An Open-label, Multi-center, Phase 1/2 Study to Assess Safety, Efficacy, and Cellular Kinetics of YTB323 in Participants With Relapsing Multiple Sclerosis With Breakthrough Disease Activity During Previous Treatment With a Highly Efficacious Therapy
This is an open-label, multi-center, non-confirmatory study to assess the safety, efficacy, and cellular kinetics of YTB323 in approximately 28 participants with Relapsing Multiple Sclerosis (RMS) with breakthrough disease activity during previous treatment with a highly efficacious therapy (BD-HET). The study design utilizes an ascending single dose design consisting of 3 sentinel cohorts followed by an expansion cohort.
• Signed informed consent, and able to communicate well with the investigator and comply with the requirements of the study
• Adequate renal, hepatic, cardiac, hematological, and pulmonary function
• Male or female participants, ≥18 years to ≤60 years at screening, with diagnosis of RMS according to the 2017 McDonald diagnostic criteria Evidence of recent (i.e. within 1 year) breakthrough disease activity while at least 6 months on a highly efficacious therapy (any of the following): rituximab (Rituxan®), ocrelizumab (Ocrevus®), natalizumab (Tysabri®), ofatumumab (Kesimpta®), ublituximab (Briumvi®) or evidence of breakthrough disease activity within 2 years after the latest alemtuzumab infusion (Lemtrada®).
‣ Evidence of breakthrough disease activity is defined as one or more of the following:
⁃ Confirmed Clinical MS relapse
⁃ Persistent radiological activity defined by one of the following:
∙ ≥2 T1 gadolinium-enhancing lesions on a single MRI scan
‣ ≥1 T1 gadolinium-enhancing lesions on two or more separate MRI scans
‣ ≥2 new T2 lesions compared to a previous scan within a period ≤1 year
⁃ Ambulatory patients (EDSS of 3 to 6 points, inclusive assessed outside of relapse)
• Disease duration less than 15 years