MB-CART2019.1 in Refractory Multiple Sclerosis

NCT07178431 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: M-2024-424
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this trial is to assess the feasibility, safety and preliminary efficacy of MB-CART2019.1 in patients with active refractory primary and secondary progressive MS.

Conditions

Multiple Sclerosis; CAR T Cell Therapy

Outcome Measures

Primary Outcomes (2)

• Primary endpoints Phase I

  * Recommended dose for phase IIa out of 2 dose levels, based on a Bayesian Optimal Interval (BOIN) design, using a target dose limited toxicity (DLT) rate of 30%, with DLT until day 28 after infusion of MB-CART2019.1. * Safety and tolerability of MB-CART2019.1 per incidence of adverse event (AE), classified according to CTCAE version 5.0. * Evaluation and classification of Cytokine Release Syndrome (CRS) until day 28 after infusion of MB-CART2019.1. * Evaluation and classification of Immune Effector cell-associated Neurotoxicity Syndrome (ICANS) until day 28 after infusion of MB-CART2019.1.

  day 28

• Primary endpoints Phase IIa

  * NEDA-3 ("no evident disease activity") at 48 weeks (fulfilling all of the following): * no relapse activity: relapse activity is defined as any new neurologic symptom consistent with MS/not explained otherwise, accompanied by new neurologic signs present for at least 24 hrs. * no disease progression in the absence of relapses using a composite endpoint of no 24-week confirmed progression: * of ≥1 point/ ≥0.5 point on the EDSS if baseline EDSS ≤5.5/ \>5.5 points ; * of ≥20% on the timed 25-foot walk test * of ≥20%on the 9-hole peg test (NHPT). * no MRI activity: MRI activity is defined as: * new and/or enlarging T2-hyperintense lesions as detected by MRI (defined as the sum of the individual number of new and/or enlarging T2 lesions at all scheduled at 48 weeks compared to baseline) or * new T1-contrast enhancing (CE) lesions as detected by MRI at 12, 24 or 48 weeks compared to baseline.

  48 weeks

Secondary Outcomes (1)

• Secondary endpoints Phase I only (primary in phase IIa)

  48 weeks

Study Arms (1)

MB-CART2019.1 in MS

EXPERIMENTAL

Biological: MB-CART2019.1

Biological: MB-CART2019.1

Interventions

MB-CART2019.1 BIOLOGICAL

CAR T cell therapy

MB-CART2019.1 in MS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals must meet all of the following criteria to be included in the trial:
• Have read, understood and signed/dated the informed consent form.
• Age ≥18 years at the time of screening.
• Diagnosis of multiple sclerosis fulfilling the 2017 McDonald criteria.
• Progressive or worsening MS according to 2014 Lublin MS phenotypic criteria
• Disease activity despite treatment:
• Definition for RRMS/SPMS:
• or more relapses or an EDSS deterioration in the previous year (1 point or more if EDSS is between 3 and 5.5; 0.5 point or more if EDSS 6-6.5) or MRI activity (presence of at least 2 new/enlarging T2 lesions or T1CE lesions) despite on/previous treatment with an escalation therapy drug (i.e. natalizumab, ofatumumab, ocrelizumab, alemtuzumab or mitoxantrone) for at least 6 months.
• Definition for PPMS:
• EDSS deterioration in the previous year (1 point or more if EDSS between 3 and 5.5; 0.5 point or more if EDSS 6-6.5) or MRI activity (presence of at least 2 new/enlarging T2 lesions or T1CE lesions) despite on/previous treatment with ocrelizumab (treatment duration ≥ 6 months).
• Evidence of intrathecal IgG production through oligoclonal bands (OCBs) present in the cerebrospinal fluid in PPMS or SPMS.
• Fully vaccinated against Hepatitis B.
• Presence of varicella-zoster virus (VZV) antibodies, or completion of at least one dose of varicella zoster glycoprotein E Shingrix vaccine at least 4 weeks prior to treatment.
• Presence of anti EBV antibodies
• Organ function / lab parameters as follows

You may not qualify if:

• Patients will be entered into this trial only if they meet none of the following criteria:
• For relapsing and progressive MS forms: the disability status according to the EDSS scale is larger than 7.0 or the age is larger than 55 years.
• Only applicable for progressive MS (PPMS/SPMS), where the disease duration is longer than 15 years.
• History of a malignancy unless disease free for ≥5 years with the exception of basal or squamous cell skin cancer
• Known history of and/or active infection with hepatitis B (hepatitis B surface antigen positive)
• Known history of infection with hepatitis C virus unless treated and confirmed to be polymerase chain reaction (PCR) negative
• Any active uncontrolled bacterial, viral or fungal infection
• A history of and/or active infection with human immunodeficiency virus (HIV)
• A history of active or latent tuberculosis (TB); TB testing should be performed at screening (Quantiferon test). Confirmed active or latent TB the patient can be re-screened after full completion of anti-tuberculosis treatment (9 months of Isoniazide therapy)
• History of neuromyelitis optica spectrum disorder (NMOSD) or MOG antibody associated disease.
• History of CNS or spinal cord tumor, metabolic or infectious causes of myelopathy, genetically inherited progressive CNS disorder, sarcoidosis or non MS-progressive neurological condition affecting the ability to perform the study assessments
• History of cytopenia consistent with MDS diagnosis
• History of sickle cell anemia or other hemoglinopathies
• Primary immune deficiency disease
• Patients with positive antiphospholipid antibodies, anti-cardiolipin or lupus anticoagulant.

Sponsors & Collaborators

• Miltenyi Biomedicine GmbH: lead

Study Sites (1)

Charité Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Volker Siffrin PD. Dr.

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trial Manager

CONTACT

+4922048306820; clinicaltrials.gov@miltenyi.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2025
• First Posted: September 17, 2025
• Study Start: January 30, 2026
• Primary Completion (Estimated): February 28, 2030
• Study Completion (Estimated): December 30, 2030
• Last Updated: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)