A Comparison of Ranibizumab and Aflibercept for the Development of Geographic Atrophy in (Wet) AMD Patients

Study Overview
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Brief Summary
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The purpose of this study was to compare the development of new geographic atrophy in patients with wet Age-related Macular Degeneration (AMD) when treated with either ranibizumab or aflibercept over 24 months. Geographic atrophy is an advanced form of AMD that can result in the progressive and irreversible loss of visual function over time.

Detailed Description
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In each arm, patients underwent three monthly loading doses (at Baseline, Week 4, and Week 8). From Week 8, after the patient had received their third injection of study treatment, the visit intervals were determined by the patient's disease activity. If any of the protocol-specified signs of disease activity were present in the study eye, the subsequent injection visit interval was kept at 4 weeks. If none of the signs were present, the subsequent injection interval was extended by 2-week increments up until a maximum of 12-weekly intervals was reached. If there were any signs of disease activity in the study eye, the treatment interval was reduced as specified in the protocol. The planned individual duration of study participation was 24 months.

Official Title
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Development of New Geographic Atrophy in Patients With Neovascular (Wet) Age-related Macular Degeneration: a Comparison of Ranibizumab and Aflibercept

Conditions
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Age-Related Macular Degeneration

Intervention / Treatment
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* Drug: Ranibizumab 0.5 mg
* Drug: Aflibercept 2.0 mg


