GOLDEN STUDY: A Study to Assess Safety and Efficacy of Multiple Doses of IONIS-FB-LRx in Participants With Geographic Atrophy Secondary to Age-Related Macular Degeneration (AMD)

Study Overview
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Brief Summary
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Evaluate the effect of IONIS-FB-LRx on the rate of change of the area of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) measured by fundus autofluorescence (FAF).

Detailed Description
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The study will assess the rate of change of the area of GA secondary to AMD by measuring FAF in up to 330 participants with GA due to AMD being treated with IONIS-FB-LRx. The study is a Phase 2, double-masked, randomized, stratified, placebo-controlled study conducted at multiple centers. It is an adaptive design in which three dose levels will be evaluated in a subset of participants (Stage 1) and, following an interim analysis, the number of participants in two of the dose cohorts will be expanded (Stage 2).

Official Title
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A Phase 2, Randomized Placebo-Controlled, Double-Masked Study to Assess Safety and Efficacy of Multiple Doses of IONIS-FB-LRx, an Antisense Inhibitor of Complement Factor B, in Patients With Geographic Atrophy Secondary to Age-Related Macular Degeneration (AMD)

Conditions
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Macular Degeneration, Geographic Atrophy

Intervention / Treatment
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* Drug: IONIS-FB-LRx
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal. Vaccination against Neisseria meningitidis and Streptococcus pneumoniae received at least 2 weeks prior to first dose of investigational product Well-demarcated geographic atrophy (GA) due to AMD Best-corrected visual acuity (BCVA) letter score of 35 letters (approx. 20/200 Snellen equivalent) or better on the ETDRS chart Must have clear ocular media and adequate pupillary dilation in the study eye to permit high-quality fundus imaging Exclusion Criteria: Clinically-significant abnormalities in medical history A lack of full recovery from any infection for at least 14 days prior to the Study Drug administration Chronic treatment with steroids, including topically or intravitreally administered History or presence of diabetic retinopathy or diabetic macular edema (DME) History or presence of a disease other than AMD that could affect vision or safety assessments Prior treatment with another investigational drug, biological agent, or device Other protocol-specified inclusion/exclusion criteria may apply

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: IONIS-FB-LRx<br>Stage 1 participants will receive IONIS-FB-LRx randomized to 1 of 3 dose levels, administered subcutaneously every 4 weeks, completing the treatment period at Week 45. Stage 2 will expand 2 of the dosing cohorts in a new randomized group of participants based on the Stage 1 interim analysis. Participants will be randomized to 1 of 2 of the expanded cohorts, administered subcutaneously every 4 weeks, completing the treatment period at Week 45. | Drug: IONIS-FB-LRx<br>* IONIS-FB-LRx at multiple ascending doses, administered subcutaneously every 4 weeks<br>* Other names: ISIS 696844;|
| Experimental: Placebo<br>Stage 1 participants will receive a placebo matching solution, administered subcutaneously every 4 weeks, completing the treatment period at Week 45. Stage 2 participants will receive a placebo matching solution, administered subcutaneously every 4 weeks, completing the treatment period at Week 45. | Drug: Placebo<br>* Placebo matching solution, administered subcutaneously every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Change from Baseline in the Geographic Atrophy (GA) Area at Week 49, as Assessed by Retinal Imaging |  | Week 49 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change in the GA area from Baseline as measured by Fundus Autofluorescence (FAF) |  | Baseline and up to Week 49 | 
| Percentage Change from Baseline in Levels of Factor B (FB) in Plasma |  | Baseline and up to Week 49 | 
| Percentage Change from Baseline in Levels of Serum AH50 Activity |  | Baseline and up to Week 49 | 
| Absolute Change from Baseline in Low Luminance Visual Acuity (LLVA) |  | Baseline and up to Week 49 |