Multiple Sclerosis
Conditions
Keywords
Progressive Multiple Sclerosis, Primary Progressive Multiple Sclerosis;, SPMS, PPMS, CAR T-Cell Therapy, C-CAR168, CD20, BCMA
Brief summary
This is a global, multicenter, Phase 1b/2 study evaluating the safety and efficacy of C-CAR168, an autologous anti-CD20/BCMA chimeric antigen receptor T-cell therapy, in participants with progressive multiple sclerosis refractory to standard-of-care therapy. The study includes participants with secondary progressive multiple sclerosis (SPMS) and primary progressive multiple sclerosis (PPMS).
Interventions
DRUGC-CAR168
Autologous anti-CD20/BCMA chimeric antigen receptor T-cell therapy administered as a single intravenous infusion following lymphodepleting chemotherapy.
Sponsors
AbelZeta Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Able to sign and date the informed consent form. * Male or female, 18-55 years of age, body weight \>=40 kg. * Diagnosis of MS according to the 2024 McDonald criteria with cohort-specific progressive MS requirements. * Cohort 1: active SPMS; Cohort 2: PPMS or non-active SPMS. * Inadequate response to at least one prior high-efficacy disease-modifying therapy administered for at least 6 months. * Documented disability progression over the prior 24 months. * EDSS 3.0 to 6.5, inclusive. * Meets protocol-defined disease-duration, CSF, organ-function, cardiac/pulmonary, pregnancy testing, contraception, vaccination, and cellular-therapy follow-up requirements. Key
Exclusion criteria
* RRMS, clinically isolated syndrome, radiologically isolated syndrome, or another diagnosis better explaining the neurologic course. * Alternative inflammatory demyelinating disorders, including AQP4-antibody-positive NMOSD and MOG-antibody-associated disease. * Active or chronic infection requiring antibiotics, or protocol-specified positive infectious disease testing. * Inadequate washout from prior MS therapy or specified recent immunomodulatory treatments. * Prior CAR T-cell therapy, other genetically modified immune cell therapy, or gene therapy. * Pregnant or breastfeeding, or planning pregnancy during the protocol-defined follow-up period. * Specified major cardiovascular, neurologic, transplant, malignancy, bleeding/thromboembolic, allergy, or protocol-compliance exclusions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Treatment-Emergent Adverse Events | Through Month 24 | Incidence and severity of treatment-emergent adverse events, serious adverse events, dose-limiting toxicities, CRS, ICANS, adverse events of special interest, and treatment- or procedure-related adverse events. |
| Proportion of Participants With 6-Month Composite Confirmed Disability Progression (6m-cCDP) Through Month 12 | Through Month 12 | Proportion of participants within each Phase 2 cohort experiencing 6-month composite confirmed disability progression through Month 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with 6m-cCDP - Through Month 12 (Phase 1b) | Through Month 12 (Phase 1b) | — |
| Proportion of participants with 3m-cCDP | Through Month 24 | — |
| Proportion of participants with 6m-cCDP | Through Month 24 | — |
| Change from baseline in Expanded Disability Status Scale EDSS) | Through Month 24 | — |
| Change from baseline in Functional Systems Score (FSS) | Through Month 24 | — |
| Change from baseline in Timed 25-Foot Walk (T25FW) | Through Month 24 | — |
| Change from baseline in 9-Hole Peg Test (9-HPT) | Month 12 and Month 24 | — |
| Time to first 3m-cCDP | Through Month 24 | — |
| Time to first 6m-cCDP | Through Month 24 | — |
| MRI lesion changes | Through Month 24 | — |
| Incidence and severity of adverse events and serious adverse events | Through Month 24 | — |
| Pharmacokinetics of C-CAR168 measured by quantitative polymerase chain reaction (qPCR) | Through Month 24 | Characterize CAR T-cell expansion and persistence using qPCR |
| Pharmacokinetics of C-CAR168 utilizing flow cytometry | Through Month 24 | Characterize T-cell expansion and persistence utilizing flow cytometry |
Contacts
CONTACTKirstin Liechty
CONTACTNurat Quadri
Outcome results
None listed