RESET-MS: A Study to Evaluate the Safety and Efficacy of CABA-201 in Participants With Multiple Sclerosis

NCT ID: NCT07006805

Last Updated: 2025-10-31

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-06-30
• Study Completion Date: 2029-10-31

Brief Summary

RESET-MS: A Phase 1/2 Open-Label Study to Evaluate the Safety and Efficacy of Autologous CD19-specific Chimeric Antigen Receptor T cells (CABA-201) in Participants with Multiple Sclerosis

Detailed Description

This is a Phase 1/2, open-label study designed to evaluate the safety, tolerability, and efficacy of different doses of CABA-201 in adult participants with MS to determine an appropriate dose for future studies. Any participant who receives CABA-201 will be followed after infusion for 156 weeks. Two cohorts of participants will be studied based upon their MS diagnosis.

• Relapsing MS Cohort (RMS Cohort): Participants with active relapsing MS, including relapsing remitting MS (RRMS) and relapsing secondary progressive MS (SPMS) that is treatment-resistant
• Progressive MS Cohort (PMS Cohort): Participants with worsening progressive MS, including primary progressive MS (PPMS) or non-relapsing SPMS that is treatment-resistant

The study will consist of 2 parts: Part A (dose escalation) and Part B (dose expansion).

Conditions

Relapsing Multiple Sclerosis (RMS); Progressive Multiple Sclerosis (PMS); Multiple Sclerosis - Relapsing Remitting; Multiple Sclerosis; Multiple Sclerosis (Relapsing Remitting); Multiple Sclerosis (MS) - Relapsing-remitting; Progressive Multiple Sclerosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Relapsing MS Cohort

Group Type: EXPERIMENTAL

CABA-201

Intervention Type: BIOLOGICAL

Single intravenous infusion of CABA-201 following preconditioning with fludarabine and cyclophosphamide

Progressive MS Cohort

Group Type: EXPERIMENTAL

CABA-201

Intervention Type: BIOLOGICAL

Single intravenous infusion of CABA-201 following preconditioning with fludarabine and cyclophosphamide

Interventions

CABA-201

Single intravenous infusion of CABA-201 following preconditioning with fludarabine and cyclophosphamide

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Able to provide informed consent.
• Age ≥18 and ≤60 years of age.
• Diagnosis of MS per the revised 2017 McDonald criteria (Thompson et al, 2018).
• For participants with relapsing forms of MS only (RMS Cohort):

1. Moderate degree of previously accumulated disability as measured by the Expanded Disability Status Scale (EDSS)

2. Documentation of clinical relapse or a positive historical gadolinium (Gd)-enhancing magnetic resonance imaging (MRI) scan prior to Screening

3. Prior treatment with a high-efficacy therapy or prior treatment failure of oral therapies

• For participants with progressive forms of MS only (PMS cohort):

1. Moderate Disability as measured by EDSS

2. Presence of abnormal function on protocol specified EDSS Functional Systems Scale

3. Objective worsening of disease prior to Screening while on standard of care therapy

• Clinical stability by vital signs assessment at the time of screening

Exclusion Criteria

• History of fulminant MS
• Clinically significant concomitant central nervous system pathologies which, in the Investigator's judgement, may confound the ability to interpret study results or complicate identification or evaluation of neurotoxicity, including but not limited to:

1. Any history of seizure disorder, even if well-controlled on antiepileptics

2. History of progressive multifocal leukoencephalopathy

• Active, inflammatory autoimmune disorder other than MS requiring immunomodulatory therapies

a. Positive human immunodeficiency virus (HIV), hepatitis C virus (HCV) antibody, or hepatitis B surface antigen test, or evidence of active or chronic tuberculosis (TB) at Screening or other chronic viral infections as described in the protocol

• Use of the following therapies:

1. Any prior or concurrent exposure to mitoxantrone, alemtuzumab, total lymphoid irradiation

2. Cladribine within 1 year of Screening

3. Any investigational agent within 4 weeks or 5 half-lives of Screening, whichever is longer

4. Other pre-specified Disease-Modifying Therapies be discontinued by the time of pre-conditioning or earlier as described in the protocol

• Known malignancy or a history of malignancy
• Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, psychiatric, cardiac, or concomitant neurological disease, including severe (requiring medical intervention) and uncontrolled infections
• Chronic pulmonary disease
• Impaired cardiac function or clinically significant cardiac disease
• Prior engineered T cell therapy involving permanent gene modification
• Prior solid organ (heart, liver, kidney, lung) transplant or hematopoietic stem cell transplant.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cabaletta Bio

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_CHAIR

Cabaletta Bio

Central Contacts

Cabaletta Bio

Role: CONTACT

clinicaltrials@cabalettabio.com

267-759-3100 ext. 4444

Other Identifiers

CAB-201-005

Identifier Type: -

Identifier Source: org_study_id