Rapcabtagene Autoleucel for Lupus Nephritis

Recruiting in Palo Alto (17 mi)

+34 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Novartis Pharmaceuticals

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy and safety of rapcabtagene autoleucel (administered once following lymphodepletion) versus Standard of Care (SOC) in patients with systemic lupus erythematosus (SLE) with active, refractory lupus nephritis (LN).

Will I have to stop taking my current medications?

The trial mentions an 'immunosuppressive washout' period, which suggests you may need to stop taking certain medications that suppress the immune system before participating. However, the protocol does not specify which medications or how long the washout period is.

What data supports the effectiveness of this treatment for lupus nephritis?

Research on similar treatments, like anti-CD19 CAR T cell therapy, shows promise in treating patients with severe and treatment-resistant systemic lupus erythematosus (SLE), which includes lupus nephritis. This suggests that Rapcabtagene Autoleucel, which is also an anti-CD19 CAR T cell therapy, might be effective for lupus nephritis. ^{1 2 3 4 5}

Is Rapcabtagene Autoleucel (Anti-CD19 CAR-T Cell Therapy) safe for humans?

Research shows that Anti-CD19 CAR-T Cell Therapy has been generally well-tolerated in patients with autoimmune diseases like lupus, with only mild side effects such as cytokine-release syndrome (a temporary immune reaction). ^{1 6 7 8 9}

How is the treatment Rapcabtagene Autoleucel different from other treatments for lupus nephritis?

Rapcabtagene Autoleucel is a unique treatment for lupus nephritis because it involves CAR-T cell therapy, which uses modified immune cells to specifically target and destroy B cells that contribute to the disease, unlike traditional treatments that use broad immunosuppressive drugs like corticosteroids and cyclophosphamide. ^{1 6 10 11 12}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

This trial is for people with active, hard-to-treat lupus nephritis—a kidney condition caused by systemic lupus erythematosus. Participants should have tried other treatments without success. Specific criteria for joining or reasons to be excluded aren't provided here.

Inclusion Criteria

SLEDAI-2K Criteria at screening: SLEDAI-2K score >= 6 points (Gladman et al 2002, Touma et al 2011), excluding points attributed to 'fever', 'lupus headache', 'alopecia', and 'organic brain syndrome'

I have active lupus affecting my kidneys without long-term damage.

I am between 18 and 65 years old and have been diagnosed with lupus according to the 2019 EULAR/ACR criteria.

Exclusion Criteria

I do not have a severe lupus flare that needs immediate treatment beyond pulse GCs.

I have hepatitis B or C.

I have signs of active or latent tuberculosis.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 6 weeks

Treatment

Participants are randomized to receive either rapcabtagene autoleucel or Standard of Care (SOC) for systemic lupus erythematosus with active, refractory lupus nephritis

104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 104 weeks

Long-term follow-up

Participants who received rapcabtagene autoleucel infusion will enter a long-term follow-up period

Up to 15 years

Treatment Details

Interventions

• Rapcabtagene Autoleucel (CAR T-cell Therapy)

Trial Overview The study tests two different dosing regimens of a new therapy called rapcabtagene autoleucel against the standard treatment for lupus nephritis. It aims to see if this new approach is more effective and safe compared to what's currently used.

Participant Groups

Group I: Regimen 2 Experimental Treatment 1 Intervention

rapcabtagene autoleucel Regimen 2

Group II: Regimen 1 Experimental Treatment 1 Intervention

rapcabtagene autoleucel Regimen 1

Group III: Standard of Care Active Control 1 Intervention

The treatment regimen must be in line with Kidney Disease Improving Global Outcomes (KDIGO) guidelines for treatment of class III/IV LN.

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

Current treatments for lupus nephritis, like corticosteroids and cyclophosphamide, are effective but come with significant side effects, highlighting the need for safer, targeted therapies.

New therapeutic strategies are being developed to specifically interrupt the disease process, such as blocking co-stimulatory molecules and targeting cytokines, which could lead to more effective and less toxic treatments for lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel approaches in the treatment of lupus nephritis. Illei, GG., Czirják, L.[2019]

In a small study of five treatment-resistant patients with systemic lupus erythematosus (SLE), CD19 CAR T cell therapy led to significant clinical improvements and remission in all participants after 3 months, demonstrating its potential efficacy.

The treatment was well tolerated, with only mild cytokine release syndrome reported, suggesting a favorable safety profile for this innovative therapy in seriously ill SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Journal Club: Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Refractory Systemic Lupus Erythematosus. Boulougoura, A., Gendelman, H., Surmachevska, N., et al.[2023]

In a study involving five patients with severe systemic lupus erythematosus (SLE), treatment with CAR T cells targeting CD19 led to complete remission of the disease in all participants after 3 months, demonstrating high efficacy.

The CAR T cell therapy was well tolerated, with only mild side effects, and patients maintained drug-free remission for an average of 8 months, even after B cells reappeared, indicating a durable response to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Mackensen, A., Müller, F., Mougiakakos, D., et al.[2023]

High-dose corticosteroids are the standard initial treatment for severe inflammation in lupus nephritis, but long-term management often requires additional therapies to address underlying immune system issues.

New treatment options for lupus nephritis include novel immunosuppressive agents and combination therapies, which may improve efficacy and reduce toxicity compared to traditional treatments like cyclophosphamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in the treatment of proliferative lupus nephritis. Balow, JE., Austin, HA.[2019]

Cyclophosphamide (CYC) is still the first-choice treatment for severe proliferative lupus nephritis, despite the availability of newer treatment options.

There is ongoing debate regarding the optimal route, dosage, and duration of CYC therapy, highlighting the need for further research to refine treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lupus nephritis: current issues. Mavragani, CP., Moutsopoulos, HM.[2019]

References

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

Novel approaches in the treatment of lupus nephritis. [2019]

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

Autologous Hematopoietic Stem Cell Transplantation for Refractory Lupus Nephritis. [2023]

3. Canada pubmed.ncbi.nlm.nih.gov

Longterm clinical and immunological effects of anti-CD20 treatment in patients with refractory systemic lupus erythematosus. [2022]

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

Journal Club: Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Refractory Systemic Lupus Erythematosus. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of low-dose and high-dose cyclophosphamide as induction therapy for lupus nephritis: a network meta-analysis. [2020]

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

Efficacy and safety of abatacept in lupus nephritis: a twelve-month, randomized, double-blind study. [2022]

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

Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Is there still a role for abatacept in the treatment of lupus? [2018]

9. England pubmed.ncbi.nlm.nih.gov

CD19-targeted chimeric antigen receptor T-cell therapy in patients with concurrent B-cell Non-Hodgkin lymphoma and rheumatic autoimmune diseases: a propensity score matching study. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Progress in the treatment of proliferative lupus nephritis. [2019]

11. Italy pubmed.ncbi.nlm.nih.gov

[The treatment of lupus nephritis, between consolidated strategies and new therapeutic options: a narrative review]. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Lupus nephritis: current issues. [2019]