A Randomized Multicenter Study for Isolated Skin Vasculitis

Study Purpose

Multi-center sequential multiple assignment randomized trial comparing the effectiveness of three different standard of care treatment options for patients with isolated skin vasculitis.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More 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, according to the investigator (e.g. chronic obstructive pulmonary disease (COPD), unstable or severe asthma). 12. Active cancer or history of malignancy within the previous 5 years (patient in remission of a cancer >5 years, or with non-metastatic prostate cancer or treated basal or squamous cell carcinoma of the skin can be enrolled). 13. Active uncontrolled or serious infection that may compromise or contra-indicate the use of the study medications. 14. Patient unable to consent. 15. Pregnant or lactating women.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT02939573
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Pennsylvania
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Robert Micheletti, MDChristian Pagnoux, MD, MPH, MSc
Principal Investigator Affiliation University of PennsylvaniaUniversity of Toronto/Mount Sinai Hospital
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherNIHNIHNIH
Overall Status Recruiting
Countries Canada, Japan, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Primary Cutaneous Vasculitis, Cutaneous Polyarteritis Nodosa, IgA Vasculitis, Henoch-Schönlein Purpura
Study Website: View Trial Website
Additional Details

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). If the patient has to discontinue the study drug within the 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) for 6 months. Endpoint in this second stage will again be the response to treatment at 6 months.

Arms & Interventions

Arms

Experimental: Stage 1

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).

Experimental: Stage 2

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.

Interventions

Drug: - Colchicine

Randomized to colchicine 0.6 mg x 2/day

Drug: - Dapsone

Randomized to dapsone 150 mg/day

Drug: - Azathioprine

Randomized to azathioprine 2 mg/kg/day

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of Kansas Medical Center, Kansas City, Kansas

Status

Recruiting

Address

University of Kansas Medical Center

Kansas City, Kansas,

Site Contact

Theresa Howard

[email protected]

Boston University School of Medicine, Boston, Massachusetts

Status

Recruiting

Address

Boston University School of Medicine

Boston, Massachusetts, 02118

Site Contact

Christina Lam, MD

[email protected]

Mayo Clinic, Rochester, Minnesota

Status

Completed

Address

Mayo Clinic

Rochester, Minnesota, 55905

Site Contact

[email protected]

Northwell Health, Lake Success, New York

Status

Recruiting

Address

Northwell Health

Lake Success, New York, 11042

Site Contact

Anita Haridat

[email protected]

Hospital for Special Surgery, New York, New York

Status

Recruiting

Address

Hospital for Special Surgery

New York, New York, 10021

Site Contact

Beemnet Amdemicael

[email protected]

Cleveland Clinic, Cleveland, Ohio

Status

Recruiting

Address

Cleveland Clinic

Cleveland, Ohio,

Site Contact

Elizabeth Kisela

[email protected]

Penn State Hershey Medical Center, Hershey, Pennsylvania

Status

Completed

Address

Penn State Hershey Medical Center

Hershey, Pennsylvania, 17033

Site Contact

[email protected]

University of Pennsylvania, Philadelphia, Pennsylvania

Status

Recruiting

Address

University of Pennsylvania

Philadelphia, Pennsylvania, 19104

Site Contact

Josh Bryer

[email protected]

University of Utah, Salt Lake City, Utah

Status

Recruiting

Address

University of Utah

Salt Lake City, Utah,

Site Contact

Lisa Webber

[email protected]

International Sites

St. Joseph's Healthcare, Hamilton, Ontario, Canada

Status

Recruiting

Address

St. Joseph's Healthcare

Hamilton, Ontario,

Site Contact

Sandra Messier

[email protected]

Toronto, Ontario, Canada

Status

Recruiting

Address

University of Toronto Mount Sinai Hospital

Toronto, Ontario,

Site Contact

Sam Jagadeesh

[email protected]

McGill University Health Centre, Montréal, Quebec, Canada

Status

Recruiting

Address

McGill University Health Centre

Montréal, Quebec, H4A 3J1

Site Contact

Michele Tobaly

[email protected]

Kyoto, Japan

Status

Recruiting

Address

Tohoku Medical and Pharmaceutical University Hospital

Kyoto, , 602-8566

Site Contact

Ito-Ihara Toshiko, MD

[email protected]