Treatments Comparison for Skin Vasculitis

(ARAMIS Trial)

Recruiting at 7 trial locations

Overseen By Carol McAlear, MA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

Disqualifiers: Systemic vasculitis, Auto-immune conditions, Cancer, Infections, 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: 11

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing three different drugs to find the best treatment for patients with isolated skin vasculitis. The drugs help by reducing inflammation and controlling the immune system.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but if you are taking prednisone for skin vasculitis, you will need to stop it within 6 weeks after starting the study drug, following a specific tapering schedule. If you are on a low and stable dose of glucocorticoids for other conditions, you can continue that dose during the study.

Is the treatment generally safe for humans?

Dapsone has been used safely in humans for various skin conditions, showing anti-inflammatory effects without increasing side effects when combined with other treatments. Azathioprine, however, may have more side effects compared to alternatives like mycophenolate mofetil, which is considered safer. ^{1 2 3 4 5}

How does the drug combination of Azathioprine, Colchicine, and Dapsone differ from other treatments for skin vasculitis?

This drug combination is unique because it combines Azathioprine, known for its safety in treating various skin conditions, with Colchicine and Dapsone, which are effective for chronic or relapsing skin vasculitis and urticarial vasculitis. Dapsone, in particular, has shown success in treating severe and chronic vasculitic ulcerations where other immunosuppressants have failed. ^{1 2 6 7 8}

What data supports the effectiveness of the drug for treating skin vasculitis?

Research shows that Dapsone, a component of the treatment, has been effective in treating severe skin vasculitis and other inflammatory skin conditions, leading to remission in some cases. Additionally, Colchicine has been beneficial in managing prolonged skin symptoms in vasculitis, particularly in cases resistant to other treatments. ^{1 2 6 9 10}

Who Is on the Research Team?

Christian Pagnoux, MD, MPH, MSc

Principal Investigator

University of Toronto/Mount Sinai Hospital

Robert Micheletti, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

Adults with isolated skin vasculitis, confirmed by biopsy, lasting at least 1 month or having multiple flares. Eligible participants have primary skin vasculitis without serious extra-skin symptoms and may have used steroids before joining. Excluded are those with contraindications to the study drugs, systemic vasculitis signs, active cancer in the last 5 years, severe infections or organ insufficiency.

Inclusion Criteria

I have a specific type of skin vasculitis without kidney problems.

I have a skin condition without serious effects on other body parts.

My vasculitis was confirmed by a skin biopsy.

Exclusion Criteria

I cannot take or have not responded to two or three of the drugs in this study.

I have a G6PD deficiency or a history of hemolytic anemia.

My kidneys are not working well, with a creatinine clearance below 60 mL/min.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Stage 1

Participants are randomized to receive one of three medications (colchicine, dapsone, or azathioprine) for 6 months

6 months

Visits at months 1, 3, and 6

Follow-up

Participants are monitored for response to treatment and side effects

6 months

Visits at months 9 and 12

Treatment Stage 2

Participants who discontinue the initial treatment are re-randomized to receive one of the remaining two medications for another 6 months

6 months

Visits at months 1, 3, and 6 of stage 2

What Are the Treatments Tested in This Trial?

Interventions

• Azathioprine
• Colchicine
• Dapsone

Trial Overview The trial is testing three treatments for skin vasculitis: Colchicine, Dapsone, and Azathioprine. It's a multi-center study where patients are randomly assigned to receive one of these standard care options to compare their effectiveness.

How Is the Trial Designed?

Group I: Stage 2 Experimental Treatment 3 Interventions

If the patient has to discontinue the study drug within the (stage 1) 6 month study period or during the subsequent follow-up period (up to month 12) because of a lack of response (or failure), flare or side effect, he/she will be randomized again to receive one of the remaining two study drugs (stage 2, with a 1:1 randomization ratio, colchicine 0.6 mg x 2/day; dapsone 150 mg/day; azathioprine 2 mg/kg/day) for 6 months. Endpoint in this second stage will again be the response to treatment at 6 months.

Group II: Stage 1 Experimental Treatment 3 Interventions

Eligible patients will be initially randomized (1:1:1) to receive one of the 3 medications under investigation (colchicine 0.6 mg x 2/day; dapsone 150 mg/day; azathioprine 2 mg/kg/day) for 6 months. Endpoint is response to treatment at month 6 (stage 1).

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

Approved in European Union as Imuran for:

• Prevention of rejection in organ transplantation
• Treatment of autoimmune diseases such as rheumatoid arthritis

Approved in United States as Imuran for:

• Prevention of rejection in organ transplantation
• Treatment of rheumatoid arthritis

Approved in Canada as Imuran for:

• Prevention of rejection in organ transplantation
• Treatment of rheumatoid arthritis

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Collaborator

Trials

508

Recruited

1,090,000+

Office of Rare Diseases (ORD)

Collaborator

Trials

44

Recruited

12,400+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Published Research Related to This Trial

A woman with severe cutaneous necrotizing vasculitis for over 10 years did not respond to various immunosuppressants, including cyclophosphamide, indicating the complexity and treatment resistance of this condition.

