Anakinra in Hidradenitis Suppurativa

May 26, 2015 updated by: Evangelos J. Giamarellos-Bourboulis, M.D., University of Athens

A Double-blind, Randomized, Placebo-controlled Clinical Trial of the Safety and Efficacy of Anakinra in Patients With Hidradenitis Suppurativa

Aim of this double-blind, randomized, controlled clinical trial is to compare the safety and the efficacy of anakinra over placebo for the management of patients with hidradenitis suppurativa (HS) of Hurley II and Hurley III disease stage. Patients will be evaluated on subsequent follow-up visits. Two scores will be applied: disease activity as assessed in the protocol by the investigator; and Sartorius score. Primary efficacy endpoint will be the comparisons of visual analogue scores, of disease activity, of Sartorius score and of dermatology life quality index between the two groups of treatment over follow-up.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Hidradenitis suppurativa (HS) is a chronic devastating skin disorder affecting areas rich in apocrine glands. Nodules appear in the affected areas; they progressively become swollen and rupture with the release of pus. This process occurs repeatedly leading to sinus tract formation and scars. This disease course creates a frustrating situation for the patients but also for physicians. Traditional treatments comprise short-courses of antibiotics and surgical excision. However, relapse is the rule so that HS leads to severe impairment of the quality of life. The Dermatology Quality Life Index (DQLI) for HS is 8.9 being higher than any other skin disorder.

This devastating disorder has often been neglected and considered a rare situation. However, HS seems to indiscriminately affect the global population. Although the exact epidemiology is largely unknown, the point-prevalence is reported to range between 1% and 4%. A recent large epidemiological survey in France reports 0.97% disease prevalence.

The exact pathophysiology of HS is unknown. Smoking, dietary habits and genetic predisposition have all been linked with HS. However, a recent survey by our group in 56 patients, disclosed a severe derangement of the monocyte function and of subsequent antigen processing in these patients. The percentage of natural killer (NK) cells was increased and that of CD4-lymphocytes decreased compared to healthy controls probably implying the existence of an autoimmune predilection for the disorder. We have previously demonstrated defective lipopolysaccharide (LPS)-induced production of the pro-inflammatory cytokines, tumour necrosis factor(TNF) and interleukin (IL)-6 by blood monocytes of patients with HS.

As a consequence, a hypothesis for the implication of some autoimmune of autoinflammatory mechanism in the pathogenesis of HS was started to be created over the last years. The hypothesis is further reinforced by positive results from the administration of TNF antagonists in prospective studies with limited number of patients one of these was conducted by our study group. Subcutaneous treatment with 50mg etanercept once weekly for 12 weeks in 10 patients, reduced patients' suffering, attenuated local signs of inflammation and retarded disease relapse.

Anakinra is a recombinant interleukin-1 (IL-1) receptor antagonist (IL-1Ra). Anakinra blocks the biologic activity of naturally occurring IL-1, including inflammation and cartilage degradation associated with rheumatoid arthritis, by competitively inhibiting the binding of IL-1 to the interleukin-1 type receptor, which is expressed in many tissues and organs. IL-1 is produced in response to inflammatory stimuli and mediates various physiologic responses, including inflammatory and immunologic reactions. The biological properties of anakinra and the existing clinical and laboratory data favoring a derangement of the immune response in HS, prompted to investigate whether anakinra would be efficient in the management of patients with HS.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Greece
      • Athens, Greece, 12462
        • 4th Department of Internal Medicine, Attikon University Hospital
      • Athens, Greece, 12462
        • 2nd Department of Dermatology, ATTIKON University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • written informed consent provided by the patient;
  • age above 18 years;
  • diagnosis of hidradenitis suppurativa; and
  • disease of Hurley II or III severity stage

Exclusion Criteria:

  • history of systemic lupus erythematosus, of rheumatoid arthritis of of seronegative inflammatory arthritis;
  • any prior administration of any type of anti-TNF therapy over the last six months;
  • administration of any live (attenuated) vaccine over the last 4 weeks;
  • history of recurrent vein thrombosis or embolism compatible with anti-cardiolipin syndrome;
  • any present or smoldering infection;
  • hepatic dysfunction defined as any value of transaminases, of γ-glutamyl transpeptidase or of bilirubin> 2 x upper normal limit;
  • history of haematological or solid tumor malignancy, arterial hypertension, liver cirrhosis, HIV infection, and hepatitis virus B or C infection
  • history of episodes mimicking demyelinating disorders or a definite diagnosis of multiple sclerosis
  • any creatinine value above 1.5 mg/dl
  • intake of corticosteroids defined as daily intake of prednisone or equivalent more than 1mg/kg for the last three weeks;
  • neutropenia defined as <1000 neutrophils/mm3; and
  • pregnancy or lactation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Water for injection
Placebo syringes will contain 0.67ml of sterile water for injection. This will be injected daily for 12 weeks.
Drug: Water for injection
Placebo syringes will contain 0.67ml of sterile water for injection. This will be injecteda daily for 12 weeks.
Other Names:
  • Sterile water
Experimental: Anakinra
Anakinra will be supplied in single use pre-filed glass syringes with 27-gauge needles. Anakinra syringe will contain 100mg of anakinra at a volume of 0.67 ml. This will be injected subcutaneously daily for 12 weeks.
Drug: Anakinra
Anakinra will be supplied in single use pre-filed glass syringes with 27-gauge needles. Anakinra syringe will contain 100mg of anakinra at a volume of 0.67 ml. This will be injected subcutaneously daily for 12 weeks.
Other Names:
  • Recombinant human IL-1 receptor antagonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The efficacy of anakinra in patients with HS of Hurley II and III stage disease.
Time Frame: 24 weeks
This will be defined by the changes of scoring parameters between the two study groups over visits.
24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The effect of anakinra in the ex vivo function of monocytes of patients with HS.
Time Frame: 24 weeks
This will be defined by the differences of cytokines produced by PBMCs between the two study groups over visits.
24 weeks
The effect of anakinra on the time to new exacerbation
Time Frame: 24 weeks
This will be defined by the differences between the two study groups over visits.
24 weeks
The safety of anakinra in patients with hidradenitis suppurativa
Time Frame: 24 weeks
This will be assessed by the development of serious and non-serious drug-related adverse events
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Athens

Investigators

  • Study Chair: Evangelos J Giamarellos-Bourboulis, MD, PhD, University of Athens, Medical School, Greece
  • Principal Investigator: Dimitrios Rigopoulos, MD, PhD, University of Athens, Medical School, Greece

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2012

Primary Completion (Actual)

February 1, 2014

Study Completion (Actual)

February 1, 2014

Study Registration Dates

First Submitted

March 15, 2012

First Submitted That Met QC Criteria

March 19, 2012

First Posted (Estimate)

March 20, 2012

Study Record Updates

Last Update Posted (Estimate)

May 27, 2015

Last Update Submitted That Met QC Criteria

May 26, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HIDRA03

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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