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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02130024
Recruitment Status : Completed
First Posted : May 2, 2014
Results First Posted : June 5, 2019
Last Update Posted : June 5, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( 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.

Condition or disease Intervention/treatment Phase
Age-Related Macular Degeneration Drug: Ranibizumab 0.5 mg Drug: Aflibercept 2.0 mg Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 281 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Masking Description: Investigators were not masked. The patients, the BCVA assessors, and the Central Reading Center (who set the treatment intervals) were masked.
Primary Purpose: Treatment
Official Title: Development of New Geographic Atrophy in Patients With Neovascular (Wet) Age-related Macular Degeneration: a Comparison of Ranibizumab and Aflibercept
Actual Study Start Date : April 11, 2014
Actual Primary Completion Date : November 15, 2017
Actual Study Completion Date : November 15, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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]
Drug: Ranibizumab 0.5 mg
Administered as an intravitreal injection
Other Name: Lucentis

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]
Drug: Aflibercept 2.0 mg
Administered as an intravitreal injection
Other Name: Eylea




Primary Outcome Measures :
  1. Mean Change in Square-root Area of Geographic Atrophy (GA) From Baseline to Month 24 [ Time Frame: 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 :
  1. Mean Change in Square-root Area of Geographic Atrophy From Baseline to Month 12 [ Time Frame: 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.

  2. Percentage of Patients With Newly Developed Geographic Atrophy During the Overall 24 Months of the Study [ Time Frame: 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.

  3. Mean Number of Intravitreal Injections From Baseline to Month 12 and to Month 24 [ Time Frame: Baseline, Month 12, Month 24 ]
    The number of intravitreal injections was calculated. One eye (study eye) contributed to the analysis.

  4. Mean Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 12 and to Month 24 [ Time Frame: 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

  5. Mean Change in Central Subfield Foveal Thickness (CSFT) From Baseline to Month 12 and to Month 24 [ Time Frame: 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

  6. Percentage of Patients Showing no Intraretinal Fluid (IRF)/Subretinal Fluid (SRF) [ Time Frame: 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.

  7. Percentage of Patients Showing Greater Than and Equal to 15 Letters Gain for BCVA From Baseline to Month 12 and to Month 24 [ Time Frame: 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.

  8. Percentage of Patients Showing Less Than and Equal to 15 Letters Loss for BCVA From Baseline to Month 12 and to Month 24 [ Time Frame: 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.

  9. Mean Number of Times a Patient Needed to Return to Monthly Intravitreal Injections Over 24 Months [ Time Frame: 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.

  10. 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 [ Time Frame: 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.

  11. Percentage of Patients With Change in Retinal Nerve Fibre Thickness From Baseline to Month 12 and Month 24 [ Time Frame: 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.

  12. Percentage of Patients With Ocular Inflammation at Baseline and 7 Days Post-injection Following 3rd Mandated Intravitreal Injection - Anterior Chamber Cells [ Time Frame: 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.

  13. Percentage of Patients With Ocular Inflammation at Baseline and 7 Days Post-injection Following 3rd Mandated Intravitreal Injection - Anterior Chamber Flare [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02130024


Locations
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Australia, New South Wales
Novartis Investigative Site
Albury, New South Wales, Australia, 2640
Novartis Investigative Site
Brookvale, New South Wales, Australia, 2100
Novartis Investigative Site
Chatswood, New South Wales, Australia, 2067
Novartis Investigative Site
Hurtsville, New South Wales, Australia, 2220
Novartis Investigative Site
Mona Vale, New South Wales, Australia
Novartis Investigative Site
Parramatta, New South Wales, Australia, 2150
Novartis Investigative Site
Strathfield, New South Wales, Australia, 2035
Novartis Investigative Site
Strathfield, New South Wales, Australia, 2135
Novartis Investigative Site
Sydney, New South Wales, Australia, 2000
Novartis Investigative Site
Sydney, New South Wales, Australia, AUSTRALIA
Novartis Investigative Site
Westmead, New South Wales, Australia, 2145
Australia, Queensland
Novartis Investigative Site
Caboolture, Queensland, Australia, 4510
Novartis Investigative Site
Redcliffe, Queensland, Australia, 4020
Novartis Investigative Site
South Brisbane, Queensland, Australia, 4101
Novartis Investigative Site
Southport, Queensland, Australia, 4215
Australia, South Australia
Novartis Investigative Site
Adelaide, South Australia, Australia, 5000
Australia, Tasmania
Novartis Investigative Site
South Launceston, Tasmania, Australia, 7249
Australia, Victoria
Novartis Investigative Site
Clayton, Victoria, Australia, 3168
Novartis Investigative Site
Malvern, Victoria, Australia, 3144
Novartis Investigative Site
Parkville,, Victoria, Australia, 3065
Australia, Western Australia
Novartis Investigative Site
Nedlands, Western Australia, Australia, 6009
Novartis Investigative Site
Subiaco, Western Australia, Australia, 6008
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] January 19, 2015
Statistical Analysis Plan  [PDF] May 4, 2018


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02130024    
Other Study ID Numbers: CRFB002AAU17
First Posted: May 2, 2014    Key Record Dates
Results First Posted: June 5, 2019
Last Update Posted: June 5, 2019
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Age-related macular degeneration
AMD
wet AMD
ranibizumab
aflibercept
geographic atrophy
inject and extend
Additional relevant MeSH terms:
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Macular Degeneration
Geographic Atrophy
Atrophy
Retinal Degeneration
Retinal Diseases
Eye Diseases
Pathological Conditions, Anatomical
Ranibizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents