Vilobelimab for Pyoderma Gangrenosum

Recruiting in Palo Alto (17 mi)

+83 other locations

Overseen by Alex GO Loayza, Prof, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: InflaRx GmbH

Must not be taking: Antibiotics, Vaccines, Corticosteroids, others

Disqualifiers: Large ulcers, Transplanted skin, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called vilobelimab to see if it can help people with a painful skin condition called ulcerative pyoderma gangrenosum. The medication works by stopping the body from making substances that cause swelling and sores. Researchers want to find out if this treatment is safe and effective for these patients.

Will I have to stop taking my current medications?

The trial requires that you stop any systemic medical treatment or biological/immunomodulatory therapy for pyoderma gangrenosum (PG) at least 4 weeks before starting the trial. However, if you are on a stable dose of a biologic or immunomodulatory therapy for another condition, you may continue it.

What data supports the effectiveness of the drug Vilobelimab for treating pyoderma gangrenosum?

While there is no direct evidence for Vilobelimab in treating pyoderma gangrenosum, similar treatments like infliximab, a TNFα inhibitor, have shown effectiveness in difficult cases of this condition. Biologics, a category of drugs that includes Vilobelimab, have been beneficial in achieving remission in patients with severe pyoderma gangrenosum. ^{1 2 3 4 5}

Is Vilobelimab (IFX-1) safe for human use?

Vilobelimab, also known as IFX-1, is a complement C5a inhibitor that has been studied for its ability to reduce inflammation in various diseases. While specific safety data for pyoderma gangrenosum is not detailed, it has been evaluated for other conditions, suggesting it has been tested in humans. ^{6 7 8 9 10}

How is the drug Vilobelimab unique for treating Pyoderma Gangrenosum?

Vilobelimab is unique because it targets a specific part of the immune system called complement factor C5a, which plays a role in inflammation. This mechanism is different from other treatments for Pyoderma Gangrenosum, which often focus on suppressing the entire immune system. ^{11 12 13 14 15}

Research Team

Alex GO Loayza, Prof, MD

Principal Investigator

university

Eligibility Criteria

Adults diagnosed with ulcerative pyoderma gangrenosum (PG) can join this trial. They must have a PG symptom score of 10 or more and at least one qualifying PG ulcer larger than 5 cm2. People are excluded if they've had certain treatments for PG, infections needing systemic treatment, vaccinations within two weeks before the trial starts, or previous exposure to vilobelimab.

Inclusion Criteria

I am 18 years old or older.

The doctor has confirmed that you have ulcerative pyoderma gangrenosum and your PARACELSUS score is 10 points or more. If your score is less than 10, the doctor needs to explain why they still think you have ulcerative pyoderma gangrenosum.

I have a skin ulcer larger than 5 cm2 that can be measured in two ways.

Exclusion Criteria

I have not had any systemic treatment for PG in the last 4 weeks.

I haven't taken antibiotics or anti-infectives for an infection in the last 2 weeks.

I have been taking more than 10 mg/day of prednisone or its equivalent for the past 4 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vilobelimab or placebo intravenously every 2 weeks for 26 weeks

26 weeks

13 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Vilobelimab (Monoclonal Antibodies)

Trial Overview The trial is testing the effectiveness and safety of a drug called vilobelimab against a placebo in treating ulcerative pyoderma gangrenosum. Participants will be randomly assigned to receive either vilobelimab or a placebo without knowing which one they're getting.

Participant Groups

Group I: vilobelimab Experimental Treatment 1 Intervention

Patients will be treated with vilobelimab IV, Q2W for 26 weeks

Group II: Placebo Placebo Group 1 Intervention

Patients will receive placebo IV in the same schedule as patients in Arm 1

Who Is Running the Clinical Trial?

InflaRx GmbH

Lead Sponsor

Trials

16

Recruited

2,300+

Founded

2007

Headquarters

Jena, Germany

Known For

Inflammation research

Top Products

Gohibic (vilobelimab)

Findings from Research

New diagnostic criteria for pyoderma gangrenosum have been proposed to help speed up diagnosis and treatment, which is crucial to reduce complications and improve patient outcomes.

For treatment, local immunosuppressive therapies are recommended for mild cases, while severe cases may require systemic glucocorticoids, ciclosporin, or TNF-alpha inhibitors, with other biologics also being explored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pyoderma gangrenosum]. Burian, EA., Karlsmark, T., Fogh, K., et al.[2021]

In a review of 148 cases of difficult-to-treat pyoderma gangrenosum (PG), it was found that the condition is more prevalent in females and those with inflammatory bowel disease, but most patients healed within a typical timeframe despite needing three or more treatments.

