QA102 Phase II Study in Subjects With Dry AMD

Study Overview
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Brief Summary
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This is a phase 2, double-masked, randomized, placebo-controlled, dose-response study. The primary objective of the study is to evaluate the efficacy of QA102 oral capsules on the development of GA or CNV in high-risk eyes.

Detailed Description
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Approximately 30 sites will randomize a total of approximately 240 subjects to 1 of 3 treatment arms in a 1:1:1 ratio (80 subjects per arm). Each subject will receive either QA102 or matching placebo BID for up to 24 months.

Official Title
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A Phase 2, Double-Masked, Randomized, Placebo-Controlled, Dose-Response Study Assessing the Safety and Efficacy of QA102 in Subjects With Dry Age-Related Macular Degeneration (AMD)

Conditions
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Dry Age-related Macular Degeneration

Intervention / Treatment
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* Drug: QA102/Placebo
* Drug: QA102
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subject must be able to understand and willing to sign a written informed consent form (ICF) prior to the initiation of any study-specific procedures. Subject must be age ≥50 years at the time of informed consent. Subject must be able to take oral medications and willing to record daily adherence to taking their assigned capsules. Subject must have adequate hematologic function, hepatic function, renal function and coagulation profile as defined in the protocol. Subject must be willing and able to comply with study procedures and examinations. Specific to the Study Eye: Subject must have one of the following: extensive intermediate-size drusen, or at least 1 large drusen, or GA ((not involving the foveal center point) secondary to AMD, with very limited aggregate size of total GA(s), as defined in the protocol. Subject must be able to correctly identify ≥35 ETDRS letters (approximately 20/200 Snellen equivalent). Specific to Fellow Eye: - Subject must have a diagnosis of advanced AMD (evidence of GA and/or CNV), to be confirmed by the CRC. Specific to Both Eyes: - Subject must have visualizable retina, clear ocular media, and adequate pupillary dilation to ensure high-quality fundus imaging. Key Exclusion Criteria: Subject received an active investigational drug within 6 weeks (or 5 half-lives of the active, whichever is longer) prior to screening for this QA102 study. Subject has ever received gene therapy (for any condition). Subject is unwilling to stop intake of Age-Related Eye Disease Studies (AREDS) vitamins for the duration of the study. Subject has a clinically significant systemic disease that might interfere with the study, in the judgment of the Investigator. Subject had major surgery within 30 days prior to Screening. Specific to Study Eye: Subject has large GA, subfoveal GA, or active or inactive CNV, as confirmed by the CRC. Subject has GA or CNV due to causes other than AMD that that developed between Visit 1 (Screening) and Visit 2 (Randomization). Subject has endophthalmitis. Subject has a hemorrhagic or serous pigment epithelial detachment (PED) within 500 µm of the foveal center point, to be confirmed by the CRC. Subject has had retinal procedures or surgeries, or has a retinal pathology, such as a macular hole. Subject has aphakia or absence of the posterior capsule. Subject has ever received, whether in an interventional trial or by prescription, an FDA- approved treatment for GA. Use of such treatment during the QA102 study period also is prohibited. (Study Eye Only) Specific to Fellow Eye: Subject has monocular vision impairment, defined as having no light perception in the fellow eye with adequate vision in the study eye. Specific to Either Eye: Subject had intraocular surgery with lens replacement within 3 months of Screening. Subject has any ophthalmic condition that could require surgery during the study period. Subject has an ocular condition that might affect adequate imaging of the retina and/or or alter visual acuity.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QA102 200mg group<br>Subjects randomized to this arm will receive one (1) 200 mg capsule of QA102 and 1 placebo capsule BID = daily dose of 400 mg QA102 for up to 24 months | Drug: QA102/Placebo<br>* Capsules<br>|
| Experimental: QA102 400mg group<br>Subjects randomized to this arm will receive two (2) 200 mg capsules of QA102 BID = daily dose of 800 mg QA102 for up to 24 months | Drug: QA102<br>* Capsules<br>|
| Placebo Comparator: Placebo group<br>Subjects randomized to this arm will receive two (2) placebo capsules BID = daily dose of 0 mg QA102 for up to 24 months | Drug: Placebo<br>* Capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of subjects with disease progression to CNV or significant GA change as defined in the protocol | In the study eye at Month 24, proportion of subjects with disease progression as defined in the protocol. | Month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from Baseline in BCVA | change from Baseline in best-corrected visual acuity (BCVA) as measured by Early Treatment Diabetic Retinopathy Study (ETDRS). | Month 1,2,3,6,9,12,15,18,21,24 | 
| The estimated mean rate of growth (slope) based on GA area | The estimated mean rate of growth (slope) based on GA area measured by FAF at ≥3 time points. | at ≥3 time points | 
| Change from Baseline in soft drusen (drusen volume, drusen size) | Change from Baseline in soft drusen (drusen volume, drusen size) as measured by SD-OCT | Month 1,2,3,6,9,12,15,18,21,24 | 
| Change from Baseline in GA area | Change of Baseline GA area to on-treatment GA area assessments | Month 1,2,3,6,9,12,15,18,21,24 | 
| Area under the curve for BCVA letters read on the ETDRS chart over the 24-month treatment period | Change from baseline BCVA letters read on the ETDRS chart to on-treatment assessments | Month 1,2,3,6,9,12,15,18,21,24 |