An open-label study to assess the safety, efficacy, and cellular kinetics of YTB323 in Relapsing Multiple Sclerosis

Phase 1/2

Not yet recruiting

• Conditions: Relapsing Multiple Sclerosis
• Interventions: Biological: rapcabtagene autoleucel (YTB323)

• Registration Number: 2024-512714-18-00
• Lead Sponsor: Novartis Pharma AG

Brief Summary

To assess the safety of single ascending doses of YTB323 in RMS patients with breakthrough disease activity during previous treatment with highly efficacious therapy

Detailed Description

All participants in this study will receive YTB323. Both the participant and the study doctor will know the participant is getting YTB323. Participants will be given one dose of YTB323. Different groups of participants may receive a higher dose of YTB323, if proven to be safe for every participant at the lower dose. Participants are in this study for 2 years and will be followed for an additional 13 years in a long-term follow up study. The main question this trial is designed to answer: Is YTB323 treatment safe for participants with relapsing MS?

Study Timeline

• Study First Posted: 2025-03-21
• Last Update Posted: 2025-04-17

Recruitment & Eligibility

• Status: Authorised, recruitment pending
• Sex: Not specified
• Target Recruitment: 15

Inclusion Criteria

Signed informed consent, and able to communicate well with the investigator and comply with the requirements of the study

Adequate renal, hepatic, cardiac, hematological, and pulmonary function (see definitions in Section 5.1)

Male or female participants, ≥18 years to ≤55 years at screening, with diagnosis of RMS according to the 2017 McDonald diagnostic criteria (Thompson et al 2018b)

XX of recent (i.e. within 1 year) breakthrough disease activity while XX. XX of breakthrough disease activity is defined as one or more of the following: a. XX

Ambulatory patients (EDSS 3 to 6 inclusive assessed outside of relapse)

Disease duration less than 10 years

Exclusion Criteria

Diagnosis of primary progressive multiple sclerosis (PPMS) according to the 2017 revision of the McDonald diagnostic criteria (Thompson et al 2018b) at screening

History of or current clinically significant CNS disease except MS (e.g. stroke, traumatic brain or spinal injury, history or presence of myelopathy) or neurological disorders which may mimic MS or ICAN at screening

Evidence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, New York Heart Association [NYHA] Class III/IV left ventricular failure, arrhythmia and uncontrolled hypertension within 6 months prior to screening), neurological disorders other than MS (including seizure disorders even when well controlled), psychiatric, pulmonary (including, history of or active severe respiratory disease, including Chronic Obstructive Pulmonary Disease, interstitial lung disease or pulmonary fibrosis), renal, hepatic, endocrine, metabolic (e.g. severe hypoproteinemia due to nephrotic syndrome), hematological disorders or gastrointestinal disease that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant, prior to screening

Have donated blood or experienced a loss of blood > 400 mL within 3 months prior screening, or longer if required by local regulations

Any prior stem cell therapy or organ transplantation or gene therapy

Any contraindications to LP, including but not limited to: • Known or suspected structural abnormality of the lumbar spine that, in the opinion of the Investigator, may interfere with the performance of the LP, or increase the risk of the procedure for the participant • Presence of risk for increased or uncontrolled bleeding including, but not limited to, vascular abnormalities or neoplasms at or near the LP site, disorders of the coagulation cascade, platelet function, or platelet count • Participants on anticoagulants (e.g., warfarin) or antiplatelets [except for low-dose aspirin (100 mg/day or lower) and low-dose ibuprofen (600 mg/day or lower) which are allowable], are not eligible to participate

Patients not willing or able to take MRI scans as per protocol. Unable to undergo MRI due to for example claustrophobia, or presents absolute contraindications to MRI (e.g., metallic implants, metallic foreign bodies, pacemaker, defibrillator)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
YTB323 Cohort 1	rapcabtagene autoleucel (YTB323)	Participants will receive one dose of YTB323
YTB323 Cohort 2	rapcabtagene autoleucel (YTB323)	Participants will recieve one dose of YTB323
YTB323 Cohort 3	rapcabtagene autoleucel (YTB323)	Participants will recieve one dose of YTB323
YTB323 Cohort 4	rapcabtagene autoleucel (YTB323)	Participants will recieve one dose of YTB323

Primary Outcome Measures

Name	Time	Method
Change in safety parameters including, but not limited to severity and frequency dose limiting toxicities (DLTs) of Adverse Events (AEs) and findings in vital signs, laboratory, ECG, neurological status, and safety MRI of the brain		Change in safety parameters including, but not limited to severity and frequency dose limiting toxicities (DLTs) of Adverse Events (AEs) and findings in vital signs, laboratory, ECG, neurological status, and safety MRI of the brain

Secondary Outcome Measures

Name	Time	Method
Clinical measures for relapses and disability (includes EDSS, XX, T25FW, 9HPT, SDMT, XX) and MRI changes in disease activity (including new and enlarging T2 lesions and Gd-enhancing T1 lesions)		Clinical measures for relapses and disability (includes EDSS, XX, T25FW, 9HPT, SDMT, XX) and MRI changes in disease activity (including new and enlarging T2 lesions and Gd-enhancing T1 lesions)
YTB323 transgene expression levels by qPCR over time in blood; cellular kinetics parameters (Cmax, AUC, Tmax, Clast, Tlast)		YTB323 transgene expression levels by qPCR over time in blood; cellular kinetics parameters (Cmax, AUC, Tmax, Clast, Tlast)
Safety data from each dose level		Safety data from each dose level
Pre-existing and treatment-induced immunogenicity (humoral, anti-YTB323 antibody; and cellular, presence of CAR19 specific CD4 and CD8 T cells measuring interferon gamma production)		Pre-existing and treatment-induced immunogenicity (humoral, anti-YTB323 antibody; and cellular, presence of CAR19 specific CD4 and CD8 T cells measuring interferon gamma production)

Trial Locations

Locations (16)

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR; 🇩🇪 Mainz, Germany

Universitaetsklinikum Ulm AöR; 🇩🇪 Ulm, Germany

Universitaetsklinikum Essen AöR; 🇩🇪 Essen, Germany

Katholisches Klinikum Bochum gGmbH; 🇩🇪 Bochum, Germany

Hospital Universitario Y Politecnico La Fe; 🇪🇸 Valencia, Spain

Hospital Universitario Ramon Y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario Reina Sofia; 🇪🇸 Cordoba, Spain

Hospital Universitari Vall D Hebron; 🇪🇸 Barcelona, Spain

Institut De Cancerologie Strasbourg Europe; 🇫🇷 Strasbourg, France

CHRU De Nancy; 🇫🇷 Nancy, France

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Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR

🇩🇪Mainz, Germany

Stefan Bittner

Site contact

+496131172805

bittner@uni-mainz.de