Assessing the safety and efficacy of YTB323 in patients with relapsing multiple sclerosis
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 study is testing a new treatment called YTB323 to see if it is safe and effective for people with relapsing multiple sclerosis who haven't responded well to other treatments.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 28 (estimated) |
| Ages | 18 Years to 60 Years |
| Sex | All |
| Sponsor | Novartis Industry-sponsored |
| Drugs / interventions | rituximab, ocrelizumab, natalizumab, ofatumumab, ublituximab, alemtuzumab |
| Locations | 18 sites (Darlinghurst, New South Wales and 17 other locations) |
| Trial ID | NCT06617793 on ClinicalTrials.gov |
What this trial studies
This open-label, multi-center study evaluates the safety, efficacy, and cellular kinetics of YTB323 in approximately 28 participants diagnosed with relapsing multiple sclerosis (RMS) who have experienced breakthrough disease activity despite previous treatment. Participants will receive a single dose of YTB323, with the possibility of escalating doses based on safety assessments. The study will last for 2 years, followed by a long-term follow-up period of 13 years to monitor ongoing effects and safety. The primary aim is to determine the safety profile of YTB323 in this patient population.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 to 60 with a diagnosis of relapsing multiple sclerosis and evidence of recent breakthrough disease activity while on highly efficacious therapies.
Not a fit: Patients who do not have relapsing multiple sclerosis or those who have not experienced breakthrough disease activity while on previous treatments may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with relapsing multiple sclerosis who have not responded adequately to existing therapies.
How similar studies have performed: Other studies utilizing CAR-T cell therapies have shown promise in treating various conditions, suggesting potential for success in this novel application for multiple sclerosis.
Eligibility criteria
Show full inclusion / exclusion 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
* Participants must receive or be current on all recommended vaccinations according to institutional, local, or global guidelines for immunocompromised patients at least 6-weeks prior to lymphodepletion
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
Where this trial is running
Darlinghurst, New South Wales and 17 other locations
- Novartis Investigative Site — Darlinghurst, New South Wales, Australia (Recruiting)
- Novartis Investigative Site — Melbourne, Victoria, Australia (Recruiting)
- Novartis Investigative Site — Montpellier, France (Recruiting)
- Novartis Investigative Site — Nancy, France (Recruiting)
- Novartis Investigative Site — Rennes, France (Recruiting)
- Novartis Investigative Site — Bochum, Germany (Recruiting)
- Novartis Investigative Site — Essen, Germany (Recruiting)
- Novartis Investigative Site — Mainz, Germany (Recruiting)
- Novartis Investigative Site — Ulm, Germany (Recruiting)
- Novartis Investigative Site — Genova, Ge, Italy (Recruiting)
- Novartis Investigative Site — Milan, Mi, Italy (Recruiting)
- Novartis Investigative Site — Barcelona, Spain (Recruiting)
- Novartis Investigative Site — Córdoba, Spain (Recruiting)
- Novartis Investigative Site — Madrid, Spain (Recruiting)
- Novartis Investigative Site — Valencia, Spain (Recruiting)
- Novartis Investigative Site — Bern, Switzerland (Recruiting)
- Novartis Investigative Site — Lausanne, Switzerland (Recruiting)
- Novartis Investigative Site — Zurich, Switzerland (Recruiting)
Study contacts
- Study coordinator: Novartis Pharmaceuticals
- Email: novartis.email@novartis.com
- Phone: +41613241111
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.