Trial Outcomes & Findings for Efficacy of Ranibizumab Prn Treatment Compared to Aflibercept Bimonthly Intravitreal Injections on Retinal Thickness Stability in Patients With Wet AMD (NCT NCT01958918)

NCT ID: NCT01958918

Last Updated: 2019-03-21

Results Overview

The thickness of the retina was measured by Spectral Domain Optical Coherence Topography (SD-OCT). The mean of the absolute values of the CSRT difference between Month 3 and 4, Month 4 and 5, and Month 5 and 6 was calculated (ie, CSRT fluctuation). A lower average CSRT fluctuation demonstrates greater retinal stability. One eye (study eye) contributed to the analysis.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

712 participants

Primary outcome timeframe

Month 3, Month 4, Month 5, Month 6

Results posted on

2019-03-21

Participant Flow

Patients were recruited from 6 sites in Austria, 2 sites in Belgium, 2 sites in Denmark and 5 sites from France.

This reporting group included all patients randomized to one of the treatment arms (Randomized Set) The Full Analysis Set (FAS) consisted of all patients who received at least one application of study treatment and had at least one post-baseline assessment for SD-OCT.

Participant milestones

Participant milestones
Measure	Ranibizumab 0.5 mg intravitreal injections of ranibizumab monthly until maximum stable BCVA with retreatment based on BCVA loss and/or SD-OCT signs of wet AMD disease activity.	Aflibercept 2 mg intravitreal injections of aflibercept monthly for the first 3 months, followed by 2 mg intravitreal injections once every 2 months (current EU SmPC label)
Overall Study STARTED	356	356
Overall Study Full Analysis Set	353	354
Overall Study COMPLETED	313	314
Overall Study NOT COMPLETED	43	42

Reasons for withdrawal

Reasons for withdrawal
Measure	Ranibizumab 0.5 mg intravitreal injections of ranibizumab monthly until maximum stable BCVA with retreatment based on BCVA loss and/or SD-OCT signs of wet AMD disease activity.	Aflibercept 2 mg intravitreal injections of aflibercept monthly for the first 3 months, followed by 2 mg intravitreal injections once every 2 months (current EU SmPC label)
Overall Study Death	1	3
Overall Study Lost to Follow-up	4	7
Overall Study Withdrawal by Subject	13	8
Overall Study Lack of Efficacy	13	10
Overall Study Adverse Event	12	12
Overall Study administrative problems	0	2

Baseline Characteristics

FAS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ranibizumab n=353 Participants 0.5 mg intravitreal injections of ranibizumab monthly until maximum stable BCVA with retreatment based on BCVA loss and/or SD-OCT signs of wet AMD disease activity.	Aflibercept n=354 Participants 2 mg intravitreal injections of aflibercept monthly for the first 3 months, followed by 2 mg intravitreal injections once every 2 months (current EU SmPC label)	Total n=707 Participants Total of all reporting groups
Age, Continuous	77.3 years STANDARD_DEVIATION 7.53 • n=5 Participants	78.0 years STANDARD_DEVIATION 7.21 • n=7 Participants	77.7 years STANDARD_DEVIATION 7.38 • n=5 Participants
Sex: Female, Male Female	210 Participants n=5 Participants	218 Participants n=7 Participants	428 Participants n=5 Participants
Sex: Female, Male Male	143 Participants n=5 Participants	136 Participants n=7 Participants	279 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	350 Participants n=5 Participants • FAS	352 Participants n=7 Participants • FAS	702 Participants n=5 Participants • FAS
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants • FAS	0 Participants n=7 Participants • FAS	1 Participants n=5 Participants • FAS
Race/Ethnicity, Customized Other	2 Participants n=5 Participants • FAS	2 Participants n=7 Participants • FAS	4 Participants n=5 Participants • FAS

PRIMARY outcome

Timeframe: Month 3, Month 4, Month 5, Month 6

Population: FAS. Number analyzed is the number of patients with a measurement

Outcome measures

Outcome measures
Measure	Ranibizumab n=345 Participants 0.5 mg intravitreal injections of ranibizumab monthly until maximum stable BCVA with retreatment based on BCVA loss and/or SD-OCT signs of wet AMD disease activity.	Aflibercept n=340 Participants 2 mg intravitreal injections of aflibercept monthly for the first 3 months, followed by 2 mg intravitreal injections once every 2 months (current EU SmPC label)
Mean of the Absolute Values of CSRT Difference Month 3 to Month 6	25.16 micrometers Standard Error 2.584	29.28 micrometers Standard Error 2.620

SECONDARY outcome

Timeframe: Month 12

Population: FAS with measurement at visit Month 12. No statistical analysis was performed.

Visual acuity was assessed in a sitting position with refraction using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters. A higher score indicates better visual acuity. ETDRS scale ranges from 0-100 letters. A score of 65 to 70 letters represents a low to moderate visual acuity

Outcome measures

Outcome measures
Measure	Ranibizumab n=313 Participants 0.5 mg intravitreal injections of ranibizumab monthly until maximum stable BCVA with retreatment based on BCVA loss and/or SD-OCT signs of wet AMD disease activity.	Aflibercept n=312 Participants 2 mg intravitreal injections of aflibercept monthly for the first 3 months, followed by 2 mg intravitreal injections once every 2 months (current EU SmPC label)
Total Best Corrected Visual Acuity (BCVA) Score Measured in ETDRS Letters at Month 12	66.4 letters Standard Deviation 18.10	68 letters Standard Deviation 17.62

SECONDARY outcome

Timeframe: Month 12

Population: FAS with measurement at Month 12. No statistical analysis was performed.

