Trial Outcomes & Findings for Wet Macular Degeneration Study to Compare Ranibizumab or Bevacizumab to Aflibercept (NCT NCT01617148)

Results Overview

The mean absolute change from baseline central subfield thickness at 12 months as measured by SDOCT

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

26 participants

Primary outcome timeframe

baseline and 12 months

Results posted on

2018-07-26

Participant Flow

Participant milestones

Participant milestones
Measure	Single Group Subjects were included in the study if they met the following criteria: (1) active subfoveal choroidal neovascularization secondary to exudative Age-related Macular Degeneration (AMD) confirmed by fluorescein angiography (2) E-ETDRS vision of 25 to 80 letters (Snellen equivalent of \~20/25 to 20/320) (3) at least one prior injection of 1.25 mg bevacizumab or 0.5 mg ranibizumab (Avastin and Lucentis, respectively; Genentech Inc, South San Francisco, California, USA) within 3 months of enrollment, and (4) had an initial response on optical coherence tomography (OCT) defined as a decrease of retinal edema and/or subretinal fluid to anti-Vascular Endothelial Growth Factor (anti-VEGF) injections followed by recurrent increase in fluid on OCT (further defined as intraretinal, cystoid, subretinal fluid, or worsening pigment epithelial detachment) or the presence of a new hemorrhage on clinical examination.
Overall Study STARTED	26
Overall Study COMPLETED	26
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Wet Macular Degeneration Study to Compare Ranibizumab or Bevacizumab to Aflibercept

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Single Group n=26 Participants Subjects were included in the study if they met the following criteria: (1) active subfoveal choroidal neovascularization secondary to exudative AMD confirmed by fluorescein angiography (2) E-ETDRS vision of 25 to 80 letters (Snellen equivalent of \~20/25 to 20/320) (3) at least one prior injection of 1.25 mg bevacizumab or 0.5 mg ranibizumab (Avastin and Lucentis, respectively; Genentech Inc, South San Francisco, CA, USA) within 3 months of enrollment, and (4) had an initial response on optical coherence tomography (OCT) defined as a decrease of retinal edema and/or subretinal fluid to anti-VEGF injections followed by recurrent increase in fluid on OCT (further defined as intraretinal, cystoid, subretinal fluid, or worsening pigment epithelial detachment) or the presence of a new hemorrhage on clinical examination.
Age, Continuous	78 years STANDARD_DEVIATION 8 • n=5 Participants
Sex/Gender, Customized Unknown	26 Participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants
Length of time since diagnosis of exudative AMD	14 months STANDARD_DEVIATION 11 • n=5 Participants
Time since last injection prior to study enrollment	50 days STANDARD_DEVIATION 24 • n=5 Participants
Previous treatment Previous treatment- Bevacizumab	7 Participants n=5 Participants
Previous treatment Previous treatment- Ranibizumab	17 Participants n=5 Participants
Previous treatment Previous treatment- Bevacizumab and Ranibizumab	2 Participants n=5 Participants
Average number of treatments prior to study entry	9.62 injections STANDARD_DEVIATION 6.58 • n=5 Participants
Average number of injections during study	7.92 injections STANDARD_DEVIATION 0.27 • n=5 Participants
E-ETDRS best-corrected visual acuity (BCVA) letter score	56.42 E-ETDRS letters STANDARD_DEVIATION 17.04 • n=5 Participants
Best Corrected Visual Acuity Snellen equivalent	0.25 E-ETDRS letters n=5 Participants
Central subfield thickness	304.08 µm STANDARD_DEVIATION 75.44 • n=5 Participants

PRIMARY outcome

Timeframe: baseline and 12 months

The mean absolute change from baseline central subfield thickness at 12 months as measured by SDOCT

Outcome measures

Outcome measures
Measure	Single Group n=26 Participants Subjects were included in the study if they met the following criteria: (1) active subfoveal choroidal neovascularization secondary to exudative AMD confirmed by fluorescein angiography (2) E-ETDRS vision of 25 to 80 letters (Snellen equivalent of \~20/25 to 20/320) (3) at least one prior injection of 1.25 mg bevacizumab or 0.5 mg ranibizumab (Avastin and Lucentis, respectively; Genentech Inc, South San Francisco, CA, USA) within 3 months of enrollment, and (4) had an initial response on optical coherence tomography (OCT) defined as a decrease of retinal edema and/or subretinal fluid to anti-VEGF injections followed by recurrent increase in fluid on OCT (further defined as intraretinal, cystoid, subretinal fluid, or worsening pigment epithelial detachment) or the presence of a new hemorrhage on clinical examination.
Change in Central Subfield Thickness From Baseline at 12 Months	-50.3 µm Standard Deviation 63.9

SECONDARY outcome

Timeframe: Baseline and 12 months

The mean absolute change from baseline in best-corrected visual acuity score at 12 months as measured by Eletronic-Early Treatment in Diabetic Retinopathy Scale (E-ETDRS) protocol. There were no sub scales used. These are common methods for ophthalmology studies to report their findings. The scale provided is the Electronic-Early Treatment in Diabetic Retinopathy Scale (E-ETDRS) best corrected visual acuity scale. Values that are higher are considered better and values that are lower are considered worse. Minimum E-ETDRS was 24 E-ETDRS letters and maximum E-ETDRS was 80 E-ETDRS letters.

