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

Age-Related Macular Degeneration Clinical Trial

— RIVAL  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02130024
• Other study ID #: CRFB002AAU17
• Status: Completed
• Phase: Phase 4
• Start date: April 11, 2014
• Est. completion date: November 15, 2017

Study information

• Verified date: October 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 281
• Est. completion date: November 15, 2017
• Est. primary completion date: November 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Age-Related Macular Degeneration
• Atrophy
• Geographic Atrophy
• Macular Degeneration

Intervention

Drug:
• Ranibizumab 0.5 mg
Administered as an intravitreal injection
• Aflibercept 2.0 mg
Administered as an intravitreal injection

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Adelaide	South Australia
Australia	Novartis Investigative Site	Albury	New South Wales
Australia	Novartis Investigative Site	Brookvale	New South Wales
Australia	Novartis Investigative Site	Caboolture	Queensland
Australia	Novartis Investigative Site	Chatswood	New South Wales
Australia	Novartis Investigative Site	Clayton	Victoria
Australia	Novartis Investigative Site	Hurtsville	New South Wales
Australia	Novartis Investigative Site	Malvern	Victoria
Australia	Novartis Investigative Site	Mona Vale	New South Wales
Australia	Novartis Investigative Site	Nedlands	Western Australia
Australia	Novartis Investigative Site	Parkville,	Victoria
Australia	Novartis Investigative Site	Parramatta	New South Wales
Australia	Novartis Investigative Site	Redcliffe	Queensland
Australia	Novartis Investigative Site	South Brisbane	Queensland
Australia	Novartis Investigative Site	South Launceston	Tasmania
Australia	Novartis Investigative Site	Southport	Queensland
Australia	Novartis Investigative Site	Strathfield	New South Wales
Australia	Novartis Investigative Site	Strathfield	New South Wales
Australia	Novartis Investigative Site	Subiaco	Western Australia
Australia	Novartis Investigative Site	Sydney	New South Wales
Australia	Novartis Investigative Site	Sydney	New South Wales
Australia	Novartis Investigative Site	Westmead	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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