Rapcabtagene Autoleucel for Systemic Sclerosis

Recruiting at 71 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Disqualifiers: Pulmonary hypertension, Renal pathology, Hypertension, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

86 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of rapcabtagene autoleucel, an experimental therapy, for individuals with a severe form of systemic sclerosis, a condition that causes hardening and tightening of the skin and connective tissues. The study compares this treatment to rituximab, which is already used for similar conditions. It targets those with severe and worsening symptoms, such as lung problems, skin issues, or heart involvement due to systemic sclerosis. Participants should have begun experiencing certain symptoms within the last seven years. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

Do I need to stop my current medications to join the trial?

The trial mentions a 'washout period' (time without taking certain medications) as part of the protocol, so you may need to stop some medications. However, the specific medications that need to be stopped are not detailed in the provided information.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that rapcabtagene autoleucel is under study to assess its safety and effectiveness. In Phase 2 trials, some safety data has been collected, indicating it was fairly well-tolerated in earlier studies. However, detailed safety information specifically for rapcabtagene autoleucel in humans remains limited.

Rituximab, the other treatment option in this trial, has FDA approval for other conditions. It has undergone safety testing and is generally considered safe for human use, though specific side effects can vary based on the individual and condition treated.

Overall, while rapcabtagene autoleucel is still under safety evaluation, rituximab has established safety data. Participants should consider these factors when deciding whether to join the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for systemic sclerosis?

Unlike the standard treatments for systemic sclerosis, which often include immunosuppressive drugs like methotrexate or mycophenolate mofetil, rapcabtagene autoleucel offers a unique approach. This treatment is a CAR-T cell therapy, which means it uses genetically modified T cells to specifically target and destroy diseased cells, potentially leading to more precise and effective treatment outcomes. Researchers are excited about rapcabtagene autoleucel because it harnesses the body's own immune system to combat the disease, which could offer a new avenue for patients who haven't responded well to traditional therapies. Additionally, the use of rituximab as an active comparator highlights the potential for rapcabtagene autoleucel to offer benefits beyond current options.

What evidence suggests that this trial's treatments could be effective for systemic sclerosis?

This trial will compare rapcabtagene autoleucel, a type of CAR T-cell therapy, with rituximab for treating systemic sclerosis. Studies have shown that rapcabtagene autoleucel effectively reduces B cells in autoimmune diseases. B cells are believed to play a key role in conditions like systemic sclerosis. Other research has demonstrated success with CAR T-cell therapies in treating conditions such as systemic lupus erythematosus, leading to significant patient improvements. These therapies work by "resetting" the immune system, which could help manage systemic sclerosis symptoms. While more data is needed specifically for rapcabtagene autoleucel in systemic sclerosis, the approach shows promise based on similar diseases. ^{1 2 4 6 7}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for individuals with severe refractory diffuse cutaneous systemic sclerosis, a type of scleroderma affecting the skin and sometimes internal organs. Specific eligibility criteria are not provided, but typically participants must meet certain health standards to be included.

Inclusion Criteria

My first symptoms of scleroderma appeared less than 7 years ago.

My condition involves severe lung, skin, or heart issues due to systemic sclerosis.

Participant must fulfill the 2013 American College of Rheumatology/ European League Against Rheumatism classification criteria for systemic sclerosis and meet the diffuse cutaneous SSc (dcSSc) subset classification according to LeRoy

Exclusion Criteria

Any participant for whom treatment with rituximab is clinically inappropriate in the opinion of the investigator

Any medical conditions that are not related to SSc that, in the opinion of the Investigator, would jeopardize the ability of the participant to tolerate lymphodepletion and anti-CD19 CAR-T cell therapy

Any condition during Screening that could prevent a complete washout of medications as required per protocol or could otherwise make the participant ineligible for anti-CD19 CAR-T therapy and further participation in the study, as judged by the Investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rapcabtagene autoleucel or rituximab, with rapcabtagene autoleucel administered once following lymphodepletion

52 weeks

Regular visits for assessment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including FVC% and mRSS

104 weeks

Long-term follow-up

Participants who received rapcabtagene autoleucel enter a long-term follow-up period lasting up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• Rapcabtagene Autoleucel
• Rituximab

Trial Overview The study is testing rapcabtagene autoleucel, given once after preparing the body's immune system (lymphodepletion), against rituximab to see which is more effective and safe for treating severe systemic sclerosis.

How Is the Trial Designed?

Group I: rapcabtagene autoleucel arm Experimental Treatment 1 Intervention

rapcabtagene autoleucel

Group II: rituximab arm Active Control 1 Intervention

rituximab

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

Published Research Related to This Trial

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]

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]

In a study of 8 patients with systemic sclerosis (SSc) treated with rituximab (RTX) over 2 years, significant improvements in lung function and skin thickening were observed, with forced vital capacity (FVC) increasing from 68.13 to 77.13 and skin thickening scores decreasing from 13.5 to 4.87.

The treatment also led to a reduction in myofibroblast scores, indicating a positive impact on skin fibrosis, suggesting that RTX may be an effective long-term treatment option for managing SSc-related lung and skin complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of long-term treatment with rituximab on pulmonary function and skin fibrosis in patients with diffuse systemic sclerosis. Daoussis, D., Liossis, SN., Tsamandas, AC., et al.[2017]

In the updated ZUMA-3 study with a median follow-up of 26.8 months, brexucabtagene autoleucel (KTE-X19) achieved a 71% complete remission rate in adults with relapsed or refractory B-precursor acute lymphoblastic leukemia, indicating its efficacy as a treatment option.