Outcome measures

Outcome measures
Measure	Single Group n=26 Participants Subjects were included in the study if they met the following criteria: (1) active subfoveal choroidal neovascularization secondary to exudative AMD confirmed by fluorescein angiography (2) E-ETDRS vision of 25 to 80 letters (Snellen equivalent of \~20/25 to 20/320) (3) at least one prior injection of 1.25 mg bevacizumab or 0.5 mg ranibizumab (Avastin and Lucentis, respectively; Genentech Inc, South San Francisco, CA, USA) within 3 months of enrollment, and (4) had an initial response on optical coherence tomography (OCT) defined as a decrease of retinal edema and/or subretinal fluid to anti-VEGF injections followed by recurrent increase in fluid on OCT (further defined as intraretinal, cystoid, subretinal fluid, or worsening pigment epithelial detachment) or the presence of a new hemorrhage on clinical examination.
Change in Best-corrected Visual Acuity From Baseline at 12 Months	9.2 E-ETDRS letters Standard Deviation 9.5

SECONDARY outcome

Timeframe: baseline and 12 months

Mean absolute change from baseline in macular volume at 12 months.

Outcome measures

Outcome measures
Measure	Single Group n=26 Participants Subjects were included in the study if they met the following criteria: (1) active subfoveal choroidal neovascularization secondary to exudative AMD confirmed by fluorescein angiography (2) E-ETDRS vision of 25 to 80 letters (Snellen equivalent of \~20/25 to 20/320) (3) at least one prior injection of 1.25 mg bevacizumab or 0.5 mg ranibizumab (Avastin and Lucentis, respectively; Genentech Inc, South San Francisco, CA, USA) within 3 months of enrollment, and (4) had an initial response on optical coherence tomography (OCT) defined as a decrease of retinal edema and/or subretinal fluid to anti-VEGF injections followed by recurrent increase in fluid on OCT (further defined as intraretinal, cystoid, subretinal fluid, or worsening pigment epithelial detachment) or the presence of a new hemorrhage on clinical examination.
Change in Macular Volume From Baseline at 12 Months.	-0.4 mm3 Standard Deviation 1.0

SECONDARY outcome

Timeframe: baseline and 12 months

Mean absolute change in cube average thickness as measured by SDOCT from baseline at 12 months.

Outcome measures

Outcome measures
Measure	Single Group n=26 Participants Subjects were included in the study if they met the following criteria: (1) active subfoveal choroidal neovascularization secondary to exudative AMD confirmed by fluorescein angiography (2) E-ETDRS vision of 25 to 80 letters (Snellen equivalent of \~20/25 to 20/320) (3) at least one prior injection of 1.25 mg bevacizumab or 0.5 mg ranibizumab (Avastin and Lucentis, respectively; Genentech Inc, South San Francisco, CA, USA) within 3 months of enrollment, and (4) had an initial response on optical coherence tomography (OCT) defined as a decrease of retinal edema and/or subretinal fluid to anti-VEGF injections followed by recurrent increase in fluid on OCT (further defined as intraretinal, cystoid, subretinal fluid, or worsening pigment epithelial detachment) or the presence of a new hemorrhage on clinical examination.
Change in Cube Average Thickness From Baseline at 12 Months	-11.9 µm Standard Deviation 27.6

SECONDARY outcome

Timeframe: baseline and 12 months

The percentage of patients who gained greater than 15 letters of vision from baseline to 12 months.

Outcome measures

Outcome measures
Measure	Single Group n=26 Participants Subjects were included in the study if they met the following criteria: (1) active subfoveal choroidal neovascularization secondary to exudative AMD confirmed by fluorescein angiography (2) E-ETDRS vision of 25 to 80 letters (Snellen equivalent of \~20/25 to 20/320) (3) at least one prior injection of 1.25 mg bevacizumab or 0.5 mg ranibizumab (Avastin and Lucentis, respectively; Genentech Inc, South San Francisco, CA, USA) within 3 months of enrollment, and (4) had an initial response on optical coherence tomography (OCT) defined as a decrease of retinal edema and/or subretinal fluid to anti-VEGF injections followed by recurrent increase in fluid on OCT (further defined as intraretinal, cystoid, subretinal fluid, or worsening pigment epithelial detachment) or the presence of a new hemorrhage on clinical examination.
Percentage of Patients Who Gained Greater Than 15 Letters of Vision From Baseline at 12 Months.	7 Participants

SECONDARY outcome

Timeframe: baseline and 12 months

The percentage of patients who lost greater than 15 letters of vision from baseline at 12 months.

