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

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

11 Nov 2025 → ongoing

Decision date (initial)

2025-03-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2024-512714-18-00

WHO UTN

U1111-1321-5044

ClinicalTrials.gov

NCT06617793

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Pharmacodynamic

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

Secondary objectives 4

1. To assess the effect of YTB323 on MS disease activity and patient function
2. To characterize the in vivo cellular kinetics (pharmacokinetics [PK]) of YTB323 in blood
3. To inform 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

Relapsing Multiple Sclerosis

Regulatory references

Scientific advice from competent authorities

National Agency For The Safety Of Medicine And Health Products, Food And Drug Administration, Paul-Ehrlich-Institut

Plan to share IPD

Yes

IPD plan description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Signed informed consent, and able to communicate well with the investigator and comply with the requirements of the study
2. Adequate renal, hepatic, cardiac, hematological, and pulmonary function (see definitions in Section 5.1)
3. Male or female participants, ≥18 years to ≤60 years at screening, with diagnosis of RMS according to the 2017 McDonald diagnostic criteria (Thompson et al 2018b)
4. 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
5. Ambulatory patients (EDSS 3 to 6 inclusive assessed outside of relapse)
6. Disease duration less than 15 years

Exclusion criteria 7

1. Diagnosis of primary progressive multiple sclerosis (PPMS) according to the 2017 revision of the McDonald diagnostic criteria (Thompson et al 2018b) 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) or neurological disorders which may mimic MS or ICAN at screening
3. 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
4. Have donated blood or experienced a loss of blood > 400 mL within 3 months prior screening, or longer if required by local regulations
5. Any prior stem cell therapy or organ transplantation or gene therapy
6. 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
7. 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)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 MRIs of the brain and spinal cord

Secondary endpoints 4

1. 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)
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 · 19 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 46 files

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

Application history

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