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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02130024




Registration number
NCT02130024
Ethics application status
Date submitted
27/03/2014
Date registered
2/05/2014
Date last updated
5/06/2019

Titles & IDs
Public title
A Comparison of Ranibizumab and Aflibercept for the Development of Geographic Atrophy in (Wet) AMD Patients
Scientific title
Development of New Geographic Atrophy in Patients With Neovascular (Wet) Age-related Macular Degeneration: a Comparison of Ranibizumab and Aflibercept
Secondary ID [1] 0 0
CRFB002AAU17
Universal Trial Number (UTN)
Trial acronym
RIVAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Age-Related Macular Degeneration 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ranibizumab 0.5 mg
Treatment: Drugs - Aflibercept 2.0 mg

Experimental: 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]

Active Comparator: 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]


Treatment: Drugs: Ranibizumab 0.5 mg
Administered as an intravitreal injection

Treatment: Drugs: Aflibercept 2.0 mg
Administered as an intravitreal injection

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline, Month 24
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline, Month 12
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline, Month 12, Month 24
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Baseline, Month 12, Month 24
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Baseline, Month 12, Month 24
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Baseline, Month 12, Month 24
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Month 2, Month 12, Month 24
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Baseline, Month 12, Month 24
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Baseline, Month 12, Month 24
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Month 24
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
Baseline, Week 5, Week 9
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
Baseline, Month 12, Month 24
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
Baseline, Week 9
Secondary outcome [13] 0 0
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.
Timepoint [13] 0 0
Baseline, Week 9

Eligibility
Key inclusion 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.
Minimum age
50 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Albury
Recruitment hospital [2] 0 0
Novartis Investigative Site - Brookvale
Recruitment hospital [3] 0 0
Novartis Investigative Site - Chatswood
Recruitment hospital [4] 0 0
Novartis Investigative Site - Hurtsville
Recruitment hospital [5] 0 0
Novartis Investigative Site - Mona Vale
Recruitment hospital [6] 0 0
Novartis Investigative Site - Parramatta
Recruitment hospital [7] 0 0
Novartis Investigative Site - Strathfield
Recruitment hospital [8] 0 0
Novartis Investigative Site - Sydney
Recruitment hospital [9] 0 0
Novartis Investigative Site - Westmead
Recruitment hospital [10] 0 0
Novartis Investigative Site - Caboolture
Recruitment hospital [11] 0 0
Novartis Investigative Site - Redcliffe
Recruitment hospital [12] 0 0
Novartis Investigative Site - South Brisbane
Recruitment hospital [13] 0 0
Novartis Investigative Site - Southport
Recruitment hospital [14] 0 0
Novartis Investigative Site - Adelaide
Recruitment hospital [15] 0 0
Novartis Investigative Site - South Launceston
Recruitment hospital [16] 0 0
Novartis Investigative Site - Clayton
Recruitment hospital [17] 0 0
Novartis Investigative Site - Malvern
Recruitment hospital [18] 0 0
Novartis Investigative Site - Parkville,
Recruitment hospital [19] 0 0
Novartis Investigative Site - Nedlands
Recruitment hospital [20] 0 0
Novartis Investigative Site - Subiaco
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
2100 - Brookvale
Recruitment postcode(s) [3] 0 0
2067 - Chatswood
Recruitment postcode(s) [4] 0 0
2220 - Hurtsville
Recruitment postcode(s) [5] 0 0
- Mona Vale
Recruitment postcode(s) [6] 0 0
2150 - Parramatta
Recruitment postcode(s) [7] 0 0
2035 - Strathfield
Recruitment postcode(s) [8] 0 0
2135 - Strathfield
Recruitment postcode(s) [9] 0 0
2000 - Sydney
Recruitment postcode(s) [10] 0 0
AUSTRALIA - Sydney
Recruitment postcode(s) [11] 0 0
2145 - Westmead
Recruitment postcode(s) [12] 0 0
4510 - Caboolture
Recruitment postcode(s) [13] 0 0
4020 - Redcliffe
Recruitment postcode(s) [14] 0 0
4101 - South Brisbane
Recruitment postcode(s) [15] 0 0
4215 - Southport
Recruitment postcode(s) [16] 0 0
5000 - Adelaide
Recruitment postcode(s) [17] 0 0
7249 - South Launceston
Recruitment postcode(s) [18] 0 0
3168 - Clayton
Recruitment postcode(s) [19] 0 0
3144 - Malvern
Recruitment postcode(s) [20] 0 0
3065 - Parkville,
Recruitment postcode(s) [21] 0 0
6009 - Nedlands
Recruitment postcode(s) [22] 0 0
6008 - Subiaco

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02130024
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications