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)

Phase 2

Completed

Brief Summary: 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: 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).

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	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.
IONIS-FB-LRx	IONIS-FB-LRx	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.

Primary Outcome Measures

Name	Time	Method
Rate of Change from Baseline in the Geographic Atrophy (GA) Area at Week 49, as Assessed by Retinal Imaging	Week 49

Secondary Outcome Measures

Name	Time	Method
Percentage Change from Baseline in Levels of Factor B (FB) in Plasma	Baseline and up to Week 49
Absolute Change from Baseline in Low Luminance Visual Acuity (LLVA)	Baseline and up to Week 49
Absolute change in the GA area from Baseline as measured by Fundus Autofluorescence (FAF)	Baseline and up to Week 57
Percentage Change from Baseline in Levels of Serum AH50 Activity	Baseline and up to Week 49