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) (SPARKLE)

May 25, 2026 updated by: Novartis Pharmaceuticals

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

315

Phase

  • Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Novartis Pharmaceuticals
  • Phone Number: +41613241111

Study Locations

  • Brazil
    • Estado de Bahia
      • Salvador, Estado de Bahia, Brazil, 41253-190
        • Recruiting
        • Novartis Investigative Site
    • Maranhão
      • São Luís, Maranhão, Brazil, 65020-070
        • Recruiting
        • Novartis Investigative Site
    • São Paulo
      • Campinas, São Paulo, Brazil, 13083-970
        • Recruiting
        • Novartis Investigative Site
      • Ribeirão Preto, São Paulo, Brazil, 14048-900
        • Recruiting
        • Novartis Investigative Site
      • Sao Jose Rio Preto, São Paulo, Brazil, 15090 000
        • Recruiting
        • Novartis Investigative Site
      • São Paulo, São Paulo, Brazil, 08270-070
        • Recruiting
        • Novartis Investigative Site
      • São Paulo, São Paulo, Brazil, 01232-010
        • Recruiting
        • Novartis Investigative Site
  • Colombia
      • Montería, Colombia, 230001
        • Recruiting
        • Novartis Investigative Site
    • Antioquia
      • Medellín, Antioquia, Colombia, 050001
        • Recruiting
        • Novartis Investigative Site
    • Valle del Cauca Department
      • Cali, Valle del Cauca Department, Colombia, 760046
        • Recruiting
        • Novartis Investigative Site
      • Cali, Valle del Cauca Department, Colombia, 760032
        • Recruiting
        • Novartis Investigative Site
  • Kenya
      • Kisumu, Kenya, 54 40100
        • Recruiting
        • Novartis Investigative Site
      • Kisumu, Kenya, 40100
        • Recruiting
        • Novartis Investigative Site
      • Siaya, Kenya, 40600
        • Recruiting
        • Novartis Investigative Site
    • Kisumu County
      • Ahero, Kisumu County, Kenya, 40100
        • Recruiting
        • Novartis Investigative Site
  • Uganda
      • Kampala, Uganda, 101
        • Recruiting
        • Novartis Investigative Site
      • Masaka, Uganda
        • Recruiting
        • Novartis Investigative Site
      • Tororo, Uganda, 10102
        • Recruiting
        • Novartis Investigative Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • University of Alabama
        • Principal Investigator:
          • Chibuzo Churchill Ilonze
        • Contact:
    • California
      • Orange, California, United States, 92868
        • Recruiting
        • Ctr for Inherited Blood Disorders
        • Contact:
        • Principal Investigator:
          • Vanessa Salinas
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • Recruiting
        • Childrens National Hospital
        • Principal Investigator:
          • Andrew Campbell
        • Contact:
    • Florida
      • Jacksonville, Florida, United States, 32209
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Recruiting
        • Augusta University Georgia
        • Principal Investigator:
          • Abdullah Kutlar
        • Contact:
      • Riverdale, Georgia, United States, 30274
        • Recruiting
        • WCG Sonar Clinical Research
        • Principal Investigator:
          • Anthony Onyegbula
        • Contact:
    • Kentucky
      • Louisville, Kentucky, United States, 40202
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Recruiting
        • The Johns Hopkins University School of Medicine
        • Contact:
        • Principal Investigator:
          • Lydia Pecker
    • Mississippi
      • Flowood, Mississippi, United States, 39232
    • New York
      • The Bronx, New York, United States, 10467
        • Recruiting
        • Childrens Hospital at Montefiore
        • Contact:
        • Principal Investigator:
          • Kaitlin Strumph.
    • North Carolina
      • Greenville, North Carolina, United States, 27834
        • Recruiting
        • East Carolina University
        • Principal Investigator:
          • Beng Fuh
        • Contact:
      • Winston-Salem, North Carolina, United States, 27157
    • Pennsylvania
      • Easton, Pennsylvania, United States, 18045
    • Texas
      • Houston, Texas, United States, 77030

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Crizanlizumab (SEG101) at 5.0 mg/kg
Participants receive Crizanlizumab (SEG101) at 5.0 mg/kg and standard of care.
Biological: Crizanlizumab
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.
Other Names:
  • SEG101, Adakveo®, Ryverna®
Placebo Comparator: Placebo
Participants receive the placebo drug and standard of care.
Drug: Placebo
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 1 year

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).
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 1 year

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.
1 year
Annualized rate of VOC by subtype of management in each treatment arm over the planned 52-week period.
Time Frame: 1 year

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.
1 year
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.
Time Frame: 1 year

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.
1 year
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.
Time Frame: 1 year

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.
1 year
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.
Time Frame: 1 year

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.
1 year
Number of participants with anti-SEG101 (crizanlizumab) antibodies (any time)
Time Frame: 2 years
Immunogenicity: measurement of anti-drug antibodies (ADA) to crizanlizumab.
2 years
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: 2 years
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.
2 years
Absolute change from baseline in hemoglobin
Time Frame: Baseline, 2 years
Assessment of safety of SEG101
Baseline, 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 24, 2024

Primary Completion (Estimated)

March 23, 2029

Study Completion (Estimated)

April 19, 2030

Study Registration Dates

First Submitted

May 27, 2024

First Submitted That Met QC Criteria

May 27, 2024

First Posted (Actual)

June 3, 2024

Study Record Updates

Last Update Posted (Actual)

May 27, 2026

Last Update Submitted That Met QC Criteria

May 25, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CSEG101A2303

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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