Trial · NCT02307682

Efficacy and Safety of RTH258 Versus Aflibercept - Study 1

NCT02307682, Phase 3, Completed, Alcon Research; results first posted 2019-10-31

3 sourcestrials-2026-11-12-0.5.0

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ConductScience Library. Efficacy and Safety of RTH258 Versus Aflibercept - Study 1. Trials, record NCT02307682. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT02307682

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: Efficacy and Safety of RTH258 Versus Aflibercept - Study 1
NCT number: NCT02307682
Status: Completed
Phases: Phase 3
Enrollment: 1,775 participants, actual
Lead sponsor: Alcon Research
Conditions: Neovascular Age-Related Macular Degeneration, Choroidal Neovascularization
Interventions: Brolucizumab ophthalmic solution, Aflibercept ophthalmic solution
First posted: 2014-12-04
Last updated: 2025-01-16
Results first posted: 2019-10-31

Source ClinicalTrials.gov

Registered outcomes33

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Change From Baseline in Best Corrected Visual Acuity (BCVA) (Letters Read) at Week 48 - Study Eye	Baseline, Week 48	BCVA (with spectacles or other visual corrective devices) was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.
Secondary	Average Change From Baseline in BCVA (Letters Read) Over the Period Week 36 Through Week 48 - Study Eye	Baseline, Weeks 36, 40, 44, 48	BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. For each subject, this endpoint was defined as the average of the changes from baseline to Weeks 36, 40, 44, and 48. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.
Secondary	Proportion of Subjects With Positive q12 (Every 12 Weeks) Treatment Status at Week 48	Weeks 16, 20, 28, 32, 40, 44, 48	Positive q12 treatment status was defined as IVT injections per planned dosing regimen (one injection every 12 weeks "q12w", after the initial three loading injections every 4 weeks "q4w"). A disease activity assessment (DAA) was performed at pre-specified visits (Weeks 16, 20, 28, 32, 40, 44) to identify q8w (one injection every 8 weeks) need. The estimate for the proportion of subjects with a positive q12w status at Week 48 were derived from Kaplan-Meier time to event analyses for the event of first q8w need, applying event allocations (in case of lack of efficacy and/or lack of safety=efficacy/safety approach) and censoring as described in the SAP. Censored subjects were considered to be not anymore under risk for a q8 need identification at later visits. Corresponding 95% Confidence Intervals (CIs) were derived from the LOGLOG transformation. No hypothesis testing was performed. This outcome measure was pre-specified for brolucizumab 3mg and 6 mg arms only.
Secondary	Proportion of Subjects With Positive q12 Treatment Status at Week 48 Within the Subjects With no q8 (Every 8 Weeks) Treatment Need During the First q12 Cycle (Week 16, Week 20)	Weeks 16, 20, 28, 32, 40, 44, 48	Positive q12 treatment status was defined as IVT injections per planned dosing regimen (one injection every 12 weeks "q12w", after the initial three loading injections every 4 weeks "q4w"). A DAA was performed at pre-specified visits (Weeks 16, 20, 28, 32, 40, 44) to identify q8w need. The estimate for the proportion of subjects with a positive q12w status at Week 48 were derived from Kaplan-Meier time to event analyses for the event of first q8w need, applying event allocations (in case of lack of efficacy and/or lack of safety=efficacy/safety approach) and censoring as described in the SAP. Censored subjects were considered to be not anymore under risk for a q8 need identification at later visits. Corresponding 95% CIs were derived from the LOGLOG transformation. No hypothesis testing was performed. This outcome measure was pre-specified for the brolucizumab 3 mg and 6 mg arms only.
Secondary	Proportion of Subjects With Positive q12 Treatment Status up to Week 96	Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92, 96	Positive q12 treatment status was defined as IVT injections per planned dosing regimen (one injection every 12 weeks "q12w", after the initial three loading injections every 4 weeks "q4w"). A DAA was performed at pre-specified visits (Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92) to identify q8w need. The estimate for the proportion of subjects with a positive q12w status at Week 48 were derived from Kaplan-Meier time to event analyses for the event of first q8w need, applying event allocations (in case of lack of efficacy and/or lack of safety=efficacy/safety approach) and censoring as described in the SAP. Censored subjects were considered to be not anymore under risk for a q8 need identification at later visits. Corresponding 95% CIs were derived from the LOGLOG transformation. No hypothesis testing was performed. This outcome measure was pre-specified for the brolucizumab 3 mg and 6 mg arms only.
Secondary	Proportion of Subjects With Positive q12 Treatment Status at Week 96 Within the Subjects With no q8 Treatment Need During the Initial q12 Cycle (Week 16, Week 20)	Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92, 96	Positive q12 treatment status was defined as IVT injections per planned dosing regimen (one injection every 12 weeks "q12w", after the initial three loading injections every 4 weeks "q4w"). A DAA was performed at pre-specified visits (Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92) to identify q8w need. The estimate for the proportion of subjects with a positive q12w status at Week 48 were derived from Kaplan-Meier time to event analyses for the event of first q8w need, applying event allocations (in case of lack of efficacy and/or lack of safety=efficacy/safety approach) and censoring as described in the SAP. Censored subjects were considered to be not anymore under risk for a q8 need identification at later visits. Corresponding 95% CIs were derived from the LOGLOG transformation. No hypothesis testing was performed. This outcome measure was pre-specified for the brolucizumab 3 mg and 6 mg arms only.
Secondary	Change From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96	BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.
Secondary	Average Change From Baseline in BCVA (Letters Read) Over the Period Week 4 to Week 48/96 - Study Eye	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96	BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.
Secondary	Average Change From Baseline in BCVA (Letters Read) Over the Period Week 12 to Week 48/96 - Study Eye	Baseline, Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96	BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.
Secondary	Average Change From Baseline in BCVA (Letters Read) Over the Period Week 84 to Week 96 - Study Eye	Baseline, Weeks 84, 88, 92, 96	BCVA (with spectacles or other visual corrective devices) was assessed using ETDRS testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.

