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)

NCT06439082 | Recruiting Phase 3 FDA Drug

• 1 other identifier: CSEG101A2303
• Study Type: interventional
• Target: 315
• Locations: 5 countries
• Sites: 31

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.

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

Outcome Measures

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).

  1 year

Secondary Outcomes (8)

• 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

  1 year

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

  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.

  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.

  1 year

Study Arms (2)

Crizanlizumab (SEG101) at 5.0 mg/kg

EXPERIMENTAL

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

Biological: Crizanlizumab

Placebo

PLACEBO COMPARATOR

Participants receive the placebo drug and standard of care.

Drug: Placebo

Interventions

Crizanlizumab BIOLOGICAL

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®

Crizanlizumab (SEG101) at 5.0 mg/kg

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 12 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• History of stem cell transplant and/or gene therapy.
• Received blood products within 30 days prior to Week 1 Day 1 dosing.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (31)

University Of Alabama

Birmingham, Alabama, 35233, 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

RECRUITING

WCG Sonar Clinical Research

Riverdale, Georgia, 30274, United States

RECRUITING

Norton Children s Hospital

Louisville, Kentucky, 40202, United States

RECRUITING

The Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

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

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, 54 40100, Kenya

RECRUITING

Novartis Investigative Site

Siaya, 40600, Kenya

RECRUITING

Novartis Investigative Site

Kampala, 101, Uganda

RECRUITING

Novartis Investigative Site

Masaka, Uganda

RECRUITING

Novartis Investigative Site

Tororo, 10102, Uganda

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell; Vaso-Occlusive Crises; Hematologic Diseases; Sickle Cell Trait

Interventions

crizanlizumab

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind Study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 27, 2024
• First Posted: June 3, 2024
• Study Start: October 24, 2024
• Primary Completion (Estimated): March 23, 2029
• Study Completion (Estimated): April 19, 2030
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

KE (4); US (13); BR (7); CO (4); UG (3)