A study to test the safety and disease progression following YTB323 (rapcabtagene autoleucel) administration in participant with progressive Multiple Sclerosis (PMS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

16 Apr 2026 → ongoing

Decision date (initial)

2025-04-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2024-514006-31-00

ClinicalTrials.gov

NCT06675864

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Pharmacokinetic

To assess the safety of single ascending doses of YTB323 in PMS patients.

Secondary objectives 4

1. To assess the effect of YTB323 on PMS disease progression and patient function.
2. To characterize the in vivo cellular kinetics (pharmacokinetics, PK) of YTB323 in blood with qPCR.
3. To assess safe dose-level(s) to be continued in phase 2 and later clinical studies.
4. To characterize the incidence and prevalence of pre-existing and treatment induced immunogenicity (cellular and humoral) of YTB323.

Conditions and MedDRA coding

Non-active Progressive Multiple Sclerosis (PMS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male or female participants 18 to 60 years (inclusive) at screening.
2. Signed informed consent must be obtained prior to participation in the study.
3. Able to communicate well with the investigator, to understand and comply with the requirements of the study including: Able to undergo LP, CSF collection, blood draws, tolerate brain and spinal MRIs, and able to participate and tolerate all study procedures at study visits.
4. Diagnosis of SPMS or PPMS according to the 2017 McDonald diagnostic criteria (Thompson et al 2018) as confirmed at screening visit.
5. Less than 15 years (inclusive) from onset of first MS symptoms as determined by the investigator during screening.
6. Ambulatory Patients (EDSS 3 to 6.5 inclusive) at screening.

Exclusion criteria 14

1. Diagnosis of relapsing multiple sclerosis (RMS) or active PMS according to the 2017 revision of the McDonald diagnostic criteria (Thompson et al 2018) at screening.
2. History of or current clinically significant CNS disease except MS (e.g. stroke, traumatic brain or spinal injury, history or presence of myelopathy, history of seizures or epilepsy) or neurological disorders which may mimic MS or ICANS at screening.
3. Evidence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, New York Heart Association Class III/IV left ventricular failure, arrhythmia and uncontrolled hypertension within 6 months prior to or during screening).
4. Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or neurological symptoms consistent with PML prior to or during screening.
5. Clinically significant, active, opportunistic, chronic or recurrent infection (including positive for hepatitis B or hepatitis C) confirmed by clinical evidence, imaging, or positive laboratory tests one month prior to leukapheresis.
6. Have donated blood or experienced a loss of blood > 400 mL within 3 months prior screening, or longer if required by local regulations.
7. Any prior stem cell therapy or organ transplantation or gene therapy.
8. 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 nonsteroidal anti-inflammatory drugs such as ibuprofen (600 mg/day or lower) which are allowed], are not eligible to participate.
9. Not willing or able to have MRI scans as per protocol e.g. due to claustrophobia, or absolute contraindications to MRI (e.g., metallic implants, metallic foreign bodies, pacemaker, defibrillator).
10. Pregnant or nursing (lactating) women.
11. Past surgical history of splenectomy.
12. Evidence of active or latent tuberculosis (TB) infection by QuantiFERON® TB-Gold assay (or equivalent) performed at Screening by central lab. In case of unclear or indeterminate test results, the Investigator should consult with an infectious disease expert to exclude the diagnosis of active or latent TB infection and document this in the source data. Participant should be excluded if they have any signs of active TB observed in available lung imaging (e.g., X-ray or HRCT).
13. Any 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 or during screening.
14. Grade 2 or higher thromboembolic event in the past 4 weeks prior to or during Screening or evidence of disorders of coagulation or platelet function including subjects that require chronic use of anticoagulation or antiplatelet drugs (please refer to the key exclusion criteria no. 8 for the exceptions).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Occurrence, severity and frequency of dose limiting toxicities (DLTs), Adverse Events (AEs) and change from baseline over 2 years in safety parameters including, but not limited to vital signs, laboratory, ECG, neurological status, and safety measures from brain and spinal cord MRIs.

Secondary endpoints 4

1. Change from baseline for clinical measures of disability (includes EDSS, T25FW, 9HPT, SDMT).
2. YTB323 transgene expression levels by qPCR over time in blood; cellular kinetics parameters (Cmax, AUC, Tmax, Clast, Tlast).
3. Safety data from each dose level.
4. 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).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 16

Locations

4 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 44 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications