This is an open-label, multi-center, non-confirmatory study to assess the safety, disease progression, and cellular kinetics following YTB323 administration to 28 participants with non-active Progressive Multiple Sclerosis (PMS). The study design utilizes an ascending single dose design consisting of 3 sentinel cohorts followed by an expansion cohort.
All participants in this study will receive YTB323. Both the participant and the study doctor will know the participant is getting YTB323. Participants will be given one dose of YTB323. Different groups of participants may receive a higher dose of YTB323, if proven to be safe for every participant at the lower dose. Participants are in this study for 2 years and will be followed for an additional 13 years in a long-term follow up study. The main question this trial is designed to answer: Is YTB323 treatment safe for participants with progressive MS?
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
28
CAR-T cell suspension for intravenous infusion
Novartis Investigative Site
Darlinghurst, New South Wales, Australia
RECRUITINGNovartis Investigative Site
Melbourne, Victoria, Australia
RECRUITINGNovartis Investigative Site
Québec, Quebec, Canada
RECRUITINGNovartis Investigative Site
Bron, France
RECRUITINGNovartis Investigative Site
Montpellier, France
RECRUITINGNovartis Investigative Site
Nancy, France
RECRUITINGNovartis Investigative Site
Rennes, France
RECRUITINGNovartis Investigative Site
Essen, Germany
RECRUITINGNovartis Investigative Site
Ulm, Germany
RECRUITINGNovartis Investigative Site
Genova, GE, Italy
RECRUITING...and 7 more locations
Number of participants with dose limiting toxicities (DLTs), Adverse Events (AEs), and Serious Adverse Events (SAEs)
Occurrence, severity, and frequency of dose limiting toxicities (DLTs), AEs and SAEs, including changes in vital signs, electrocardiograms (ECGs), laboratory parameters, neurological status and magnetic resonance (MRI) of the brain and spinal cord qualifying and reported as AEs.
Time frame: Day 1 through Year 2
Measure of Disability: Expanded Disability Status Scale (EDSS).
EDSS is used to measure the change in disability level in participants using a scale from 0 to 10. The higher the score, the greater the degree of disability.
Time frame: Day 1 through Year 2
Measure of Disability: Short Form Health Survey (SF-36 v2)
The Short Form Health Survey (SF-36 v2) is a widely used and extensively studied instrument to measure health-related quality of life among healthy participants and participants with acute and chronic conditions. It consists of eight subscales that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Two overall summary scores, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) also can be computed. The SF 36 has proven useful in monitoring general and specific populations, comparing the relative burden of different diseases, differentiating the health benefits produced by different treatments, and in screening individual participants.
Time frame: Day 1 through Year 2
Measure of Disability: Timed 25 Foot Walk (T25FW)
The T25FW is a mobility test based on a timed walk of 25 feet that is administered by a trained administrator. The participant is directed to walk the clearly marked 25-foot distance as quickly as possible. Longer completion time corresponds with decreased mobility.
Time frame: Day 1 through Year 2
Measure of Disability: 9 Hole Peg Test (9HPT)
The 9HPT is a finger dexterity test that is administered by a trained administrator. The participant is directed to put 9 pegs, one by one, onto and then off the holder board as quickly as possible starting with using only the dominant hand, and then repeated with the non-dominant hand. Longer completion times are associated with decreased finger dexterity.
Time frame: Day 1 through Year 2
Measure of Disability: Symbol Digit Modalities Test (SDMT)
The SDMT is a timed cognition test administered by a trained administrator. The test assesses sustained attention, processing speed, visual scanning, and motor speed to determine cognitive impairment. Participants are given a coding key which contains abstract symbols that correspond to specific numbers. Participants are timed how quickly and accurately they are able to substitute the symbols for the numbers and is scored by the number of correctly coded items.
Time frame: Day 1 through Year 2
Modified Fatigue Impact Scale (MFIS)
The MFIS is a questionnaire to assess fatigue-related symptoms in patients with MS.
Time frame: Day 1 through Year 2
Whole Blood Pharmacokinetics (PK) of YTB323 - CMAX
Measured by Cmax - The maximum plasma concentration of YTB323
Time frame: Day 1 through Year 2
Whole Blood Pharmacokinetics (PK) of YTB323 - AUC
Measured by AUC - Area under the curve of YTB323
Time frame: Day 1 Through Year 2
Whole Blood Pharmacokinetics (PK) of YTB323 - Tmax
Measured by Tmax - Time to Reach the Maximum Concentration After Drug Administration of YTB323
Time frame: Day 1 Through Year 2
Whole Blood Pharmacokinetics (PK) of YTB323 - Clast
Clast is defined as the Last observed (quantifiable) plasma concentration (Clast
Time frame: Day 1 Through Year 2
Whole Blood Pharmacokinetics (PK) of YTB323 - Tlast
Tlast is defined as Time of Last Measurable Concentration
Time frame: Day 1 through Year 2
Humoral Immunogenicity of YTB323
Incidence and prevalence of pre-existing and treatment induced humoral immunogenicity of YTB323
Time frame: Day 1 through Year 2
Cellular Immunogenicity of YTB323
Incidence and prevalence of pre-existing and treatment induced cellular immunogenicity of YTB323
Time frame: Day 1 through Year 2
Safety data including dose limiting toxicities (DLTs), Adverse Events (AEs), and Serious Adverse Events (SAEs) from each dose level
Safety data from each dose level will be used to assess safe dose-level(s) to be continued in phase 2 and later clinical studies
Time frame: Day 1 through Year 2
Novartis Pharmaceuticals
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