Ocular Biodistribution Study for Topically Applied ESBA105

This study has been completed.
Sponsor:
Information provided by:
ESBATech AG
ClinicalTrials.gov Identifier:
NCT00820014
First received: January 8, 2009
Last updated: September 23, 2010
Last verified: January 2009
  Purpose

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.


Condition Intervention Phase
Cataract
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: Evaluation of Tolerability, Safety and Ocular Pharmacokinetics of Topically Applied ESBA105 in Patients Undergoing Cataract Surgery or Combined Cataract Surgery and Vitrectomy

Resource links provided by NLM:


Further study details as provided by ESBATech AG:

Primary Outcome Measures:
  • Determination of intraocular ESBA105 levels, local biodistribution (aqueous and vitreous humor) and intraocular pharmacokinetics upon topical administration. [ Time Frame: Collection of respective biological matrices at occasion of ocular surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Exploratory assessment of the anti-inflammatory potential of prophylactic, topical ESBA105 for prevention of post-surgical inflammation following cataract surgery. [ Time Frame: 10 Days following ocular surgery ] [ Designated as safety issue: No ]
  • Assessment of local tolerability and safety of topical ESBA105. [ Time Frame: up to 10 Days following ocular surgery ] [ Designated as safety issue: No ]
  • Assessment of systemic exposure upon topical application of ESBA105. [ Time Frame: 1 Day following ocular surgery ] [ Designated as safety issue: No ]

Enrollment: 79
Study Start Date: January 2009
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
ESBA105 eye drops
Drug: Placebo
Placebo control (vehicle) eye drops applied 4-times a day for 4 days before ocular surgery
Placebo Comparator: 2
Placebo control (vehicle)
Drug: Placebo
Placebo control (vehicle) eye drops applied 4-times a day for 4 days before ocular surgery

Detailed 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.

  Eligibility

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

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
  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: NCT00820014

Locations
Switzerland
Pallas Gruppe
Olten, Solothurn, Switzerland, 4600
Kantonsspital Luzern, Augenklinik, CH-6000 Luzern 16, Switzerland
Luzern, Switzerland, 6000
Sponsors and Collaborators
ESBATech AG
Investigators
Principal Investigator: Michael A Thiel, MD, PhD Kantonsspital Luzern, Augenklinik, CH-6000 Luzern 16, Switzerland
  More Information

No publications provided

Responsible Party: Peter Lichtlen, Medical Director, ESBATech AG
ClinicalTrials.gov Identifier: NCT00820014     History of Changes
Other Study ID Numbers: ESBA105CRD03
Study First Received: January 8, 2009
Last Updated: September 23, 2010
Health Authority: Switzerland: Swissmedic
Switzerland: Ethikkommission

Keywords provided by ESBATech AG:
ESBA105
scFv antibody fragment
cataract surgery
pharmacokinetics
biodistribution
Irvine-Gass syndrome

Additional relevant MeSH terms:
Cataract
Lens Diseases
Eye Diseases

ClinicalTrials.gov processed this record on August 18, 2014