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: - Written informed consent. Inclusion criteria specific to the study eye: Diagnosis of active subfoveal Choroidal Neovascularisation (CNV) secondary to wet Age-related Macular Degeneration (AMD); Best Corrected Visual Acuity (BCVA) score of 23 letters or more as measured by 3-metre Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts. Exclusion criteria: Pregnant, nursing, or at risk of becoming pregnant during the study; Inability to comply with the study or follow-up procedures; Recent (3 months) stroke or myocardial infarction; uncontrolled hypertension; hypersensitivity to the study treatments or to fluorescein; In either eye: active periocular or ocular infection or inflammation; iris neovascularisation; uncontrolled or neovascular glaucoma; or one or more patch of geographic atrophy (GA) as specified in the protocol. Exclusion criteria specific to the study eye: Prior or current treatment with anti-angiogenic drugs or corticosteroids; Other eye conditions as specified in the protocol; Any intraocular procedure carried out within 2 months before baseline or anticipated within 6 months following baseline.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ranibizumab 0.5 mg<br>3 monthly loading doses (Baseline, Week 4, and Week 8), followed by an individualised treatment and evaluation regimen according to disease activity [treat and extend] | Drug: Ranibizumab 0.5 mg<br>* Administered as an intravitreal injection<br>* Other names: Lucentis;|
| Active Comparator: Aflibercept 2.0 mg<br>3 monthly loading doses (Baseline, Week 4, and Week 8), followed by an individualised treatment and evaluation regimen according to disease activity [treat and extend] | Drug: Aflibercept 2.0 mg<br>* Administered as an intravitreal injection<br>* Other names: Eylea;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Square-root Area of Geographic Atrophy (GA) From Baseline to Month 24 | Multimodal images of the eye were obtained by trained study site personnel and forwarded to an independent Central Reading Center, where the area of GA was measured. Area was treated as zero if GA was reported as absent (Overall determination of GA presence). Mean change from baseline in GA area was reported in square root-transformed data (mm). One eye (study eye) contributed to the analysis. | Baseline, Month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Ocular Inflammation at Baseline and 7 Days Post-injection Following 3rd Mandated Intravitreal Injection - Anterior Chamber Cells | Anterior cell grade was assessed by the Investigator during slit lamp examination and graded on a 5-point scale: Grade 0=0 cells; Grade 1=1 to 10 cells; Grade 2=11 to 20 cells; Grade 3=21 to 50 cells; Grade 4=>50 cells. The presence of blood cells (red and white) in the anterior chamber of the eye (the fluid-filled space inside the eye between the iris and the cornea's innermost surface) is a sign of intraocular inflammation. A score of 0 indicates an absence of inflammation. One eye (study eye) contributed to the analysis. | Baseline, Week 9 | 
| Percentage of Patients With Ocular Inflammation at Baseline and 7 Days Post-injection Following 3rd Mandated Intravitreal Injection - Anterior Chamber Flare | Anterior chamber flare was assessed by the investigator during slit lamp examination and graded on a 5-point scale, with 0 = none; 1 = mild (trace to clearly noticeable, visible); 2 = moderate; 3 = marked; and 4 = severe. The presence of flare (increased protein levels) in the anterior chamber of the eye (the fluid-filled space inside the eye between the iris and the cornea's innermost surface) is a sign of intraocular inflammation. A score of 0 indicates an absence of inflammation. Proportion of patients is reported as a percentage. One eye (study eye) contributed to the analysis. | Baseline, Week 9 | 
| Percentage of Patients Showing Less Than and Equal to 15 Letters Loss for BCVA From Baseline to Month 12 and to Month 24 | Visual acuity was assessed with spectacles or other visual corrective devices in place using logMAR charts and recorded in number of letters correctly identified. A gain in letters correctly identified indicates an improvement in visual acuity, while a loss indicates a worsening. One eye (study eye) contributed to the analysis. | Baseline, Month 12, Month 24 | 
| Mean Number of Times a Patient Needed to Return to Monthly Intravitreal Injections Over 24 Months | The number of times the patient returned to a monthly injection interval (from an extended interval) at least once during the 24-month study was calculated. One eye (study eye) contributed to the analysis. | Month 24 | 
| Mean Change in Vascular Endothelial Growth Factor (VEGF) Plasma Concentration From Baseline to 7 Days After the Second and 7 Days After the Third Mandated Intravitreal Injection of Treatment | Blood for VEGF plasma concentration analysis was collected at Baseline and again at 7 days after the injection at Week 4 and 7 days after the injection at Week 8. | Baseline, Week 5, Week 9 | 
| Percentage of Patients With Change in Retinal Nerve Fibre Thickness From Baseline to Month 12 and Month 24 | Retinal nerve fibre thickness was assessed using Optical Coherence Tomography (OCT) and measured in micrometers. A negative change in value (i.e. thinner nerve fibre) indicates nerve damage. One eye (study eye) contributed to the analysis. | Baseline, Month 12, Month 24 | 
| Mean Change in Square-root Area of Geographic Atrophy From Baseline to Month 12 | Multimodal images of the eye were obtained by trained study site personnel and forwarded to an independent Central Reading Center, where the area of GA was measured. Area was treated as zero if GA was reported as absent (Overall determination of GA presence). Mean change from baseline in GA area was reported in square root-transformed data (mm). One eye (study eye) contributed to the analysis. | Baseline, Month 12 | 
| Percentage of Patients With Newly Developed Geographic Atrophy During the Overall 24 Months of the Study | Multimodal images of the eye were obtained by trained study site personnel and forwarded to an independent Central Reading Center. A patient was considered to have developed new GA if they did not have any GA at the start of the study period and were subsequently diagnosed with GA during the study period (diagnosis of GA change from No to Yes). The analysis of new GA development was restricted to only those subjects without GA reported at baseline. One eye (study eye) contributed to the analysis. | Baseline, Month 12, Month 24 | 
| Mean Number of Intravitreal Injections From Baseline to Month 12 and to Month 24 | The number of intravitreal injections was calculated. One eye (study eye) contributed to the analysis. | Baseline, Month 12, Month 24 | 
| Mean Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 12 and to Month 24 | Visual acuity was assessed with spectacles or other visual corrective devices in place using logMAR charts and recorded in number of letters correctly identified. BCVA change was defined as a change in letters correctly identified from the baseline assessment. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis | Baseline, Month 12, Month 24 | 
| Mean Change in Central Subfield Foveal Thickness (CSFT) From Baseline to Month 12 and to Month 24 | CSFT (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using Optical Coherence Tomography (OCT) and measured in micrometers. A negative change value indicates an improvement, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis | Baseline, Month 12, Month 24 | 
| Percentage of Patients Showing no Intraretinal Fluid (IRF)/Subretinal Fluid (SRF) | Intraretinal fluid and subretinal fluid was assessed using Optical Coherence Tomography (OCT) and recorded as Present/Absent. One eye (study eye) contributed to the analysis. | Month 2, Month 12, Month 24 | 
| Percentage of Patients Showing Greater Than and Equal to 15 Letters Gain for BCVA From Baseline to Month 12 and to Month 24 | Visual acuity was assessed with spectacles or other visual corrective devices in place using logMAR charts and recorded in number of letters correctly identified. A gain in letters correctly identified indicates an improvement in visual acuity, while a loss indicates a worsening. One eye (study eye) contributed to the analysis. | Baseline, Month 12, Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMD, Age-related macular degeneration, wet AMD, ranibizumab, aflibercept, geographic atrophy, inject and extend