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
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).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Single intravenous infusion of CABA-201 following preconditioning with fludarabine and cyclophosphamide
Primary (Part A: Dose Escalation) incidence and severity of adverse events
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.
Time frame: Up to 28 days after CABA-201 infusion
Primary (Part B: Dose Expansion) incidence of and severity of adverse events in order to confirm the dose(s) of CABA-201
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.
Time frame: Up to 28 days after CABA-201 infusion
Part A and Part B: To evaluate the incidence and severity of adverse events
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.
Time frame: Up to 156 weeks after CABA-201 infusion
Part A and Part B: To characterize the pharmacodynamics (PD)
Levels of B cells in the blood
Time frame: Up to 156 weeks after CABA-201 infusion
Part A and Part B: To characterize the pharmacokinetics (PK)
Levels of CABA-201-positive T cells in the blood
Time frame: Up to 156 weeks after CABA-201 infusion
Part A and Part B: To evaluate disease related biomarkers
Levels of MS biomarkers in the blood and CSF
Time frame: Up to 156 weeks after CABA-201 infusion
Part A and Part B: To evaluate the effects of CABA-201 on MS disease activity as measured by Magnetic Resonance Imaging (MRI)
Incidence of accumulated MS-related lesions
Time frame: Up to 156 weeks after CABA-201 infusion
Part A and Part B: The effects of CABA-201 on MS disease activity as measured by EDSS
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.
Time frame: Up to 156 weeks after CABA-201 infusion
Part A and Part B: To evaluate the effect of CABA-201 on use of subsequent MS-related therapy
Proportion of participants who require no subsequent MS-related immunomodulatory therapy
Time frame: Up to 156 weeks after CABA-201 infusion
Part A and Part B: To evaluate the effect of CABA-201 on patient reported and health outcomes as measured by SF-36 v2
Change in SF-36 v2
Time frame: Up to 156 weeks after CABA-201 infusion
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.