1 to 10 of 33Source ClinicalTrials.gov

See all 33 registered outcomes

Outcomes33

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Change From Baseline in Best Corrected Visual Acuity (BCVA) (Letters Read) at Week 48 - Study Eye	Baseline, Week 48	Full Analysis Set (FAS) - Last Observation Carried Forward (LOCF)	letters	MEAN
SECONDARY	Average Change From Baseline in BCVA (Letters Read) Over the Period Week 36 Through Week 48 - Study Eye	Baseline, Weeks 36, 40, 44, 48	FAS - LOCF	letters	MEAN
SECONDARY	Proportion of Subjects With Positive q12 (Every 12 Weeks) Treatment Status at Week 48	Weeks 16, 20, 28, 32, 40, 44, 48	FAS - efficacy/safety approach	proportion of subjects	NUMBER
SECONDARY	Proportion of Subjects With Positive q12 Treatment Status at Week 48 Within the Subjects With no q8 (Every 8 Weeks) Treatment Need During the First q12 Cycle (Week 16, Week 20)	Weeks 16, 20, 28, 32, 40, 44, 48	FAS - efficacy/safety approach	proportion of subjects	NUMBER
SECONDARY	Proportion of Subjects With Positive q12 Treatment Status up to Week 96	Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92, 96	FAS - efficacy/safety approach	proportion of subjects	NUMBER
SECONDARY	Proportion of Subjects With Positive q12 Treatment Status at Week 96 Within the Subjects With no q8 Treatment Need During the Initial q12 Cycle (Week 16, Week 20)	Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92, 96	FAS - efficacy/safety approach	proportion of subjects	NUMBER
SECONDARY	Change From Baseline in BCVA (Letters Read) at Each Post-baseline Visit - Study Eye	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96	FAS - LOCF	letters	MEAN
SECONDARY	Average Change From Baseline in BCVA (Letters Read) Over the Period Week 4 to Week 48/96 - Study Eye	Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96	FAS - LOCF	letters	MEAN
SECONDARY	Average Change From Baseline in BCVA (Letters Read) Over the Period Week 12 to Week 48/96 - Study Eye	Baseline, Weeks 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96	FAS - LOCF	letters	MEAN
SECONDARY	Average Change From Baseline in BCVA (Letters Read) Over the Period Week 84 to Week 96 - Study Eye	Baseline, Weeks 84, 88, 92, 96	FAS - LOCF	letters	MEAN

