Clinical trial NCT02130024: A Comparison of Ranibizumab and Aflibercept for the Development of Geographic Atrophy in (Wet) AMD Patients
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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Age-Related Macular Degeneration
Keywords: Age-related macular degeneration
AMD
wet AMD
ranibizumab
aflibercept
geographic atrophy
inject and extend
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-05-02
Enrollment: 281
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Mean Change in Square-root Area of Geographic Atrophy (GA) From Baseline to Month 24
timeFrame: Baseline, Month 24
Secondary outcomes:
measure: Mean Change in Square-root Area of Geographic Atrophy From Baseline to Month 12
timeFrame: Baseline, Month 12
measure: Percentage of Patients With Newly Developed Geographic Atrophy During the Overall 24 Months of the Study
timeFrame: Baseline, Month 12, Month 24
measure: Mean Number of Intravitreal Injections From Baseline to Month 12 and to Month 24
timeFrame: Baseline, Month 12, Month 24
measure: Mean Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 12 and to Month 24
timeFrame: Baseline, Month 12, Month 24
measure: Mean Change in Central Subfield Foveal Thickness (CSFT) From Baseline to Month 12 and to Month 24
timeFrame: Baseline, Month 12, Month 24
measure: Percentage of Patients Showing no Intraretinal Fluid (IRF)/Subretinal Fluid (SRF)
timeFrame: Month 2, Month 12, Month 24
measure: Percentage of Patients Showing Greater Than and Equal to 15 Letters Gain for BCVA From Baseline to Month 12 and to Month 24
timeFrame: Baseline, Month 12, Month 24
measure: Percentage of Patients Showing Less Than and Equal to 15 Letters Loss for BCVA From Baseline to Month 12 and to Month 24
timeFrame: Baseline, Month 12, Month 24
measure: Mean Number of Times a Patient Needed to Return to Monthly Intravitreal Injections Over 24 Months
timeFrame: Month 24
measure: 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
timeFrame: Baseline, Week 5, Week 9
measure: Percentage of Patients With Change in Retinal Nerve Fibre Thickness From Baseline to Month 12 and Month 24
timeFrame: Baseline, Month 12, Month 24
measure: Percentage of Patients With Ocular Inflammation at Baseline and 7 Days Post-injection Following 3rd Mandated Intravitreal Injection - Anterior Chamber Cells
timeFrame: Baseline, Week 9
measure: Percentage of Patients With Ocular Inflammation at Baseline and 7 Days Post-injection Following 3rd Mandated Intravitreal Injection - Anterior Chamber Flare
timeFrame: Baseline, Week 9
Other outcomes:
Locations:
city: Albury
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Brookvale
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Chatswood
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Hurtsville
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Mona Vale
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Parramatta
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Strathfield
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Strathfield
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Sydney
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Sydney
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Westmead
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Caboolture
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Redcliffe
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: South Brisbane
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Southport
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Adelaide
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: South Launceston
country: Australia
facility: Novartis Investigative Site
state: Tasmania
city: Clayton
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Malvern
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Parkville,
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Nedlands
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Subiaco
country: Australia
facility: Novartis Investigative Site
state: Western Australia
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
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.
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.