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NCT06439082PHASE3Recruiting

A Study to Investigate the Efficacy and Safety of Crizanlizumab (5 mg/kg) Compared With Placebo in Adolescent and Adult Sickle Cell Disease Patients Who Experience Frequent Vaso-Occlusive Crises (SPARKLE)

Novartis Pharmaceuticals

Start Date

10/24/2024

Completion Date

7/29/2030

Summary

A phase III, multi-center, randomized, placebo-controlled, double-blind study to assess efficacy and safety of crizanlizumab (5 mg/kg) versus placebo, with or without hydroxyurea/hydroxycarbamide therapy, in adolescent and adult Sickle Cell Disease patients with frequent vaso-occlusive crises.

Detailed Description

Study CSEG101A2303 (SPARKLE) is a Phase III, multicenter, randomized, double-blind study to assess efficacy and safety of crizanlizumab 5 mg/kg versus placebo, with or without hydroxyurea/ hydroxycarbamide therapy (HU/HC), in Sickle Cell Disease patients aged 12 years and older with frequent vaso-occlusive crises (4-12 events in 12 months prior to the screening visit). Participants will be randomized in a 2:1 ratio to the crizanlizumab 5 mg/kg or placebo treatment arm. Central randomization will be stratified by concomitant HU/HC usage (yes/no) and region (South America, North America, and sub-Saharan Africa) at baseline.

Eligibility Criteria

Age Range: 12 years to 100 years

Key Inclusion Criteria: 1. 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. 2. 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. 3. 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. 4. 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: 1. 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. 2. History of stem cell transplant and/or gene therapy. 3. Received blood products within 30 days prior to Week 1 Day 1 dosing. 4. 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. 5. 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. 6. 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.

Interventions

BIOLOGICAL

Crizanlizumab

DRUG

Placebo

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Conditions

Sickle Cell Disease

Locations

University Of Alabama

Birmingham, Alabama 35233

United States

Ctr for Inherited Blood Disorders

Orange, California 92868

United States

Childrens National Hospital

Washington D.C., District of Columbia 20010

United States

University of Florida

Jacksonville, Florida 32209

United States

Augusta University Georgia

Augusta, Georgia 30912

United States

WCG Sonar Clinical Research

Riverdale, Georgia 30274

United States

Norton Children s Hospital

Louisville, Kentucky 40202

United States

The Johns Hopkins University School of Medicine

Baltimore, Maryland 21205

United States

Southern Specialty Research

Flowood, Mississippi 39232

United States

Childrens Hospital at Montefiore

The Bronx, New York 10467

United States

East Carolina University

Greenville, North Carolina 27834

United States

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina 27157

United States

Spoknwrdclinicaltrials

Easton, Pennsylvania 18045

United States

U of TX Health Science Ct

Houston, Texas 77030

United States

Novartis Investigative Site

Salvador, Estado de Bahia 41253-190

Brazil

Novartis Investigative Site

São Luís, Maranhão 65020-070

Brazil

Novartis Investigative Site

Campinas, São Paulo 13083-970

Brazil

Novartis Investigative Site

Ribeirão Preto, São Paulo 14048-900

Brazil

Novartis Investigative Site

Sao Jose Rio Preto, São Paulo 15090 000

Brazil

Novartis Investigative Site

São Paulo, São Paulo 01232-010

Brazil

Novartis Investigative Site

São Paulo, São Paulo 08270-070

Brazil

Novartis Investigative Site

Medellín, Antioquia 050001

Colombia

Novartis Investigative Site

Cali, Valle del Cauca Department 760032

Colombia

Novartis Investigative Site

Cali, Valle del Cauca Department 760046

Colombia

Novartis Investigative Site

Montería, 230001

Colombia

Novartis Investigative Site

Ahero, Kisumu County 40100

Kenya

Novartis Investigative Site

Kisumu, 40100

Kenya

Novartis Investigative Site

Kisumu, 54 40100

Kenya

Novartis Investigative Site

Siaya, 40600

Kenya

Novartis Investigative Site

Kampala, 101

Uganda

Novartis Investigative Site

Masaka,

Uganda

Novartis Investigative Site

Tororo, 10102

Uganda