A Multiple Dose Study of AVD-104 for Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD)

Study Overview
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Brief Summary
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Investigate the Safety, Pharmacokinetics, and Treatment effects of Single and Multi-dose of Intravitreal AVD-104 in participants with geographic atrophy secondary to age-related macular degeneration.

Detailed Description
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Part 1 of the trial will be a multi-center, open label safety and dose escalation study with a potential enrollment of 30 participants having geographic atrophy (GA) secondary to macular degeneration. They will receive a single intravitreal injection of study drug (AVD-104) and will be followed for 3 months for safety observation. They will have both aqueous humor and peripheral blood drawn for pharmacokinetic and pharmacodynamic evaluations. Part 2 will be a multi-center, double masked, randomized trial to evaluate the treatment effect of AVD-104 on participants with geographic atrophy secondary to macular degeneration. Participants will be randomized to high dose AVD-104, low dose AVD-104, sham, or active comparator (avacincaptad) in a 2:2:2:1 ratio. The primary endpoint will be the difference in the rate of growth of the GA area between treated participants versus sham as measured by fundus autofluorescence.

Official Title
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A Single and Multiple Dose Study to Evaluate Safety, Pharmacokinetics, and Treatment Effect of Intravitreal AVD-104 in Participants With Geographic Atrophy Secondary to Age-related Macular Degeneration

Conditions
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Geographic Atrophy of the Macula, Macular Degeneration

Intervention / Treatment
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* Drug: AVD-104
* Procedure: Sham injection
* Drug: Avacincaptad


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part 1: BCVA in the study eye using ETDRS Chart Visual Acuity Scale (VAS) of 5 to 55 letters (equivalent to Snellen VA of approximately 20/800 - 20/80) If GA is multifocal, at least one focal lesion must be ≥ 1.25 mm2 (0.5 DA) GA may be center involved. Part 2: BCVA in the study eye using ETDRS Chart VAS of 24 letters or better (equivalent to Snellen VA of 20/320 or better) Confirmed diagnosis of AMD that is non-center involving (i.e., non-sub-foveal) GA in 75% of participants. Center involvement allowed in 25% of participants. The entire GA lesion must be completely visualized on the macula centered image and must be able to be imaged in its entirety and not contiguous with any areas of peripapillary atrophy. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: Part 1 and 2 - Presence of the following ocular conditions - in the Study Eye: Exudative AMD or choroidal neovascularization (CNV), including any evidence of retinal pigment epithelium rips or evidence of neovascularization anywhere based on spectral domain optical coherence tomography (SD-OCT) imaging and/or fluorescein angiography as assessed by the Reading Center. Any ocular condition other than GA secondary to AMD that may require surgery or medical intervention during the study period or, in the opinion of the Investigator, could compromise visual function during the study period.

Ages Eligible for Study
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Minimum Age: 55 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
Interventional Model Description: Part 1 - Open Label, Multi-Center, Dose Escalation
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br>Participants will receive a single intravitreal injection of AVD-104 at one of 4 escalating doses. All participants will be followed up for safety until Month 3. Participants from Part 1 will be offered the opportunity to receive monthly injections of high dose AVD-104 once the 6-month timepoint has been reached for 50% of the participants in Part 2. These participants will be followed for safety only. | Drug: AVD-104<br>* Intravitreal injection<br>|
| Active Comparator: Part 2: High dose AVD-104<br>82 participants will be randomized and treated with bimonthly intravitreal injections of high-dose AVD-104 for the first 12 months. They will continue monthly injections for months 13-24. | Drug: AVD-104<br>* Intravitreal injection<br>|
| Active Comparator: Part 2: Low dose AVD-104<br>82 participants will be randomized and treated with monthly intravitreal injections of low dose AVD-104 for 24 months. | Drug: AVD-104<br>* Intravitreal injection<br>|
| Sham Comparator: Part 2: Sham<br>82 participants will be randomized to receive sham injections monthly for 24 months | Procedure: Sham injection<br>* A sham injection with no scleral penetration<br>|
| Active Comparator: Part 2: Avacincaptad<br>41 participants will be randomized to receive monthly injections of avacincaptad (2 mg. intravitreal) | Drug: Avacincaptad<br>* Intravitreal injection of 2 mg avacincaptad<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Dose Limiting Toxicity in Part 1 | The number of participants experiencing a dose limiting toxicity corresponding to a category of 3 or greater on the National Cancer Institute Common Terminology Criteria for Adverse Events | 3 months | 
| The Rate of Change in Area of Geographic Atrophy at Month 12 in Participants in Part 2 | The rate of change from baseline in area of GA as measured by fundus autofluorescence at month 12. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Acuity Change from Baseline in Participants in Part 2 | The change from baseline in best-corrected visual acuity (BCVA) (assessed with ETDRS visual acuity) in Participants at Month 12 | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Age-related Macular Degeneration, Geographic Atrophy, Dry AMD