What is the mechanism of action of this treatment?

The most common treatments for Pemphigus Vulgaris (PV) include therapies that target the immune system to reduce the production of autoantibodies against desmoglein 3, a protein essential for cell adhesion in the skin. DSG3-CAART (Desmoglein 3 Chimeric Autoantibody Receptor T cells) is a novel treatment that specifically targets and eliminates the autoreactive B cells responsible for the autoimmune response in PV. By removing these cells, DSG3-CAART aims to halt the production of harmful antibodies, thereby preventing blister formation and promoting skin healing. This targeted approach is crucial for PV patients as it addresses the root cause of the disease, offering the potential for more effective and sustained remission compared to traditional immunosuppressive therapies.

What side effects are associated with this type of intervention?

Common treatments for Pemphigus Vulgaris include corticosteroids, immunosuppressants, and biologics. Corticosteroids can cause side effects such as weight gain, hypertension, diabetes, and increased risk of infections. Immunosuppressants like azathioprine and mycophenolate mofetil may lead to bone marrow suppression, liver toxicity, and increased susceptibility to infections. Biologics, such as rituximab, can result in infusion reactions, infections, and potential reactivation of hepatitis B. For treatments like DSG3-CAART, potential side effects could include cytokine release syndrome, neurotoxicity, and increased risk of infections, similar to other CAR T-cell therapies.

What prior FDA approvals exist?

The FDA has approved several treatments for Pemphigus Vulgaris, primarily focusing on immunosuppressive therapies and biologics. Rituximab, a monoclonal antibody targeting CD20 on B cells, is one of the key FDA-approved treatments for PV. It works by depleting B cells, which are responsible for the production of autoantibodies against desmoglein, a protein critical for cell adhesion in the skin. Other treatments include corticosteroids and immunosuppressants like mycophenolate mofetil and azathioprine, which help control the autoimmune response. While these treatments are effective, they are not as targeted as the DSG3-CAART therapy being studied, which specifically aims to eliminate the cells causing the autoimmune response in PV.

What other types of research exist?

Promising novel alternatives to DSG3-CAART for Pemphigus Vulgaris patients include: 1) Rituximab, an anti-CD20 monoclonal antibody, which has shown success in treating refractory cases of autoimmune blistering diseases. 2) CABA-201, CD19-specific Chimeric Antigen Receptor T cells, which target B cells involved in the autoimmune response. 3) Intravenous immunoglobulin (IVIG) therapy, which has been effective in therapy-resistant cases. 4) Emerging gene therapies and protein replacement therapies, which are being explored for their potential to correct underlying genetic defects and restore normal protein function.

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CAR T-cell Therapy

DSG3-CAART Cell Therapy for Pemphigus Vulgaris

Phase 1

Recruiting

Research Sponsored by Cabaletta Bio

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

mPV inadequately managed by at least one standard immunosuppressive therapies

Confirmed diagnosis of mPV by prior or screening biopsy and prior positive anti- DSG3 antibody ELISA

Must not have

Other autoimmune disorder requiring immunosuppressive therapies

Prednisone > 0.25mg/kg/day

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 36 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing new cell therapies for patients with pemphigus vulgaris who don't respond to standard treatments. The therapies involve modifying the patient's own immune cells to better fight the disease and potentially provide long-term relief.

Who is the study for?

This trial is for patients with mucosal-dominant pemphigus vulgaris (mPV) who haven't responded well to standard treatments. They must have active mPV symptoms, a positive anti-DSG3 antibody test, and a confirmed diagnosis. People can't join if they've had certain other treatments recently or have another autoimmune disease needing treatment.

What is being tested?

The study is testing DSG3-CAART, an experimental cell therapy aimed at achieving long-lasting remission in mPV patients. The goal is to find the highest dose that's safe and work out the best schedule for giving it to patients.

What are the potential side effects?

Since this is a phase 1 trial determining the maximum tolerated dose of DSG3-CAART, specific side effects are not listed but may include reactions related to immune system activation or suppression.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My mPV has not improved with standard immune treatments.

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I have been diagnosed with mucous membrane pemphigoid and tested positive for anti-DSG3.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am on immunosuppressive drugs for an autoimmune disorder.

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I am taking more than 0.25mg/kg/day of Prednisone.

Select...

I have skin lesions due to pemphigus vulgaris, showing more skin than mouth involvement.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 36 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 36 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 36 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Adverse events, including Dose Limit Toxicity

Secondary study objectives

Cellular kinetics profile of DSG3-CAART

Change in DSG3 autoantibody titer

Clinical remission: complete remission off therapy and complete remission on minimal therapy

+11 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: DSG3-CAART or CABA-201Experimental Treatment1 Intervention

Cohort A: Fractionated infusions of DSG3-CAART at increasing dose levels (6-9 groups) administered as a single cycle. Cohort B: Consolidation of infusion of DSG3-CAART to fewer fractionations than in Cohort A using the selected dose from Cohort A (1 group) administered as a single cycle. Cohort C: Infusion of final selected dose and fractionation of DSG3-CAART from Cohorts A and B (1 group) administered as a single cycle. OR CABA-201 Cohort: Single infusion of CABA-201.

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Pemphigus Vulgaris (PV) include therapies that target the immune system to reduce the production of autoantibodies against desmoglein 3, a protein essential for cell adhesion in the skin. DSG3-CAART (Desmoglein 3 Chimeric Autoantibody Receptor T cells) is a novel treatment that specifically targets and eliminates the autoreactive B cells responsible for the autoimmune response in PV. By removing these cells, DSG3-CAART aims to halt the production of harmful antibodies, thereby preventing blister formation and promoting skin healing. This targeted approach is crucial for PV patients as it addresses the root cause of the disease, offering the potential for more effective and sustained remission compared to traditional immunosuppressive therapies.