YTB323 for Multiple Sclerosis
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18 - 65
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Novartis Pharmaceuticals
No Placebo Group
Trial Summary
What is the purpose of this trial?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.
How is the treatment YTB323 different from other treatments for multiple sclerosis?
YTB323, also known as rapcabtagene autoleucel, is a type of CAR-T cell therapy, which is a novel approach that involves modifying a patient's own immune cells to better target and attack disease. This treatment is unique because it uses a chimeric antigen receptor (CAR) to direct T cells against specific targets, which is different from traditional multiple sclerosis treatments that typically focus on managing symptoms or slowing disease progression.
12345Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, if you are on anticoagulants or antiplatelet drugs, you may not be eligible, except for low-dose aspirin or ibuprofen.
Eligibility Criteria
This trial is for adults aged 18-60 with Progressive Multiple Sclerosis (PMS) who can handle certain medical procedures like lumbar punctures and MRIs. They should have a confirmed diagnosis of SPMS or PPMS, be able to walk (EDSS ≤6.5), show recent disease progression, and have had PMS for less than 15 years without relapses or new brain lesions in the last year.Inclusion Criteria
Key
My condition is diagnosed as SPMS or PPMS according to 2017 criteria.
I am between 18 and 60 years old.
My condition has been diagnosed for less than 15 years.
I can walk with assistance.
I have not had a relapse in the past year.
Participant Groups
The study tests YTB323, a potential treatment for PMS. It's an open-label trial where all participants receive the drug. The study has an ascending single dose design with initial small groups followed by more participants to assess safety and effects on disease progression.
4Treatment groups
Experimental Treatment
Group I: YTB323 Cohort 4Experimental Treatment1 Intervention
Participants will receive one dose of YTB323
Group II: YTB323 Cohort 3Experimental Treatment1 Intervention
Participants will receive one dose of YTB323
Group III: YTB323 Cohort 2Experimental Treatment1 Intervention
Participants will receive one dose of YTB323
Group IV: YTB323 Cohort 1Experimental Treatment1 Intervention
Participants will receive one dose of YTB323
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Novartis Investigative SiteQuebec, Canada
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Who is running the clinical trial?
Novartis PharmaceuticalsLead Sponsor
References
EMA Review of Axicabtagene Ciloleucel (Yescarta) for the Treatment of Diffuse Large B-Cell Lymphoma. [2022]On June 28, 2018, the Committee for Advanced Therapies and the Committee for Medicinal Products for Human Use adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Yescarta for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma, after two or more lines of systemic therapy. Yescarta, which was designated as an orphan medicinal product and included in the European Medicines Agency's Priority Medicines scheme, was granted an accelerated review timetable. The active substance of Yescarta is axicabtagene ciloleucel, an engineered autologous T-cell immunotherapy product whereby a patient's own T cells are harvested and genetically modified ex vivo by retroviral transduction using a retroviral vector to express a chimeric antigen receptor (CAR) comprising an anti-CD19 single chain variable fragment linked to CD28 costimulatory domain and CD3-zeta signaling domain. The transduced anti-CD19 CAR T cells are expanded ex vivo and infused back into the patient, where they can recognize and eliminate CD19-expressing cells. The benefits of Yescarta as studied in ZUMA-1 phase II (NCT02348216) were an overall response rate per central review of 66% (95% confidence interval, 56%-75%) at a median follow-up of 15.1 months in the intention to treat population and a complete response rate of 47% with a significant duration. The most common adverse events were cytokine release syndrome, neurological adverse events, infections, pyrexia, diarrhea, nausea, hypotension, and fatigue. IMPLICATIONS FOR PRACTICE: Yescarta (axicabtagene ciloleucel) was the first chimeric antigen receptor T-cell therapy to be submitted for evaluation to the European Medicines Agency and admitted into the "priority medicine" scheme; it was granted accelerated assessment on the basis of anticipated clinical benefit in relapsed/refractory diffuse large B-cell lymphoma, a condition of unmet medical need. Indeed, Yescarta showed an overall response rate of 66% and a complete response rate of 47% with a significant duration and a manageable toxicity that compared very favorably with historical controls. Here the analysis of benefits and risks is presented, and specific challenges with this important novel product are highlighted, providing further insights and reflections for future medical research.
Axicabtagene ciloleucel and brexucabtagene autoleucel in relapsed and refractory diffuse large B-cell and mantle cell lymphomas. [2021]Axicabtagene ciloleucel and brexucabtagene autoleucel are anti-CD19 T-cell therapies that utilize the same second-generation chimeric antigen receptor with a CD28 costimulatory subunit. They have demonstrated high rates of response in high-risk patients with relapsed and refractory B-cell malignancies in multicenter clinical trials, including diffuse large B-cell and mantle cell lymphomas. The high clinical activity has led to the US FDA approval of axicabtagene ciloleucel for diffuse large B-cell lymphoma, and brexucabtagene autoleucel for mantle cell lymphoma. While they are highly effective, they have significant toxicities, including cytokine release syndrome and neurologic toxicities, which can be severe and require specialized management. This review will discuss the development, efficacy and safety of axicabtagene ciloleucel and brexucabtagene autoleucel in B-cell lymphomas.
Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis. [2022]Currently, three chimeric antigen receptor (CAR)-T cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel have been approved by the U.S. Food and Drug Administration for the treatment of large B cell lymphoma, which provide a novel and promising choice for patients with relapsed or refractory to traditional anti-tumor treatments. Thus, it is pertinent to describe the efficacy and safety profile of the three products available by summarizing the current evidence.
CAR T-cell therapy for B-cell lymphoma. [2022]Chimeric antigen receptor-modified (CAR) T-cell therapy targeting CD19 has revolutionized the treatment of relapsed or refractory B-cell lymphomas. Based on unprecedented response rates and durability of response in high risk B-cell lymphoma patients, anti-CD19 CAR T-cell therapy was rapidly approved by the FDA for a variety of lymphoma subtypes. Anti-CD19 CAR T-cell therapy is now considered standard of care for patients with relapsed or refractory (R/R) aggressive non-Hodgkin's Lymphoma (NHL) after 2 or more lines of therapy. Three second-generation anti-CD19 CAR T-cell products have been FDA approved for R/R aggressive B-cell lymphoma and FDA approval has been obtained for Mantle Cell Lymphoma and Follicular lymphoma as well. This has ensured broad access to CAR T-cell therapy for patients with NHL and new real-world trials have helped confirm feasibility of CAR T-cell therapy for a broad patient population. The emergence of CAR T-cell therapy will likely provide a new patient population who is status post anti-CD19 CAR T-cell therapy. Investigation of mechanisms of failure of CAR T-cell therapy and clinical trials to study strategies to address this are thus required. Here we provide a thorough review on the use of the FDA approved anti-CD19 CAR T-cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel in patients with indolent or aggressive B-cell lymphoma, and touch on mechanisms of failure of CAR T-cell therapy and potential approaches which are currently under investigation to address this.
Equecabtagene Autoleucel: First Approval. [2023]Equecabtagene autoleucel (Fucaso®), an autologous anti-B cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR)-T cell therapy that uses lentivirus as a gene vector to transfect autologous T cells, is being developed by IASO Biotechnology and Innovent Biologics, Inc. for the treatment of multiple myeloma (MM) and autoimmune diseases of the nervous system, including neuromyelitis optica spectrum disorder (NMOSD). Equecabtagene autoleucel was granted conditional approval in China in June 2023 for the treatment of adults with relapsed or refractory MM (RRMM) who have progressed after ≥ 3 lines of therapy (≥ 1 proteasome inhibitor and an immunomodulator). This article summarizes the milestones in the development of equecabtagene autoleucel leading to this first approval in patients with RRMM who have progressed after multiple lines of therapy.