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 (TALON Ext)

A 56-week Phase IIIb/IV, Open-label, One-arm Extension Study to Assess the Efficacy and Safety of Brolucizumab 6 mg in a Treat-to-Control Regimen With Maximum Treatment Intervals up to 20 Weeks for the Treatment of Patients With Neovascular Age-related Macular Degeneration Who Have Completed the CRTH258A2303 (TALON) Study

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.

Study Overview

• Status: Completed
• Conditions: Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Drug: brolucizumab

Detailed Description

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
• Enrollment (Actual): 248
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Albury, New South Wales, Australia, 2640
      • Novartis Investigative Site
    • Hurstville, New South Wales, Australia, 2220
      • Novartis Investigative Site
    • Parramatta, New South Wales, Australia, 2150
      • Novartis Investigative Site
    • Sydney, New South Wales, Australia, 2000
      • Novartis Investigative Site
  • Victoria
    • Glen Waverley, Victoria, Australia, 3150
      • Novartis Investigative Site
    • Rowville, Victoria, Australia, 3179
      • Novartis Investigative Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Novartis Investigative Site
• Belgium
  • Hasselt, Belgium, 3500
    • Novartis Investigative Site
• Czechia
  • Praha, Czechia, 12808
    • Novartis Investigative Site
  • Praha 10, Czechia, 100 34
    • Novartis Investigative Site
  • CZE
    • Hradec Kralove, CZE, Czechia, 500 05
      • Novartis Investigative Site
• France
  • Bordeaux, France, 33000
    • Novartis Investigative Site
  • Creteil, France, 94000
    • Novartis Investigative Site
  • Marseille, France, F 13008
    • Novartis Investigative Site
  • Montauban, France, 82000
    • Novartis Investigative Site
  • Nantes Cedex 1, France, 44093
    • Novartis Investigative Site
  • Paris, France, 75015
    • Novartis Investigative Site
  • Paris cedex 10, France, 75010
    • Novartis Investigative Site
  • Rueil Malmaison, France, 92500
    • Novartis Investigative Site
  • Indre Et Loire
    • Saint Cyr sur Loire, Indre Et Loire, France, 37540
      • Novartis Investigative Site
  • Rhone
    • Lyon cedex 04, Rhone, France, 69317
      • Novartis Investigative Site
• Germany
  • Freiburg, Germany, 79106
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
• Israel
  • Jerusalem, Israel, 9112001
    • Novartis Investigative Site
  • Ramat Gan, Israel, 52621
    • Novartis Investigative Site
  • Zerifin, Israel, 6093000
    • Novartis Investigative Site
• Italy
  • PG
    • Perugia, PG, Italy, 06100
      • Novartis Investigative Site
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Novartis Investigative Site
  • Daegu, Korea, Republic of, 705703
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 05505
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 07301
    • Novartis Investigative Site
  • Gyeonggi Do
    • Bundang Gu, Gyeonggi Do, Korea, Republic of, 13620
      • Novartis Investigative Site
  • Seocho Gu
    • Seoul, Seocho Gu, Korea, Republic of, 06591
      • Novartis Investigative Site
• Malaysia
  • Melaka Malaysia
    • Melaka, Melaka Malaysia, Malaysia, 75000
      • Novartis Investigative Site
  • Selangor
    • Batu Caves, Selangor, Malaysia, 68100
      • Novartis Investigative Site
    • Shah Alam, Selangor, Malaysia, 40000
      • Novartis Investigative Site
• Netherlands
  • Den Bosch, Netherlands, 5223 GZ
    • Novartis Investigative Site
  • Nijmegen, Netherlands, 6525 EX
    • Novartis Investigative Site
• Portugal
  • Porto, Portugal, 4099-001
    • Novartis Investigative Site
  • Vila Franca de Xira, Portugal, 2600-009
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08025
    • Novartis Investigative Site
  • Barcelona, Spain, 08024
    • Novartis Investigative Site
  • Cordoba, Spain, 14012
    • Novartis Investigative Site
  • Zaragoza, Spain, 50009
    • Novartis Investigative Site
  • Cataluna
    • Barcelona, Cataluna, Spain, 08022
      • Novartis Investigative Site
  • Catalunya
    • Sant Cugat, Catalunya, Spain, 08190
      • Novartis Investigative Site
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Novartis Investigative Site
  • Valencia
    • Burjassot, Valencia, Spain, 46100
      • Novartis Investigative Site
• Sweden
  • Oerebro, Sweden, 701 85
    • Novartis Investigative Site
  • Vasteras, Sweden, 72189
    • Novartis Investigative Site
• Switzerland
  • Binningen, Switzerland, 4102
    • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 11217
    • Novartis Investigative Site
  • Taipei, Taiwan, 103616
    • Novartis Investigative Site
  • Taoyuan, Taiwan, 33305
    • Novartis Investigative Site
• United States
  • California
    • Huntington Beach, California, United States, 92647
      • Novartis Investigative Site
  • Florida
    • Fort Lauderdale, Florida, United States, 33309
      • Novartis Investigative Site
  • Indiana
    • Indianapolis, Indiana, United States, 46280
      • Novartis Investigative Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55435
      • Novartis Investigative Site
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed informed consent
2. Successfully completed TALON core study at week 64 (End of Study)

Exclusion Criteria:

1. Medical condition or personal circumstance which precludes study participation or compliance with study procedures, as assessed by the Investigator
2. Discontinued study treatment in the core study
3. Anti-VEGF treatment is futile in the study eye, in the Investigator's opinion.
4. Pregnant or nursing (lactating) women
5. Women of child-bearing potential not using highly effective methods of contraception

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: brolucizumab 6 mg; Participants received brolucizumab 6 mg/0.05 mL solution by intravitreal injection in a Treat-to-Control regimen with injection intervals from 4 up to 20 weeks. Intervals could have changed in steps of 4 weeks at a time per investigators' decisions determined by the disease activity.	Drug: brolucizumab; brolucizumab 6 mg/0.05 mL solution for intravitreal injection; Other Names: RTH258

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Extension study baseline, average of Week 52 and Week 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	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.	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.	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	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.	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	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.	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.

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2020
• Primary Completion (Actual): March 28, 2023
• Study Completion (Actual): March 28, 2023

Study Registration Dates

• First Submitted: October 1, 2020
• First Submitted That Met QC Criteria: October 15, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: anti-VEGF; Macular degeneration; neovascular age-related macular degeneration; choroidal neovascularization; vision loss; wet AMD; individualized treatment; wet age-related macular degeneration; wet macular degeneration; age-related macular degeneration (ARMD); macula damage; retina damage; dry macular degeneration; Subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration
• Other Study ID Numbers: CRTH258A2303E1; 2020-002349-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No