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)

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Биопрепарат 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.
• Препарат 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.

Первичные конечные точки

• 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 [Срок оценки: 1 year]

Вторичные конечные точки (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 [Срок оценки: 1 year]
• Annualized rate of VOC by subtype of management in each treatment arm over the planned 52-week period. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: 1 year]
• Number of participants with anti-SEG101 (crizanlizumab) antibodies (any time) [Срок оценки: 2 years]
• Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: 2 years]
• Absolute change from baseline in hemoglobin [Срок оценки: Baseline, 2 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 14 центров

• University Of Alabama — Birmingham
• Ctr for Inherited Blood Disorders — Orange
• Childrens National Hospital — Washington D.C.
• University of Florida — Jacksonville
• Augusta University Georgia — Augusta
• WCG Sonar Clinical Research — Riverdale
• Norton Children s Hospital — Louisville
• The Johns Hopkins University School of Medicine — Baltimore
• … и ещё 6 центров

Бразилия · 7 центров

• Novartis Investigative Site — Salvador
• Novartis Investigative Site — São Luís
• Novartis Investigative Site — Campinas
• Novartis Investigative Site — Ribeirão Preto
• Novartis Investigative Site — Sao Jose Rio Preto
• Novartis Investigative Site — São Paulo
• Novartis Investigative Site — São Paulo

Колумбия · 4 центра

• Novartis Investigative Site — Medellín
• Novartis Investigative Site — Cali
• Novartis Investigative Site — Cali
• Novartis Investigative Site — Montería

Kenya · 4 центра

• Novartis Investigative Site — Ahero
• Novartis Investigative Site — Kisumu
• Novartis Investigative Site — Kisumu
• Novartis Investigative Site — Siaya

Uganda · 3 центра

• Novartis Investigative Site — Kampala
• Novartis Investigative Site — Masaka
• Novartis Investigative Site — Tororo

Идентификаторы

NCT: NCT06439082 · CSEG101A2303

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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