"criterion_text":"- Written informed consent must be obtained prior to any screening procedures"}
• {"criterion_text":"- Male or female patients aged 12 years and older on the day of signing informed consent. Adolescents include patients aged 12 to 17 years old and adults ≥ 18 years"}
• {"criterion_text":"- Confirmed diagnosis of SCD by Hb electrophoresis or high-performance liquid chromatography (HPLC) (performed locally). All SCD genotypes are eligible, genotyping is not required for study entry."}
• {"criterion_text":"- Experienced at least 2 VOCs leading to healthcare visit within the 12 months prior to screening visit as determined by medical history. Prior VOC leading to healthcare visit must resolve at least 7 days prior to Week 1 Day 1 and must include: 1.\tPain crisis defined as an acute onset of pain for which there is no other medically determined explanation other than vaso- occlusion 2.\twhich requires a visit to a medical facility and/or healthcare professional, 3.\tand receipt of oral/parenteral opioids or parenteral nonsteroidal anti-inflammatory drug (NSAID) analgesics Acute chest syndrome (ACS), priapism and hepatic or splenic sequestration will be considered VOC in this study"}
• {"criterion_text":"- If receiving HU/HC or L-glutamine (local HA approved medicinal product), must have been receiving the drug for at least 6 months and at a stable dose for at least 3 months prior to Screening visit and plan to continue taking it at the same dose and schedule until the subject has reached one year of study treatment. Patients who have not been receiving such drug must not have received it for at least 6 months prior to Screening visit to be included. Patients must have evidence of insufficient control of acute pain, such as at least one VOC leading to healthcare visit while on HU/HC or L-Glutamine treatment. If receiving erythropoietin stimulating agent, must have been receiving the drug for at least 6 months prior to Screening visit and plan to continue taking the treatment to maintain stable Hb levels at least until the subject has reached one year of study treatment"}
• {"criterion_text":"- Patients must meet the following central laboratory values prior to Week 1 Day 1: •\tAbsolute Neutrophil Count ≥1.0 x 109/L •\tPlatelet count ≥75 x 109/L •\tHemoglobin: for adults (Hb) ≥4.0 g/dL and for adolescents (Hb) ≥5.5 g/dL •\tGlomerular filtration rate ≥ 45 mL/min/1.73 m2 using CKD-EPI formula in adults, and Shwartz formula in adolescents •\tDirect (conjugated) bilirubin < 2.0 x ULN •\tAlanine transaminase (ALT) < 3.0 x ULN"}
• {"criterion_text":"- ECOG performance status ≤ 2.0 for adults and Karnofsky ≥ 50% for adolescents"}

Exclusion criteria

• {"criterion_text":"- History of stem cell transplant."}
• {"criterion_text":"- Participating in a chronic transfusion program (pre-planned series of transfusions for prophylactic purposes) and/or planning on undergoing an exchange transfusion during the duration of the study; episodic transfusion in response to worsened anemia or VOC is permitted"}
• {"criterion_text":"- Contraindication or hypersensitivity to any drug or metabolites from similar class as study drug or to any excipients of the study drug formulation. 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."}
• {"criterion_text":"- Received active treatment on another investigational trial within 30 days (or 5 half-lives of that agent, whichever is greater) prior to Screening visit or plans to participate in another investigational drug trial."}
• {"criterion_text":"- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant unless they are using highly effective methods of contraception during dosing and for 15 weeks after stopping treatment."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- History or current diagnosis of ECG abnormalities indicating significant risk of safety such as: •\tConcomitant clinically significant cardiac arrhythmias (e.g ventricular tachycardia), and clinically significant second or third degree AV block without a pacemaker •\tHistory of familial long QT syndrome or know family history of Torsades de Pointes"}
• {"criterion_text":"- Not able to understand and to comply with study instructions and requirements."}
• {"criterion_text":"- Received prior treatment with crizanlizumab or other selectin targeting agent"}

Primary endpoints

• {"endpoint_text":"- Annualized rate of VOC events leading to healthcare visit in each treatment group over the first year post randomization","definition_or_measurement_approach":"Annualized rate of VOCs that lead to a healthcare visit, measured per treatment group over the first year after randomization (count of VOC events leading to healthcare visit, annualized over the first year post-randomization)."}

