Safety and Efficacy of IONIS-FB-Lrx in up to 120 Patients 55 and Older With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD)

Study Overview
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Brief Summary
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The purpose of this study is to assess the Safety and Efficacy of IONIS-FB-Lrx for up to 120 patients with Geographic Atrophy secondary to Age Related Macular Degeneration

Detailed Description
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This study will assess changes in complement factor B over a 69-week treatment period in a patient population 55 and older with well-demarcated Geographic Atrophy secondary to Age Related Macular Degeneration

Official Title
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A Phase 2, Placebo-Controlled, Double-Masked Study to Assess Safety and Efficacy of ISIS 696844, an Antisense Inhibitor of Complement Factor B, in Patients With Geographic Atrophy Secondary (GA) to Age-Related Macular Degeneration (AMD)

Conditions
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Geographic Atrophy, Age Related Macular Degeneration

Intervention / Treatment
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* Drug: IONIS-FB-Lrx
* Drug: Placebo (sterline saline 0.9%)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Must have given written informed consent and be able to comply with study requirements Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal. Males must be surgically sterile or, if engaged in sexual relations with a female of child bearing potential, the subject must be using an acceptable contraceptive method from the time of signing the informed consent form until at least a period of 13 weeks after the last dose of Study Drug (ISIS 696844 or placebo) Well-demarcated Geographic Atrophy due to Age Related Macular Degeneration Key Exclusion Criteria: Clinically-significant abnormalities in medical history Diagnosis of primary or secondary immunodeficiencies of B lymphocyte function, splenectomy, glomerulonephritis or history of recurrent meningococcal disease Diabetes mellitus or thyroid disease unless well controlled for a period of at least 3 months Clinically-significant abnormalities in screening laboratory values Unwillingness to be administered, or history of a serious reaction to protocol required vaccines Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B History or presence of a disease other than AMD in study eye

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IONIS-FB-Lrx<br> | Drug: IONIS-FB-Lrx<br>* Single Dose of IONIS-FB-Lrx administered once weekly for weeks 1-3, and every other week or less frequently until week 70<br>|
| Placebo Comparator: Placebo (sterile saline 0.9%)<br> | Drug: Placebo (sterline saline 0.9%)<br>* Calculated volume to match active comparator. Administered subcutaneously weekly for weeks 1-3, and every other week or less frequently until week 70<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of IONIS-FB-Lrx | The Efficacy of IONIS-FB-Lrx will be measured by the percent change in plasma complement factor B level | Up to 74 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events that are related to treatment with IONIS-FB-Lrx | The safety and tolerability of IONIS-FB-Lrx will be assessed by determining the incidence and severity of adverse events that are related to treatment with IONIS-FB-Lrx | Up to 86 weeks | 
| Proportion of patients in each treatment group achieving a >50% reduction of plasma complement factor B | Proportion of patients in each treatment group achieving a >50% reduction of plasma complement factor B from Baseline to Post-Treatment | Up to 74 weeks | 
| Effect of IONIS-FB-Lrx on the rate of change of the area of GA secondary to AMD | Effect of IONIS-FB-Lrx on the rate of change of the area of GA secondary to AMD as measured by Fundus Autofluorescence from Baseline to Post-Treatment | Up to 74 weeks | 
| Effect of factor B reduction on other components of the complement pathways in AMD patients | Effect of factor B reduction on other components of the complement pathways such as AH50, CH50 and Bb in AMD patients from Baseline to Post-Treatment | Up to 74 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Geographic Atrophy, Age Related Macular Degeneration, IONIS-FB-Lrx, Complement Factor B