The study suggests that initiating biologic therapies earlier may be beneficial for PG patients, highlighting the need for standardized terminology in the field to improve treatment comparisons and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recalcitrant Pyoderma Gangrenosum: Clinical Burden and Unmet Needs. Becker, SL., Velasco, R., Ortega-Loayza, AG.[2023]

A patient with treatment-resistant pyoderma gangrenosum, associated with inflammatory bowel disease, did not respond to multiple immunosuppressive therapies but showed significant improvement after switching to adalimumab, a fully humanized anti-TNF-alpha monoclonal antibody.

This case suggests that adalimumab may be an effective treatment option for pyoderma gangrenosum, particularly in patients who do not respond to other TNF-alpha inhibitors like infliximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab therapy for recalcitrant pyoderma gangrenosum. Fonder, MA., Cummins, DL., Ehst, BD., et al.[2020]

Pyoderma gangrenosum (PG) is primarily treated with systemic agents, including corticosteroids, cyclosporine A, and biologics like infliximab and adalimumab, with the best evidence supporting the use of cyclosporine, prednisolone, and infliximab, particularly in patients with ulcerative colitis or Crohn's disease.

Future treatments for PG may improve due to ongoing clinical studies that aim to enhance understanding of the disease and develop targeted therapies that offer higher efficacy and fewer side effects compared to traditional immunosuppressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment options for pyoderma gangrenosum. Quist, SR., Kraas, L.[2019]

A young boy with refractory idiopathic childhood pyoderma gangrenosum, who had been suffering from the condition since age 3, showed poor responses to various cytotoxic and steroid treatments.

After starting infliximab, the boy experienced a dramatic improvement and achieved full recovery, which was maintained over a 2-year follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infliximab in treatment of idiopathic refractory childhood pyoderma gangrenosum (PG). Salehzadeh, F., Mohammadikebar, Y., Enteshary, A., et al.[2020]

Vedolizumab is an effective treatment for moderate to severe Crohn's disease and ulcerative colitis, as demonstrated in phase III GEMINI studies, which included induction and maintenance therapy.

A case report highlights that vedolizumab may also help manage severe pyoderma gangrenosum in a Crohn's disease patient, although more clinical data is needed to confirm its efficacy for extraintestinal manifestations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vedolizumab (Entyvio®) for the Treatment of Pyoderma Gangrenosum in a Crohn's Disease Patient. Groudan, K., Gupta, K., Singhania, R.[2021]

Infliximab, a monoclonal antibody that targets TNF-alpha, was successfully used to treat a 57-year-old female patient with refractory pyoderma gangrenosum linked to inactive Crohn's disease.

This case suggests that Infliximab can be a safe and effective treatment option for pyoderma gangrenosum associated with Crohn's disease, even when the bowel disease is not currently active, although multiple infusions may be necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infliximab for treatment of pyoderma gangrenosum associated with clinically inactive Crohn's disease. A case report. Kouklakis, G., Moschos, J., Leontiadis, GI., et al.[2015]

In a 26-week study involving 22 Japanese patients with pyoderma gangrenosum, adalimumab led to a significant reduction in ulcer size, with 54.5% of patients achieving complete skin re-epithelialization by week 26.

Adalimumab was generally well tolerated, although 18 patients experienced adverse events, primarily infections, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on adalimumab for pyoderma gangrenosum. Yamamoto, T.[2021]

IFX-1, a complement C5a inhibitor, shows promise in treating pyoderma gangrenosum (PG) by reducing neutrophil activation and inflammation, which are key factors in the disease's pathogenesis.

Early clinical investigations suggest that IFX-1 may be effective for PG and other neutrophilic conditions, but further studies are needed to determine the best dosing and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pyoderma gangrenosum: proposed pathogenesis and current use of biologics with an emphasis on complement C5a inhibitor IFX-1. Lu, JD., Milakovic, M., Ortega-Loayza, AG., et al.[2022]

The pilot registry, which included 52 patients with pyoderma gangrenosum (PG), found that systemic immunomodulators used at the baseline visit were significantly associated with improved healing outcomes (P = 0.048).

Most patients were treated with first-line systemic immunosuppressants, highlighting the need for standardized wound care regimens and data collection to better evaluate treatment effectiveness in PG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pyoderma gangrenosum study pilot registry: The first step to a better understanding. Orfaly, VE., Reese, AM., Friedman, M., et al.[2022]

In active vitiligo patients, there is a significant increase in pro-inflammatory dendritic cells (CD11b+CD11c+) and pro-inflammatory cytokine IL-17A, which may contribute to skin depigmentation.

