Clinical trial NCT04005352: Study to Assess the Efficacy and Safety of Brolucizumab 6mg Compared to Aflibercept 2 mg in a Treat-to-control Regimen (TALON)
Official title: A 64-week, Two-arm, Randomized, Double-masked, Multicenter, Phase IIIb Study Assessing the Efficacy and Safety of Brolucizumab 6 mg Compared to Aflibercept 2 mg in a Treat-to-control Regimen in Patients With Neovascular Agerelated Macular Degeneration (TALON)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Age-related Macular Degeneration
Keywords: Age-related Macular Degeneration
Macular Degeneration
Wet Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
AMD
nAMD
wet AMD
RTH258
Brolucizumab
double blind
age-related macular degeneration (ARMD)
vision loss
macula damage
retina damage
dry macular degeneration
Subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-07-02
Enrollment: 734
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double arm, multi-center
Primary purpose: TREATMENT

Brief summary: This was a 64-week randomized, double-masked, multi-center, active-controlled, two-arm study in patients with neovascular age related macular degeneration (nAMD) who have not previously received anti- vascular endothelial growth factor (VEGF) treatment.

Detailed description: At the baseline Visit, subjects who met the eligibility criteria were randomized in a 1:1 ratio to receive either: -Brolucizumab 6 mg: 3 × 4-week injections and one 8-week injection, followed by Treat-to- Control treatment from Week 16 up to Week 60/62

-Aflibercept 2 mg: 3 × 4-week injections and one 8-week injection, followed by Treat-to-Control treatment from Week 16 up to Week 60/62.

For all subjects, the last potential study treatment was at the Week 60 visit (or at the Week 62 visit for subjects whose actual treatment interval would require a treatment at Week 62). The initiation phase starts on Day 1 and ends on Week 16. Treat to Control regimen starts on Week 16 until end of treatment (Week 60/62).

In both treatment arms, treatment intervals after the initiation phase were either 8 weeks, 12 weeks, or 16 weeks. Per the original protocol, if it was determined that a patient required more frequent injections than q8w, he/she would be moved to a q4w treatment interval. However, this option was removed per Protocol amendment 02, after which, dosing intervals shorter than q8w were not permitted.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent must be obtained prior to participation in the study
* Male or female patients ≥ 50 years of age at screening who are treatment naive
* Active choroidal neovascularization (CNV) secondary to AMD that affects the central subfield, including retinal angiomatous proliferation (RAP) with a CNV component, confirmed by presence of active leakage from CNV seen by fluorescein angiography and sequellae of CNV, e.g. pigment epithelial detachment (PED), subretinal or sub-retinal pigment epithelium (sub-RPE) hemorrhage, blocked fluorescence, macular edema (study eye)
* Presence of intraretinal fluid (IRF) or subretinal fluid (SRF) that affects the central subfield, as seen by Spectral Domain Optical Coherence Tomography (SD-OCT) (study eye)
* Best-corrected visual acuity (BCVA) score between 83 and 38 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at both screening and baseline visit (study eye)

Exclusion Criteria:

* Ocular conditions/disorders at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require planned medical or surgical intervention during the first 12-month study period, structural damage of the fovea, atrophy or fibrosis at the center of the fovea (study eye)
* Any active intraocular or periocular infection or active intraocular inflammation, at screening or baseline (study eye)
* Uncontrolled glaucoma defined as intraocular pressure (IOP) \> 25 mmHg on medication, or according to investigator's judgment, at screening or baseline (study eye)
* Ocular treatments: previous treatment with any anti-vascular endothelial growth factor (VEGF) drugs or investigational drugs, intraocular or periocular steroids, macular laser photocoagulation, photodynamic therapy, vitreoretinal surgery, intraocular surgery (study eye)
* Stroke or myocardial infarction during the 6-month period prior to baseline
* Systemic anti-VEGF therapy at any time.

