Zimura in Participants With Geographic Atrophy Secondary to Dry Age-Related Macular Degeneration

Study Overview
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Brief Summary
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The objectives of this study were to evaluate the safety and efficacy of Zimura intravitreal (IVT) administration when administered in participants with geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD).

Detailed Description
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Participants will receive monthly intravitreal injections of Zimura or Sham for 18 months.

Official Title
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A Phase 2/3 Randomized, Double-Masked, Controlled Trial to Assess the Safety and Efficacy of Intravitreous Administration of Zimura™ (Anti-C5 Aptamer) in Subjects With Geographic Atrophy Secondary to Dry Age-Related Macular Degeneration

Conditions
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Geographic Atrophy, Macular Degeneration

Intervention / Treatment
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* Drug: Zimura
* Other: Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants of either gender aged ≥ 50 years Diagnosis of Non-foveal GA secondary to dry AMD Exclusion Criteria: Evidence of Choroidal Neovascularization (CNV) GA secondary to any condition other than AMD Any prior treatment for AMD or any prior intravitreal treatment for any indication in either eye, except oral supplements of vitamins and minerals Any intraocular surgery or thermal laser within three (3) months of trial entry Any prior thermal laser in the macular region, regardless of indication Any ocular or periocular infection in the twelve (12) weeks Previous therapeutic radiation in the region of the study eye Any sign of diabetic retinopathy in either eye

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zimura 1 mg [Part 1]<br>Participants received 1 mg of Zimura in the study eye administered via IVT injection (50 µL) on Day 1 and monthly up to 18 months. | Drug: Zimura<br>* Zimura 20 mg/mL solution for intravitreal (IVT) injection<br>* Other names: avacincaptad pegol;|
| Experimental: Zimura 2 mg [Part 1]<br>Participants received 2 mg of Zimura in the study eye administered via IVT injection (100 µL) on Day 1 and monthly up to 18 months. | Drug: Zimura<br>* Zimura 20 mg/mL solution for intravitreal (IVT) injection<br>* Other names: avacincaptad pegol;|
| Sham Comparator: Sham [Part 1]<br>Participants received a Sham injection of an empty, needleless syringe administered in the study eye on Day 1 and monthly up to 18 months. | Other: Sham<br>* The Sham procedure included the blunt opening of an empty, needleless syringe barrel placed on the conjunctiva in the inferotemporal quadrant of the eyeball to simulate the pressure of an injection.<br>|
| Experimental: Zimura 2 mg (Zimura 2mg+Sham) [Part 2]<br>Participants received 2 mg of Zimura in the study eye administered via IVT injection (100 µL) and a subsequent Sham administration on Day 1 and monthly up to 18 months. | Drug: Zimura<br>* Zimura 20 mg/mL solution for intravitreal (IVT) injection<br>* Other names: avacincaptad pegol;Other: Sham<br>* The Sham procedure included the blunt opening of an empty, needleless syringe barrel placed on the conjunctiva in the inferotemporal quadrant of the eyeball to simulate the pressure of an injection.<br>|
| Experimental: Zimura 4 mg (Zimura 2mg+Zimura 2mg) [Part 2]<br>Participants received 4 mg of Zimura in the study eye administered via two consecutive IVT injections (2 x 100 µL) on Day 1 and monthly up to 18 months. | Drug: Zimura<br>* Zimura 20 mg/mL solution for intravitreal (IVT) injection<br>* Other names: avacincaptad pegol;|
| Sham Comparator: Sham (Sham+Sham) [Part 2]<br>Participants received two consecutive Sham injections of empty, needleless syringes administered in the study eye on Day 1 and monthly up to 18 months. | Other: Sham<br>* The Sham procedure included the blunt opening of an empty, needleless syringe barrel placed on the conjunctiva in the inferotemporal quadrant of the eyeball to simulate the pressure of an injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Geographic Atrophy as Measured by Fundus Autofluorescence | The least squares mean change in geographic atrophy (GA) from baseline to Month 12 was measured by fundus autofluorescence (FAF). The square root of the GA area was used in the analysis. Per statistical analysis plan, only the Zimura 2 mg and 4 mg groups were evaluated for this primary endpoint; the Zimura 1 mg group was for descriptive purposes only. | Baseline and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Best Corrected Visual Acuity Using Early Treatment Diabetic Retinopathy Study Letters | The least squares mean change in best-corrected visual acuity (BCVA) from baseline to Month 12 was measured using early treatment diabetic retinopathy study [ETDRS] letters. Per statistical analysis plan, only the Zimura 2 mg and 4 mg groups were evaluated for the secondary endpoints; the Zimura 1 mg group was for descriptive purposes only. | Baseline and 12 months | 
| Change From Baseline in Low Luminance BCVA Using Early Treatment Diabetic Retinopathy Study Letters | The least squares mean change in low luminance (LL) BCVA from baseline to Month 12 was measured using ETDRS letters. Per statistical analysis plan, only the Zimura 2 mg and 4 mg groups were evaluated for the secondary endpoints; the Zimura 1 mg group was for descriptive purposes only. | Baseline and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Geographic Atrophy (GA), Dry age-related macular degeneration, AMD, Zimura, Anti-inflammatory, complement factor C5 inhibitor, ARC1905, avacincaptad pegol