A Study to Compare the Efficacy and Safety of BMS-986353 (Zolacabtagene- Autoleucel / Zola-cel), CD19-CAR T Cells, Versus Standard of Care in Participants With Active Systemic Sclerosis

Официальное название

A Phase 3, Randomized, Open-label, Multicenter Study to Compare the Efficacy and Safety of BMS-986353, CD19-targeted NEX-T CAR T Cells, Versus Standard of Care in Participants With Active Systemic Sclerosis (Breakfree-SSc)

Обзор

The purpose of this study is to compare the efficacy and safety of BMS-986353 versus standard of care in participants with active Systemic Sclerosis

Подробное описание

Participants in Arm B may receive BMS-986353 following confirmation of progression on standard of care.

Вмешательства

• Препарат BMS-986353
  Specified dose on specified days
• Препарат Fludarabine
  Specified dose on specified days
• Препарат Cyclophosphamide
  Specified dose on specified days
• Препарат Tocilizumab
  Specified dose on specified days
• Препарат Rituximab
  Specified dose on specified days
• Препарат Nintedanib
  Specified dose on specified days

Первичные конечные точки

• The absolute change from baseline in Forced Vital Capacity (FVC) in mL [Срок оценки: At 12 months]

Вторичные конечные точки (12)

• The absolute change from baseline in Modified Rodnan Skin Score (mRSS) [Срок оценки: At month 12]
• The absolute change from baseline in Quantitative Interstitial Lung Disease-Whole Lung (QILD-WL) score [Срок оценки: Up to month 36]
• Time to progression, defined as the time from randomization to progressive disease [Срок оценки: Approximately 54 months]
• The change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue [Срок оценки: Up to month 36]
• The change from baseline in Scleroderma Clinical Index (ScleroID) [Срок оценки: Up to month 36]
• The change from baseline in Scleroderma Health Assessment Questionnaire - Disability Index (SHAQ-DI) [Срок оценки: Up to month 36]
• The change from baseline in PROMIS-29 [Срок оценки: Up to month 36]
• The change from baseline in St. George's Respiratory Questionnaire (SGRQ) [Срок оценки: Up to month 36]
• The change from baseline in EuroQol 5 Dimensions 5 Level (EQ-5D-5L) visual analog scale [Срок оценки: Up to month 36]
• The change from baseline in EQ-5D-5L Utility Index [Срок оценки: Up to month 36]
• The absolute change from baseline in FVC in mL [Срок оценки: Up to month 36]
• The absolute change from baseline in FVC in mL/year [Срок оценки: Up to month 36]

Критерии участия

Критерии включения

\- Participants must fulfill the 2013 American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) classification criteria for Systemic Sclerosis (SSc), and additionally have the following:.

i) Positive Antinuclear Antibodies (ANA) with nucleolar pattern and/or anti-Topoisomerase I (anti-Scl-70) antibodies.

ii) Confirmation of Interstitial Lung Disease (ILD) on centrally read High-Resolution Computed Tomography (HRCT) with ≥ 10% total lung involvement, with at least one of the following attributed to active SSc:.

A. Arthritis.

B. Myositis.

C. Carditis.

D. Progressive skin disease.

E. Elevated inflammatory markers.

\- Participants must have a non-response or intolerance despite ≥ 6 months of treatment with at least one immunomodulatory drug. Non-response is defined as a patient, who in the opinion of the investigator, is not adequately controlled/treated and requires treatment escalation.

Критерии исключения

• Participants must not have a requirement for supplemental oxygen therapy and/or Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) ≤ 40% (Hemoglobin (Hgb) corrected) at screening.
• Participants must not have moderate to severe Pulmonary Arterial Hypertension (PAH) requiring PAH-specific combination treatment
• Participants must not have pulmonary comorbidity including chronic obstructive pulmonary disease or asthma requiring daily oral corticosteroids, cigarette smoking (including e-cigarettes) within 3 months before screening or unwilling to avoid smoking throughout the study, and/or clinically significant abnormalities on HRCT not attributable to SSc assessed by the central reader at screening.
• Participants must not have gastrointestinal (GI) dysmotility requiring Total Parenteral Nutrition (TPN).
• Participants must not have current gangrene of a digit
• Other protocol-defined Inclusion/Exclusion criteria apply.

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

Открытое

Основная цель

Лечение

Центры проведения

США · 17 центров

• Local Institution - 0035 — Scottsdale
• University of Colorado Anschutz Medical Campus — Aurora
• Local Institution - 0001 — Denver
• Local Institution - 0069 — Miami
• Emory University School of Medicine — Atlanta
• Local Institution - 0139 — Chicago
• Local Institution - 0084 — Worcester
• Local Institution - 0034 — Ann Arbor
• … и ещё 9 центров

Германия · 7 центров

• Local Institution - 0046 — Berlin
• Local Institution - 0016 — Cologne
• Local Institution - 0028 — Erlangen
• Local Institution - 0042 — Leipzig
• Local Institution - 0032 — München
• Local Institution - 0033 — Tübingen
• Local Institution - 0038 — Würzburg

Япония · 7 центров

• Local Institution - 0026 — Sapporo
• Local Institution - 0132 — Yokohama
• Local Institution - 0137 — Suita
• Local Institution - 0117 — Bunkyo-ku
• Local Institution - 0123 — Fukuoka
• Local Institution - 0136 — Maebashi
• Local Institution - 0118 — Okayama

Франция · 6 центров

• Local Institution - 0031 — Strasbourg
• Local Institution - 0061 — Toulouse
• Local Institution - 0049 — Bordeaux
• Local Institution - 0012 — Bron
• Local Institution - 0052 — Paris
• Local Institution - 0141 — Rennes

Италия · 4 центра

• Local Institution - 0103 — Rome
• Local Institution - 0004 — Milan
• Local Institution - 0108 — Pisa
• Local Institution - 0106 — Milan

Испания · 4 центра

• Local Institution - 0129 — A Coruña
• Local Institution - 0138 — Barcelona
• Local Institution - 0060 — Barcelona
• Local Institution - 0009 — Málaga

Великобритания · 4 центра

• Local Institution - 0140 — London
• Local Institution - 0063 — Leeds
• Local Institution - 0059 — London
• Local Institution - 0091 — Sheffield

Швейцария · 3 центра

• Local Institution - 0047 — Basel
• Local Institution - 0068 — Bern
• Local Institution - 0078 — Zurich

Бельгия · 2 центра

• Local Institution - 0057 — Leuven
• Local Institution - 0080 — Liège

Канада · 2 центра

• Local Institution - 0104 — Halifax
• Local Institution - 0088 — Sherbrooke

Идентификаторы

NCT: NCT07335562 · CA061-1005 · 2025-524337-11 · U1111-1330-3381

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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