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

Neovascular Age-related Macular Degeneration Clinical Trial

— TALON Ext  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04597632
• Other study ID #: CRTH258A2303E1
• Secondary ID: 2020-002349-40
• Status: Completed
• Phase: Phase 3
• Start date: December 16, 2020
• Est. completion date: March 28, 2023

Study information

• Verified date: May 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 248
• Est. completion date: March 28, 2023
• Est. primary completion date: March 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-related Macular Degeneration
• Wet Macular Degeneration

Intervention

Drug:
• brolucizumab
brolucizumab 6 mg/0.05 mL solution for intravitreal injection

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Albury	New South Wales
Australia	Novartis Investigative Site	Glen Waverley	Victoria
Australia	Novartis Investigative Site	Hurstville	New South Wales
Australia	Novartis Investigative Site	Nedlands	Western Australia
Australia	Novartis Investigative Site	Parramatta	New South Wales
Australia	Novartis Investigative Site	Rowville	Victoria
Australia	Novartis Investigative Site	Sydney	New South Wales
Belgium	Novartis Investigative Site	Hasselt
Czechia	Novartis Investigative Site	Hradec Kralove	CZE
Czechia	Novartis Investigative Site	Praha
Czechia	Novartis Investigative Site	Praha 10
France	Novartis Investigative Site	Bordeaux
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Lyon cedex 04	Rhone
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Montauban
France	Novartis Investigative Site	Nantes Cedex 1
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris cedex 10
France	Novartis Investigative Site	Rueil Malmaison
France	Novartis Investigative Site	Saint Cyr sur Loire	Indre Et Loire
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Mainz
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Zerifin
Italy	Novartis Investigative Site	Perugia	PG
Korea, Republic of	Novartis Investigative Site	Bundang Gu	Gyeonggi Do
Korea, Republic of	Novartis Investigative Site	Busan
Korea, Republic of	Novartis Investigative Site	Daegu
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho Gu
Malaysia	Novartis Investigative Site	Batu Caves	Selangor
Malaysia	Novartis Investigative Site	Melaka	Melaka Malaysia
Malaysia	Novartis Investigative Site	Shah Alam	Selangor
Netherlands	Novartis Investigative Site	Den Bosch
Netherlands	Novartis Investigative Site	Nijmegen
Portugal	Novartis Investigative Site	Porto
Portugal	Novartis Investigative Site	Vila Franca de Xira
Spain	Novartis Investigative Site	Barcelona	Cataluna
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Burjassot	Valencia
Spain	Novartis Investigative Site	Cordoba
Spain	Novartis Investigative Site	Pamplona	Navarra
Spain	Novartis Investigative Site	Sant Cugat	Catalunya
Spain	Novartis Investigative Site	Zaragoza
Sweden	Novartis Investigative Site	Oerebro
Sweden	Novartis Investigative Site	Vasteras
Switzerland	Novartis Investigative Site	Binningen
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taoyuan
United States	Novartis Investigative Site	Fort Lauderdale	Florida
United States	Novartis Investigative Site	Germantown	Tennessee
United States	Novartis Investigative Site	Huntington Beach	California
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Czechia,  France,  Germany,  Israel,  Italy,  Korea, Republic of,  Malaysia,  Netherlands,  Portugal,  Spain,  Sweden,  Switzerland,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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.
Secondary	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.

External Links

•   Plain Language Trial Summary