1 to 10 of 33Source ClinicalTrials.gov

See all 33 outcomes

Results by group1,112

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Value	Spread	Units
Change From Baseline in Best Corrected Visual Acuity (BCVA) (Letters Read) at Week 48 - Study Eye	Brolucizumab 3 mg	5.9	Standard Deviation 13.49	letters
Change From Baseline in Best Corrected Visual Acuity (BCVA) (Letters Read) at Week 48 - Study Eye	Brolucizumab 6 mg	6.4	Standard Deviation 14.40	letters
Change From Baseline in Best Corrected Visual Acuity (BCVA) (Letters Read) at Week 48 - Study Eye	Aflibercept 2 mg	7.0	Standard Deviation 13.16	letters
Average Change From Baseline in BCVA (Letters Read) Over the Period Week 36 Through Week 48 - Study Eye	Brolucizumab 3 mg	6.0	Standard Deviation 13.37	letters
Average Change From Baseline in BCVA (Letters Read) Over the Period Week 36 Through Week 48 - Study Eye	Brolucizumab 6 mg	6.5	Standard Deviation 13.85	letters
Average Change From Baseline in BCVA (Letters Read) Over the Period Week 36 Through Week 48 - Study Eye	Aflibercept 2 mg	6.9	Standard Deviation 12.61	letters
Proportion of Subjects With Positive q12 (Every 12 Weeks) Treatment Status at Week 48	Brolucizumab 3 mg	0.4939	95% Confidence Interval 0.4393 to 0.5461	proportion of subjects
Proportion of Subjects With Positive q12 (Every 12 Weeks) Treatment Status at Week 48	Brolucizumab 6 mg	0.5563	95% Confidence Interval 0.5016 to 0.6075	proportion of subjects
Proportion of Subjects With Positive q12 Treatment Status at Week 48 Within the Subjects With no q8 (Every 8 Weeks) Treatment Need During the First q12 Cycle (Week 16, Week 20)	Brolucizumab 3 mg	0.8085	95% Confidence Interval 0.7454 to 0.8574	proportion of subjects
Proportion of Subjects With Positive q12 Treatment Status at Week 48 Within the Subjects With no q8 (Every 8 Weeks) Treatment Need During the First q12 Cycle (Week 16, Week 20)	Brolucizumab 6 mg	0.8539	95% Confidence Interval 0.7987 to 0.8950	proportion of subjects

1 to 10 of 1,112Source ClinicalTrials.gov

See all 1,112 results by group

Participant flow12

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	Brolucizumab 3 mg	360
Overall Study	STARTED	Brolucizumab 6 mg	361
Overall Study	STARTED	Aflibercept 2 mg	361
Overall Study	Randomized and Treated	Brolucizumab 3 mg	358
Overall Study	Randomized and Treated	Brolucizumab 6 mg	360
Overall Study	Randomized and Treated	Aflibercept 2 mg	360
Overall Study	COMPLETED	Brolucizumab 3 mg	310
Overall Study	COMPLETED	Brolucizumab 6 mg	304
Overall Study	COMPLETED	Aflibercept 2 mg	297
Overall Study	NOT COMPLETED	Brolucizumab 3 mg	50

1 to 10 of 12Source ClinicalTrials.gov

See all 12 participant flow

Adverse events813

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk
other	Cataract - Study eye	Eye disorders	Brolucizumab 3mg	18	358
other	Cataract - Study eye	Eye disorders	Brolucizumab 6mg	19	360
other	Cataract - Study eye	Eye disorders	Aflibercept 2mg	13	360
other	Conjunctival haemorrhage - Study eye	Eye disorders	Brolucizumab 3mg	39	358
other	Conjunctival haemorrhage - Study eye	Eye disorders	Brolucizumab 6mg	29	360
other	Conjunctival haemorrhage - Study eye	Eye disorders	Aflibercept 2mg	32	360
other	Dry eye - Fellow eye	Eye disorders	Brolucizumab 3mg	16	358
other	Dry eye - Fellow eye	Eye disorders	Brolucizumab 6mg	15	360
other	Dry eye - Fellow eye	Eye disorders	Aflibercept 2mg	24	360
other	Dry eye - Study eye	Eye disorders	Brolucizumab 3mg	20	358

1 to 10 of 813Source ClinicalTrials.gov

See all 813 adverse events

Adverse event totals9

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Brolucizumab 3mg	9	358
Total, all-cause mortality	Brolucizumab 6mg	8	360
Total, all-cause mortality	Aflibercept 2mg	12	360
Total, other adverse events	Brolucizumab 3mg	239	358
Total, other adverse events	Brolucizumab 6mg	228	360
Total, other adverse events	Aflibercept 2mg	228	360
Total, serious adverse events	Brolucizumab 3mg	94	358
Total, serious adverse events	Brolucizumab 6mg	95	360
Total, serious adverse events	Aflibercept 2mg	114	360

Source ClinicalTrials.gov

Papers5

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as	Source
30986442	DERIVED	PubMed
33207259	DERIVED	PubMed
34968756	DERIVED	PubMed
38360182	DERIVED	PubMed
39033924	DERIVED	PubMed

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons0

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

None in this release.

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

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