Multiple SclerosisPhase 1/2NCT07178431
MB-CART2019.1 in Refractory Multiple Sclerosis
A Phase 1/2 study testing MB-CART2019.1 in people with Multiple Sclerosis and CAR T Cell Therapy, run by Miltenyi Biomedicine GmbH at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Multiple Sclerosis, CAR T Cell Therapy
- What is being tested?
- MB-CART2019.1
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteGermany
- Study dates
- 1 Apr 2026to 16 Aug 2030
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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:
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- Definition for RRMS/SPMS:
- 1 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
- Absolute Neutrophil count > 2000/uL
- Platelets > 150,000/uL
- Absolute Lymphocyte count > 1000/uL
- Serum IgG > 500 mg/dl
- Hemoglobin > 9g/dl
- Adequate renal, hepatic, pulmonary and cardiac function defined as
- Creatinine ,< 2mg/dl or creatinine clearance > to 60ml/min
- ALT/AST < 3x ULN
- Total bilirubin < 1,5 mg/dl, except for subjects with Gilbert syndrome.
- Cardiac ejection fraction > 40%, no evidence of significant pericardial effusion (echography) or clinically significant ECG findings
- Baseline oxygen saturation > 94% on air room
- Negative test for Hepatitis B core antibody and Hepatitis C core antibody, CMV, VZ, Herpes simplex virus 1 and 2 ab
- Negative test for Myelin-Oligodendrocyte-Glycoprotein (MOG) and Aquaporin-4 (AQP-4) autoantibodies
- Women of childbearing potential (WOCBP) must be able and willing to use at least one highly effective method of contraception from the time of consent until 12 months after the administration of MB-CART2019.1. WOCBP must refrain from donating eggs during the same period. A woman is considered of childbearing potential, i.e., fertile, following menarche and until having been postmenopausal for at least 12 months or unless otherwise permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. For the definition and a list of highly effective methods of contraception, see Appendix 1 Contraception Guidelines.
- Men whose sexual partners are WOCBP must be able and willing to use at least one highly effective method of contraception (used by themselves or their female partners; see Appendix 1 Contraception Guidelines) from the time of consent until 12 months after the administration of MB-CART2019.1.
- Willingness and ability to comply with all trial procedures.
- Adequate vital signs.
Who cannot join
- 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
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- 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.
- History of moderate or worse renal impairment (eGFR < 30 ml/min/1.73 m2)
- Prevalent inflammatory diseases of the GI tract (e.g. Inflammatory bowel disease, Peptic ulcer) which could result in a higher risk for gastrointestinal perforation.
- The following cardiac conditions:
- New York Heart Association Stage III or IV congestive heart failure Myocardial infarction or coronary artery bypass graft ≤ 6 months prior to enrollment History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
- History of severe non-ischemic cardiomyopathy Medications:
- Systemic corticosteroids >10 mg within 7 days prior to leukapheresis; T cell targeting drugs (e.g. mycophenolate mofetil, calcineurin inhibitors) within 21 days prior to leukapheresis, Previous CAR T cell therapy, Live vaccines within 30 days prior to leukapheresis, Current Cytotoxic drugs Other MS disease modifying drugs (as stated in 5.8.1.)
- Hypersensitivity against any drug or its ingredients/impurities that is scheduled or likely to be given during trial participation, e.g. as part of the mandatory preparative lymphodepletion or rescue medication/salvage therapies for treatment related toxicities;
- Contraindication of trial related procedures as judged by the investigator
- Pregnant of breast-feeding females; female patients of child-bearing potential not willing to practice a highly effective form of birth control from leukapheresis and for 12 months after dosing the IMP
- Concurrent participation in another interventional trial
- Inability to understand the procedures and risks associated with the Trial.
- Any additional contraindication of trial related procedures as judged by the investigator
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site, 1 recruiting
- Recruiting
Charité Universitätsmedizin Berlin
Berlin, 13353
Volker Siffrin PD. Dr., 0049 30 450-560-022, volker.siffrin@charite.de
About this study
Official title: An Open Label Phase I/IIa, Multicenter, Interventional Single-arm Trial of MB-CART 2019.1 in Patients With Refractory Multiple Sclerosis (MS)
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.
