NCT04597632: TALON Ext

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

Completed Phase 3 Results posted Last updated 9 October 2024

What this trial tests

Phase 3 trial testing brolucizumab in Neovascular Age-related Macular Degeneration in 248 participants. Completed in 28 March 2023.

Timeline

16 December 2020

Primary endpoint
28 March 2023

28 March 2023

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	248
Start date	16 December 2020
Primary completion	28 March 2023
Estimated completion	28 March 2023
Sites	60 locations across France, Italy, Netherlands, Malaysia, Belgium, Sweden, Taiwan, Germany

Drugs / interventions tested

• brolucizumab (BROLUCIZUMAB) — full drug profile →

Conditions studied

• Neovascular Age-related Macular Degeneration — all drugs for Neovascular Age-related Macular Degeneration →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

50 and older, any sex, with Neovascular Age-related Macular Degeneration. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

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

20 weeks

Group	Value	95% CI
Brolucizumab 6 mg	68

16 weeks

Group	Value	95% CI
Brolucizumab 6 mg	59

12 weeks

Group	Value	95% CI
Brolucizumab 6 mg	47

8 weeks

Group	Value	95% CI
Brolucizumab 6 mg	49

4 weeks

Group	Value	95% CI
Brolucizumab 6 mg	14

Average Change in BCVA From Baseline to Week 52 and Week 56 for the Study Eye Primary · Extension study baseline, average of Week 52 and Week 56

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

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	-1.8	± 8.29
Aflibercept 2 mg (Core Study)	-2.9	± 7.33
Brolucizumab 6 mg (Extension Study Total)	-2.3	± 7.88

Average Change in Central Subfield Thickness (CSFT) From Baseline to Week 52 and Week 56 - Study Eye Secondary · Extension study baseline, average of Week 52 and Week 56

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.

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	5.9	± 24.43
Aflibercept 2 mg (Core Study)	-14.1	± 60.67
Brolucizumab 6 mg (Extension Study Total)	-3.3	± 45.83

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 Secondary · Weeks 52 and 56

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

Week 52 IRF assessment - Present (n=103,90,193)

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	10
Aflibercept 2 mg (Core Study)	14
Brolucizumab 6 mg (Extension Study Total)	24

Week 52 IRF assessment - Absent (n=103,90,193)

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	93
Aflibercept 2 mg (Core Study)	76
Brolucizumab 6 mg (Extension Study Total)	169

Week 52 SRF assessment - Present (n=103,90,193)

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	14
Aflibercept 2 mg (Core Study)	9
Brolucizumab 6 mg (Extension Study Total)	23

Week 52 SRF assessment - Absent (n=103,90,193)

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	89
Aflibercept 2 mg (Core Study)	81
Brolucizumab 6 mg (Extension Study Total)	170

Week 52 Sub-RPE fluid - Present (n=103,90,193)

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	52
Aflibercept 2 mg (Core Study)	44
Brolucizumab 6 mg (Extension Study Total)	96

Week 52 Sub-RPE fluid - Absent (n=103,90,193)

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	51
Aflibercept 2 mg (Core Study)	46
Brolucizumab 6 mg (Extension Study Total)	97

Week 52 IRF and/or SRF - Present (n=103,90,193)

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	23
Aflibercept 2 mg (Core Study)	22
Brolucizumab 6 mg (Extension Study Total)	45

Week 52 IRF and/or SRF - Absent (n=103,90,193)

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	102
Aflibercept 2 mg (Core Study)	89
Brolucizumab 6 mg (Extension Study Total)	191

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 Secondary · up to Week 56

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

20 Weeks

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	49
Aflibercept 2 mg (Core Study)	19

16 Weeks

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	29
Aflibercept 2 mg (Core Study)	30

12 Weeks

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	21
Aflibercept 2 mg (Core Study)	26

8 Weeks

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	23
Aflibercept 2 mg (Core Study)	26

4 Weeks

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	8
Aflibercept 2 mg (Core Study)	6

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 Secondary · up to Week 56

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

20 Weeks

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	54
Aflibercept 2 mg (Core Study)	20

16 Weeks

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	28
Aflibercept 2 mg (Core Study)	31

12 Weeks

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	23
Aflibercept 2 mg (Core Study)	34

8 Weeks

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	22
Aflibercept 2 mg (Core Study)	18

4 Weeks

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	3
Aflibercept 2 mg (Core Study)	4

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 Secondary · Extension study baseline, up to Week 56

Change in last interval with no disease activity

16 Weeks

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	0
Aflibercept 2 mg (Core Study)	2

12 Weeks

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	8
Aflibercept 2 mg (Core Study)	5

8 Weeks

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	21
Aflibercept 2 mg (Core Study)	32

4 Weeks

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	49
Aflibercept 2 mg (Core Study)	28

0 Weeks

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	41
Aflibercept 2 mg (Core Study)	31

- 4 Weeks

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	8
Aflibercept 2 mg (Core Study)	7

-8 Weeks

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	2
Aflibercept 2 mg (Core Study)	2

-12 Weeks

Group	Value	95% CI
Brolucizumab 6 mg (Core Study)	1
Aflibercept 2 mg (Core Study)	0

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

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.