Outcome measures

Outcome measures
Measure	Single Group n=26 Participants Subjects were included in the study if they met the following criteria: (1) active subfoveal choroidal neovascularization secondary to exudative AMD confirmed by fluorescein angiography (2) E-ETDRS vision of 25 to 80 letters (Snellen equivalent of \~20/25 to 20/320) (3) at least one prior injection of 1.25 mg bevacizumab or 0.5 mg ranibizumab (Avastin and Lucentis, respectively; Genentech Inc, South San Francisco, CA, USA) within 3 months of enrollment, and (4) had an initial response on optical coherence tomography (OCT) defined as a decrease of retinal edema and/or subretinal fluid to anti-VEGF injections followed by recurrent increase in fluid on OCT (further defined as intraretinal, cystoid, subretinal fluid, or worsening pigment epithelial detachment) or the presence of a new hemorrhage on clinical examination.
Percentage of Patients Who Lost Greater Than 15 Letters of Vision From Baseline at 12 Months	0 Participants

SECONDARY outcome

Timeframe: month 12

Percentage of subjects who had vision acuity of 20/40 or better at month 12.

Outcome measures

Outcome measures
Measure	Single Group n=26 Participants Subjects were included in the study if they met the following criteria: (1) active subfoveal choroidal neovascularization secondary to exudative AMD confirmed by fluorescein angiography (2) E-ETDRS vision of 25 to 80 letters (Snellen equivalent of \~20/25 to 20/320) (3) at least one prior injection of 1.25 mg bevacizumab or 0.5 mg ranibizumab (Avastin and Lucentis, respectively; Genentech Inc, South San Francisco, CA, USA) within 3 months of enrollment, and (4) had an initial response on optical coherence tomography (OCT) defined as a decrease of retinal edema and/or subretinal fluid to anti-VEGF injections followed by recurrent increase in fluid on OCT (further defined as intraretinal, cystoid, subretinal fluid, or worsening pigment epithelial detachment) or the presence of a new hemorrhage on clinical examination.
Percentage of Subjects Who Were 20/40 or Better at Month 12.	13 Participants

SECONDARY outcome

Timeframe: month 12

Percentage of subjects who had visual acuity of 20/200 or worse at month 12.

Outcome measures

Outcome measures
Measure	Single Group n=26 Participants Subjects were included in the study if they met the following criteria: (1) active subfoveal choroidal neovascularization secondary to exudative AMD confirmed by fluorescein angiography (2) E-ETDRS vision of 25 to 80 letters (Snellen equivalent of \~20/25 to 20/320) (3) at least one prior injection of 1.25 mg bevacizumab or 0.5 mg ranibizumab (Avastin and Lucentis, respectively; Genentech Inc, South San Francisco, CA, USA) within 3 months of enrollment, and (4) had an initial response on optical coherence tomography (OCT) defined as a decrease of retinal edema and/or subretinal fluid to anti-VEGF injections followed by recurrent increase in fluid on OCT (further defined as intraretinal, cystoid, subretinal fluid, or worsening pigment epithelial detachment) or the presence of a new hemorrhage on clinical examination.
Percentage of Subjects Who Were 20/200 or Worse at Month 12.	3 Participants

Adverse Events

Single Group

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Single Group n=26 participants at risk Subjects were included in the study if they met the following criteria: (1) active subfoveal choroidal neovascularization secondary to exudative AMD confirmed by fluorescein angiography (2) E-ETDRS vision of 25 to 80 letters (Snellen equivalent of \~20/25 to 20/320) (3) at least one prior injection of 1.25 mg bevacizumab or 0.5 mg ranibizumab (Avastin and Lucentis, respectively; Genentech Inc, South San Francisco, CA, USA) within 3 months of enrollment, and (4) had an initial response on optical coherence tomography (OCT) defined as a decrease of retinal edema and/or subretinal fluid to anti-VEGF injections followed by recurrent increase in fluid on OCT (further defined as intraretinal, cystoid, subretinal fluid, or worsening pigment epithelial detachment) or the presence of a new hemorrhage on clinical examination.
Eye disorders Cataract progression	3.8% 1/26

Other adverse events

Other adverse events
Measure	Single Group n=26 participants at risk Subjects were included in the study if they met the following criteria: (1) active subfoveal choroidal neovascularization secondary to exudative AMD confirmed by fluorescein angiography (2) E-ETDRS vision of 25 to 80 letters (Snellen equivalent of \~20/25 to 20/320) (3) at least one prior injection of 1.25 mg bevacizumab or 0.5 mg ranibizumab (Avastin and Lucentis, respectively; Genentech Inc, South San Francisco, CA, USA) within 3 months of enrollment, and (4) had an initial response on optical coherence tomography (OCT) defined as a decrease of retinal edema and/or subretinal fluid to anti-VEGF injections followed by recurrent increase in fluid on OCT (further defined as intraretinal, cystoid, subretinal fluid, or worsening pigment epithelial detachment) or the presence of a new hemorrhage on clinical examination.
Eye disorders Cataract progression	3.8% 1/26

Additional Information

Dr. Rishi Singh

Cleveland Clinic Foundation

Phone: 330-888-4000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place