Clinical trial NCT00969293: Study to Assess the Safety and Tolerability of a Single Administration of FOV2302 (Ecallantide) in Patients With Macular Edema Associated With Central Retinal Vein Occlusion
Official title: An Open-label, Dose Escalating Study to Assess the Safety and Tolerability of a Single Administration of FOV2302 (Ecallantide) in Patients With Macular Edema Associated With Central Retinal Vein Occlusion
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Macular Edema
Central Retinal Vein Occlusion
Keywords: Macular Edema
Occlusive retinal vascular disease
Central Retinal Vein Occlusion
CRVO
Lead sponsor: Fovea Pharmaceuticals SA
Sponsor class: INDUSTRY
First posted: 2009-09-01
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the safety and tolerability of a single administration of FOV2302 (ecallantide) in patients with macular edema associated with central retinal vein occlusion.

Detailed description: Occlusive retinal vascular disease is not uncommon. Central retinal vein occlusion (CRVO) is the second most common vision-impairing vascular disorder of the retina following diabetic retinopathy. Severe visual loss from CRVO is caused by a combination of retinal edema and neovascular proliferation and ischemia. Vascular endothelial factors as they stimulate angiogenesis and increase vascular permeability, are majors pathogenic factors in CRVO. Counteracting these neovascular effects provide significant therapeutic benefit to subjects suffering from this disorder. Macular edema in this condition results from a conjunction of several, as yet, partially unknown factors.

Macular edema may occur in diseases causing cumulative injury over many years, such as diabetic retinopathy, or as a result of more acute events, such as branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO).

Eligibility criteria: Inclusion Criteria:

* Recent onset (\< 6 months), non-ischemic CRVO (defined as association of documented retinal hemorrhage in all 4 quadrants of the retina with dilated veins) in patients who have not received treatment for their condition (e.g., no periocular depot or intraocular treatment \[including corticosteroid and anti-VEGF\], systemic corticosteroids or laser nor hemodilution).
* Retinal thickness measured by Stratus OCT \> 250µm in the central subfield of study eye at baseline.
* BCVA score (measured by the ETDRS chart between 5 letters (20/800 Snellen equivalent) and 65 letters (20/50) in the study eye at baseline.
* Media clarity, pupillary dilation and participant cooperation sufficient for adequate fundus photographs.
* Females of childbearing potential using adequate birth control at Day 0 until study completion.
* Patient able (in the opinion of the investigator) and willing to return for all scheduled visits and assessments.
* Ability to read, understand and willingness to provide informed consent.

Exclusion Criteria:

* Rubeosis iridis or neovascular glaucoma at baseline.
* Preretinal neovascularisation at baseline.
* Ischemic CRVO, defined by more than 10 disc area of non-perfusion on fluorescein angiography at baseline.
* Any grade of diabetic retinopathy.
* Other eye condition that could contribute to macular edema or cause retinal vascular changes (including vitreomacular traction, uveitis and inflammatory disease, etc).
* Patients who have received treatment for their condition (e.g., no periocular depot or intraocular treatment \[including corticosteroid and anti-VEGF\], systemic corticosteroids or laser nor hemodilution).
* Ocular surgery (including cataract extraction, scleral buckle, etc.) and/or YAG capsulotomy within 3 months preceding treatment date or anticipated within the 3 months following treatment administration.
* Poorly controlled ocular hypertension and/or glaucoma (IOP greater than 25 mmHg despite maximal therapy).
* History of pars plana vitrectomy.
* Aphakia or anterior chamber intraocular lens.
* Presence of visible sclera thinning or ectasia.
* Presence of substantial cataract or other media opacity that, in the opinion of the investigator, is likely to interfere with visualization of the fundus or completion of study measurements.
* Any active ocular or peri-ocular infection (including conjunctivitis, chalazion or significant blepharitis).

Primary outcomes:
measure: Safety and tolerability parameters to determine MTD: 1. Systemic parameters: adverse events (AEs), coagulation parameters (APTT, ACT) 2. Ophthalmologic parameters: BCVA, OCT, ocular inflammation, IOP
timeFrame: 3 months post-dose
Secondary outcomes:
measure: Assess the pharmacodynamics up to five dose levels of a single administration of FOV2302 (ecallantide) by longitudinal measurements of the percent change of the macula thickness versus baseline as measured by OCT
timeFrame: 3 months post-dose
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU d'Amiens, Centre Saint-Victor
city: Creteil
country: France
facility: Centre Intercommunal de Creteil
city: Dijon
country: France
facility: CHU de Dijon, Hôpital Général
city: Marseille
country: France
facility: Clinique Monticelli
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: Centre Hospitalier National d'Ophthalmologies des XV-XX
city: Paris
country: France
facility: Hopital Lariboisiere
city: Paris
country: France
facility: Fondation Rothschild
Study officials:
affiliation: Hopital Lariboisiere
name: Alain Gaudric, MD
role: STUDY_CHAIR
References: