Safety Study of Zimura™in Combination With Anti-VEGF Therapy in Patients With Neovascular AMD

Study Overview
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Brief Summary
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The primary objective is to assess the safety of intravitreal (IVT) Zimura® administered in combination with anti-VEGF Therapy (AVASTIN®, EYLEA®, OR LUCENTIS®) in anti-VEGF treatment experienced subjects with neovascular age-related macular degeneration (AMD)

Official Title
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A Phase 2A Randomized Open-Label Controlled Trial to Assess the Safety of Zimura™ (Anti-C5 Aptamer) Administered in Combination With Anti-VEGF Therapy in Treatment Experienced Patients With Neovascular Age-Related Macular Degeneration

Conditions
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Macular Degeneration

Intervention / Treatment
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* Drug: Zimura
* Drug: Avastin
* Drug: Lucentis
* Drug: Eylea


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Treatment experienced subjects defined as subjects with 1 prior dose of same intravitreal anti-VEGF therapy given within the past 8 weeks for neovascular age-related macular degeneration (NVAMD) in the study eye. There must be < 0 letters of improvement in Snellen (not ETDRS Snellen equivalent) visual acuity since the start of anti-VEGF treatment. Presence of subfoveal active choroidal neovascularization (CNV) Exclusion Criteria: Intravitreal treatment in the study eye prior to the Day 1 visit, regardless of indication, with the exception of the 1 prior anti-VEGF injections. Presence of other causes of choroidal neovascularization, including pathologic myopia, ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, and multifocal choroiditis. Non-pharmacologic treatment (intraocular surgery or thermal laser) within three months of trial entry. Prior thermal laser in the macular region, regardless of indication. Ocular or periocular infection in the past twelve weeks. History of any of the following conditions or procedures in the study eye: rhegmatogenous retinal detachment, pars plana vitrectomy, filtering surgery, glaucoma drainage device, or corneal transplant. Previous therapeutic radiation in the region of the study eye. Evidence of diabetic retinopathy

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zimura and Avastin<br>Participants receive three monthly Avastin treatments (Day 1, Month 1, and Month 2) followed by Zimura administered on the same day. All participants will receive treatment every 3 months for a total of 18 months. If there is a loss of visual acuity during the intervening visits, participants may be retreated with Avastin and Zimura. | Drug: Zimura<br>* Zimura 2 mg, administered by intravitreal injection<br>* Other names: ARC1905;Drug: Avastin<br>* Avastin 1.25 mg, administered by intravitreal injection<br>* Other names: Bevacizumab;|
| Experimental: Zimura and Lucentis<br>Participants receive three monthly Lucentis treatments (Day 1, Month 1, and Month 2) followed by Zimura administered on the same day. All participants will receive treatment every 3 months for a total of 18 months. If there is a loss of visual acuity during the intervening visits, participants may be retreated with Lucentis and Zimura. | Drug: Zimura<br>* Zimura 2 mg, administered by intravitreal injection<br>* Other names: ARC1905;Drug: Lucentis<br>* Lucentis 0.5 mg, administered by intravitreal injection<br>* Other names: Ranibizumab;|
| Experimental: Zimura and Eylea<br>Participants receive three monthly Eylea treatments (Day 1, Month 1, and Month 2) followed by Zimura administered on the same day. All participants will receive treatment every 3 months for a total of 18 months. If there is a loss of visual acuity during the intervening visits, participants may be retreated with Eylea and Zimura. | Drug: Zimura<br>* Zimura 2 mg, administered by intravitreal injection<br>* Other names: ARC1905;Drug: Eylea<br>* Eylea 2 mg, administered by intravitreal injection<br>* Other names: Aflibercept;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With >0 Letter Loss | Vision testing is performed using retroilluminated modified Ferris-Bailey Early Treatment Diabetic Retinopathy Study (ETDRS) charts at 4 meters. Observed VA loss at Month 12 from Day 1 was assessed. | Month 12 | 
| Percentage of Participants With >0 Letter Loss | Vision testing is performed using retroilluminated modified Ferris-Bailey Early Treatment Diabetic Retinopathy Study (ETDRS) charts at 4 meters. Observed VA loss at Month 18 from Day 1 was assessed. | Month 18 | 
| Percentage of Participants With >5 Letter Loss | Vision testing is performed using retroilluminated modified Ferris-Bailey ETDRS charts at 4 meters. Observed VA loss at Month 12 from Day 1 was assessed. | Month 12 | 
| Percentage of Participants With >5 Letter Loss | Vision testing is performed using retroilluminated modified Ferris-Bailey ETDRS charts at 4 meters. Observed VA loss at Month 18 from Day 1 was assessed. | Month 18 | 
| Percentage of Participants With >10 Letter Loss | Vision testing is performed using retroilluminated modified Ferris-Bailey ETDRS charts at 4 meters. Observed VA loss at Month 12 from Day 1 was assessed. | Month 12 | 
| Percentage of Participants With >10 Letter Loss | Vision testing is performed using retroilluminated modified Ferris-Bailey ETDRS charts at 4 meters. Observed VA loss at Month 18 from Day 1 was assessed. | Month 18 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neovascular age-related macular degeneration (NVAMD)