A Study of C-CAR168 in Participants With Progressive Multiple Sclerosis

Multi-center, Phase 1b/2 Clinical Study of an Autologous Anti-CD20/BCMA Chimeric Antigen Receptor T-Cell Therapy (C-CAR168) for the Treatment of Progressive Multiple Sclerosis Refractory to Standard Therapy

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: C-CAR168

• Study Type: Interventional
• Enrollment (Estimated): 119
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Kirstin Liechty; Phone Number: 240-552-5870; Email: kirstin.liechty@abelzeta.com
• Study Contact Backup: Name: Nurat Quadri; Phone Number: 1 240 552 5870; Email: clinicaltrials@abelzeta.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: C-CAR168; Participants will receive: Leukapheresis Fludarabine Cyclophosphamide Single intravenous infusion of C-CAR168	Drug: C-CAR168; Autologous anti-CD20/BCMA chimeric antigen receptor T-cell therapy administered as a single intravenous infusion following lymphodepleting chemotherapy.; Other Names: Autologous anti-CD20/BCMA CAR T-cell therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Treatment-Emergent Adverse Events	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.	Through Month 24
Proportion of Participants With 6-Month Composite Confirmed Disability Progression (6m-cCDP) Through Month 12	Proportion of participants within each Phase 2 cohort experiencing 6-month composite confirmed disability progression through Month 12	Through Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Characterize CAR T-cell expansion and persistence using qPCR	Through Month 24
Pharmacokinetics of C-CAR168 utilizing flow cytometry	Characterize T-cell expansion and persistence utilizing flow cytometry	Through Month 24

Collaborators and Investigators

• Sponsor: AbelZeta Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2027
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): February 1, 2030

Study Registration Dates

• First Submitted: September 8, 2026
• First Submitted That Met QC Criteria: September 11, 2026
• First Posted (Actual): September 17, 2026

Study Record Updates

• Last Update Posted (Actual): September 17, 2026
• Last Update Submitted That Met QC Criteria: September 11, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: CD20; BCMA; SPMS; Progressive Multiple Sclerosis; PPMS; CAR T-Cell Therapy; C-CAR168; Primary Progressive Multiple Sclerosis
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Pathological Conditions, Signs and Symptoms; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive
• Other Study ID Numbers: ABZT-412

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data collected during this study will not be made available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No