Anakinra for Inflammatory Pustular Skin Diseases

NCT01794117 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 13007113-AR-0071
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Inflammatory pustular skin diseases are a type of autoinflammatory disease in which the immune system attacks the bodys tissues. These diseases cause painful and itchy skin rashes, eye and mouth irritation, joint pain and fever. Several drugs for treating these diseases suppress the immune system. However, they can cause severe side effects when taken over a long period of time.
• Interleukin 1 (IL-1) is a small protein that may be important in causing the inflammation seen in pustular skin disease. Anakinra is a drug that works by blocking IL-1. It has been effective in treating some inflammatory conditions such as rheumatoid arthritis. However, anakinra has not been studied for use in patients with pustular skin disease. Researchers want to see whether anakinra will be effective in treating pustular skin disease. Objectives: \- To see if anakinra can be used to treat inflammatory pustular skin disease. Eligibility: \- Individuals at least 18 years of age who have inflammatory pustular skin disease. Design:
• Participants will be screened with a physical exam and medical history. Their disease will be evaluated with blood tests, urine tests and imaging studies. Skin biopsies may also be collected.
• Participants will have an initial visit to receive the first dose of anakinra. They will be shown how to give themselves daily injections of anakinra.
• Participants will take anakinra for up to 12 weeks as long as there are no severe side effects. During this time, they will keep a study diary to record the severity of any rashes, pustules, itching, fevers, and skin or joint pain. They will bring this diary to their study visits.
• Participants will have study visits at weeks 4, 8 and 12. Treatment will be monitored at these visits with blood tests, urine tests and physical exams. Depending on the effects of the treatment, participants may have the dose of anakinra increased or decreased.
• Participants will have a final study visit 4 weeks after they stop taking anakinra.

Conditions

Sneddon-Wilkinson; Acrodermatitis Continua of Hallopeau; Pustular Psoriasis; Palmoplantar Pustulosis

Keywords

Anakinra; Pustular Psoriasis; Palmoplantar Pustulosis; DITRA; Subcorneal Pustular Dermatosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants Treated With Anakinra Who Achieve 50% Disease Improvement by the End of Week 12, as Measured by Total Body Surface Area Involvement (TBSAI50)

  Total Body Surface Area Involvement (TBSAI) is defined as the amount of total amount of active disease involvement on a given patient. 50% improvement was the amount of change that we judged at the start of the study would qualify as significant improvement.

  12 Weeks

Other Outcomes (2)

• Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

  Up to 16 weeks for participants who completed active treatment (12 weeks) and 4 weeks of follow-up.

• Average Change in Total Body Surface Area Index (TBSAI)

  Baseline and 12 Weeks

Study Arms (1)

Arm A/Anakinra 100 mg/day

EXPERIMENTAL

An initial dose of anakinra 100 mg/day will be administered daily via self-administered subcutaneous injection. If active disease persists at this dose, anakinra dose may be escalated up to 200 mg/day injected subcutaneously daily at week 4 and 300mg at week 8.

Drug: Anakinra

Interventions

Anakinra DRUG

An initial dose of anakinra 100 mg/day will be administered daily via self-administered subcutaneous injection. If active disease persists at this dose, anakinra dose may be escalated up to 200 mg/day injected subcutaneously daily at week 4 and 300mg/day at week 8.

