Back to resultsA Comparison of Ranibizumab and Aflibercept for the Development of Geographic Atrophy in (Wet) AMD Patients (RIVAL)
Primary Purpose
Age-Related Macular Degeneration
Status
Completed
Phase
Phase 4
Locations
Australia
Study Type
Interventional
Intervention
Ranibizumab 0.5 mg
Aflibercept 2.0 mg
Sponsored by
About this trial
This is an interventional treatment trial for Age-Related Macular Degeneration focused on measuring Age-related macular degeneration, AMD, wet AMD, ranibizumab, aflibercept, geographic atrophy, inject and extend
Eligibility Criteria
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.
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Ranibizumab 0.5 mg
Aflibercept 2.0 mg
Arm Description
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]
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]
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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
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
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT02130024
First Posted
March 27, 2014
Last Updated
February 28, 2019
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02130024
Brief Title
A Comparison of Ranibizumab and Aflibercept for the Development of Geographic Atrophy in (Wet) AMD Patients
Acronym
RIVAL
Official Title
Development of New Geographic Atrophy in Patients With Neovascular (Wet) Age-related Macular Degeneration: a Comparison of Ranibizumab and Aflibercept
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
April 11, 2014 (Actual)
Primary Completion Date
November 15, 2017 (Actual)
Study Completion Date
November 15, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Age-Related Macular Degeneration
Keywords
Age-related macular degeneration, AMD, wet AMD, ranibizumab, aflibercept, geographic atrophy, inject and extend
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Participant
Masking Description
Investigators were not masked. The patients, the BCVA assessors, and the Central Reading Center (who set the treatment intervals) were masked.
Allocation
Randomized
Enrollment
281 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ranibizumab 0.5 mg
Arm Type
Experimental
Arm Description
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]
Arm Title
Aflibercept 2.0 mg
Arm Type
Active Comparator
Arm Description
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]
Intervention Type
Drug
Intervention Name(s)
Ranibizumab 0.5 mg
Other Intervention Name(s)
Lucentis
Intervention Description
Administered as an intravitreal injection
Intervention Type
Drug
Intervention Name(s)
Aflibercept 2.0 mg
Other Intervention Name(s)
Eylea
Intervention Description
Administered as an intravitreal injection
Primary Outcome Measure Information:
Title
Mean Change in Square-root Area of Geographic Atrophy (GA) From Baseline to Month 24
Description
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.
Time Frame
Baseline, Month 24
Secondary Outcome Measure Information:
Title
Mean Change in Square-root Area of Geographic Atrophy From Baseline to Month 12
Description
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.
Time Frame
Baseline, Month 12
Title
Percentage of Patients With Newly Developed Geographic Atrophy During the Overall 24 Months of the Study
Description
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.
Time Frame
Baseline, Month 12, Month 24
Title
Mean Number of Intravitreal Injections From Baseline to Month 12 and to Month 24
Description
The number of intravitreal injections was calculated. One eye (study eye) contributed to the analysis.
Time Frame
Baseline, Month 12, Month 24
Title
Mean Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 12 and to Month 24
Description
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
Time Frame
Baseline, Month 12, Month 24
Title
Mean Change in Central Subfield Foveal Thickness (CSFT) From Baseline to Month 12 and to Month 24
Description
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
Time Frame
Baseline, Month 12, Month 24
Title
Percentage of Patients Showing no Intraretinal Fluid (IRF)/Subretinal Fluid (SRF)
Description
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.
Time Frame
Month 2, Month 12, Month 24
Title
Percentage of Patients Showing Greater Than and Equal to 15 Letters Gain for BCVA From Baseline to Month 12 and to Month 24
Description
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.
Time Frame
Baseline, Month 12, Month 24
Title
Percentage of Patients Showing Less Than and Equal to 15 Letters Loss for BCVA From Baseline to Month 12 and to Month 24
Description
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.
Time Frame
Baseline, Month 12, Month 24
Title
Mean Number of Times a Patient Needed to Return to Monthly Intravitreal Injections Over 24 Months
Description
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.
