A study to test the safety and disease progression following YTB323 administration in participant with progressive Multiple Sclerosis (PMS)
- Conditions
- Non-active Progressive Multiple Sclerosis (PMS)
- Interventions
- Biological: rapcabtagene autoleucel (YTB323)
- Registration Number
- 2024-514006-31-00
- Lead Sponsor
- Novartis Pharma AG
- Brief Summary
To assess the safety of single ascending doses of YTB323 in PMS patients.
- 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 progressive MS?
Recruitment & Eligibility
- Status
- Authorised, recruitment pending
- Sex
- Not specified
- Target Recruitment
- 18
Male or female participants 18 to 60 years (inclusive) at screening.
Signed informed consent must be obtained prior to participation in the study.
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 MRI, and able to participate and tolerate all study procedures at study visits.
Diagnosis of SPMS or PPMS according to the 2017 McDonald diagnostic criteria (Thompson et al 2018) as confirmed at screening visit.
Disease duration less than 15 years.
Ambulatory Patients (EDSS 3 to 6.5 inclusive) at screening.
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.
Pregnant or nursing (lactating) women.
Past surgical history of splenectomy.
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).
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 screening.
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).
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.
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 screening).
Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or neurological symptoms consistent with PML prior to screening.
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.
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 nonsteroidal anti-inflammatory drugs such as ibuprofen (600 mg/day or lower) which are allowed], are not eligible to participate.
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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- 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 receive one dose of YTB323 YTB323 Cohort 3 rapcabtagene autoleucel (YTB323) Participants will receive one dose of YTB323 YTB323 Cohort 4 rapcabtagene autoleucel (YTB323) Participants will receive one dose of YTB323
- Primary Outcome Measures
Name Time Method 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 MRI. 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 MRI.
- Secondary Outcome Measures
Name Time Method Change from baseline for clinical measures of disability (includes EDSS, T25FW, 9HPT, SDMT). Change from baseline for clinical measures of disability (includes EDSS, T25FW, 9HPT, SDMT).
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 (15)
Centre Hospitalier Universitaire De Rennes
🇫🇷Rennes, France
Hospices Civils De Lyon
🇫🇷Bron, France
CHRU De Nancy
🇫🇷Nancy, France
Les Hopitaux Universitaires De Strasbourg
🇫🇷Strasbourg Cedex 2, France
Institut De Cancerologie Strasbourg Europe
🇫🇷Strasbourg, France
Centre Hospitalier Universitaire De Montpellier
🇫🇷Montpellier Cedex 5, France
Universitaetsklinikum Ulm AöR
🇩🇪Ulm, Germany
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
🇩🇪Mainz, Germany
Universitaetsklinikum Essen AöR
🇩🇪Essen, Germany
Ospedale San Raffaele S.r.l.
🇮🇹Milan, Italy
Scroll for more (5 remaining)Centre Hospitalier Universitaire De Rennes🇫🇷Rennes, FranceLaure MICHELSite contact33299284266Laure.michel@chu-rennes.fr