Etanercept in Hidradenitis Suppurativa

This study has been completed.
Sponsor:
Information provided by:
University of Athens
ClinicalTrials.gov Identifier:
NCT00329823
First received: May 23, 2006
Last updated: NA
Last verified: May 2006
History: No changes posted
  Purpose

The rationale of the protocol is based on the reported beneficiary results of case-patients by the administration of other anti-TNF drug (infliximab) in separate cases on the grounds of a probable autoimmune predisposition of the disease. The objective of this study is to clarify the potency of etanercept for the therapy of hidradenitis suppurativa.


Condition Intervention Phase
Hidradenitis Suppurativa
Drug: Etanercept sc 50mg per week for 12 weeks
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of the Safety and Efficacy of Etanercept for the Therapy of Hydradenitis Suppurativa

Resource links provided by NLM:


Further study details as provided by University of Athens:

Primary Outcome Measures:
  • Endpoints :
  • The disease activity index based on a calculated score.
  • The sum of the [diameter X severity] for each affected area.
  • Patient’s global assessment of disease activity scores based on a VAS scale
  • of 1-10.
  • The number of newly presented lesions.

Estimated Enrollment: 10
Study Start Date: September 2005
Estimated Study Completion Date: May 2006
Detailed Description:

Hidradenitis suppurativa is a disorder of unknown etiology. Various hypotheses have implicated obesity, diabetes mellitus, genetic predisposition and tight clothing as probable contributing factors. Although patients are presenting with suppuration of their lesions, typical furuncles are absent (1). Administration of antibiotics offers transient relief of symptoms whereas therapies like androgens, isotretinoin and methotrexate have failed to disclose clinical benefit (2).

More than thirty out-patients with hidradenitis suppurativa are followed up at the clinic of the “Immunology of Infectious Diseases” of the ATTIKON University Hospital of Athens. None of them is presenting with diabetes mellitus and their CD4 cell counts are within normal limits. However, their testing for the function of monocytes is often abnormal. This test involves the isolation of monocytes and the ex vivo release of pro-inflammatory cytokines both without and after stimulation by bacterial endotoxins and lipoteichoic acid. Results have shown an increased baseline secretion and poor response of monocytes after stimulation.

Case reports with limited number of patients have disclosed clinical benefit of an other anti-TNF drug (infliximab) after one or two doses administration in hidradenitis suppurativa. These reports involve retrospective results of five patients (3) or single cases (4,5). The rationale of the administration of etanercept in hidradenitis suppurativa is based on the following data: a) etanercept has been proven effective for the management of psoriasis that is considered a skin disorder with autoimmune background (6); and b) laboratory findings of our patients with hidradenitis suppurativa point towards an altered immune response of their adaptive immunity (7).

Tumor necrosis factor (TNF) is a dominant cytokine in the inflammatory process of rheumatoid arthritis. Elevated levels of TNF are also found in the synovium of patients with psoriatic arthritis. Etanercept is a competitive inhibitor of TNF-binding to its cell surface receptors and thereby inhibits the biological activity of TNF. TNF and lymphotoxin are pro-inflammatory cytokines that bind to two distinct cell surface receptors: the 55-kilodalton (p55) and 75-kilodalton (p75) tumor necrosis factor receptors (TNFRs). Both TNFRs exist naturally in membrane-bound and soluble forms. Soluble TNFRs are thought to regulate TNF biological activity.

TNF and lymphotoxin exist predominantly as homotrimers, with their biological activity dependent on cross-linking of cell surface TNFRs. Dimeric soluble receptors such as etanercept possess a higher affinity for TNF than monomeric receptors and are considerably more potent competitive inhibitors of TNF binding to its cellular receptors. In addition, use of an immunoglobulin Fc region as a fusion element in the construction of a dimeric receptor imparts a longer serum half-life.

OBJECTIVE

The objective of this study is to clarify the potency of etanercept for the therapy of hidradenitis suppurativa.

RATIONALE

The rationale of the protocol is based on the reported beneficiary results of case-patients by the administration of other anti-TNF drug (infliximab) in separate cases on the grounds of a probable autoimmune predisposition of the disease.

  Eligibility

Ages Eligible for Study:   17 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Definitive diagnosis of hidradenitis suppurativa
  • Age > 16 years
  • No presence of infections other then hidradenitis suppurativa.
  • Disease activity index > 20
  • Signed informed consent

Exclusion Criteria:

  • Received any live (attenuated) vaccines within 4 weeks of enrolment visits
  • Has a history of anti-cardiolipin antibodies associated with a thrombotic event
  • Has a history of confirmed blood dyscrasias
  • Has a significant active infection or any underlying diseases that could predispose subjects to infections (ie. Advanced or poorly controlled diabetes).
  • Demonstrates liver function abnormality [SCOT, SGPT>2 X upper limit of normal]
  • Has significant concurrent medical diseases including cancer or a history of cancer (other than resected cutaneous basal and squamous cell carcinoma) within 5 years of entering the enrollement period incompensated congestive heart failure, myocardial infarction within 12 months, unstable angina pectoris, uncontrolled hypertension, severe pulmonary disease, history of HIV infection, or central nervous system demyelinating events suggestive of multiple sclerosis.
  • Has a history of known liver cirrhosis, fibrosis or fatty liver
  • Has a history of any viral hepatitis
  • Has renal disease (creatinine level > 175μmol/L)
  • Has leucopenia (WBC <3500 x 106 /L)
  • Has Thrombocytopenia (PLT’s < 125 x 109 /L)
  • Is pregnant or breast feeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00329823

Locations
Greece
4th Department of Internal Medicine, University of Athens, Medical School
Athens, Greece, 124 64
Sponsors and Collaborators
University of Athens
Investigators
Study Director: Evangelos J Giamarellos-Bourboulis, MD, PhD 4th Department of Internal Medicine, University of Athens, Greece
Study Chair: Helen Giamarellou, MD, PhD 4th Department of Internal Medicine, University of Athens, Greece
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00329823     History of Changes
Other Study ID Numbers: 2004-004555-19
Study First Received: May 23, 2006
Last Updated: May 23, 2006
Health Authority: Greece: National Organization of Medicines

Keywords provided by University of Athens:
Hidradenitis suppurativa, etanercept

Additional relevant MeSH terms:
Hidradenitis
Hidradenitis Suppurativa
Sweat Gland Diseases
Skin Diseases
Skin Diseases, Bacterial
Bacterial Infections
Skin Diseases, Infectious
Infection
Suppuration
TNFR-Fc fusion protein
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 22, 2014