Treatment with DADPS (dapsone) resulted in complete remission of her chronic vasculitic ulcerations, suggesting that dapsone may be an effective option for managing severe cases of cutaneous vasculitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Refractory cutaneous necrotizing vasculitis. Successful sulfone therapy]. Seybold, H., Simon, M., Schuler, G., et al.[2018]

Dapsone, traditionally used for leprosy, showed rapid improvement in two patients with cutaneous dermatomyositis who were unresponsive to other treatments, indicating its potential efficacy in this condition.

Both patients experienced exacerbations of their symptoms upon withdrawal of Dapsone, which improved again when the medication was reintroduced, suggesting a strong therapeutic response linked to Dapsone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous involvement of dermatomyositis can respond to Dapsone therapy. Cohen, JB.[2019]

A 10-year-old boy with immunoglobulin A vasculitis (IgAV) experienced prolonged skin symptoms that were resistant to multiple treatments, but he achieved remission with colchicine after 12 months of illness.

Colchicine was effective in controlling the boy's chronic cutaneous manifestations without causing adverse effects, highlighting its potential as a beneficial treatment for IgAV patients with similar symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of IgA vasculitis with prolonged cutaneous manifestation with colchicine in a 10-year-old boy. Okura, Y., Hiramatsu, Y., Shimomura, M., et al.[2022]

The treatment approach for leukocytoclastic immune-complex vasculitis (LcV) varies based on the presence of IgA in immune complexes, with IgG- or IgM-associated LcV generally having a better prognosis and often requiring only symptomatic treatment.

In cases of severe conditions like ANCA-associated systemic vasculitis and giant cell arteriitis, rapid and aggressive treatment with glucocorticoids is crucial for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapy of vasculitides and vasculopathies]. Sunderkötter, C., de Groot, K.[2021]

Dapsone was used to treat chronic purpuric skin lesions in three children with Henoch-Schönlein purpura, leading to fast and complete healing of the lesions.

One child experienced methemoglobinemia, a known side effect of dapsone, emphasizing the importance of careful prescription and monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dapsone for chronic skin lesions in 3 children suffering from Henoch-Schönlein vasculitis]. Mazille, N., Lipsker, D., Fischbach, M.[2021]

In four patients with pemphigus vulgaris, while high-dose prednisone was initially effective, adding azathioprine did not help reduce steroid doses and even worsened the disease, highlighting its limited efficacy in this context.

The combination of cyclophosphamide and dapsone with prednisone led to clinical and serologic remission without significant side effects, suggesting that cyclophosphamide can be a valuable alternative treatment when azathioprine fails.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of cyclophosphamide in azathioprine failures in pemphigus. Ahmed, AR., Hombal, S.[2019]

Mycophenolate mofetil is emerging as a safer alternative to azathioprine for treating autoimmune bullous diseases like bullous pemphigoid and pemphigus vulgaris, as it has a lower risk of myelosuppression and hepatotoxicity.

While cyclophosphamide remains effective for severe cases, its high cumulative dose raises safety concerns, highlighting the need for randomized controlled studies to compare its efficacy and safety against newer treatments like rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunosuppressive therapy for autoimmune bullous diseases. Meurer, M.[2021]

Dapsone was effective in treating a female patient with urticarial vasculitis (U.V.) and metabolic syndrome, leading to clinical improvement and normalization of hypocomplementemia after previous treatments failed.

This case suggests that dapsone may serve as a viable alternative treatment for U.V. when systemic corticosteroids and other common medications are contraindicated or ineffective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Urticaria vasculitis and sulfone, a case report]. Wozel, G., Thiele, B.[2013]

Azathioprine is favored by dermatologists for its good safety profile and effectiveness in treating conditions like bullous pemphigoid and chronic eczematous dermatitides, making it a preferred choice for many skin diseases.

Cyclophosphamide, while more toxic, is justified for severe diseases such as Wegener's granulomatosis due to its greater efficacy, whereas cyclosporine shows promise for conditions like psoriasis but requires careful monitoring due to uncertain long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunosuppressive agents in dermatology. Ho, VC., Zloty, DM.[2013]

Two patients with a rare form of discoid lupus erythematosus affecting only the palms and soles did not respond to standard treatments, highlighting the challenges in managing this condition.

Both patients showed significant improvement when treated with azathioprine after failing conventional therapies, suggesting that azathioprine may be an effective option for difficult-to-treat cases of this disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistant discoid lupus erythematosus of palms and soles: successful treatment with azathioprine. Ashinoff, R., Werth, VP., Franks, AG.[2019]

Citations

1. Germany pubmed.ncbi.nlm.nih.gov

[Refractory cutaneous necrotizing vasculitis. Successful sulfone therapy]. [2018]

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

Cutaneous involvement of dermatomyositis can respond to Dapsone therapy. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Successful treatment of IgA vasculitis with prolonged cutaneous manifestation with colchicine in a 10-year-old boy. [2022]

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

[Therapy of vasculitides and vasculopathies]. [2021]

5. France pubmed.ncbi.nlm.nih.gov

[Dapsone for chronic skin lesions in 3 children suffering from Henoch-Schönlein vasculitis]. [2021]

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

Use of cyclophosphamide in azathioprine failures in pemphigus. [2019]

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

Immunosuppressive therapy for autoimmune bullous diseases. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

[Urticaria vasculitis and sulfone, a case report]. [2013]

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

Immunosuppressive agents in dermatology. [2013]

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

Resistant discoid lupus erythematosus of palms and soles: successful treatment with azathioprine. [2019]