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

Cabaletta Bio

Status and phase

Begins enrollment in 3 months

Phase 2

Phase 1

Conditions

Multiple Sclerosis (Relapsing Remitting)

Progressive Multiple Sclerosis (PMS)

Relapsing Multiple Sclerosis (RMS)

Multiple Sclerosis (MS) - Relapsing-remitting

Multiple Sclerosis

Progressive Multiple Sclerosis

Multiple Sclerosis - Relapsing Remitting

Treatments

Biological: CABA-201

Study type

Interventional

Funder types

Industry

Identifiers

NCT07006805

CAB-201-005

Details and patient eligibility

About

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

Full 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).

Enrollment

12 estimated patients

Sex

All

Ages

18 to 60 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

The main inclusion criteria include the following:

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

The main exclusion criteria include the following:

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.