Time Frame
Month 24
Title
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
Description
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.
Time Frame
Baseline, Week 5, Week 9
Title
Percentage of Patients With Change in Retinal Nerve Fibre Thickness From Baseline to Month 12 and Month 24
Description
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.
Time Frame
Baseline, Month 12, Month 24
Title
Percentage of Patients With Ocular Inflammation at Baseline and 7 Days Post-injection Following 3rd Mandated Intravitreal Injection - Anterior Chamber Cells
Description
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.
Time Frame
Baseline, Week 9
Title
Percentage of Patients With Ocular Inflammation at Baseline and 7 Days Post-injection Following 3rd Mandated Intravitreal Injection - Anterior Chamber Flare
Description
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.
Time Frame
Baseline, Week 9
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Albury
State/Province
New South Wales
ZIP/Postal Code
2640
Country
Australia
Facility Name
Novartis Investigative Site
City
Brookvale
State/Province
New South Wales
ZIP/Postal Code
2100
Country
Australia
Facility Name
Novartis Investigative Site
City
Chatswood
State/Province
New South Wales
ZIP/Postal Code
2067
Country
Australia
Facility Name
Novartis Investigative Site
City
Hurtsville
State/Province
New South Wales
ZIP/Postal Code
2220
Country
Australia
Facility Name
Novartis Investigative Site
City
Mona Vale
State/Province
New South Wales
Country
Australia
Facility Name
Novartis Investigative Site
City
Parramatta
State/Province
New South Wales
ZIP/Postal Code
2150
Country
Australia
Facility Name
Novartis Investigative Site
City
Strathfield
State/Province
New South Wales
ZIP/Postal Code
2035
Country
Australia
Facility Name
Novartis Investigative Site
City
Strathfield
State/Province
New South Wales
ZIP/Postal Code
2135
Country
Australia
Facility Name
Novartis Investigative Site
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2000
Country
Australia
Facility Name
Novartis Investigative Site
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
AUSTRALIA
Country
Australia
Facility Name
Novartis Investigative Site
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Novartis Investigative Site
City
Caboolture
State/Province
Queensland
ZIP/Postal Code
4510
Country
Australia
Facility Name
Novartis Investigative Site
City
Redcliffe
State/Province
Queensland
ZIP/Postal Code
4020
Country
Australia
Facility Name
Novartis Investigative Site
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Name
Novartis Investigative Site
City
Southport
State/Province
Queensland
ZIP/Postal Code
4215
Country
Australia
Facility Name
Novartis Investigative Site
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Novartis Investigative Site
City
South Launceston
State/Province
Tasmania
ZIP/Postal Code
7249
Country
Australia
Facility Name
Novartis Investigative Site
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
Novartis Investigative Site
City
Malvern
State/Province
Victoria
ZIP/Postal Code
3144
Country
Australia
Facility Name
Novartis Investigative Site
City
Parkville,
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Facility Name
Novartis Investigative Site
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Novartis Investigative Site
City
Subiaco
State/Province
Western Australia
ZIP/Postal Code
6008
Country
Australia
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32374423
Citation
Li E, Donati S, Lindsley KB, Krzystolik MG, Virgili G. Treatment regimens for administration of anti-vascular endothelial growth factor agents for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2020 May 5;5(5):CD012208. doi: 10.1002/14651858.CD012208.pub2.
Results Reference
derived
PubMed Identifier
30676617
Citation
Gillies MC, Hunyor AP, Arnold JJ, Guymer RH, Wolf S, Ng P, Pecheur FL, McAllister IL. Effect of Ranibizumab and Aflibercept on Best-Corrected Visual Acuity in Treat-and-Extend for Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial. JAMA Ophthalmol. 2019 Apr 1;137(4):372-379. doi: 10.1001/jamaophthalmol.2018.6776.
Results Reference
derived
Learn more about this trial
A Comparison of Ranibizumab and Aflibercept for the Development of Geographic Atrophy in (Wet) AMD Patients
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