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RecruitingNCT06439082SPARKLEUpdated Sep 15, 2026

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)

A Phase 3 interventional study of Crizanlizumab and Placebo in Sickle Cell Disease, sponsored by Novartis Pharmaceuticals. Recruiting at 35 sites in 5 countries. Open to participants aged 12 Years to 100 Years. Per ClinicalTrials.gov, last updated 2026-09-15.

Sponsored by Novartis Pharmaceuticals · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
354
Allocation
Randomized
Ages
12 Years to 100 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • 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
03

Who can participate

Ages eligible
12 Years to 100 Years
Sexes eligible
All
Accepts healthy volunteers
No

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.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
354 participants (estimated)

Study arms

  • Experimental
    Crizanlizumab (SEG101) at 5.0 mg/kg

    Participants receive Crizanlizumab (SEG101) at 5.0 mg/kg and standard of care.

    Biological: Crizanlizumab

  • Placebo comparator
    Placebo

    Participants receive the placebo drug and standard of care.

    Drug: Placebo

Interventions

  • BiologicalCrizanlizumab

    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.

    Also known as: SEG101, Adakveo®, Ryverna®

  • DrugPlacebo

    Placebo is supplied in single use 10 mL glass vials at a concentration of 0 mg/mL. This is a concentrate for solution for IV infusion.

05

What researchers measure

Primary outcomes

  1. 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).

    Time frame: 1 year

Secondary outcomes

  1. 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.

    Time frame: 1 year

  2. Annualized rate of VOC by subtype of management in each treatment arm over the planned 52-week period.

    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.

    Time frame: 1 year

  3. 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.

    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.

    Time frame: 1 year

  4. 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.

    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.

    Time frame: 1 year

  5. 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.

    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.

    Time frame: 1 year

  6. Number of participants with anti-SEG101 (crizanlizumab) antibodies (any time)

    Immunogenicity: measurement of anti-drug antibodies (ADA) to crizanlizumab.

    Time frame: 2 years

  7. Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)

    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.

    Time frame: 2 years

  8. Absolute change from baseline in hemoglobin

    Assessment of safety of SEG101

    Time frame: Baseline, 2 years

06

Study locations

35 of 35 sites recruiting
  • University Of Alabama
    Birmingham, Alabama 35233, United States
    • Jeanine Dumas · Contact · jdumas@uabmc.edu · +1 205 638 9285
    • Chibuzo Churchill Ilonze · Principal investigator
    Recruiting
  • Ctr for Inherited Blood Disorders
    Orange, California 92868, United States
    Recruiting
  • Childrens National Hospital
    Washington D.C., District of Columbia 20010, United States
    Recruiting
  • University of Florida
    Jacksonville, Florida 32209, United States
    Recruiting
  • Augusta University Georgia
    Augusta, Georgia 30912, United States
    • Latanya Bowman · Contact · lbowman@augusta.edu · +1 706 721 2941
    • Abdullah Kutlar · Principal investigator
    Recruiting
  • WCG Sonar Clinical Research
    Riverdale, Georgia 30274, United States
    Recruiting
  • Uni of Illinois Hospital and HSC
    Chicago, Illinois 60612, United States
    • Taif Hassan · Contact · tohassan@uic.edu
    • Santosh Saraf · Principal investigator
    Recruiting
  • Norton Children s Hospital
    Louisville, Kentucky 40202, United States
    Recruiting
  • The Johns Hopkins University School of Medicine
    Baltimore, Maryland 21205, United States
    • Goodness Che · Contact · anchang1@jhmi.edu · +1 410 955 2812
    • Lydia Pecker · Principal investigator
    Recruiting
  • Southern Specialty Research
    Flowood, Mississippi 39232, United States
    Recruiting
  • Childrens Hospital at Montefiore
    The Bronx, New York 10467, United States
    Recruiting
  • East Carolina University
    Greenville, North Carolina 27834, United States
    Recruiting
  • Wake Forest University Baptist Medical Center
    Winston-Salem, North Carolina 27157, United States
    Recruiting
  • Spoknwrdclinicaltrials
    Easton, Pennsylvania 18045, United States
    Recruiting
  • Thomas Jefferson University Me
    Philadelphia, Pennsylvania 19107, United States
    Recruiting
  • Texas Childrens Cancer and Hematology Center
    Houston, Texas 77030, United States
    Recruiting
  • U of TX Health Science Ct
    Houston, Texas 77030, United States
    Recruiting
  • Novartis Investigative Site
    Salvador, Estado de Bahia 41253-190, Brazil
    Recruiting
  • Novartis Investigative Site
    São Luís, Maranhão 65020-070, Brazil
    Recruiting
  • Novartis Investigative Site
    Campinas, São Paulo 13083-970, Brazil
    Recruiting
  • Novartis Investigative Site
    Ribeirão Preto, São Paulo 14048-900, Brazil
    Recruiting
  • Novartis Investigative Site
    Sao Jose Rio Preto, São Paulo 15090-000, Brazil
    Recruiting
  • Novartis Investigative Site
    São Paulo, São Paulo 01232-010, Brazil
    Recruiting
  • Novartis Investigative Site
    São Paulo, São Paulo 08270-070, Brazil
    Recruiting
  • Novartis Investigative Site
    Medellín, Antioquia 050001, Colombia
    Recruiting
  • Novartis Investigative Site
    Cali, Valle del Cauca Department 760032, Colombia
    Recruiting
  • Novartis Investigative Site
    Cali, Valle del Cauca Department 760046, Colombia
    Recruiting
  • Novartis Investigative Site
    Montería, 230001, Colombia
    Recruiting
  • Novartis Investigative Site
    Ahero, Kisumu County 40100, Kenya
    Recruiting
  • Novartis Investigative Site
    Kisumu, 40100, Kenya
    Recruiting
  • Novartis Investigative Site
    Kisumu, 40103, Kenya
    Recruiting
  • Novartis Investigative Site
    Siaya, 40600, Kenya
    Recruiting
  • Novartis Investigative Site
    Kampala, 101, Uganda
    Recruiting
  • Novartis Investigative Site
    Masaka, 001, Uganda
    Recruiting
  • Novartis Investigative Site
    Tororo, 10102, Uganda
    Recruiting
07

References and documents

Individual participant data

Plan to share: Yes — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT06439082
Lead sponsor
Novartis Pharmaceuticals
Responsible party
Sponsor
First posted
Jun 3, 2024
Start date
Oct 24, 2024
Primary completion
Jul 2, 2029 (estimated)
Completion
Jul 29, 2030 (estimated)
Last update
Sep 15, 2026

Study contacts

Novartis Pharmaceuticals
Contact
novartis.email@novartis.com
1-888-669-6682
Novartis Pharmaceuticals
Contact
+41613241111

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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