Clinical trial NCT00935883: Complement Inhibition With Eculizumab for the Treatment of Non-Exudative Macular Degeneration (AMD)
Official title: Eculizumab for the Treatment of Non-Exudative Age-Related Macular Degeneration: An Exploratory Study to Evaluate the Effects of C5 Inhibition on Drusen and Geographic Atrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Age-Related Macular Degeneration
Keywords: Age Related macular Degeneration
Macular Degeneration
Drusen
Geographic atrophy
Eculizumab
Soliris
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: Alexion Pharmaceuticals, Inc.
First posted: 2009-07-09
Enrollment: 60
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and efficacy of eculizumab for the treatment of dry AMD as evaluated by the change in drusen volume and area of geographic atrophy.

Detailed description: This is a randomized, double-arm, double-masked study designed to evaluate the safety and efficacy of eculizumab for the treatment of patients with dry AMD. There are three stages in the study: the screening period, the treatment period, and the follow-up period.During the screening period patients will be evaluated for eligibility. Eligible patients will receive either eculizumab or placebo for 24 weeks.

A total of 60 patients will be enrolled and divided equally between the drusen cohort and the GA cohort. A 2:1 randomization will result in 20 patients in each cohort receiving eculizumab while 10 patients receive placebo.

The treatment period will begin two weeks after administration of the meningococcal vaccine. During the treatment period, patients will receive eculizumab or placebo over a period of approximately 26 weeks. Patient will treatment according to the following regimen:

Induction Period: patient will receive eculizumab 600 mg or 900 mg via IV infusion over approximately 30 minutes once a week (7 ± 2 days) for 4 weeks followed by 900 mg eculizumab for the fifth dose 7 days later (7 ± 2 days).

Maintenance Period: patient will receive eculizumab 900 mg or 1200 mg via IV infusion over approximately 30 minutes every 2 weeks (14 ± 2 days).

After the final scheduled dose of eculizumab or Placebo at week 24, patients will return for follow-up exam 2 weeks, 3 months, and 6 months after the final dose.

Eligibility criteria: Inclusion Criteria:

* Ability to provide written informed consent and comply with study assessments for the full duration of the study
* Age \> 50 years
* In the study eye(s), the presence of non-exudative AMD documented by fundus photography, autofluorescence, fluorescein angiography, and spectral domain OCT.
* Visual acuity of 20/63 or better (BCVA score of at least 59 letters) as measured on an ETDRS chart.
* Able and willing to comply with study procedures.

Exclusion Criteria:

* Visual acuity worse than 20/63
* Any history of choroidal neovascularization in the study eye
* Unresolved meningococcal disease.
* Confounding ocular conditions such as amblyopia; aphakia; myopia requiring \>6 diopters of correction; pigment epithelial detachment; uncontrolled glaucoma (intraocular pressure ≥ 25 mmHg despite treatment with anti-glaucoma medication); steroid-induced ocular hypertension; retinal inflammatory disease; central serous choroidopathy; prior or current retinal detachment; macular edema; cystic lesion (individual cysts or cystoid macular edema); ocular herpes simplex virus; severe non-proliferative or worse diabetic retinopathy; anterior ischemic optic neuropathy; RPE tear involving the macula; pseudovitelliform macular degeneration; vitreo-retinal traction maculopathy; vitreous hemorrhage, history of or current rhegmatogenous retinal detachment or macular hole; uveitis; diffuse choroidal atrophy; optic atrophy (as evidenced by pallor); intraocular inflammation; ocular or periocular infection; moderate or worse dry eye syndrome; clinically significant cataract or opacification of the posterior capsule which, in the Investigator's opinion, would progress during the course of the study and could affect central vision; other ocular conditions that the Investigator believes may be a confounding factor in this study
* Refusal to be vaccinated against Neisseria meningitides or an active Neisseria meningitides infection

Primary outcomes:
measure: Growth of Geographic Atrophy
timeFrame: 6 months
measure: Decrease in Drusen Volume
timeFrame: 6 Months
Secondary outcomes:
measure: Change in Visual Acuity for Drusen Group
timeFrame: Baseline/ 6 Months
measure: Change in Visual Acuity for Geographic Atrophy Group
timeFrame: Baseline/ 6 Months
Other outcomes:
Locations:
city: Miami
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
Study officials:
affiliation: University of Miami
name: Philip J Rosenfeld, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yehoshua Z, de Amorim Garcia Filho CA, Nunes RP, Gregori G, Penha FM, Moshfeghi AA, Zhang K, Sadda S, Feuer W, Rosenfeld PJ. Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration: the COMPLETE study. Ophthalmology. 2014 Mar;121(3):693-701. doi: 10.1016/j.ophtha.2013.09.044. Epub 2013 Nov 26.
citation: Garcia Filho CA, Yehoshua Z, Gregori G, Nunes RP, Penha FM, Moshfeghi AA, Zhang K, Feuer W, Rosenfeld PJ. Change in drusen volume as a novel clinical trial endpoint for the study of complement inhibition in age-related macular degeneration. Ophthalmic Surg Lasers Imaging Retina. 2014 Jan-Feb;45(1):18-31. doi: 10.3928/23258160-20131217-01.
citation: Stetson PF, Yehoshua Z, Garcia Filho CA, Portella Nunes R, Gregori G, Rosenfeld PJ. OCT minimum intensity as a predictor of geographic atrophy enlargement. Invest Ophthalmol Vis Sci. 2014 Feb 10;55(2):792-800. doi: 10.1167/iovs.13-13199.