Complement Inhibition With Eculizumab for the Treatment of Non-Exudative Macular Degeneration (AMD)

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Age-Related Macular Degeneration

Intervention / Treatment
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* Drug: Eculizumab
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Saline<br>Randomized patients in the drusen or the GA cohort will receive placebo saline infusions as a comparator | Drug: Saline<br>* Induction Period: patient will receive saline via IV infusion over approximately 30 minutes once a week (7 ± 2 days) for 4 weeks followed by saline for the fifth dose 7 days later (7 ± 2 days). Maintenance Period: patient will receive saline via IV infusion over approximately 30 minutes every 2 weeks (14 ± 2 days) until week 24. Observation period: patient will then be observed for 6 months off treatment with follow-up visits scheduled for 9 months and 12 months.<br>* Other names: PBS;|
| Active Comparator: Eculizumab<br>Randomized patients in the drusen or the GA cohort will receive active treatment with eculizumab | Drug: Eculizumab<br>* 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 or 1200 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) until week 24. Observation period: patient will then be observed for 6 months off treatment with follow-up visits scheduled for 9 months and 12 months.<br>* Other names: Soliris;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth of Geographic Atrophy |  | 6 months | 
| Decrease in Drusen Volume |  | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Visual Acuity for Drusen Group | Visual function was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning. Maximum score would be 100 letters read and minimum would be count fingers, hand motion and light perception if there were no letters read on the chart. | Baseline/ 6 Months | 
| Change in Visual Acuity for Geographic Atrophy Group | Visual function was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. A higher score represents better functioning. Maximum score would be 100 letters read and minimum would be count fingers, hand motion and light perception if there were no letters read on the chart. | Baseline/ 6 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Age Related macular Degeneration, Macular Degeneration, Drusen, Geographic atrophy, Eculizumab, Soliris