Phase 2 Study Evaluating Rapcabtagene Autoleucel in Participants With Diffuse Cutaneous Systemic Sclerosis

Официальное название

A Phase II, Multi-part, Randomized, Open-label, Assessor-blinded, Active-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Rapcabtagene Autoleucel Versus Rituximab Treatment in Participants With Severe Refractory Diffuse Cutaneous Systemic Sclerosis

Обзор

The purpose of this study is to evaluate the efficacy, safety and tolerability of rapcabtagene autoleucel (administered once following lymphodepletion) in participants with severe refractory diffuse cutaneous systemic sclerosis relative to rituximab.

Подробное описание

This is a phase 2, multi-part, five-year, randomized, open-label, assessor-blinded, multicenter study to evaluate the efficacy and safety of rapcabtagene autoleucel versus rituximab in participants with severe refractory diffuse cutaneous systemic sclerosis (dcSSc). This study comprises two cohorts:

* A Lead-in Cohort enrolling participants to receive rapcabtagene autoleucel. * A Randomized Cohort enrolling participants to receive rapcabtagene autoleucel or rituximab. Participants in the rituximab arm whose disease is not fully controlled may receive rapcabtagene autoleucel treatment once the participant is confirmed to be eligible per protocol.

After end of study, participants who received rapcabtagene autoleucel infusion will enter a long-term follow-up (LTFU) period after rapcabtagene autoleucel infusion. This LTFU will be described in a separate study protocol.

Вмешательства

• Биопрепарат rapcabtagene autoleucel
  single infusion of rapcabtagene autoleucel after lymphodepleting therapy with fludarabine (adjusted based on renal impairment) and cyclophosphamide daily for 3 days.
• Биопрепарат rituximab
  rituximab intravenous infusion (i.v.) as per protocol

Первичные конечные точки

• Achievement of a treatment response as per the Revised Composite Response Index in Systemic Sclerosis 50 (rCRISS50) definition at Week 52. [Срок оценки: Week 52]

Вторичные конечные точки (4)

• Change from baseline in Forced Vital Capacity (FVC)% predicted at Week 52 [Срок оценки: Baseline, Week 52]
• Change from baseline in modified Rodnan Skin Score (mRSS) at Week 52. [Срок оценки: Baseline, Week 52]
• Change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 52. [Срок оценки: Baseline, Week 52]
• Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: Up to end of study, assessed up to approximately 5 years]

Критерии участия

Критерии включения

• Participant must fulfill the 2013 American College of Rheumatology/ European League Against Rheumatism classification criteria for systemic sclerosis and meet the diffuse cutaneous SSc (dcSSc) subset classification according to LeRoy.
• Disease onset from the first non-Raynaud symptoms attributable to SSc (e.g., puffy hands, scleroderma, digital ulcers, arthralgia, dyspnea) within 7 years prior to the Screening visit.
• Severe, progressive systemic sclerosis disease defined by at least one of the following:

• Progressive systemic sclerosis-associated interstitial lung disease
• Severe, progressive systemic sclerosis skin disease
• Clinically significant systemic sclerosis-associated cardiac involvement at Screening
• All recommended vaccinations received according to institutional, local or global guidelines for immuno-compromised patients.

Критерии исключения

• Any condition during Screening that could prevent a complete washout of medications as required per protocol or could otherwise make the participant ineligible for anti-CD19 CAR-T therapy and further participation in the study, as judged by the Investigator.
• Participants with history of hypersensitivity to excipients in rapcabtagene autoleucel or to rituximab.
• Any participant for whom treatment with rituximab is clinically inappropriate in the opinion of the investigator.
• Any medical conditions that are not related to SSc that, in the opinion of the Investigator, would jeopardize the ability of the participant to tolerate lymphodepletion and anti-CD19 CAR-T cell therapy.
• Rheumatic disease other than dcSSc, (except secondary Sjogren's syndrome or scleroderma myopathy),including limited cutaneous systemic sclerosis (lcSSc) or sine scleroderma at Screening.
• Participants with pre-existing pulmonary hypertension.
• Significant renal pathology at Screening.
• Participants with uncontrolled stage II hypertension at Screening.
• Vaccination with live attenuated vaccines within 6 weeks prior to randomization.