Number of subjects with at least one AE

Group	Value	95% CI
Brolucizumab 6 mg	63

Cataract

Group	Value	95% CI
Brolucizumab 6 mg	9

Eye pain

Group	Value	95% CI
Brolucizumab 6 mg	6

Visual acuity reduced

Group	Value	95% CI
Brolucizumab 6 mg	6

Intraocular pressure increased

Group	Value	95% CI
Brolucizumab 6 mg	5

Retinal haemorrhage

Group	Value	95% CI
Brolucizumab 6 mg	4

Ocular discomfort

Group	Value	95% CI
Brolucizumab 6 mg	3

Vitreous floaters

Group	Value	95% CI
Brolucizumab 6 mg	3

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

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.

Number of subjects with at least one AE

Group	Value	95% CI
Brolucizumab 6 mg	82

COVID-19

Group	Value	95% CI
Brolucizumab 6 mg	10

Nasopharyngitis

Group	Value	95% CI
Brolucizumab 6 mg	8

Fall

Group	Value	95% CI
Brolucizumab 6 mg	7

Basal cell carcinoma

Group	Value	95% CI
Brolucizumab 6 mg	5

All Collected Deaths Secondary · On-treatment death reporting - from first dose until 30 days after last dose for a maximum timeframe of approximately 56 weeks. Post-treatment death reporting - greater than 30 days after the last dose of study drug.

On treatment death monitoring occurred after the first dose of study drug in the extension study until 30 days after the last administration of study drug for a maximum timeframe of approximately 56 weeks. Post-treatment death monitoring occurred greater than 30 days after the last administration of study drug.

On-treatment Deaths

Group	Value	95% CI
Brolucizumab 6 mg	0

Post-treatment Deaths

Group	Value	95% CI
Brolucizumab 6 mg	1

Total Deaths

Group	Value	95% CI
Brolucizumab 6 mg	1

Adverse events — posted to ClinicalTrials.gov

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.. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Brolucizumab 6mg

Serious: 26/248 (10%)

Deaths: 1/248

Serious adverse events (31 terms)

Reaction	System	Brolucizumab 6mg
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Atrial fibrillation	Cardiac disorders	—
Fall	Injury, poisoning and procedural complications	—
Retinal detachment - Fellow eye	Eye disorders	—
Retinal occlusive vasculitis - Study eye	Eye disorders	—
Uveitis - Study eye	Eye disorders	—
Vitreal cells - Fellow eye	Eye disorders	—
Vitreal cells - Study eye	Eye disorders	—
Inguinal hernia	Gastrointestinal disorders	—
Pneumonia	Infections and infestations	—
Pyelonephritis acute	Infections and infestations	—
Urinary tract infection	Infections and infestations	—
Whipple's disease	Infections and infestations	—
Contusion	Injury, poisoning and procedural complications	—
Lower limb fracture	Injury, poisoning and procedural complications	—
Meniscus injury	Injury, poisoning and procedural complications	—
Procedural vomiting	Injury, poisoning and procedural complications	—
Rib fracture	Injury, poisoning and procedural complications	—
Spinal compression fracture	Injury, poisoning and procedural complications	—
Chondropathy	Musculoskeletal and connective tissue disorders	—
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Lung neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Ischaemic stroke	Nervous system disorders	—

Other adverse events (9 terms — click to expand)

Reaction	System	Brolucizumab 6mg
Neovascular age-related macular degeneration - Fellow eye	Eye disorders	—
COVID-19	Infections and infestations	—
Cataract - Study eye	Eye disorders	—
Nasopharyngitis	Infections and infestations	—
Cataract - Fellow eye	Eye disorders	—
Fall	Injury, poisoning and procedural complications	—
Eye pain - Study eye	Eye disorders	—
Visual acuity reduced - Study eye	Eye disorders	—
Intraocular pressure increased - Study eye	Investigations	—

Most-reported serious reactions: Basal cell carcinoma, Atrial fibrillation, Fall, Retinal detachment - Fellow eye, Retinal occlusive vasculitis - Study eye, Uveitis - Study eye, Vitreal cells - Fellow eye, Vitreal cells - Study eye.

Data from ClinicalTrials.gov NCT04597632 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.