Exploratory Study on Topical ESBA105 in Acute Anterior Uveitis

This study has been completed.
Sponsor:
Information provided by:
ESBATech AG
ClinicalTrials.gov Identifier:
NCT00823173
First received: January 14, 2009
Last updated: May 25, 2011
Last verified: September 2010
  Purpose

The purpose of this study is to determine whether ESBA105, a topically applied TNF-alpha inhibitor, is safe and clinically active when applied to the eye of patients suffering from acute anterior uveitis


Condition Intervention Phase
Anterior Uveitis
Biological: ESBA105
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Exploratory Study to Assess the Safety, Tolerability and Clinical Activity of Topically Applied ESBA105 in Patients With Acute Anterior Uveitis

Resource links provided by NLM:


Further study details as provided by ESBATech AG:

Primary Outcome Measures:
  • Changes in the level of intraocular inflammation (anterior chamber cell count according to SUN Working group criteria) [ Time Frame: 28 Days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Nature and incidence of adverse events, physical and ophthalmological findings and laboratory test results [ Time Frame: 28 Days ] [ Designated as safety issue: Yes ]
  • Systemic exposure to study drug [ Time Frame: 28 Days ] [ Designated as safety issue: Yes ]
  • Changes in disease severity as assessed by visual analogue scale (VAS) [ Time Frame: 28 Days ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: January 2009
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Topical ESBA105
ESBA105 applied as eye drops
Biological: ESBA105
ESBA105 eye drops (10mg/mL), initially applied in hourly dosing intervals, followed by later dose tapering (prolongation of dosing intervals)

Detailed Description:

Acute anterior uveitis (AAU) is a common, recurrent disease characterized by inflammation of the iris and ciliary body. Though usually effectively treated by topical corticosteroids, novel treatment modalities are required to overcome the limitations and adverse effect problems associated with the use of corticosteroids. TNF-alpha has been recognized as a central disease mediator in AAU, as shown by preclinical models and clinical data with systemically applied TNF-alpha inhibitors.

ESBA105 is a topically applied TNF-alpha inhibitor that is characterized by efficient penetration into the eye resulting in high intraocular drug levels. A recently completed Phase I trial confirmed that safety and tolerability of topical ESBA105 in healthy individuals is excellent and systemic exposure is low.

In this pilot trial, the safety, local tolerability and clinical activity of topical ESBA105 in the treatment of patients with acute anterior uveitis shall be explored.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed and dated informed consent.
  • Patients with the typical presentation of HLA-B27 positive AAU (unilateral, painful anterior uveitis of sudden onset).
  • 2+ anterior chamber cells according to the SUN Working Group criteria, as assessed by slit lamp biomicroscopy.
  • Start of the typical first symptoms of the current attack, defined as the point in time when the patient felt the first sensation of the attack, within the last 72 hours before initiation of treatment with the study medication.
  • Negative pregnancy test for females of childbearing potential (pre menopausal, <2 years post-menopausal, not surgically sterile).
  • Patients with a negative QuantiFERON TB Gold test result.
  • Patients who currently have no clinically apparent symptoms of an HLA B27 associated acute extraocular disorder requiring systemic immunosuppressive therapy.
  • Patients who are willing and able to cooperate with study requirements.

Exclusion Criteria:

  • IOP elevation requiring therapy.
  • Uncontrolled diabetes mellitus and diabetic retinopathy.
  • Patients with a single eye or a pinhole Snellen visual acuity 20/200 or worse in the non study eye.
  • Patients with 1+ or less anterior chamber cells.
  • Patients with 3+ or 4+ anterior chamber cells or hypopyon.
  • Patients in whom the time of the beginning of the current attack can not be determined.
  • Patients exhibiting corneal ulceration or a history of recurrent herpetic keratitis or clinical evidence of herpetic dermatitis.
  • Patients currently treated with topical corticosteroids.
  • Patients treated with systemic immunosuppressive therapy within the last 2 months.
  • Patients treated with a systemically administered TNF-alpha inhibitor within the last 2 months.
  • Pregnant or breast-feeding women or women of childbearing potential, who with their partners refuse to use 2 reliable methods of contraception (including 1 barrier method) during the study.
  • Male patients with a female partner who could become pregnant and who refuse, with their partner, to use 2 reliable methods of contraception (including 1 barrier method) during the study.
  • Patients whose clinical presentation is suggestive for an active bacterial, viral or fungal infection anywhere in the body.
  • Patients with history of recurrent infections, or a clinical presentation suggestive of a chronic infection requiring antimicrobial therapy (e.g. syphilis) including active episodes of serious viral infections by, e.g. herpes simplex, herpes zoster, cytomegalic or hepatitis viruses or clinical signs of fungal infections, such as histoplasmosis, aspergillosis or coccidiomycosis.
  • Patients presenting with higher intraocular pressure in the uveitic eye than in the contralateral eye.
  • Patients with known carrier status of human immunodeficiency virus, hepatitis B or hepatitis C.
  • Patients with a history of demyelinating disease (multiple sclerosis) or optic neuritis.
  • Patients with positive or unclear QuantiFERON TB Gold test result or history of high risk exposure to Mycobacterium tuberculosis.
  • Patients with known coexisting malignancy.
  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: NCT00823173

Locations
Germany
Universitäts-Augenklinik
Tübingen, Baden-Würtemberg, Germany, 72076
Uveitis-Zentrum Franziskus Hospital
Münster, Nordrhein-Westfalen, Germany, 48145
Charité Humboldt University
Berlin, Germany, 13353
Sponsors and Collaborators
ESBATech AG
Investigators
Study Chair: Manfred Zierhut, MD Universitäts-Augenklinik Tübingen
  More Information

No publications provided

Responsible Party: Sushanta Mallick, Head Clinical Trial Management, ESBATech AG
ClinicalTrials.gov Identifier: NCT00823173     History of Changes
Other Study ID Numbers: ESBA105CRD04
Study First Received: January 14, 2009
Last Updated: May 25, 2011
Health Authority: Germany: Paul-Ehrlich-Institut
Germany: Ethics Commission

Keywords provided by ESBATech AG:
Uveitis
TNF-alpha
Topical
ESBA105
scFv antibody fragment
ocular inflammation

Additional relevant MeSH terms:
Uveitis
Chorioretinitis
Uveitis, Anterior
Iridocyclitis
Uveal Diseases
Eye Diseases
Retinitis
Retinal Diseases
Choroiditis
Choroid Diseases
Uveitis, Posterior
Panuveitis
Iris Diseases

ClinicalTrials.gov processed this record on September 22, 2014