Number of incorrectly read words (IREST) was assessed using International Reading Speed Texts (IResT) and measured in words per minute.

Outcome measures

Outcome measures
Measure	Ranibizumab n=253 Participants 0.5 mg intravitreal injections of ranibizumab monthly until maximum stable BCVA with retreatment based on BCVA loss and/or SD-OCT signs of wet AMD disease activity.	Aflibercept n=251 Participants 2 mg intravitreal injections of aflibercept monthly for the first 3 months, followed by 2 mg intravitreal injections once every 2 months (current EU SmPC label)
IREST at Month 12	5.7 incorrect words per minute Standard Deviation 21.19	6.1 incorrect words per minute Standard Deviation 21.86

SECONDARY outcome

Timeframe: Month 12

Population: FAS with measurement at Month 12. No statistical analysis was performed.

Vision-related quality of life was assessed by the patient using the National Eye Institute Visual Function Questionnaire. The scores of 12 subscales (general health, general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision, and peripheral vision) were added together for a total (composite) score, which ranged from 0 to 100. A higher score indicates poorer function.

Outcome measures

Outcome measures
Measure	Ranibizumab n=305 Participants 0.5 mg intravitreal injections of ranibizumab monthly until maximum stable BCVA with retreatment based on BCVA loss and/or SD-OCT signs of wet AMD disease activity.	Aflibercept n=297 Participants 2 mg intravitreal injections of aflibercept monthly for the first 3 months, followed by 2 mg intravitreal injections once every 2 months (current EU SmPC label)
National Eye Institute Visual Functioning Questionnaire Composite Score (VFQ-25) at Month 12	80.0 units on a scale Standard Deviation 14.43	79.1 units on a scale Standard Deviation 14.95

SECONDARY outcome

Timeframe: Month 3 to Month 6, Month 12

Population: Full Analysis Set with measure. No statistical analysis was performed.

Correlation coefficient calculated based on Pearson's correlation between each corresponding parameter and CSRT stability.

Outcome measures

Outcome measures
Measure	Ranibizumab n=353 Participants 0.5 mg intravitreal injections of ranibizumab monthly until maximum stable BCVA with retreatment based on BCVA loss and/or SD-OCT signs of wet AMD disease activity.	Aflibercept n=354 Participants 2 mg intravitreal injections of aflibercept monthly for the first 3 months, followed by 2 mg intravitreal injections once every 2 months (current EU SmPC label)
Correlations Between CSRT Fluctuation (Month 3 to 6) and Functional Outcomes at Month 12 (Full Analysis Set) Total BCVA Score	-0.2194 correlation coefficient	0.0155 correlation coefficient
Correlations Between CSRT Fluctuation (Month 3 to 6) and Functional Outcomes at Month 12 (Full Analysis Set) IREST reading speed (words/minute)	0.0889 correlation coefficient	0.0450 correlation coefficient
Correlations Between CSRT Fluctuation (Month 3 to 6) and Functional Outcomes at Month 12 (Full Analysis Set) VFQ-25 composite score	0.1064 correlation coefficient	0.0847 correlation coefficient

Adverse Events

Ranibizumab 0.5 mg

Serious events: 67 serious events

Other events: 156 other events

Deaths: 1 deaths

Aflibercept 2 mg

Serious events: 74 serious events

Other events: 156 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Ranibizumab 0.5 mg n=356 participants at risk Ranibizumab 0.5 mg	Aflibercept 2 mg n=356 participants at risk Aflibercept 2 mg
Eye disorders Conjunctival haemorrhage	11.5% 41/356 • 1 year AE additional description	7.9% 28/356 • 1 year AE additional description
Eye disorders Dry eye	5.1% 18/356 • 1 year AE additional description	3.1% 11/356 • 1 year AE additional description
Eye disorders Eye pain	6.7% 24/356 • 1 year AE additional description	6.5% 23/356 • 1 year AE additional description
Eye disorders Ocular hyperaemia	5.6% 20/356 • 1 year AE additional description	2.5% 9/356 • 1 year AE additional description
Eye disorders Visual acuity reduced	5.3% 19/356 • 1 year AE additional description	7.0% 25/356 • 1 year AE additional description
Infections and infestations Influenza	6.2% 22/356 • 1 year AE additional description	3.4% 12/356 • 1 year AE additional description
Infections and infestations Viral upper respiratory tract infection	12.1% 43/356 • 1 year AE additional description	17.4% 62/356 • 1 year AE additional description
Investigations Intraocular pressure increased	8.1% 29/356 • 1 year AE additional description	6.5% 23/356 • 1 year AE additional description
Musculoskeletal and connective tissue disorders Back pain	3.4% 12/356 • 1 year AE additional description	5.9% 21/356 • 1 year AE additional description
Vascular disorders Hypertension	4.5% 16/356 • 1 year AE additional description	5.9% 21/356 • 1 year AE additional description

Additional Information

Study Director

Novartis Pharma AG

Phone: +41613241111

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and condition of Novartis'agreements with its investigator may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER