Ocular Biodistribution Study for Topically Applied ESBA105

Cataract Clinical Trial

Official title:

Evaluation of Tolerability, Safety and Ocular Pharmacokinetics of Topically Applied ESBA105 in Patients Undergoing Cataract Surgery or Combined Cataract Surgery and Vitrectomy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00820014
• Other study ID #: ESBA105CRD03
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 8, 2009
• Last updated: September 23, 2010
• Start date: January 2009
• Est. completion date: September 2010

Study information

• Verified date: January 2009
• Source: ESBATech AG
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: SwissmedicSwitzerland: Ethikkommission
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether ESBA105, a single-chain (scFv) antibody against TNF-alpha, efficiently penetrates into the anterior chamber and the vitreous body upon topical administration to the eye.

Description:

ESBA105 is a topically administered tumour necrosis factor alpha (TNF-alpha) inhibitor that has significant therapeutic potential in various inflammatory intraocular diseases. In animal experiments, ESBA105 was shown to efficiently penetrate into the inner of the eye upon topical administration, associated with very low systemic exposure. A recently completed Phase I trial with topical ESBA105 has confirmed the safety of topical administration to the human eye and the low systemic exposure using this route of administration.

This study is designed to determine the intraocular levels and the specific intraocular distribution pattern of ESBA105 following topical administration to the human eye. In addition it shall be explored whether topical administration of ESBA105 reduces intraocular inflammation following cataract surgery.

Three different dose regimens will be applied to four different patient cohorts. Three patient cohorts will be conducted in an open label design and one in a double-masked, placebo controlled design.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: September 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female Caucasian patients =18 years.

• Written informed consent prior to any study procedures including screening tests for eligibility.

• Patients should be in good health as determined by past medical history, physical examination, vital signs, electrocardiogram (ECG), and laboratory tests at screening.

• Ability to administer eye drops (personally or administered by another person).

Cataract patients:

• Eligible for routine, uncomplicated senile cataract surgery.

Vitrectomy patients:

• Diagnosis of epiretinal fibroplasia requiring vitrectomy and cataract surgery.

Exclusion Criteria:

• Treated glaucoma / elevated intraocular pressure (IOP) requiring therapy.

• History of chronic or recurrent intraocular inflammatory disease.

• Uncontrolled diabetes mellitus (fasting blood glucose >15 mmol/L).

• Diabetic retinopathy with history of laser photocoagulation.

• Patients with a single eye or a pinholed visual acuity (VA) 20/200 or worse measured on Snellen chart in the non-study eye.

• Iris atrophy in the eye to undergo surgery.

• Pregnant or breast-feeding women or women of childbearing potential, who with their partners refuse to use 2 reliable methods of contraception

• History of collagenosis or systemic vasculitis.

• Patients who have had ocular surgery (including laser surgery) in the study eye within 3 months or in the contralateral eye within 2 weeks prior to screening.

• Patients who have an active systemic or local (anywhere in the body) bacterial and/or viral infection.

• Positive or unclear QuantiFERON-TB Gold assay result.

• Participation in a clinical study with investigational drugs within 3 months prior to screening.

• Inability to comply with the study requirements.

• Patients with known, severely impaired hepatic function, or laboratory values reflecting inadequate hepatic function.

• Patients with pre-existing chronic renal failure defined by a calculated creatinine clearance (CrCl) of < 40 mL/min, using the Cockcroft-Gault estimate for glomerular filtration rate

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Cataract

Intervention

Drug:
• Placebo
Placebo control (vehicle) eye drops applied 4-times a day for 4 days before ocular surgery

Locations

Country	Name	City	State
Switzerland	Kantonsspital Luzern, Augenklinik, CH-6000 Luzern 16, Switzerland	Luzern
Switzerland	Pallas Gruppe	Olten	Solothurn

Sponsors (1)

Lead Sponsor	Collaborator
ESBATech AG

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of intraocular ESBA105 levels, local biodistribution (aqueous and vitreous humor) and intraocular pharmacokinetics upon topical administration.		Collection of respective biological matrices at occasion of ocular surgery	No
Secondary	Exploratory assessment of the anti-inflammatory potential of prophylactic, topical ESBA105 for prevention of post-surgical inflammation following cataract surgery.		10 Days following ocular surgery	No
Secondary	Assessment of local tolerability and safety of topical ESBA105.		up to 10 Days following ocular surgery	No
Secondary	Assessment of systemic exposure upon topical application of ESBA105.		1 Day following ocular surgery	No