A Study to Investigate the Efficacy and Safety of Crizanl... | NCT06439082

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Crizanlizumab (SEG101) at 5.0 mg/kg	Experimental	Participants receive Crizanlizumab (SEG101) at 5.0 mg/kg and standard of care.	Biological: Crizanlizumab
Placebo	Placebo Comparator	Participants receive the placebo drug and standard of care.	Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Crizanlizumab	Biological	Crizanlizumab is supplied in single use 10 mL glass vials at a concentration of 10 mg/mL. One vial contains 100 mg of crizanlizumab. This is a concentrate for solution for IV infusion.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Annualized rate of VOCs that are healthcare professional (HCP)-managed (including VOCs leading to management at a health care facility or those managed via remote consultation) in each treatment arm	Vaso oclusive crisis (VOC) is defined as a pain crisis (acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) lasting for at least 4 hours which is treated as per local guidelines with standard of care therapy used to treat VOC. Acute chest syndrome (ACS), priapism and hepatic or splenic sequestration will be considered VOC in this study. VOCs included are those HCP-managed in a healthcare facility and HCP-managed via remote consultation. Annualized rate of VOC events = (Number of VOC events * 365)/(number of days in the observation period). Observation period = time from date of randomization to minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-Glutamine (or other therapies such as Voxelotor and erythropoietin therapies to treat SCD and/or to prevent/reduce VOCs), date of randomization + 365 days).	1 year

Secondary Outcomes

Measure	Description	Time Frame
The annualized rate of all VOCs including VOCs that are HCP-managed (either at a health care facility or via remote consultation) as well as those that are self-managed without recommendations from HCP during the event in each treatment arm	VOCs can be categorized as those HCP-managed in a healthcare facility, HCP-managed via remote consultation, or self-managed without recommendations from HCP during the event. Annualized rate of VOC events = (Number of VOC events * 365)/(number of days in the observation period). To capture VOC events that are self-managed, and in order to avoid VOC recall bias and to make sure the pain events are captured in real-time, a cloud-based application will be used and setup an account for each participant.

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Participants must be aged 12 years and older on the day of signing informed consent. Adolescents include participants aged 12 to <18 years old and adults include participants aged 18 years and older.
Confirmed diagnosis of SCD by Hb electrophoresis or high-performance liquid chromatography (HPLC) (performed locally or by central laboratory if not available locally). All SCD genotypes are eligible.
Experienced 4 to 12 VOCs (refer to Section 8.3.1 for study definition of VOC) that are HCP-managed (including VOCs leading to management at a health care facility or those managed via remote consultation) within the 12 months prior to the screening visit. Baseline VOCs are determined by medical history and are required to be documented at source.
If the participant is on HU/HC, they must be taking it for at least 6 months and at stable dose for at least 3 months prior to the Screening visit and plan to continue taking it at the same dose and schedule until at least the participant has reached 52 weeks of the planned study treatment. Participants who have initiated HU/HC 6-12 months prior to the screening visit must have evidence of insufficient control of acute pain despite initiation. These participants must have a cumulative of 4-12 VOCs in the 12 months prior to the screening period, with at least 2 during the last 6 months while on HU/HC. If receiving erythropoietin stimulating agent, the participant must have been receiving the drug for at least 6 months prior to screening visit and plan to continue taking the drug at the same dose and schedule until the participant has reached 52 weeks of the planned study treatment.

Participants who have not been receiving HU/HC, and/or erythropoietin stimulating agent must not have received it for at least 6 months prior to screening visit.

Key Exclusion Criteria:

Fewer than 4 or more than 12 VOCs that are HCP-managed (including VOCs leading to management at a health care facility or those managed via remote consultation) within the 12 months prior to screening visit as determined by medical history and documented at source.
History of stem cell transplant and/or gene therapy.
Received blood products within 30 days prior to Week 1 Day 1 dosing.
Any documented history of a clinical stroke or intracranial hemorrhage, or an uninvestigated neurologic finding within the past 12 months before screening visit. Silent infarct only present on imaging is not excluded.
Participating in a chronic transfusion program (pre-planned series of transfusions for prophylactic purposes) and/or planning to undergo an exchange transfusion during the duration of the study; episodic transfusion in response to worsened anemia or VOC is permitted.
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.

Name	Role	Phone	Extension	Email
Novartis Pharmaceuticals	Contact	1-888-669-6682		novartis.email@novartis.com
Novartis Pharmaceuticals	Contact	+41613241111

Facility	Status	City	State	ZIP	Country	Contacts
University Of Alabama	Recruiting	Birmingham	Alabama	35233	United States

IPD Sharing Statement Module

ID	Term
D000755	Anemia, Sickle Cell
D000098644	Vaso-Occlusive Crises
D006402	Hematologic Diseases
D012805	Sickle Cell Trait

ID	Term
D000745	Anemia, Hemolytic, Congenital
D000743	Anemia, Hemolytic
D000740	Anemia
D006425	Hemic and Lymphatic Diseases
D006453	Hemoglobinopathies
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities