YTB323 for Multiple Sclerosis

Recruiting at 5 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Novartis Pharmaceuticals

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: RMS, CNS disease, Cardiovascular, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: Day 1

28 Participants Needed

Trial Summary

Will 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.

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. ^{1 2 3 4 5}

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.

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

My condition is diagnosed as SPMS or PPMS according to 2017 criteria.

I have signed the consent form to participate in this study.

My latest brain MRI showed no enhancing lesions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of YTB323, with dose escalation in cohorts if proven safe

Day 1

1 visit (in-person)

Follow-up

Participants are monitored for safety, disease progression, and cellular kinetics

2 years

Regular visits over 2 years

Long-term follow-up

Participants are followed for an additional 13 years to assess long-term safety and outcomes

13 years

Treatment Details

Interventions

• rapcabtagene autoleucel (YTB323)

Trial Overview 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.

Participant Groups

Group I: YTB323 Cohort 4 Experimental Treatment 1 Intervention

Participants will receive one dose of YTB323

Group II: YTB323 Cohort 3 Experimental Treatment 1 Intervention

Participants will receive one dose of YTB323

Group III: YTB323 Cohort 2 Experimental Treatment 1 Intervention

Participants will receive one dose of YTB323

Group IV: YTB323 Cohort 1 Experimental Treatment 1 Intervention

Participants will receive one dose of YTB323

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

Axicabtagene ciloleucel and brexucabtagene autoleucel are effective anti-CD19 T-cell therapies that have shown high response rates in patients with relapsed and refractory B-cell malignancies, leading to FDA approvals for specific types of lymphoma.

Despite their effectiveness, these therapies can cause significant toxicities, such as cytokine release syndrome and neurologic issues, which necessitate careful management and monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel and brexucabtagene autoleucel in relapsed and refractory diffuse large B-cell and mantle cell lymphomas. Reagan, PM., Friedberg, JW.[2021]

Equecabtagene autoleucel (Fucaso®) is a CAR-T cell therapy specifically designed to target B cell maturation antigen (BCMA) and has been conditionally approved in China for treating adults with relapsed or refractory multiple myeloma (RRMM) after at least three prior therapies.

This therapy represents a significant advancement in treatment options for RRMM patients, particularly those who have not responded to other treatments, highlighting its potential efficacy in a challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Equecabtagene Autoleucel: First Approval. Keam, SJ.[2023]

The three CAR-T cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) show promising efficacy in treating large B cell lymphoma, with overall response rates of nearly 70% and complete response rates exceeding 50% across 33 studies involving 2,172 patients.

However, axicabtagene ciloleucel and tisagenlecleucel are associated with significant risks of severe neurotoxicity and life-threatening cytokine release syndrome, necessitating careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Meng, J., Wu, X., Sun, Z., et al.[2022]

Yescarta (axicabtagene ciloleucel) is an engineered T-cell therapy that showed a 66% overall response rate and a 47% complete response rate in treating relapsed or refractory diffuse large B-cell lymphoma, based on a phase II study with a median follow-up of 15.1 months.

The therapy was associated with manageable adverse events, including cytokine release syndrome and neurological issues, making it a promising option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Axicabtagene Ciloleucel (Yescarta) for the Treatment of Diffuse Large B-Cell Lymphoma. Papadouli, I., Mueller-Berghaus, J., Beuneu, C., et al.[2022]

CAR T-cell therapy targeting CD19 has transformed the treatment landscape for relapsed or refractory B-cell lymphomas, leading to rapid FDA approval for multiple lymphoma subtypes due to high response rates and durability.

Three second-generation anti-CD19 CAR T-cell products have been approved for use in aggressive non-Hodgkin's lymphoma, and ongoing research is focused on understanding treatment failures and improving outcomes for patients who do not respond to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for B-cell lymphoma. Denlinger, N., Bond, D., Jaglowski, S.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel and brexucabtagene autoleucel in relapsed and refractory diffuse large B-cell and mantle cell lymphomas. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Equecabtagene Autoleucel: First Approval. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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]

4. England pubmed.ncbi.nlm.nih.gov

EMA Review of Axicabtagene Ciloleucel (Yescarta) for the Treatment of Diffuse Large B-Cell Lymphoma. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for B-cell lymphoma. [2022]