Secondary endpoints

• {"endpoint_text":"- Annualized rate of all VOCs leading to healthcare visit and treated at home (based on documentation by health care provider following contact with participant) over the first year post randomization","definition_or_measurement_approach":"Annualized rate of all VOCs (both those leading to healthcare visit and those treated at home) based on documentation by healthcare provider following contact with participant, measured over the first year post-randomization."}
• {"endpoint_text":"- Annualized rate of VOCs managed at home over the first year post randomization","definition_or_measurement_approach":"Annualized rate of VOCs managed at home during the first year after randomization."}
• {"endpoint_text":"- Duration of VOCs leading to healthcare visit over the first year post randomization","definition_or_measurement_approach":"Measured duration (time) of VOC episodes that lead to healthcare visit during the first year post-randomization."}
• {"endpoint_text":"- Number and percentage of participants free from VOCs leading to healthcare visit in each group over the first year post randomization","definition_or_measurement_approach":"Count and percentage of participants in each treatment group who experience no VOCs leading to a healthcare visit during the first year post-randomization."}
• {"endpoint_text":"- The time to first and second VOC calculated respectively as the time from date of randomization until the first and the second VOC leading to healthcare visit over the first year post randomization","definition_or_measurement_approach":"Time-to-event endpoints: time from randomization to first VOC and to second VOC leading to healthcare visit, assessed over the first year post-randomization."}
• {"endpoint_text":"- Annualized rate of visits to clinic, Emergency room (ER) and hospitalizations, both overall and VOC-related over the first year post randomization","definition_or_measurement_approach":"Annualized rate of healthcare utilization (clinic visits, ER visits, hospitalizations), both overall and VOC-related, over the first year post-randomization."}
• {"endpoint_text":"- Evolution of albuminuria and ACR over the first year post randomization","definition_or_measurement_approach":"Change/evolution in albuminuria and albumin-to-creatinine ratio (ACR) measured over the first year post-randomization."}
• {"endpoint_text":"- PK parameters after the first and fifth dose (e.g., AUC, Cmax, Tmax, half-life)","definition_or_measurement_approach":"Pharmacokinetic parameters measured after the first and fifth dose, examples include AUC, Cmax, Tmax, and half-life."}
• {"endpoint_text":"- PD parameter (P-selectin inhibition) after the first and fifth dose","definition_or_measurement_approach":"Pharmacodynamic assessment of P-selectin inhibition measured after the first and fifth dose."}
• {"endpoint_text":"- Annualized rate of VOCs leading to healthcare visit","definition_or_measurement_approach":"Annualized rate of VOCs leading to healthcare visit (repeat/measured over intended analysis periods)."}
• {"endpoint_text":"- Annualized rate of all VOCs leading to healthcare visit and treated at home","definition_or_measurement_approach":"Annualized rate of all VOCs that either lead to healthcare visit or are treated at home, measured over analysis period."}
• {"endpoint_text":"- Annualized rate of VOCs managed at home","definition_or_measurement_approach":"Annualized rate of VOCs managed at home."}
• {"endpoint_text":"- Number, seriousness, severity, and causality assessments of treatment-emergent adverse events, including infections (serious, non-serious and opportunistic infections) and other safety data as considered appropriate","definition_or_measurement_approach":"Safety outcomes: counts and assessments of treatment-emergent adverse events (TEAEs), including classification by seriousness, severity, and causality; includes infections and other relevant safety data."}
• {"endpoint_text":"- Absolute change from baseline in hemoglobin","definition_or_measurement_approach":"Absolute change in hemoglobin from baseline at scheduled timepoints."}
• {"endpoint_text":"- Growth and sexual maturity assessment in adolescents (Tanner stage)","definition_or_measurement_approach":"Assessment of growth and sexual maturity in adolescent participants using Tanner staging."}
• {"endpoint_text":"- Immunogenicity: measurement of anti-drug antibodies (ADA) to crizanlizumab","definition_or_measurement_approach":"Measurement of anti-drug antibodies (ADA) to crizanlizumab to assess immunogenicity."}

Belgium

Latest Decision Or Authorization Date

30-09-2025

Number Of Sites

2

Number Of Participants

11

Finland

Latest Decision Or Authorization Date

03-04-2024

Number Of Sites

1

Number Of Participants

1

France

Latest Decision Or Authorization Date

22-04-2024

Number Of Sites

2

Number Of Participants

5

Netherlands

Latest Decision Or Authorization Date

02-10-2025

Number Of Sites

3

Number Of Participants

4

Spain

Latest Decision Or Authorization Date

12-02-2026

Number Of Sites

3

Number Of Participants

10

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

IQVIA Limited

Responsibilities

Multiple IQVIA entries; responsibilities include endpoint adjudication and ECG vendor services (contact emails: lindsay.dolan@iqvia.com; ishrat.raji@iqvia.com; dimple.gusain@iqvia.com)

Name

Parexel International (IRL) Limited

Responsibilities

sponsorDuties code: 12 (clinical trial support/contact Clinicaltrial.Enquiries@parexel.com)

Name

Syneos Health Clinical Spain S.L.

Responsibilities

sponsorDuties code: 1 (contact Cornelia.mainhoefer@syneoshealth.com)

Third parties

• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties code: 3; contact lindsay.dolan@iqvia.com","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Movianto Belgium","duties_or_roles":"Delivery of local equipment and return of IMP","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Syneos Health Clinical Spain S.L.","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Illingworth Research Group Limited","duties_or_roles":"Home nursing services","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"sponsorDuties code: 12","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited (second entry)","duties_or_roles":"Endpoint adjudication","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"SGS France","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Creapharm Clinical Supplies","duties_or_roles":"Storage relabeling and destruction of IMP","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Labcorp Early Development Laboratories Limited","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Navigate Biopharma Services Inc.","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Finland","full_name":"Tamro Oyj","duties_or_roles":"IMP delivery and IMP returns","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited (third entry)","duties_or_roles":"ECG vendor","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Corevitas LLC","duties_or_roles":"Trial feedback","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"IQVIA RDS Spain S.L.","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Kayentis","duties_or_roles":"eCOA","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Spain","full_name":"Rps Research Iberica S.L.","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Pharmaceutical company"}