A phase 2b randomized, double-masked, controlled trial to establish the safety and efficacy of intravitreous administration of Fovista® (Anti-PDGFBB pegylated aptamer) administered in combination with Avastin® compared to Avastin® monotherapy in subjects with subfoveal neovascular age-related macular degeneration.
- Conditions
- retina aging10047518
- Registration Number
- NL-OMON43730
- Lead Sponsor
- OPHTHOTECH CORPORATIO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 100
General Inclusion Criteria
1. Subjects of either gender aged * 50 years.
2. Performance Status 2 according to Eastern Cooperative Oncology Group (ECOG) / World Health Organization (WHO) scale .
3. Women must agree to be using two forms of effective contraception, be post-menopausal for at least 12 months prior to trial entry, or surgically sterile; if of child-bearing potential, a serum pregnancy test must be performed within 14 days prior to the first injection with a negative result. The two forms of effective contraception must be implemented during the trial and for at least 60 days following the last dose of test medication.
4. Provide written informed consent.
5. Ability to comply with study and follow-up procedures and return for all trial visits.;Ophtalmic Inclusion Criteria ;1. Presence of subfoveal active CNV. Active CNV* is defined as the presence of fluorescein leakage consistent with choroidal neovascularization.
2. Presence of subretinal or intraretinal fluid in the anatomic fovea by OCT.
3. Best corrected visual acuity in the study eye between 20/63 and 20/200, inclusive.
4. Total area of the lesion (including blood, neovascularization, and scar/atrophy) must be * 9 disc areas (DA), of which at least 50% must be active CNV.
5. Clear ocular media and adequate pupillary dilatation to allow collection of fundus photographs and fluorescein angiograms of a sufficient quality to be analyzed.
6. Intraocular pressure (IOP) of 21 mmHg or less.
General Exclusion Criteria
1. Any of the following underlying conditions or diseases including:
* A definitive diagnosis of diabetes mellitus or diabetic retinopathy (regardless of HbA1c level)
* HbA1c value of *6.5%* (*If the HbA1c value is * 6.5% and * 6.9%, and the patient has no signs or symptoms of diabetes mellitus, has a normal creatinine, has no diabetic retinopathy and no glycosuria, then the patient may have an oral glucose tolerance test (OGTT) at the discretion of the investigator. If the 2-hour glucose value on OGTT is <200 mg/dL (<11.1mmol/L), then the patient may be enrolled)
* History of other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk for treatment complications.
* History or evidence of severe cardiac disease (e.g., NYHA Functional Class III or IV - see Appendix 17.6), history or clinical evidence of unstable angina, acute coronary syndrome, myocardial infarction or coronary artery revascularization within 6 months, or ventricular tachyarrythmias requiring ongoing treatment.
* Stroke (within 12 months of trial entry).
* Any major surgical procedure within one month of trial entry.
2. Any treatment with an investigational agent in the 60 days prior to randomization for any condition.
3. Known serious allergies to the fluorescein dye used in angiography (mild allergy amenable to treatment is allowable), or to the components or formulation of either Fovista® or Avastin®.;Opthalmic Exclusion Criteria
1. Any prior treatment for AMD in the study eye prior to the Day 1 visit, except oral supplements of vitamins and minerals.
2. Any prior intravitreal treatment in the study eye prior to the Day 1 visit, regardless of indication (including intravitreal corticosteroids).
3. Subjects with subfoveal scar or subfoveal atrophy (by OCT and/or by Fundus Photography)
4. More than 50% of the total lesion size consisting of subretinal hemorrhage.
5. Presence of retinal angiomatous proliferation (RAP).
6. Presence of significant serous pigment epithelial detachments (PEDs), such as large PEDs that constitute greater than 50% of the total lesion or have a vertical height of * 500 *m.
7. Presence of pure PED.
8. Presence of pigment epithelial tears or rips.
9. Presence of intraocular inflammation (* trace cell or flare), significant epiretinal membrane (causing distortion of macular anatomy and/or opacification), significant vitreomacular traction (causing distortion of macular anatomy), macular hole (full or partial thickness) or vitreous hemorrhage.
10. Aphakia or absence of the posterior capsule. Absence of an intact posterior capsule is allowed if it occurred as a result of YAG laser posterior capsulotomy in association with prior posterior chamber IOL implantation.
11. History of idiopathic or autoimmune-associated uveitis in either eye.
12. Significant media opacities, including cataract, which might interfere with visual acuity, assessment of toxicity, or fundus photography in the study eye. Subjects should not be entered if there is likelihood that they will require cataract surgery in the study eye in the next 12 months.
13. Presence of other causes of choroidal neovascularization, includi
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary efficacy endpoint is the mean change in visual acuity (ETDRS<br /><br>letters) from baseline at the Month 18 visit. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Efficacy Endpoints:<br /><br>* The proportion of subjects in each treatment group gaining 20 or more ETDRS<br /><br>letters from baseline at the Month 18 visit.<br /><br>* The proportion of subjects in each treatment group gaining 25 or more ETDRS<br /><br>letters from baseline at the Month 18 visit.<br /><br>* The proportion of subjects in each treatment group losing 5 or more ETDRS<br /><br>letters from baseline at the Month 18 visit.<br /><br>* The mean change in visual acuity (ETDRS letters) from baseline at the Month 5<br /><br>and Month 11 visit.<br /><br><br /><br>Safety Endpoints<br /><br>* Adverse events (AEs) and serious adverse events (SAEs)<br /><br>* Vital signs (pulse, systolic and diastolic blood pressure)<br /><br>* Ophthalmic variables (IOP, ophthalmic examination, fluorescein angiograms and<br /><br>OCT)<br /><br>* ECG (12-lead)<br /><br>* Laboratory variables (blood: hematology, renal function, hepatic function,<br /><br>and electrolytes; urinalysis) </p><br>