Primary outcomes:
measure: Distribution of the Last Interval With no Disease Activity up to Week 32 - Study Eye
timeFrame: Up to Week 32
measure: Average Change From Baseline at Week 28 and Week 32 in Best-corrected Visual Acuity (BCVA) - Study Eye
timeFrame: Baseline, Week 28 and Week 32
Secondary outcomes:
measure: Distribution of the Last Interval With no Disease Activity up to Week 64 - Study Eye
timeFrame: Up to Week 64
measure: Distribution of the Maximal Intervals With no Disease Activity up to Week 64 - Study Eye
timeFrame: Up to Week 64
measure: Number of Participants With no Disease Activity - Study Eye
timeFrame: Weeks 14 and 16
measure: Time From Last Loading Injection to First Visit With No Disease Activity (Weeks) - 75th Percentile - Study Eye
timeFrame: Up to Week 64
measure: Time-to-first Dry Retina - Time to the First Visit With no Intraretinal Fluid (IRF) or Subretinal Fluid (SRF) - Study Eye
timeFrame: Up to Week 64
measure: Average Change From Baseline at Week 60 and Week 64 in Best-corrected Visual Acuity (BCVA) - Study Eye
timeFrame: Baseline, Week 60 and Week 64
measure: Number of Participants With Best-corrected Visual Acuity Improvements of ≥ 15 Letters in BCVA From Baseline or Reached BCVA ≥ 84 Letters up to Week 32/64 Per Treatment Arm - Study Eye
timeFrame: Baseline, Week 32, and Week 64
measure: Number of Participants With Best-corrected Visual Acuity ≥ 69 Letters - Study Eye
timeFrame: Week 32 and Week 64
measure: Average Change From Baseline in Central Subfield Thickness (CSFT) - Study Eye
timeFrame: Baseline, Weeks 28 and 32 and at Weeks 60 and 64
measure: Number of Participants With Presence of Intraretinal Fluid and/or Subretinal Fluid in the Central Subfield - Study Eye
timeFrame: At Weeks 28, 32, 60 and 64
measure: Number of Participants With Presence of Sub-Retinal Pigment Epithelium Fluid in the Central Subfield - Study Eye
timeFrame: At Weeks 28, 32, 60 and 64
measure: Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Composite Scores - Study Eye
timeFrame: Baseline, Week 32, and Week 64
measure: Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - General Vision - Study Eye
timeFrame: Baseline, Week 32, and Week 64
measure: Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Ocular Pain - Study Eye
timeFrame: Baseline, Week 32, and Week 64
measure: Change From Baseline n Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Near Activities - Study Eye
timeFrame: Baseline, Week 32, and Week 64
measure: Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Distance Activities - Study Eye
timeFrame: Baseline, Week 32, and Week 64
measure: Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Social Functioning - Study Eye
timeFrame: Baseline, Week 32, and Week 64
measure: Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Mental Health - Study Eye
timeFrame: Baseline, Week 32, and Week 64
measure: Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Role Difficulties - Study Eye
timeFrame: Baseline, Week 32, and Week 64
measure: Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Dependency - Study Eye
timeFrame: Baseline, Week 32, and Week 64
measure: Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Driving - Study Eye
timeFrame: Baseline, Week 32, and Week 64
measure: Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Color Vision - Study Eye
timeFrame: Baseline, Week 32, and Week 64
measure: Change From Baseline in Visual Function Questionnnaire-25 (VFQ-25) - Subscale Score - Peripheral Vision - Study Eye
timeFrame: Baseline, Week 32, and Week 64
measure: Number of Participants With Treatment Emergent Ocular Adverse Events (Greater Than or Equal to 1% in Any Treatment Arm) by Preferred Term for the Study Eye
timeFrame: Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 483 days, approx. 69 weeks, 1.3 years.
measure: Number of Participants With Treatment Emergent Non-ocular Adverse Events (Greater Than or Equal to 2% in Any Treatment Arm) - Summary Table
timeFrame: Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of 483 days, approx. 69 weeks, 1.3 years.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Huntington Beach
country: United States
facility: Novartis Investigative Site
state: California
city: Loma Linda
country: United States
facility: Novartis Investigative Site
state: California
city: Riverside
country: United States
facility: Novartis Investigative Site
state: California
city: Santa Ana
country: United States
facility: Novartis Investigative Site
state: California
city: Fort Lauderdale
country: United States
facility: Novartis Investigative Site
state: Florida
city: Fort Myers
country: United States
facility: Novartis Investigative Site
state: Florida
city: Orlando
country: United States
facility: Novartis Investigative Site
state: Florida
city: Pinellas Park
country: United States
facility: Novartis Investigative Site
state: Florida
city: Winter Haven
country: United States
facility: Novartis Investigative Site
state: Florida
city: Springfield
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Indianapolis
country: United States
facility: Novartis Investigative Site
state: Indiana
city: West Des Moines
country: United States
facility: Novartis Investigative Site
state: Iowa
city: Minneapolis
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Hickory
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Portland
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Springfield
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Germantown
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Austin
country: United States
facility: Novartis Investigative Site
state: Texas
city: Bellaire
country: United States
facility: Novartis Investigative Site
state: Texas
city: Fort Worth
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: De Santa Fe
city: Caba
country: Argentina
facility: Novartis Investigative Site
city: Albury
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Hurstville
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Parramatta
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Sydney
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Southport
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Glen Waverley
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Rowville
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Nedlands
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Alken
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Brampton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Boisbriand
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Zlin
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Hradec Kralove
country: Czechia
facility: Novartis Investigative Site
state: CZE
city: Ostrava Poruba
country: Czechia
facility: Novartis Investigative Site
city: Praha 10
country: Czechia
facility: Novartis Investigative Site
city: Praha
country: Czechia
facility: Novartis Investigative Site
city: Saint Cyr sur Loire
country: France
facility: Novartis Investigative Site
state: Indre Et Loire
city: Lyon cedex 04
country: France
facility: Novartis Investigative Site
state: Rhone
city: Bordeaux
country: France
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Montauban
country: France
facility: Novartis Investigative Site
city: Nantes Cedex 1
country: France
facility: Novartis Investigative Site
city: Paris cedex 10
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Rueil Malmaison
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Duesseldorf
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Gottingen
country: Germany
facility: Novartis Investigative Site
city: Kempten
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Zerifin
country: Israel
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Palermo
country: Italy
facility: Novartis Investigative Site
state: PA
city: Perugia
country: Italy
facility: Novartis Investigative Site
state: PG
city: Novara
country: Italy
facility: Novartis Investigative Site
city: Bundang Gu
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho Gu
city: Busan
country: Korea, Republic of
facility: Novartis Investigative Site
city: Daegu
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Melaka
country: Malaysia
facility: Novartis Investigative Site
state: Melaka Malaysia
city: Batu Caves
country: Malaysia
facility: Novartis Investigative Site
state: Selangor
city: Shah Alam
country: Malaysia
facility: Novartis Investigative Site
state: Selangor
city: Hertogenbosch
country: Netherlands
facility: Novartis Investigative Site
city: Nijmegen
country: Netherlands
facility: Novartis Investigative Site
city: Coimbra
country: Portugal
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Vila Franca de Xira
country: Portugal
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluna
city: Sant Cugat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: Burjassot
country: Spain
facility: Novartis Investigative Site
state: Valencia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Cordoba
country: Spain
facility: Novartis Investigative Site
city: Zaragoza
country: Spain
facility: Novartis Investigative Site
city: Oerebro
country: Sweden
facility: Novartis Investigative Site
city: Vasteras
country: Sweden
facility: Novartis Investigative Site
city: Binningen
country: Switzerland
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Bradford
country: United Kingdom
facility: Novartis Investigative Site
state: West Yorkshire
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Rugby
country: United Kingdom
facility: Novartis Investigative Site
city: Sunderland
country: United Kingdom
facility: Novartis Investigative Site
city: Torquay
country: United Kingdom
facility: Novartis Investigative Site
city: Wolverhampton
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: