Clinical trial • Phase II • Immunology|Rare Disease

RAPCABTAGENE AUTOLEUCEL for Diffuse cutaneous systemic sclerosis (dcSSc)

Phase II trial of RAPCABTAGENE AUTOLEUCEL for Diffuse cutaneous systemic sclerosis (dcSSc).

Overview

Trial Therapeutic Area
Immunology|Rare Disease
Trial Disease
Diffuse cutaneous systemic sclerosis (dcSSc)
Trial Stage
Phase II
Drug Modality
Cell therapy|Monoclonal antibody
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
07-06-2024
First CTIS Authorization Date
02-10-2024

Trial design

Randomised, open-label, rituximab (comparator). dose and schedule not specified in the provided data.-controlled Phase II trial in Czechia, Hungary, Belgium and others.

Randomised
Yes
Open Label
Yes
Comparator
Rituximab (comparator). Dose and schedule not specified in the provided data.
Target Sample Size
61
Trial Duration For Participant
1825

Eligibility

Recruits 61 Vulnerable population selected. Informed consent is obtained from adult participants via the Main ICF (Adult). The documentation set includes language-specific ICFs and separate information/consent documents for pregnant participants, female partners, follow-up for pregnant participants, data protection consent and optional assessments. No specific assent or minor consent procedures are provided in the available documents..

Vulnerable Population
Vulnerable population selected. Informed consent is obtained from adult participants via the Main ICF (Adult). The documentation set includes language-specific ICFs and separate information/consent documents for pregnant participants, female partners, follow-up for pregnant participants, data protection consent and optional assessments. No specific assent or minor consent procedures are provided in the available documents.

Inclusion criteria

  • {"criterion_text":"- Participant must fulfill the 2013 American College of Rheumatology/ European League Against Rheumatism classification criteria for systemic sclerosis (van den Hoogen et al 2013) and meet the diffuse cutaneous SSc (dcSSc) subset classification according to LeRoy (LeRoy et al 1988)"}
  • {"criterion_text":"- 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"}
  • {"criterion_text":"- 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"}

Exclusion criteria

  • {"criterion_text":"- 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"}
  • {"criterion_text":"- Participants with history of hypersensitivity to excipients in rapcabtagene autoleucel or to rituximab"}
  • {"criterion_text":"- Any participant for whom treatment with rituximab is clinically inappropriate in the opinion of the investigator"}
  • {"criterion_text":"- 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"}
  • {"criterion_text":"- Rheumatic disease other than dcSSc, (except secondary Sjogren’s syndrome or scleroderma myopathy), including limited cutaneous systemic sclerosis (lcSSc) or sine scleroderma at Screening"}
  • {"criterion_text":"- Participants with pre-existing pulmonary hypertension."}
  • {"criterion_text":"- Significant renal pathology at Screening, including: • Scleroderma renal crisis • Confirmed diagnosis of glomerulonephritis"}
  • {"criterion_text":"- Participants with uncontrolled stage II hypertension at Screening."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Achievement of a treatment response as per the rCRISS50 definition at Week 52","definition_or_measurement_approach":"Proportion of participants achieving a Revised Composite Response Index in Systemic Sclerosis 50 (rCRISS50) response at Week 52 (as per the rCRISS50 definition)"}

Secondary endpoints

  • {"endpoint_text":"- Change from baseline in FVC% predicted at Week 52","definition_or_measurement_approach":"Change from baseline in forced vital capacity percent predicted (FVC% predicted) at Week 52"}
  • {"endpoint_text":"- Change from baseline in mRSS at Week 52","definition_or_measurement_approach":"Change from baseline in Modified Rodnan Skin Score (mRSS) at Week 52"}
  • {"endpoint_text":"- Change from baseline in HAQ-DI at Week 52","definition_or_measurement_approach":"Change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 52"}
  • {"endpoint_text":"- Safety evaluation includes adverse events, laboratory parameters, vital signs, ECGs, and mortality","definition_or_measurement_approach":"Safety assessed by monitoring adverse events, laboratory parameters, vital signs, ECGs, and mortality"}

Recruitment

Planned Sample Size
61
Recruitment Window Months
94
Consent Approach
Informed consent is obtained from adult participants using the Main ICF (Adult). Consent documentation is provided in multiple country languages (examples in the documents list: English, German, French, Spanish, Italian, Hungarian, Czech, Dutch, Danish). Separate ICFs/info sheets are provided for pregnant participants, female partners, follow-up procedures, molecular pre-screening, and optional assessments. No pediatric assent processes are included in the available documents.

