A Randomized Multicenter Study for Isolated Skin Vasculitis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 February 2024
• Main ID: NCT02939573
• Date of registration: 18/10/2016
• Prospective Registration: Yes
• Primary sponsor: University of Pennsylvania
• Public title: A Randomized Multicenter Study for Isolated Skin Vasculitis ARAMIS
• Scientific title: A Randomized Multicenter Study for Isolated Skin Vasculitis
• Date of first enrolment: January 1, 2017
• Target sample size: 90
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02939573
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Canada, Japan, United States

Contacts

• Name: Robert Micheletti, MD
• Affiliation: University of Pennsylvania

• Name: Carol McAlear, MA

• Name: Christian Pagnoux, MD, MPH, MSc
• Affiliation: University of Toronto/Mount Sinai Hospital

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Patients with primary skin vasculitis, not associated with any significant
extra-cutaneous involvement that would require specific immunosuppressive therapy.
Eligible patients will have a diagnosis of either:

- Isolated cutaneous small vessel (SV) or medium-sized vessel (MV) vasculitis or
cutaneous polyarteritis nodosa (PAN)

- IgA vasculitis (IgA, formerly Henoch-Schönlein purpura), without active and/or
progressing renal involvement (stable glomerular filtration rate (GFR) >60
ml/min; absence of, or mild-and-stable microscopic hematuria without red blood
cell casts; absence of, or mild-and-stable proteinuria (<1g/24 hours); not
requiring systemic immunosuppressive therapy).

These conditions, when skin-limited, are all currently treated in similar manners in
practice. Mild arthralgias, myalgias, peripheral limb edema, fatigue, weight loss =6
lbs or 3 kg within past 3 months, low-grade fever, and mild anemia (Hb = 10 g/dL) will
be allowed.

2. The diagnosis of vasculitis must have been confirmed by skin biopsy prior to
enrollment (earlier, at diagnosis, and/or just prior to enrollment) that has included
an immunofluorescence study (in the case of small vessel vasculitis).

3. Patients must have active cutaneous vasculitis lasting for at least 1 month
continuously and/or have had 2 or more flares over the six months preceding enrollment
(post-inflammatory lesions such as hyperpigmentation or healing ulceration(s) are not
to be considered active vasculitis).

4. Patients must have active / ongoing cutaneous vasculitis lesions at the time of
enrollment (post-inflammatory lesions such as hyperpigmentation or healing
ulceration(s) are not to be considered active vasculitis).

5. Patients may have a contra-indication to one of the study drug or have been treated
prior to enrollment with one of the study medications but failed to respond to it
(according to the study definitions of failure and if they have been on the drug at
the target dose or higher for 3 months or longer) or had to stop it because of an
adverse event. Such patients can be enrolled directly in the second stage of the study
and be randomized to receive one of the two other study drugs. The number of such
patients enrolled directly in stage 2 will be capped at 10 (10% of the total
recruitment target).

6. Patients may have received systemic glucocorticoids for their cutaneous vasculitis
before enrollment. For the patients on prednisone at the time of enrollment,
prednisone should be stopped within a maximum of 6 weeks after enrollment and
initiation of the study drug, following a pre-defined tapering schedule. Patients on
long-term, low and stable dose of glucocorticoids (=5 mg/day prednisone-equivalent)
for other conditions (e.g., asthma or adrenal insufficiency) can be enrolled if the
likelihood of requiring a dose increase for this other condition is low during the 6
month study period (these patients will remain on that low and stable dose during the
study period, with the option to receive one short course of prednisone at higher
doses for skin vasculitis flare during the first 3 months of the study period, like
any other patients enrolled).

