Anakinra in Hidradenitis Suppurativa

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Hidradenitis Suppurativa

Intervention / Treatment
-----------------
* Drug: Water for injection
* Drug: Anakinra


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Water for injection<br>Placebo syringes will contain 0.67ml of sterile water for injection. This will be injected daily for 12 weeks. | Drug: Water for injection<br>* Placebo syringes will contain 0.67ml of sterile water for injection. This will be injecteda daily for 12 weeks.<br>* Other names: Sterile water;|
| Experimental: Anakinra<br>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<br>* 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.<br>* 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. | 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. | 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 | 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 | This will be assessed by the development of serious and non-serious drug-related adverse events | 24 weeks |