Conversely, anti-inflammatory dendritic cells (CD11b+) are reduced in active vitiligo, suggesting an imbalance in immune response that could exacerbate the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic cells sub-sets are associated with inflammatory cytokine production in progressive vitiligo disease. Srivastava, N., Bishnoi, A., Parsad, D., et al.[2022]

Plasmacytoid dendritic cells (pDC) are involved in the immune response in progressive vitiligo, producing interferon (IFN)-alpha and contributing to the local immune environment.

The presence of MxA, a protein linked to IFN-α, in perilesional skin suggests that early immune responses may drive the progression of vitiligo, highlighting a new innate immune pathway in the disease's development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Type I interferon signature in the initiation of the immune response in vitiligo. Bertolotti, A., Boniface, K., Vergier, B., et al.[2014]

Treatment with a PD-L1 fusion protein significantly reversed depigmentation in Pmel-1 vitiligo mice, suggesting its potential as a therapeutic target for vitiligo.

The mechanism of action involves an increase in regulatory T cells (Tregs) in the skin, spleen, and circulation, indicating that PD-L1 therapy may inhibit the immune response responsible for depigmentation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-L1 reverses depigmentation in Pmel-1 vitiligo mice by increasing the abundance of Tregs in the skin. Miao, X., Xu, R., Fan, B., et al.[2019]

In a study of 20 patients with active non-segmental vitiligo (NSV) undergoing 36 sessions of narrowband ultraviolet B (NB-UVB) therapy, significant changes were observed in immune markers: levels of IL-17 and IL-22 decreased while FoxP3 levels increased after treatment.

The study suggests that NB-UVB therapy may improve vitiligo by restoring the balance between Th17 cells (which promote inflammation) and regulatory T cells (Tregs, which help control immune responses), indicating a potential mechanism of action for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T helper 17 and Tregs: a novel proposed mechanism for NB-UVB in vitiligo. Hegazy, RA., Fawzy, MM., Gawdat, HI., et al.[2023]

A 38-year-old male with inflammatory vitiligo with raised borders (IVRB) showed significant improvement after receiving two courses of oral prednisone and whole-body narrow-band ultraviolet B (NB-UVB) therapy.

The treatment not only halted the spread of the disease but also led to substantial repigmentation, suggesting that early and aggressive intervention can be effective for this rare subtype of vitiligo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repigmentation of extensive inflammatory vitiligo with raised borders using early and aggressive treatment. Gunasekera, N., Murphy, GF., Sheth, VM.[2015]

References

1. Denmark pubmed.ncbi.nlm.nih.gov

[Pyoderma gangrenosum]. [2021]

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

Recalcitrant Pyoderma Gangrenosum: Clinical Burden and Unmet Needs. [2023]

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

Adalimumab therapy for recalcitrant pyoderma gangrenosum. [2020]

4. Germany pubmed.ncbi.nlm.nih.gov

Treatment options for pyoderma gangrenosum. [2019]

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

Infliximab in treatment of idiopathic refractory childhood pyoderma gangrenosum (PG). [2020]

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

Vedolizumab (Entyvio®) for the Treatment of Pyoderma Gangrenosum in a Crohn's Disease Patient. [2021]

7. Romania pubmed.ncbi.nlm.nih.gov

Infliximab for treatment of pyoderma gangrenosum associated with clinically inactive Crohn's disease. A case report. [2015]

8. Spain pubmed.ncbi.nlm.nih.gov

An update on adalimumab for pyoderma gangrenosum. [2021]

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

Pyoderma gangrenosum: proposed pathogenesis and current use of biologics with an emphasis on complement C5a inhibitor IFX-1. [2022]

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

Pyoderma gangrenosum study pilot registry: The first step to a better understanding. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Dendritic cells sub-sets are associated with inflammatory cytokine production in progressive vitiligo disease. [2022]

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

Type I interferon signature in the initiation of the immune response in vitiligo. [2014]

13. England pubmed.ncbi.nlm.nih.gov

PD-L1 reverses depigmentation in Pmel-1 vitiligo mice by increasing the abundance of Tregs in the skin. [2019]

14. Denmark pubmed.ncbi.nlm.nih.gov

T helper 17 and Tregs: a novel proposed mechanism for NB-UVB in vitiligo. [2023]

15. Switzerland pubmed.ncbi.nlm.nih.gov

Repigmentation of extensive inflammatory vitiligo with raised borders using early and aggressive treatment. [2015]