7. Participant age 18 years or greater.

Exclusion Criteria:

1. Presence of significant extra-cutaneous manifestations suggestive of a systemic
vasculitis or more diffuse condition. The presence of mild arthralgias, myalgias,
peripheral limb edema, fatigue, weight loss =6 lbs or 3 kg within past 3 months,
low-grade fever, and mild anemia [Hb = 10 g/dL] are not exclusion criteria. Mild and
stable microscopic hematuria without RBC casts and/or mild and stable proteinuria
(<1g/24 hours) are not exclusion criteria. These latter patients must not require
systemic immunosuppressive therapy because of possible renal involvement and their GFR
must be >60 ml/min.

2. Known systemic and/or non-skin-isolated vasculitis, such as granulomatosis with
polyangiitis, eosinophilic granulomatosis with polyangiitis, cryoglobulinemic
vasculitis, systemic polyarteritis nodosa, central nervous system vasculitis and
patients with detectable antineutrophil cytoplasmic antibody (ANCA) by
immunofluorescence or ELISA.

3. Hypocomplementemic urticarial vasculitis, cryoglobulinemic vasculitis, and other known
secondary skin vasculitides such as those secondary to systemic lupus erythematosus,
Sjögren syndrome, another auto-immune condition, a cancer, a hematological disorder,
an ongoing active infection, or an ongoing medication. Investigators should consider
such underlying diagnoses and perform and interpret appropriate laboratory work-up
where indicated based on clinical presentation.

4. History of significant intolerance, allergy or serious adverse events to any of the
study medications: such patients can be enrolled directly in the second stage of the
study and be randomized to receive one of the two other study drugs. The number of
patients enrolled directly in stage 2 of the study will be capped at 10 (10%).

5. Patients who have contra-indications to two or three of the study drugs (azathioprine,
colchicine, or dapsone), or have been treated prior to enrollment with two or three of
the study drugs but failed to respond to them, or had to stop two or three of them
because of adverse events.

6. Deficit in glucose-6-phosphate dehydrogenase (G6PD) or history of hemolytic anemia
(all patients must be tested for G6PD at the screening visit to assess for their
eligibility): such patients can be enrolled directly in the second stage of the study
and be randomized to receive one of the two other study drugs (azathioprine or
colchicine). The number of patients enrolled directly in stage 2 of the study will be
capped at 10 (10%).

7. Low or absent thiopurine methyltransferase (TPMT) activity (if known, not a
requirement for study entry): Patients known to have low or absent TPMT can be
enrolled directly in the second stage of the study and be randomized to receive one of
the two other study drugs (dapsone or colchicine).

8. Evidence of significant hepatic insufficiency or liver function tests > 2 times the
upper limit of normal.

9. Evidence of significant renal insufficiency or creatinine clearance < 60 mL/min.

10. Evidence of significant or symptomatic anemia or Hb < 10 g/dL.

11. Comorbid condition that has moderate or high likelihood of requiring intermittent
courses of prednisone within the study period, a


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Primary Cutaneous Vasculitis

Henoch-Schönlein Purpura

Cutaneous Polyarteritis Nodosa

IgA Vasculitis

Intervention(s)

Drug: Dapsone

Drug: Colchicine

Drug: Azathioprine

Primary Outcome(s)

Efficacy of the study drugs for the treatment of skin vasculitis. [Time Frame: Response to therapy at month 6 of the pooled study stages 1 and 2.]

Secondary Outcome(s)

Skindex29 score [Time Frame: Assessed at months 1, 3, 6, 9, and 12.]

Response rates for each of the study drugs [Time Frame: Response evaluated months 3, 6 and 12]

Patient's global assessment of response [Time Frame: Assessed at months 0, 1, 3, 6, 9, and 12.]

Physician's global assessment of response [Time Frame: Assessed at months 0, 1, 3, 6, 9, and 12.]

Health-related quality of life [Time Frame: Assessed at months 1, 3, 6, 9, and 12.]

Secondary ID(s)

U54AR057319

VCRC5562

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Center for Advancing Translational Sciences (NCATS)

Office of Rare Diseases (ORD)

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