Read the detailed description
This is a phase l/ll open-label, multicentre, interventional single-arm trial of MB-CART2019.1 in patients with active refractory primary and secondary Multiples Sclerosis.
During the treatment, the patients will undergo a leukapheresis, a lymphodepleting chemotherapy and an administration of the expanded MB-CART2019.1. Phase I is to establish the safety and tolerability of MB-CART2019.1 and to determine a recommended dose for phase IIa (RP2D). During Phase IIa the treatment response after infusion of MB-CART2019.1 as defined by NEDA-3 ("no evident disease activity") will be evaluated. Therefore a BOIN trial design will be used to guide dose escalation and de-escalation decisions in phase I. The second phase will evaluate the efficacy and safety in patients treated with the recommended dose from phase I. The phase II part follows a Simon's 'minimax' two stage design.
- Conditions
- Multiple Sclerosis, CAR T Cell Therapy
- Being tested
- MB-CART2019.1
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MB-CART2019.1Biological
CAR T cell therapy
| Study group | Role | What they receive |
|---|---|---|
| MB-CART2019.1 in MS | Experimental | Biological: MB-CART2019.1 Receives: Biological: MB-CART2019.1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 48 weeks
Secondary outcomes (1)
Secondary endpoints Phase I only (primary in 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 ;
- no 24-week confirmed progression of ≥20% on the timed 25-foot walk test and
- no 24-week confirmed progression 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.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2025
- Study start1 Apr 2026
- Primary completion16 Aug 2030 (estimated)
- Study completion16 Aug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Miltenyi Biomedicine GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Volker Siffrin PD. Dr., Principal investigator, Charite University, Berlin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07178431
- Sponsor's protocol ID
- M-2024-424
- Status last verified
- Apr 2026
- First submitted
- 28 Jul 2025
- Last updated
- 11 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Phase I/IIa, Multicenter, Interventional Single-arm Trial of MB-CART 2019.1 in Patients With Refractory Multiple Sclerosis (MS)
- ClinicalTrials.gov ID
- NCT07178431
- Acronym / sponsor ID
- M-2024-424
- Conditions
- Multiple Sclerosis, CAR T Cell Therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- Miltenyi Biomedicine GmbHIndustry (pharma, biotech, devices)
- Study start
- 1 Apr 2026 (actual)
- Primary completion
- 16 Aug 2030 (estimated)
- Study completion
- 16 Aug 2030 (estimated)
- First posted
- 17 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a phase l/ll open-label, multicentre, interventional single-arm trial of MB-CART2019.1 in patients with active refractory primary and secondary Multiples Sclerosis.
During the treatment, the patients will undergo a leukapheresis, a lymphodepleting chemotherapy and an administration of the expanded MB-CART2019.1. Phase I is to establish the safety and tolerability of MB-CART2019.1 and to determine a recommended dose for phase IIa (RP2D). During Phase IIa the treatment response after infusion of MB-CART2019.1 as defined by NEDA-3 ("no evident disease activity") will be evaluated. Therefore a BOIN trial design will be used to guide dose escalation and de-escalation decisions in phase I. The second phase will evaluate the efficacy and safety in patients treated with the recommended dose from phase I. The phase II part follows a Simon's 'minimax' two stage design.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MB-CART2019.1 in MS | Experimental | Biological: MB-CART2019.1Biological: MB-CART2019.1 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (32 listed)
- 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:
Key exclusion criteria (27 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MB-CART2019.1CAR T cell therapy | Biological | MB-CART2019.1 in MS |
Primary outcome
Primary endpoints Phase I
Time frame: day 28
* 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.
Primary endpoints Phase IIa
Time frame: 48 weeks
* 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.
1 secondary outcome
Secondary endpoints Phase I only (primary in phase IIa)
Time frame: 48 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Volker Siffrin PD. Dr. principal investigator
Charite University, Berlin, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MB-CART2019.1 in people with Multiple Sclerosis and CAR T Cell Therapy, run by Miltenyi Biomedicine GmbH at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 32 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clinical Trial Manager (+4922048306820, clinicaltrials.gov@miltenyi.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary endpoints Phase I (time frame: day 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2026.