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

Phase 4

Completed

Conditions: Age-Related Macular Degeneration

Interventions: Drug: Aflibercept 2.0 mg
Drug: Ranibizumab 0.5 mg

Registration Number: NCT02130024

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 281

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aflibercept 2.0 mg	Aflibercept 2.0 mg	3 monthly loading doses (Baseline, Week 4, and Week 8), followed by an individualised treatment and evaluation regimen according to disease activity \[treat and extend\]
Ranibizumab 0.5 mg	Ranibizumab 0.5 mg	3 monthly loading doses (Baseline, Week 4, and Week 8), followed by an individualised treatment and evaluation regimen according to disease activity \[treat and extend\]

Primary Outcome Measures

Name	Time	Method
Mean Change in Square-root Area of Geographic Atrophy (GA) From Baseline to Month 24	Baseline, 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.

Secondary Outcome Measures

Name	Time	Method
Mean Change in Square-root Area of Geographic Atrophy From Baseline to Month 12	Baseline, 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.
Mean Number of Intravitreal Injections From Baseline to Month 12 and to Month 24	Baseline, Month 12, Month 24	The number of intravitreal injections was calculated. One eye (study eye) contributed to the analysis.
Percentage of Patients Showing no Intraretinal Fluid (IRF)/Subretinal Fluid (SRF)	Month 2, Month 12, Month 24	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.
Percentage of Patients With Newly Developed Geographic Atrophy During the Overall 24 Months of the Study	Baseline, Month 12, Month 24	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.
Mean Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 12 and to Month 24	Baseline, Month 12, 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
Mean Change in Central Subfield Foveal Thickness (CSFT) From Baseline to Month 12 and to Month 24	Baseline, Month 12, 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
Percentage of Patients With Ocular Inflammation at Baseline and 7 Days Post-injection Following 3rd Mandated Intravitreal Injection - Anterior Chamber Cells	Baseline, Week 9	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.
Percentage of Patients With Change in Retinal Nerve Fibre Thickness From Baseline to Month 12 and Month 24	Baseline, Month 12, 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.
Percentage of Patients Showing Greater Than and Equal to 15 Letters Gain for BCVA From Baseline to Month 12 and to Month 24	Baseline, Month 12, 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.
Percentage of Patients Showing Less Than and Equal to 15 Letters Loss for BCVA From Baseline to Month 12 and to Month 24	Baseline, Month 12, 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.
Mean Number of Times a Patient Needed to Return to Monthly Intravitreal Injections Over 24 Months	Month 24	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.
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	Baseline, Week 5, Week 9	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.
Percentage of Patients With Ocular Inflammation at Baseline and 7 Days Post-injection Following 3rd Mandated Intravitreal Injection - Anterior Chamber Flare	Baseline, Week 9	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.