Also known as: Kineret

Arm A/Anakinra 100 mg/day

Eligibility Criteria

• Age: 18 Years - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Females and males, aged greater than or equal to 18.
• Patients must demonstrate active noninfectious inflammatory pustular skin lesions resembling pustular psoriasis and involving greater than or equal to 5% total body surface area, or palmoplantar involvement. Conditions may include, but are not be limited to, pustular psoriasis, Sneddon-Wilkinson disease, subcorneal pustular dermatosis, reactive arthritis, palmoplantar pustulosis, acrodermatitis continua of Hallopeau and palmoplantar pustular psoriasis.
• Patients must have histopathologic confirmation of epidermal neutrophilic pustular skin disease.
• If taking immunosuppressants, retinoids or anti-neutrophil therapy, participants must maintain stable doses of these medications during the 2 weeks prior to study initiation.
• Patients must have stable topical medication regimen for 2 weeks prior to study initiation.
• Patients must have normal organ and marrow function as defined below:
• leukocytes greater than or equal to 3,000/mcL
• absolute neutrophil count greater than or equal to1,500/mcL
• platelets greater than or equal to 100,000/mcL
• creatinine within normal institutional limits OR creatinine clearance greater than or equal to 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal.
• Quantiferon tuberculosis (TB) Gold must be performed for screening for mycobacterium tuberculosis infection. However, a tuberculin skin test may be placed if the Quantiferon TB gold test is indeterminate. Patients must have a negative Quantiferon TB Gold (or tuberculin skin test) or evidence of appropriate treatment prior to study entry.
• Patients must be able to understand and sign a written informed consent document and complete study-related procedures and questionnaires.

You may not qualify if:

• Enrollment in any other investigational treatment study or use of an investigational agent, or has not yet completed at least 3 half-lives since ending another investigational device or drug trial.
• History of treatment with canakinumab within the 12 months prior to study initiation.
• History of anakinra use.
• History of phototherapy within 2 weeks prior to study initiation.
• Patients may NOT concurrently be on biologic therapy such as etanercept, adalimumab, alefacept, infliximab, rituximab or rilonacept. If there is a history of use of biologic agents, there must be a washout period of at least 3 half-lives prior to study initiation.
• Subjects who experience a significant flare after discontinuation of a tumor necrosis factor (TNF) inhibitor as part of this study that requires urgent medical management or hospitalization, or in the estimation of the principal investigator poses excessive risk to the patient to enter the study.
• Other defined dermatologic conditions which may include pustules as part of the clinical presentation, but which clinically and/or histologically do not resemble pustular psoriasis. Examples include, but are not limited to acute generalized exanthematous pustulosis (Acute generalized exanthematous pustulosis (AGEP), a drug-induced pustular dermatosis typically caused by beta-lactam antibiotics, tetracyclines, oral antifungals and other drugs), bacterial or fungal folliculitis, cutaneous candidiasis, tinea pedis, tinea corporis, neutrophilic eccrine hidradenitis or eosinophilic pustular folliculitis (Ofuji syndrome).
• Known diagnosis of Deficiency of the interleukin-1 receptor antagonist (DIRA).
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to anakinra or other agents used in study. Known hypersensitivity to Chinese hamster ovary (CHO)-cell derived biologics or any components of anakinra.
• Treatment with a live virus vaccine during the 3 months prior to baseline visit. No live vaccines will be allowed throughout the course of this study.
• Patients with active or untreated malignancy-- with the exception of cutaneous basal or squamous cell carcinomas, or in situ cervical carcinoma-- are ineligible because of the immunomodulating effects of anakinra. The risk of recurrent malignancy secondary to this drug is unknown.
• Presence of active infection. History of exposure to TB (positive purified protein derivative (PPD) or Quantiferon TB gold) who have not been treated with a TB prophylaxis regimen for at least one month.
• Chest x-ray demonstrating pleural scarring and/or calcified granuloma consistent with prior or current untreated TB.
• History of chronic or recurrent infection including but not limited to human immunodeficiency virus (HIV), hepatitis B or hepatitis C.
• Individuals with severe or uncontrolled recurrent cutaneous infections who are considered at elevated risk for serious infection on anakinra therapy will be excluded per physician discretion.

Sponsors & Collaborators

• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Psoriasis; Skin Diseases, Vesiculobullous

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Dr. Edward W. Cowen
• Organization: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

cowene@mail.nih.gov

301-827-2328

Study Officials

• Edward W Cowen, M.D.

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 15, 2013
• First Posted: February 18, 2013
• Study Start: July 22, 2013
• Primary Completion: March 19, 2019
• Study Completion: October 7, 2019
• Last Updated: April 30, 2021
• Results First Posted: April 30, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)