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.
Brief Title
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)
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.
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.
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1-888-669-6682
Central Contact Email
novartis.email@novartis.com
Central Contact Role
Contact
Central Contact Phone
+41613241111
Completion Date
Completion Date Type
Estimated
Conditions
SICKLE CELL DISEASE
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.
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.
Inclusion Criteria
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.
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.
Gender
All
Gender Based
false
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
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
100 Years
Minimum Age
12 Years
NCT Id
NCT06439082
Org Class
Industry
Org Full Name
Novartis
Org Study Id
CSEG101A2303
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome Description
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).
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).
Outcome 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
Outcome Time Frame
1 year
Secondary Outcomes
Outcome Description
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.
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.
Outcome Time Frame
1 year
Outcome 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
Outcome Description
Vaso oclusive crisis (VOC) is defined as a pain crisis lasting for at least 4 hours which is treated as per local guidelines with standard of care therapy. Acute chest syndrome (ACS), priapism and hepatic or splenic sequestration will be considered VOC in this study.
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 is the number of VOC events during a year period.
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 is the number of VOC events during a year period.
Outcome Time Frame
1 year
Outcome Measure
Annualized rate of VOC by subtype of management in each treatment arm over the planned 52-week period.
Outcome Description
VOC is defined as a pain crisis lasting for at least 4 hours which is treated as per local guidelines with standard of care therapy. 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.
Time to first occurrence of VOC that is HCP-managed (either at a health care facility or via remote consultation) is defined as the time from the date of randomization to the date of the first occurrence of the VOC.
VOCs included are those HCP-managed in a healthcare facility and HCP-managed via remote consultation.
Time to first occurrence of VOC that is HCP-managed (either at a health care facility or via remote consultation) is defined as the time from the date of randomization to the date of the first occurrence of the VOC.
Outcome Time Frame
1 year
Outcome 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.
Outcome Description
To assess the number of participants free from VOCs leading to healthcare visit.
VOC is defined as a pain crisis lasting for at least 4 hours which is treated as per local guidelines with standard of care therapy. ACS, priapism and hepatic or splenic sequestration will be considered VOC in this study. A participant is free from VOC if they do not have a VOC crisis.
VOC is defined as a pain crisis lasting for at least 4 hours which is treated as per local guidelines with standard of care therapy. ACS, priapism and hepatic or splenic sequestration will be considered VOC in this study. A participant is free from VOC if they do not have a VOC crisis.
Outcome Time Frame
1 year
Outcome 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.
Outcome Description
VOC is defined as a pain crisis lasting for at least 4 hours which is treated as per local guidelines with standard of care therapy. ACS, priapism and hepatic or splenic sequestration will be considered VOC in this study.
Duration of HCP-managed VOC is defined as end date of the VOC - start date of the VOC + 1 day.
Duration of HCP-managed VOC is defined as end date of the VOC - start date of the VOC + 1 day.
Outcome Time Frame
1 year
Outcome 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.
Outcome Description
Immunogenicity: measurement of anti-drug antibodies (ADA) to crizanlizumab.
Outcome Time Frame
2 years
Outcome Measure
Number of participants with anti-SEG101 (crizanlizumab) antibodies (any time)
Outcome Description
Incidence and severity of AEs and SAEs by treatment group, including changes in vital signs, electrocardiograms (ECGs), and laboratory results qualifying and reported as AEs.
Outcome Time Frame
2 years
Outcome Measure
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Outcome Description
Assessment of safety of SEG101
Outcome Time Frame
Baseline, 2 years
Outcome Measure
Absolute change from baseline in hemoglobin
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
100
Minimum Age Number (converted to Years and rounded down)
12
Investigators
Investigator Type
Principal Investigator
Investigator Name
Kaitlin Strumph
Investigator Email
kstrumph@montefiore.org
Investigator Department
Pediatrics
Investigator Division
Pediatric Hematology-Oncology
Investigator Sponsor Organization
External
Study Department
Pediatrics
Study Division
Pediatrics Hematology (non-malignant)
Categories Mesh Debug
Blood Disorders --- ANEMIA, SICKLE CELL
Sickle Cell Disorders --- ANEMIA, SICKLE CELL
Blood Disorders --- HEMATOLOGIC DISEASES
Blood Disorders --- ANEMIA, HEMOLYTIC, CONGENITAL
Blood Disorders --- ANEMIA, HEMOLYTIC
Blood Disorders --- ANEMIA
MeSH Terms
ANEMIA, SICKLE CELL
VASO-OCCLUSIVE CRISES
HEMATOLOGIC DISEASES
SICKLE CELL TRAIT
ANEMIA, HEMOLYTIC, CONGENITAL
ANEMIA, HEMOLYTIC
ANEMIA
HEMIC AND LYMPHATIC DISEASES
HEMOGLOBINOPATHIES
GENETIC DISEASES, INBORN
CONGENITAL, HEREDITARY, AND NEONATAL DISEASES AND ABNORMALITIES
CRIZANLIZUMAB