Methods

  • Site-based recruitment at participating hospitals/clinics across the listed Member States (country-specific site lists and contact points provided in Part II submissions).
  • Use of recruitment arrangements and advertisement materials (documents K1_Recruitment Arrangements and K2_Advertisements are listed per country) for outreach and participant identification.
  • Patient-facing materials and site training materials produced by third parties (e.g., Publicis Healthcare Communications Group Limited) to support recruitment and information.
  • Patient retention support (hotel and travel reimbursement) provided by Greenphire LLC as noted in sponsor third-party duties.

Geography

Czechia

Earliest CTIS Part Ii Submission Date
29-01-2025
Latest Decision Or Authorization Date
02-04-2026
Processing Time Days
428
Number Of Sites
2
Number Of Participants
4

Sites

Site Name
Revmatologicky Ustav
Department Name
#2751: Revmatologicky Ustav
Contact Person Name
Michal Tomcik
Contact Person Email
michal.tomcik@lf1.cuni.cz
Site Name
University Hospital Olomouc
Department Name
#2752: III. Interni klinika nefrologicka, revmatologicka a endokrinologicka
Contact Person Name
Martina Skacelova
Contact Person Email
martina.skacelova@fnol.cz

Hungary

Earliest CTIS Part Ii Submission Date
21-02-2025
Latest Decision Or Authorization Date
01-04-2026
Processing Time Days
404
Number Of Sites
2
Number Of Participants
5

Sites

Site Name
University Of Debrecen
Department Name
3052: Department of Internal Medicine
Contact Person Name
Arpad Illes
Contact Person Email
llesarpaddr@gmail.com
Site Name
Semmelweis University
Department Name
3051: Department of Rheumatology and Immunology
Contact Person Name
Gyorgy Nagy
Contact Person Email
gyorgyngy@gmail.com

Belgium

Earliest CTIS Part Ii Submission Date
08-11-2024
Latest Decision Or Authorization Date
30-03-2026
Processing Time Days
507
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Universitair Ziekenhuis Gent
Department Name
#2951: Rheumatology
Contact Person Name
Vanessa Smith
Contact Person Email
Vanessa.smith@ugent.be

France

Earliest CTIS Part Ii Submission Date
09-09-2024
Latest Decision Or Authorization Date
03-04-2026
Processing Time Days
571
Number Of Sites
18
Number Of Participants
8

Sites

Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
2054: Immunologie Clinique
Contact Person Name
Thierry MARTIN

Netherlands

Earliest CTIS Part Ii Submission Date
05-09-2024
Latest Decision Or Authorization Date
30-03-2026
Processing Time Days
571
Number Of Sites
2
Number Of Participants
5

Sites

Site Name
Universitair Medisch Centrum Utrecht
Department Name
1002: Rheumatology
Contact Person Name
Julia Spierings
Contact Person Email
J.Spierings@umcutrecht.nl
Site Name
Leids Universitair Medisch Centrum (LUMC)
Department Name
#1001: Hematology
Contact Person Name
Joost Vermaat
Contact Person Email
j.s.p.vermaat@lumc.nl

Germany

Earliest CTIS Part Ii Submission Date
06-09-2024
Latest Decision Or Authorization Date
02-04-2026
Processing Time Days
573
Number Of Sites
16
Number Of Participants
16

Sites

Site Name
Universitaetsmedizin Goettingen
Department Name
2164: Klinik fuer Nephrologie und Rheumatologie
Contact Person Name
Viktor Korendovych

Austria

Earliest CTIS Part Ii Submission Date
03-02-2025
Latest Decision Or Authorization Date
31-03-2026
Processing Time Days
421
Number Of Sites
3
Number Of Participants
3

Sites

Site Name
Medical University Of Graz
Department Name
Department of rheumatology
Contact Person Name
Jens Thiel
Contact Person Email
jens.thiel@medunigraz.at