Patients treated with KTE-X19 had a median overall survival of 25.4 months, significantly longer than the 5.5 months observed in matched historical controls, demonstrating a meaningful survival benefit with manageable safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study. Shah, BD., Ghobadi, A., Oluwole, OO., et al.[2023]

CAR-T therapies, specifically idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), show significant potential in treating heavily pretreated relapsed/refractory multiple myeloma (RRMM), with updated clinical trial data indicating they can elicit responses in these patients.

Indirect comparisons suggest that cilta-cel may provide deeper and more durable responses than ide-cel in patients with triple class-exposed RRMM, although direct head-to-head trials are necessary to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in the Use of Chimeric Antigen Receptor-Expressing T-Cell Therapies for Treatment of Multiple Myeloma. Martin, T., Jackson, CC., Pacaud, L., et al.[2023]

Rituximab (RTX) was found to be effective in treating systemic sclerosis (SSc), particularly in patients with early and rapidly progressive forms of the disease, as evidenced by stabilization of pulmonary symptoms and improvement in skin scores after treatment.

The study included 10 patients with diffuse SSc, showing that even those with long-term illness may experience benefits from RTX, supporting its use as a potential treatment option for this challenging autoimmune disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab for the therapy of systemic sclerosis: a series of 10 cases in a single center. Vilela, VS., Maretti, GB., Gama, LM., et al.[2018]

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]

Chimeric antigen receptor (CAR) T-cell therapy, such as tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta), is an effective treatment for relapsed/refractory B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma, utilizing genetically modified T-cells that target the CD19 antigen.

This collaborative work provides practical guidance for healthcare centers on how to select patients for these commercially available CAR T-cell therapies, ensuring appropriate use and maximizing treatment benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Eligibility of patients for CAR T-cell: Expert opinion-based collaborative work by the SFGM-TC]. Beauvais, D., Bachy, E., Baruchel, A., et al.[2021]

Autologous haematopoietic stem cell transplantation (HSCT) has shown promising results in treating severe systemic sclerosis (SSc), with about 70% of patients experiencing significant improvement in skin thickening and stabilization of vital organ involvement after treatment.

The treatment has a manageable safety profile, with a treatment-related mortality rate of 8.5%, and ongoing Phase III trials are exploring its efficacy further, suggesting that high-dose immunosuppression may help re-regulate the immune system in SSc patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haematopoietic stem cell transplantation for the treatment of systemic sclerosis and other autoimmune disorders. Tyndall, A., Matucci-Cerinic, M.[2019]

In an open-label study of 8 patients with early diffuse systemic sclerosis (dcSSc), a two-treatment course of rituximab (RTX) significantly improved skin scores and reduced disease activity over 24 months, indicating potential efficacy for managing skin disease.

The treatment was well tolerated, with no serious adverse events linked to RTX, and it effectively depleted B cells, suggesting a mechanism of action that may contribute to the observed clinical improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year results of an open pilot study of a 2-treatment course with rituximab in patients with early systemic sclerosis with diffuse skin involvement. Smith, V., Piette, Y., van Praet, JT., et al.[2015]

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]

In an observational study of 8 patients with refractory systemic sclerosis (SSc)-associated calcinosis treated with rituximab (RTX), 50% experienced significant clinical improvement, including reduced pain and no new episodes of inflammation or skin ulceration.

Rituximab showed a low incidence of adverse effects, with only one patient (12.5%) developing mild upper respiratory infections, suggesting it may be a safe option for treating severe cases of calcinosis in SSc.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of rituximab for the treatment of refractory systemic sclerosis associated calcinosis: A case series and systematic review of the literature. Narváez, J., Pirola, JP., LLuch, J., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06655896

NCT06655896 | Phase 2 Study Evaluating Rapcabtagene ... The purpose of this study is to evaluate the efficacy, safety and tolerability of rapcabtagene autoleucel (administered once following lymphodepletion) in ...

2. novartis.com novartis.com/clinicaltrials/study/nct06655896

Phase 2 Study Evaluating Rapcabtagene Autoleucel in ... The purpose of this study is to evaluate the efficacy, safety and tolerability of rapcabtagene autoleucel (administered once following lymphodepletion)

3. ard.bmj.com ard.bmj.com/content/annrheumdis/83/Suppl_1/327.1.full.pdf

Scientific Abstracts 327 However, safety and efficacy of CD19-CAR-T cell therapy in autoimmune disease has to be demonstrated in controlled clinical studies. Objectives: ...

4. bu.trialstoday.org bu.trialstoday.org/trial/NCT06655896

Boston University - Clinical & Translational Science Institute The purpose of this study is to evaluate the efficacy, safety and tolerability of rapcabtagene autoleucel (administered once following ...

5. healio.com healio.com/news/rheumatology/20250625/car-tcell-therapies-show-promise-immune-reset-in-multiple-diseases-at-eular-2025

CAR T-cell therapies show promise, immune reset in ... Patients with systemic lupus erythematosus who received autologous chimeric antigen receptor T-cell therapy enjoyed potent B-cell depletion and recovery.

6. novartis.com novartis.com/clinicaltrials/study/nct06675864

Open-label, Multi-center, Phase I/II Study to Assess Safety ... This is an open-label, multi-center, non-confirmatory study to assess the safety, disease progression, and cellular kinetics following YTB323 administration.

7. clinicaltrial.be clinicaltrial.be/en/details/456008?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Phase 2 Study Evaluating Rapcabtagene Autoleucel in ... This is a phase 2, multi-part, five-year, randomized, open-label, assessor-blinded, multicenter study to evaluate the efficacy and safety of rapcabtagene ...