Multiple Sclerosis, Multiple Sclerosis (MS) - Relapsing-remitting, Multiple Sclerosis - Relapsing Remitting, Multiple Sclerosis (Relapsing Remitting), Progressive Multiple Sclerosis, Progressive Multiple Sclerosis (PMS), Relapsing Multiple Sclerosis (RMS)
Conditions
Keywords
CABA-201, Rese-cel, autoimmune disease, anti-CD19 CAR-T therapy, cellular therapy, Multiple Sclerosis, Relapsing MS, RRMS, Progressive MS, PPMS, SPMS, Neurology, Resecabtagene autoleucel
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).
Interventions
BIOLOGICALCABA-201
Single intravenous infusion of CABA-201 following preconditioning with fludarabine and cyclophosphamide
Sponsors
Cabaletta Bio
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary (Part A: Dose Escalation) incidence and severity of adverse events | Up to 28 days after CABA-201 infusion | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal result of an investigation), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. The term AE is used to include both serious and non-serious AEs. |
| Primary (Part B: Dose Expansion) incidence of and severity of adverse events in order to confirm the dose(s) of CABA-201 | Up to 28 days after CABA-201 infusion | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal result of an investigation), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. The term AE is used to include both serious and non-serious AEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A and Part B: To evaluate the incidence and severity of adverse events | Up to 156 weeks after CABA-201 infusion | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal result of an investigation), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. The term AE is used to include both serious and non-serious AEs. |
| Part A and Part B: To characterize the pharmacodynamics (PD) | Up to 156 weeks after CABA-201 infusion | Levels of B cells in the blood |
| Part A and Part B: To characterize the pharmacokinetics (PK) | Up to 156 weeks after CABA-201 infusion | Levels of CABA-201-positive T cells in the blood |
| Part A and Part B: To evaluate disease related biomarkers | Up to 156 weeks after CABA-201 infusion | Levels of MS biomarkers in the blood and CSF |
| Part A and Part B: To evaluate the effects of CABA-201 on MS disease activity as measured by Magnetic Resonance Imaging (MRI) | Up to 156 weeks after CABA-201 infusion | Incidence of accumulated MS-related lesions |
| Part A and Part B: The effects of CABA-201 on MS disease activity as measured by EDSS | Up to 156 weeks after CABA-201 infusion | The EDSS is a scale for assessing neurologic impairment in MS. Values are from 0 points (normal neurological examination) up to 10 points (death). Higher scores represent increased disability. |
| Part A and Part B: To evaluate the effect of CABA-201 on use of subsequent MS-related therapy | Up to 156 weeks after CABA-201 infusion | Proportion of participants who require no subsequent MS-related immunomodulatory therapy |
| Part A and Part B: To evaluate the effect of CABA-201 on patient reported and health outcomes as measured by SF-36 v2 | Up to 156 weeks after CABA-201 infusion | Change in SF-36 v2 |
Contacts
STUDY_CHAIRMedical Monitor
Cabaletta Bio
Outcome results
None listed