Denmark

Earliest CTIS Part Ii Submission Date
21-01-2025
Latest Decision Or Authorization Date
30-03-2026
Processing Time Days
433
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Aarhus University Hospital
Department Name
#3151: Led- og Bindevævssygdomme Klinik
Contact Person Name
Ellen-Margrethe Hauge
Contact Person Email
ellen.hauge@aarhus.rm.dk

Spain

Earliest CTIS Part Ii Submission Date
06-09-2024
Latest Decision Or Authorization Date
06-04-2026
Processing Time Days
577
Number Of Sites
18
Number Of Participants
18

Sites

Site Name
Hospital Universitario Reina Sofia
Department Name
2457: Reumatología
Contact Person Name
Alejandro Escudero Contreras

Italy

Earliest CTIS Part Ii Submission Date
19-09-2024
Latest Decision Or Authorization Date
02-04-2026
Processing Time Days
560
Number Of Sites
17
Number Of Participants
17

Sites

Site Name
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Department Name
2252 U.O.C. Reumatologia e Immunologia Clinica
Contact Person Name
Paola Toniati
Contact Person Email
paola.toniati@icloud.com

Sponsor

Primary sponsor

Full Name
Novartis Pharma AG
Organisation Type
Pharmaceutical company
Country Of Registered Address
Switzerland

Contract research organisations

Name
Parexel International Corp.
Responsibilities
Ancillary supplies for infusion; clinical operations support
Name
IQVIA Limited
Responsibilities
Patient profiles; clinical trial information support
Name
Syneos Health Inc.
Responsibilities
Operational support / CRO-type responsibilities

Third parties

  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Electronic Clinical Outcome Assessments (eCOA, ePRO, ClinRO); Medical Image Analysis/Review – CT, ECHO, x-ray, MRI, ultrasound etc; ECG Analysis/Review, Spirometry, DLCO (various entries across third party records)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Patient retention; hotel and travel reimbursement","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"EPL Pathology Archives LLC","duties_or_roles":"Aliquoting","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"Ancillary supplies for infusion","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Patient profiles; general clinical trial information support","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"Clinical trial enquiries / support (role code 12 listed)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Somalogic Operating Co. Inc.","duties_or_roles":"Analysis","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"Central laboratory services","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Navigate Biopharma Services Inc.","duties_or_roles":"PK Analysis","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"Pharmacokinetics (PK) IG (Cellular) analysis; Flow sample testing","organisation_type":"Pharmaceutical company"}
  • {"country":"Denmark","full_name":"Clinigma ApS","duties_or_roles":"Patient experience exit interview","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Operational support (listed duty code 1)","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Publicis Healthcare Communications Group Limited","duties_or_roles":"Patient facing materials (informative videos, print material), Site training materials","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc. (additional entry)","duties_or_roles":"Medical Image Analysis/Review (CT, ECHO, x-ray, MRI, ultrasound etc)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc. (ECG/Spirometry entry)","duties_or_roles":"ECG Analysis/Review, Spirometry, DLCO","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
YTB323
Active Substance
RAPCABTAGENE AUTOLEUCEL
Modality
Cell therapy
Routes Of Administration
Intravenous use
Route
Intravenous
Authorisation Status
prodAuthStatus:1
Investigational Product Name
RITUXIMAB
Active Substance
RITUXIMAB
Modality
Monoclonal antibody
Routes Of Administration
Intravenous use
Route
Intravenous
Authorisation Status
prodAuthStatus:2
Orphan Designation
Yes
Investigational Product Name
CYCLOPHOSPHAMIDE
Active Substance
CYCLOPHOSPHAMIDE
Modality
Small molecule
Routes Of Administration
Intravenous use
Route
Intravenous
Authorisation Status
prodAuthStatus:2
Investigational Product Name
FLUDARABINE PHOSPHATE
Active Substance
FLUDARABINE PHOSPHATE
Modality
Small molecule
Routes Of Administration
Intravenous use
Route
Intravenous
Authorisation Status
prodAuthStatus:2
Investigational Product Name
TOCILIZUMAB
Active Substance
TOCILIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
Intravenous use
Route
Intravenous
Authorisation Status
prodAuthStatus:2
Combination Treatment
Yes

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