An Open-label Study to Assess the Safety, Efficacy, and Cellular Kinetics of YTB323 in Relapsing Multiple Sclerosis

Launched by NOVARTIS PHARMACEUTICALS · Sep 26, 2024

Keywords

ClinConnect Summary

This clinical trial is looking at a new treatment called YTB323 for people with relapsing multiple sclerosis (RMS) who have not responded well to their current medications. The study will include about 28 participants who have shown signs of disease activity despite being on effective treatments for at least six months. To be eligible, participants should be between 18 and 55 years old, be able to understand and follow the study instructions, and have a recent history of disease activity, such as relapses or new lesions on MRI scans.

Participants in this trial will receive YTB323 and will be monitored for its safety and effectiveness. The study will involve some initial smaller groups of participants before expanding to include more people. Throughout the trial, participants can expect regular health check-ups and MRI scans to see how the treatment is working. It's important to note that there are specific criteria for joining the study, such as not having any serious heart or neurological issues, and participants should not have had certain previous treatments like stem cell therapy. Overall, this trial aims to better understand how YTB323 can help individuals struggling with RMS.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 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:
• • 1. Confirmed Clinical MS relapse
• 2. 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
• Exclusion Criteria:
• • Diagnosis of primary progressive multiple sclerosis (PPMS) according to the 2017 revision of the McDonald diagnostic criteria at screening
• • History of or current clinically significant CNS disease (e.g. stroke, traumatic brain or spinal injury, history or presence of myelopathy) or neurological disorders which may mimic MS or ICANS at screening
• • Evidence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, New York Heart Association (NYHA) Class III/IV left ventricular failure, arrhythmia and uncontrolled hypertension within 6 months prior to screening), neurological disorders other than MS (including seizure disorders even when well controlled), psychiatric, pulmonary (including, history of or active severe respiratory disease, including Chronic Obstructive Pulmonary Disease, interstitial lung disease or pulmonary fibrosis), renal, hepatic, endocrine, metabolic (e.g. severe hypoproteinemia due to nephrotic syndrome), hematological disorders or gastrointestinal disease that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant, prior to screening
• • Have donated blood or experienced a loss of blood \> 400 mL within 3 months prior screening, or longer if required by local regulations
• • Any prior stem cell therapy or organ transplantation or gene therapy
• * Any contraindications to LP, including but not limited to:
• • Known or suspected structural abnormality of the lumbar spine that, in the opinion of the Investigator, may interfere with the performance of the LP, or increase the risk of the procedure for the participant
• • Presence of risk for increased or uncontrolled bleeding including, but not limited to, vascular abnormalities or neoplasms at or near the LP site, disorders of the coagulation cascade, platelet function, or platelet count
• • Participants on anticoagulants (e.g., warfarin) or antiplatelets \[except for low-dose aspirin (100 mg/day or lower) and low-dose ibuprofen (600 mg/day or lower) which are allowable\], are not eligible to participate
• • Participants not willing or able to take MRI scans as per protocol. Unable to undergo MRI due to for example claustrophobia, or presents absolute contraindications to MRI (e.g., metallic implants, metallic foreign bodies, pacemaker, defibrillator)
• • Other protocol-defined inclusion/exclusion criteria may apply