Other protocol-defined inclusion/exclusion criteria may 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

Простое слепое

Основная цель

Лечение

Центры проведения

США · 14 центров

• UCLA — Los Angeles
• UCSF — San Francisco
• UCSF — San Francisco
• Sutter Health Network — San Pablo
• FL Medical Clinic Orlando Health — Zephyrhills
• Northwestern University — Chicago
• University Of Iowa — Iowa City
• Boston Medical Center — Boston
• … и ещё 6 центров

Италия · 12 центров

• Novartis Investigative Site — Ancona
• Novartis Investigative Site — Bergamo
• Novartis Investigative Site — Brescia
• Novartis Investigative Site — Genova
• Novartis Investigative Site — Milan
• Novartis Investigative Site — Milan
• Novartis Investigative Site — Pescara
• Novartis Investigative Site — Perugia
• … и ещё 4 центра

Испания · 11 центров

• Novartis Investigative Site — Santiago Compostela
• Novartis Investigative Site — Santander
• Novartis Investigative Site — Pamplona
• Novartis Investigative Site — Barcelona
• … и ещё 7 центров

Германия · 10 центров

• Novartis Investigative Site — Freiburg im Breisgau
• Novartis Investigative Site — Göttingen
• Novartis Investigative Site — Leipzig
• Novartis Investigative Site — Halle
• Novartis Investigative Site — Jena
• Novartis Investigative Site — Berlin
• Novartis Investigative Site — Lübeck
• Novartis Investigative Site — Mainz
• … и ещё 2 центра

Франция · 8 центров

• Novartis Investigative Site — Bordeaux
• Novartis Investigative Site — Dijon
• Novartis Investigative Site — Lille
• Novartis Investigative Site — Lyon
• Novartis Investigative Site — Montpellier
• Novartis Investigative Site — Paris
• Novartis Investigative Site — Rennes
• Novartis Investigative Site — Strasbourg

Япония · 7 центров

• Novartis Investigative Site — Sapporo
• Novartis Investigative Site — Sendai
• Novartis Investigative Site — Suita
• Novartis Investigative Site — Bunkyo-ku
• Novartis Investigative Site — Fukuoka
• Novartis Investigative Site — Ishikawa
• Novartis Investigative Site — Kyoto

Бразилия · 5 центров

• Novartis Investigative Site — Salvador
• Novartis Investigative Site — Curitiba
• Novartis Investigative Site — Barretos
• Novartis Investigative Site — São Paulo
• Novartis Investigative Site — São Paulo

Израиль · 3 центра

• Novartis Investigative Site — Haifa
• Novartis Investigative Site — Ramat Gan
• Novartis Investigative Site — Tel Aviv

South Korea · 3 центра

• Novartis Investigative Site — Seoul
• Novartis Investigative Site — Seoul
• Novartis Investigative Site — Seoul

Швейцария · 3 центра

Список центров уточняется — проверьте первичный протокол.

Аргентина · 2 центра

• Novartis Investigative Site — CABA
• Novartis Investigative Site — Córdoba

Австралия · 2 центра

• Novartis Investigative Site — Camperdown
• Novartis Investigative Site — Darlinghurst

Австрия · 2 центра

• Novartis Investigative Site — Graz
• Novartis Investigative Site — Vienna

Чехия · 2 центра

• Novartis Investigative Site — Olomouc
• Novartis Investigative Site — Prague

Венгрия · 2 центра

• Novartis Investigative Site — Debrecen
• Novartis Investigative Site — Budapest

Бельгия · 1 центр

• Novartis Investigative Site — Ghent

Дания · 1 центр

• Novartis Investigative Site — Aarhus N

Нидерланды · 1 центр

• Novartis Investigative Site — Utrecht

Сингапур · 1 центр

• Novartis Investigative Site — Singapore

Тайвань · 1 центр

Список центров уточняется — проверьте первичный протокол.

Великобритания · 1 центр

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06655896 · CYTB323K12201 · 2023-510380-34-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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