An Extension Study Assessing the Efficacy and Safety of Brolucizumab in a Treat-to-Control Regimen in Patients With Neovascular Age-related Macular Degeneration Who Have Completed the CRTH258A2303 (TALON) Study

Novartis Pharmaceuticals248 enrolled

Overview

The purpose of this extension study was to evaluate the efficacy and safety of brolucizumab used in a Treat-to-Control-regimen for treatment of patients with neovascular age-related macular degeneration who have completed the CRTH258A2303 (TALON) study. The main objective was to assess brolucizumab's potential for long durability up to 20 weeks. All eligible participants were treated with brolucizumab regardless of their treatment in the TALON study. The study period was 56 weeks including post-treatment follow-up.

This was a 56-week, open-label, one-arm extension study in subjects who had completed the CRTH258A2303 (TALON) (NCT04005352) study, referred to as the core study in this document. Subjects who provided written informed consent and met all the inclusion and none of the exclusion criteria were enrolled into this extension study to receive brolucizumab 6 mg in a treat-to-control (TtC) regimen, irrespective of the treatment received in the core study. The maximum study duration for a subject was 56 weeks, including post-treatment follow-up. There were two periods in this study: * Treat-to-Control treatment period: from Baseline (Day 1) to Week 52 * Post-treatment follow-up period: from Week 52 to Week 56. All participants were treated with brolucizumab regardless of their treatment in the TALON study (brolucizumab or aflibercept). Treatment intervals were then extended by 4 weeks at a time based on the investigator's judgment of visual and/or anatomic outcomes. The treatment intervals were to have been 4 weeks at a time if disease activity recurs.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

248

Conditions

Outcomes

Primary Outcomes

Duration of the Last Interval With no Disease Activity up to Week 56 - Study Eye

Number of subjects in every 4 weeks (q4w), every 8 weeks (q8w), every 12 weeks (q12w) and every 20 weeks (q20w) intervals at last interval with no disease activity up to Week 56. Last interval with no disease activity (number of weeks): Number of subjects at 20/16/12/8/4-weeks intervals up to Week 56 for the study eye in the extension study

Time frame: Up to Week 56

Average Change in BCVA From Baseline to Week 52 and Week 56 for the Study Eye

Best-Corrected Visual Acuity (BCVA) was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual Function of the study eye was assessed using the ETDRS protocol. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. The average change in BCVA from Baseline of the extension study at Week 52 and Week 56 was estimated by an analysis of variance (ANOVA) with baseline age categories, baseline BCVA categories and treatment arm in the core study included as fixed effects. Last observation carried forward (LOCF) was used to impute missing BCVA values.

Time frame: Extension study baseline, average of Week 52 and Week 56

Secondary Outcomes

Average Change in Central Subfield Thickness (CSFT) From Baseline to Week 52 and Week 56 - Study Eye

Central Subfield Thickness (μm): Analysis of Variance (ANOVA) results for the average change from extension study Baseline at Week 52 and Week 56 for the study eye in the extension study by core study treatment arm. Central Subfield Thickness was assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.

Time frame: Extension study baseline, average of Week 52 and Week 56

Number (%) of Subjects With Presence of IRF and/or SRF, and Sub-RPE Fluid in the Study Eye at Week 52 and Week 56 Overall and by Core Study Treatment Arm

Intraretinal Fluid (IRF) and Subretinal Fluid (SRF) status in the central subfield as assessed by Spectral Domain Ocular Coherence Tomography (SD-OCT): Number (%) of subjects with presence of IRF and/or SRF, and sub-Retinal Pigment Epithelium (RPE) fluid in the study eye at Week 52 and Week 56 overall and by core study treatment arm

Time frame: Weeks 52 and 56

Last Interval With no Disease Activity (Number of Weeks): Number (%) of Subjects at 20/16/12/8/4-weeks Intervals up to Week 56 for the Study Eye in the Extension Study by Core Study Randomized Treatment Arm

Duration of the last interval with no disease activity up to Week 52 by core study treatment arm.

Time frame: up to Week 56

Maximal Interval With no Disease Activity (Number of Weeks): Number (%) of Subjects at 20/16/12/8/4-weeks Intervals up to Week 56 for the Study Eye in the Extension Study

Duration of the maximal intervals with no disease activity up to Week 52 by core study treatment arm.

Time frame: up to Week 56

Number (%) of Subjects With Change in Duration of Last Interval With no Disease Activity Between Baseline of the Extension Study and Week 56 by Core Study Treatment Arm

Change in last interval with no disease activity

Time frame: Extension study baseline, up to Week 56

Treatment-emergent Ocular Adverse Events (Greater Than or Equal to 1.0%) by Preferred Term for the Study Eye

An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.

Time frame: Adverse events are reported from the first dose of study-drug until the end of treatment at week 52, plus 4 weeks safety follow-up, for a maximum timeframe of approximately 56 weeks.

Treatment-emergent Non-ocular Adverse Events (Greater Than or Equal to 2%) by Preferred Term