Clinical trial NCT06439082: 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)
Official title: A Phase III, Multicenter, 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Sickle Cell Disease
Keywords: Sickle Cell Disease
SCD
SEG101
Crizanlizumab
Hydroxyurea/ Hydroxycarbamide Therapy
Vaso-Occlusive Crises
Sickle Cell Anemia
blood disorders
hemoglobin
red blood cells
sickle-like shape
mutation in hemoglobin gene
sickle-cell trait
sickle-cell crisis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2024-06-03
Enrollment: 315
Sex: ALL
Minimum age (years): 12
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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: 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.

Primary outcomes:
measure: 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
timeFrame: 1 year
Secondary outcomes:
measure: 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
timeFrame: 1 year
measure: Annualized rate of VOC by subtype of management in each treatment arm over the planned 52-week period.
timeFrame: 1 year
measure: The time to first VOC that is HCP-managed (including VOCs leading to management at a health care facility or those managed via remote consultation) between treatment arms.
timeFrame: 1 year
measure: Proportion of participants free from VOCs that are HCP-managed (including VOCs leading to management at a health care facility or those managed via remote consultation) in each treatment arm over the planned 52-week treatment period.
timeFrame: 1 year
measure: Duration of VOCs that are HCP-managed (including VOCs leading to management at a health care facility or those managed via remote consultation) in each treatment arm over the planned 52-week treatment period.
timeFrame: 1 year
measure: Number of participants with anti-SEG101 (crizanlizumab) antibodies (any time)
timeFrame: 2 years
measure: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: 2 years
measure: Absolute change from baseline in hemoglobin
timeFrame: Baseline, 2 years
Other outcomes:
Locations:
city: Washington
country: United States
facility: Childrens National Hospital
state: District of Columbia
city: Jacksonville
country: United States
facility: University of Florida
state: Florida
city: Augusta
country: United States
facility: Augusta University Georgia
state: Georgia
city: Riverdale
country: United States
facility: WCG Sonar Clinical Research
state: Georgia
city: Bronx
country: United States
facility: Childrens Hospital at Montefiore
state: New York
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Houston
country: United States
facility: Texas Childrens Hospital
state: Texas
city: Medellin
country: Colombia
facility: Novartis Investigative Site
state: Antioquia
city: Cali
country: Colombia
facility: Novartis Investigative Site
state: Valle Del Cauca
city: Cali
country: Colombia
facility: Novartis Investigative Site
state: Valle Del Cauca
city: Monteria
country: Colombia
facility: Novartis Investigative Site
Study officials:
References: