Guselkumab for Benign Familial Pemphigus

Overseen By Sheila Garcia, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Immunosuppressants, Biologics

Disqualifiers: Malignancy, HIV, Hepatitis, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 24 weeks

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you need to be on a stable dose of any systemic therapies for Hailey-Hailey disease for at least 3 months. Some medications like methotrexate, low-dose prednisone, and TNF-α inhibitors are allowed, but others like azathioprine are not permitted.

Is Guselkumab safe for use in humans?

There is no specific safety data available for Guselkumab (also known as Tremfya or CNTO1959) in the provided research articles. ^{1 2 3 4 5}

How is the drug Guselkumab different from other treatments for benign familial pemphigus?

Guselkumab is unique because it targets a specific protein called interleukin-23 (IL-23), which plays a role in inflammation, whereas traditional treatments for pemphigus often involve broad immunosuppressive drugs like glucocorticoids that can have significant side effects. This targeted approach may offer a more precise treatment with potentially fewer adverse effects. ^{6 7 8 9 10}

What is the purpose of this trial?

Hailey-Hailey disease (HHD) is a debilitating genetic skin disorder, affecting mainly body folds with erythema and painful erosions and blisters. Histopathological findings include epidermal hyperplasia, suprabasilar clefting, dyskeratosis and acantholysis of keratinocytes. A final diagnosis of HHD is usually confirmed based on clinical and histopathological findings in line with genetic testing. Several treatment options have been proposed for this chronic and disabling disorder, however, there is no reproducibly effective therapeutic for it. The primary objective is to evaluate the treatment response of guselkumab. Single-center, non-randomized, single-arm, open-label, phase II trial to evaluate the efficacy and safety of guselkumab for the treatment of patients with HHD.

Research Team

Keith Choate, MD, PhD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for individuals with Hailey-Hailey Disease, a genetic skin condition causing painful blisters. Participants must have a confirmed diagnosis through clinical evaluation, skin biopsy, and genetic testing.

Inclusion Criteria

My diagnosis of Hailey-Hailey disease is confirmed by tests and biopsy results.

I've been on a stable dose of my current medication for HHD for 3 months and don't plan to change it.

My condition affects multiple parts of my body and is moderately severe.

Exclusion Criteria

Positive tuberculin skin test or positive QuantiFERON TB test

Pregnant, nursing, planning pregnancy, or planning to father a child during or after study agent injection

Known allergies, hypersensitivity, or intolerance to guselkumab or its excipients

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive guselkumab 100mg at the FDA-approved psoriasis dose. Clinical follow-up visits are scheduled at 4, 12, and 24 weeks after initiation of therapy.

24 weeks

3 visits (in-person) at weeks 4, 12, and 24

Follow-up

A 12-week follow-up period post-administration of the final dose of guselkumab to monitor safety. Laboratory monitoring and assessments are conducted.

12 weeks

3 visits (in-person) at 1 month, 3 months, and 6 months

Treatment Details

Interventions

• Guselkumab

Trial Overview The trial tests Guselkumab's effectiveness in treating HHD. It's an open-label, phase II study where all participants receive the drug without being compared to another treatment or placebo.

Participant Groups

Group I: Guselkumab Experimental Treatment 1 Intervention

Participants with HHD with be given guselkumab

Guselkumab is already approved in United States, European Union for the following indications:

Approved in United States as Tremfya for:

• Moderate to severe plaque psoriasis
• Psoriatic arthritis
• Moderately to severely active ulcerative colitis

Approved in European Union as Tremfya for:

• Moderate to severe plaque psoriasis
• Psoriatic arthritis
• Moderately to severely active ulcerative colitis

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Ricardo Attar

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology, University of Buenos Aires

Dr. Anastasia G. Daifotis

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2023

MD

Findings from Research

In a study of 15 patients with familial benign chronic pemphigus, 9 showed positive patch test reactions, indicating a higher likelihood of developing contact allergies to topical treatments.

The most common allergens identified were neomycin sulfate, bacitracin, and certain corticosteroids, suggesting that patients with this condition may need to be cautious with these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contact allergies in patients with familial benign chronic pemphigus (Hailey-Hailey disease) Reitamo, S., Remitz, A., Lauerma, AI., et al.[2019]

A meta-analysis of seven studies involving 296 patients showed that biologic agents like rituximab, dupilumab, omalizumab, and mepolizumab are associated with fewer adverse events compared to traditional systemic corticosteroids in treating pemphigoid.

While biologics demonstrated comparable efficacy and relapse rates to corticosteroids, rituximab specifically showed a significantly higher effectiveness, with a risk ratio of 2.10, indicating it may be a particularly effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of biological agents for pemphigoid: a systematic review and meta-analysis. Lin, Z., Zhao, Y., Li, F., et al.[2023]

Corticosteroids remain the standard treatment for pemphigus, but due to long-term side effects, steroid-sparing agents like azathioprine and rituximab are often used in combination to enhance safety and efficacy.

Emerging therapeutic options and personalized medicine approaches are being explored to optimize treatment for pemphigus, with specific combinations suggested for different patient conditions, such as those who are pregnant or at high risk for infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and future treatment options for pemphigus: Is it time to move towards more effective treatments? Tavakolpour, S.[2021]

Pemphigus is a group of chronic inflammatory disorders caused by autoantibodies targeting desmosomal proteins, leading to blistering in the skin and mucous membranes, with genetic factors influencing susceptibility, particularly certain HLA alleles.

Treatment typically involves immunosuppressive agents like corticosteroids, but newer therapies aim to block the harmful signaling from autoantibodies, highlighting the need for a multidisciplinary approach due to potential side effects from long-term treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive review on the pathophysiology, clinical variants and management of pemphigus (Review). Costan, VV., Popa, C., Hâncu, MF., et al.[2021]

In a study of 53 patients with treatment-resistant pemphigus, 84.9% achieved complete remission after receiving rituximab, indicating its effectiveness as a treatment option.

The average follow-up was 56 months, with a relapse occurring around 12 months after treatment, suggesting that additional rituximab cycles may be necessary to maintain remission, although further research is needed to determine the best dosing strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term experience with rituximab therapy for treatment-resistant moderate-to-severe pemphigus. Bozca, BC., Bilgiç, A., Uzun, S.[2022]

Dupilumab, a monoclonal antibody that targets IL-4 and IL-13, showed significant improvement in skin lesions for two patients with atypical pemphigus erythematosus, suggesting its potential as a new treatment option.

The use of dupilumab allowed for the reduction of glucocorticosteroid doses, indicating a possible way to minimize the side effects associated with traditional therapies for pemphigus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The complicated use of dupilumab in the treatment of atypical generalized pemphigus Erythematous: A report of two cases. Chen, J., Chen, S., Wu, X., et al.[2023]

A case study of a girl with childhood pemphigus vulgaris, who did not respond to multiple treatments, showed a positive response to rituximab, an anti-CD20 monoclonal antibody, indicating its potential efficacy in treating this rare condition in children.

Following rituximab treatment, there was a significant decrease in circulating antibodies against desmoglein 1 and 3, which are involved in the disease, suggesting that rituximab effectively targets the underlying autoimmune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of refractory childhood pemphgus vulgaris with anti-CD20 monoclonal antibody (rituximab). Kong, HH., Prose, NS., Ware, RE., et al.[2015]

Recent research has identified new clinical variants of pemphigus, including pemphigus herpetiformis, IgA pemphigus, and paraneoplastic pemphigus, which are characterized by unique clinical presentations and specific target antigens.

Understanding the immunopathology and target antigens of these variants is crucial for developing effective treatment strategies and improving patient outcomes in this group of autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The new pemphigus variants. Robinson, ND., Hashimoto, T., Amagai, M., et al.[2019]

Pemphigus vulgaris (PV) is a serious autoimmune disease characterized by the production of IgG autoantibodies against desmoglein 3, leading to painful oral lesions and skin blisters, with a strong genetic predisposition observed in certain ethnic groups.

Current treatment primarily involves systemic immunosuppression with corticosteroids and other agents, but newer therapies are being explored that may offer effective management with fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral mucosal disease: pemphigus. Scully, C., Mignogna, M.[2009]

In a study of 59 pemphigus patients treated with rituximab over a median of 104 months, 39% achieved complete remission off therapy after the first cycle, which increased to 61% with additional treatments.

Rituximab was highly effective in reinducing complete remission in 94% of cases for patients who relapsed, and lower baseline levels of desmoglein-specific antibodies were linked to better long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes of rituximab therapy in pemphigus. Shimanovich, I., Baumann, T., Schmidt, E., et al.[2021]

References

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

Contact allergies in patients with familial benign chronic pemphigus (Hailey-Hailey disease) [2019]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of biological agents for pemphigoid: a systematic review and meta-analysis. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Current and future treatment options for pemphigus: Is it time to move towards more effective treatments? [2021]

4. Greece pubmed.ncbi.nlm.nih.gov

Comprehensive review on the pathophysiology, clinical variants and management of pemphigus (Review). [2021]

5. England pubmed.ncbi.nlm.nih.gov

Long-term experience with rituximab therapy for treatment-resistant moderate-to-severe pemphigus. [2022]

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

The complicated use of dupilumab in the treatment of atypical generalized pemphigus Erythematous: A report of two cases. [2023]

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

Successful treatment of refractory childhood pemphgus vulgaris with anti-CD20 monoclonal antibody (rituximab). [2015]

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

The new pemphigus variants. [2019]

9. Scotland pubmed.ncbi.nlm.nih.gov

Oral mucosal disease: pemphigus. [2009]

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

Long-term outcomes of rituximab therapy in pemphigus. [2021]