A Study of Danicopan in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration

Study Overview
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Brief Summary
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This is a dose finding study designed to evaluate the efficacy, safety, and pharmacokinetics of danicopan in participants with GA secondary to AMD. The study consists of a Screening Period of up to 6 weeks, a 104-week masked Treatment Period, followed by a 30-day Follow-up after the last dose. This study will have 4 treatments arms: 100 milligrams (mg) twice daily (bid), 200 mg bid, 400 mg once daily (qd), and matching placebo.

Official Title
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A Phase 2, Double-Masked, Placebo-Controlled, Dose Range Finding Study of Danicopan (ALXN2040) in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD)

Conditions
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Geographic Atrophy

Intervention / Treatment
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* Drug: Danicopan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Vaccination for Neisseria meningitidis. Capable of giving signed informed consent. Presentation of GA secondary to AMD in at least 1 eye The entire GA lesion must be > 1 μm outside of the foveal center Key Exclusion Criteria: GA in the study eye due to cause other than AMD. Have previously received intravitreal anti-vascular endothelial growth factor injections in study eye for intraocular vascular disease. Have previously received any stem cell/gene therapy for any ophthalmological condition in either eye. Use of any investigational medicinal product (ie, participation in interventional clinical studies for any ophthalmic indications) or use of any regulatory approved treatment for GA in the study eye regardless of route of administration within the last 3 months or 5 half-lives of the last dose of the investigational or commercial product (whichever is longer). Presence of active ocular diseases in the study eye that in the opinion of the Investigator compromises or confounds visual function or interferes with study assessments. Known or suspected complement deficiency. History or presence of any medical or psychological condition that, in the opinion of the Principal Investigator, would make the patient inappropriate for the study. Hypersensitivity to fluorescein sodium for injection, the investigational drug (danicopan) or any of its excipients. Note: Additional inclusion/exclusion criteria may apply, per protocol.

Ages Eligible for Study
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Minimum Age: 60 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 |
| --- | --- |
| Experimental: Danicopan: 100 mg<br>Participants will receive danicopan 100 mg bid during the masked Treatment Period. Once the optimal dose is identified, participants who have at least 52 weeks of treatment will be switched to the optimal dose for the remainder of the study. | Drug: Danicopan<br>* Oral tablet.<br>* Other names: ALXN2040;|
| Experimental: Danicopan: 200 mg<br>Participants will receive danicopan 200 mg bid during the masked Treatment Period. Once the optimal dose is identified, participants who have at least 52 weeks of treatment will be switched to the optimal dose for the remainder of the study. | Drug: Danicopan<br>* Oral tablet.<br>* Other names: ALXN2040;|
| Experimental: Danicopan: 400 mg<br>Participants will receive danicopan 400 mg qd during the masked Treatment Period. Once the optimal dose is identified, participants who have at least 52 weeks of treatment will be switched to the optimal dose for the remainder of the study. | Drug: Danicopan<br>* Oral tablet.<br>* Other names: ALXN2040;|
| Placebo Comparator: Placebo<br>Participants will receive matching placebo and will be re-randomized to one of the active treatment groups at Week 52, or to the optimal dose, if already identified. | Drug: Danicopan<br>* Oral tablet.<br>* Other names: ALXN2040;Drug: Placebo<br>* Oral tablet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline To Week 52 In The Square Root (sqrt) Of Total GA Lesion Area In The Study Eye As Measured By Fundus Autofluorescence (FAF) |  | Baseline, Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline To Week 104 In The Sqrt Of The Total GA Lesion Area In The Study Eye As Measured By FAF |  | Baseline, Week 104 | 
| Change From Baseline To Week 52 And Week 104 In The Total GA Lesion Area In The Study Eye As Measured By FAF |  | Baseline, Week 52 and Week 104 | 
| Change From Baseline To Week 52 And Week 104 In Monocular Best-corrected Visual Acuity (BCVA) Scores In The Study Eye As Assessed By The Early Treatment Diabetic Retinopathy Study (ETDRS) Chart |  | Baseline, Week 52 and Week 104 | 
| Change From Baseline To Week 52 And Week 104 In Monocular Low Luminance Visual Acuity (LLVA) Scores In The Study Eye As Assessed By The ETDRS Chart |  | Baseline, Week 52 and Week 104 | 
| Change From Baseline To Week 52 And Week 104 In Low Luminance Deficit (BCVA-LLVA) In The Study Eye |  | Baseline, Week 52 and Week 104 | 
| Change From Baseline To Week 52 And Week 104 In Monocular Reading Speeds In The Study Eye As Assessed By Minnesota Low Vision Reading Test (MNRead) Acuity Charts Or Radner Reading Charts |  | Baseline, Week 52 and Week 104 | 
| Plasma Concentration Of Danicopan Over Time |  | Up to 4 hours postdose | 
| PD Biomarkers, Ex Vivo Serum Alternative Pathway Activity, And Plasma Bb Concentration Over Time |  | Up to 4 hours postdose | 
| Change From Baseline To Week 52 and Week 104 in National Eye Institute Visual Function Questionnaire (NEI VFQ-25) scores |  | Baseline, Week 52 and Week 104 | 
| Incidence Of Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), And Ocular TEAEs, SAEs, And Clinical Laboratory Abnormalities, And Events Leading To Discontinuation Of Study Drug Throughout The Study |  | Day 1 through Week 104 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Geographic Atrophy, GA, Danicopan, ALXN2040, Complement Inhibition, AMD