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)
Purpose
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.
Condition
- Sickle Cell Disease
Eligibility
- Eligible Ages
- Between 12 Years and 100 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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. 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.
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. 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.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Masking Description
- Double-blind Study
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Crizanlizumab (SEG101) at 5.0 mg/kg |
Participants receive Crizanlizumab (SEG101) at 5.0 mg/kg and standard of care. |
|
|
Placebo Comparator Placebo |
Participants receive the placebo drug and standard of care. |
|
Recruiting Locations
University Of Alabama
Birmingham 4049979, Alabama 4829764 35233
Birmingham 4049979, Alabama 4829764 35233
Childrens National Hospital
Washington D.C. 4140963, District of Columbia 4138106 20010
Washington D.C. 4140963, District of Columbia 4138106 20010
University of Florida
Jacksonville 4160021, Florida 4155751 32209
Jacksonville 4160021, Florida 4155751 32209
Augusta University Georgia
Augusta 4180531, Georgia 4197000 30912
Augusta 4180531, Georgia 4197000 30912
WCG Sonar Clinical Research
Riverdale 4219001, Georgia 4197000 30274
Riverdale 4219001, Georgia 4197000 30274
Norton Children s Hospital
Louisville 4299276, Kentucky 6254925 40202
Louisville 4299276, Kentucky 6254925 40202
The Johns Hopkins University School of Medicine
Baltimore 4347778, Maryland 4361885 21205
Baltimore 4347778, Maryland 4361885 21205
Southern Specialty Research
Flowood 4426822, Mississippi 4436296 39232
Flowood 4426822, Mississippi 4436296 39232
Childrens Hospital at Montefiore
The Bronx 5110266, New York 5128638 10467
The Bronx 5110266, New York 5128638 10467
East Carolina University
Greenville 4469160, North Carolina 4482348 27834
Greenville 4469160, North Carolina 4482348 27834
Wake Forest University Baptist Medical Center
Winston-Salem 4499612, North Carolina 4482348 27157
Winston-Salem 4499612, North Carolina 4482348 27157
Spoknwrdclinicaltrials
Easton 5188140, Pennsylvania 6254927 18045
Easton 5188140, Pennsylvania 6254927 18045
U of TX Health Science Ct
Houston 4699066, Texas 4736286 77030
Houston 4699066, Texas 4736286 77030
More Details
- NCT ID
- NCT06439082
- Status
- Recruiting
- Sponsor
- Novartis Pharmaceuticals
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.