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

Official title

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

Overview

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.

Detailed description

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.

Interventions

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

Primary outcome measures

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

Secondary outcome measures (4)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 14 centers

• 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
• … and 6 more centers

Italy · 12 centers

• 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
• … and 4 more centers

Spain · 11 centers

• Novartis Investigative Site — Santiago Compostela
• Novartis Investigative Site — Santander
• Novartis Investigative Site — Pamplona
• Novartis Investigative Site — Barcelona
• … and 7 more centers

Germany · 10 centers

• 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
• … and 2 more centers

France · 8 centers

• 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

Japan · 7 centers

• 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

Brazil · 5 centers

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

Israel · 3 centers

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

South Korea · 3 centers

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

Switzerland · 3 centers

Center list to be confirmed — check the primary protocol.

Argentina · 2 centers

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

Australia · 2 centers

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

Austria · 2 centers

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

Czechia · 2 centers

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

Hungary · 2 centers

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

Belgium · 1 center

• Novartis Investigative Site — Ghent

Denmark · 1 center

• Novartis Investigative Site — Aarhus N

Netherlands · 1 center

• Novartis Investigative Site — Utrecht

Singapore · 1 center

• Novartis Investigative Site — Singapore

Taiwan · 1 center

Center list to be confirmed — check the primary protocol.

United Kingdom · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