Clinical trial NCT01972789: Comparison of Treatment Regimens Using Ranibizumab: Intensive (Resolution of Intra- and Sub-retinal Fluid) vs Relaxed (Resolution of Intra-retinal Fluid and/or Sub-retinal Fluid >200µm at the Foveal Centre)
Official title: A Phase IV, Randomised, Single Masked Study Investigating the Efficacy and Safety of Ranibizumab "Inject and Extend" Using an Intensive Retinal Fluid Retreatment Regimen Compared to a Relaxed Retinal Fluid Retreatment Regimen in Patients With Wet Age-related Macular Degeneration (AMD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Subfoveal Choroidal Neovascularization CNV Secondary to Wet Age-related Macular Degeneration AMD
Keywords: Subfoveal choroidal neovascularization (CNV)
wet age-related macular degeneration(AMD)
inject and extend
retinal fluid
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-10-30
Enrollment: 349
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: To evaluate and compare two individualised ranibizumab treatment regimens, differentiated by the definition of disease activity, which determines the treatment interval until the next injection. The results will be used to generate recommendations about ranibizumab treatment when using an 'inject and extend' approach to maximise patient outcomes, while reducing the need for potentially unnecessary intravitreal injections. This study will also investigate if genotypic expression influences response to intravitreal injections of ranibizumab between the two treatment arms.

The study hypothesis is that intravitreal ranibizumab when administered to resolve IRF (and/or SRF \>200 μm at the foveal centre) results in visual acuity benefit that is not clinically worse than intravitreal ranibizumab when administered to completely resolve both IRF and SRF in patients with wet AMD


Eligibility criteria: Inclusion Criteria:

1. Diagnosis of subfoveal CNV secondary to wet AMD without restriction of lesion size, with visual impairment being exclusively due to an active wet AMD lesion. Active lesions will be characterised by any of the following: abnormal retinal thickness, with evidence of intraretinal, subretinal or sub-pigment epithelial fluid accumulation, confirmed by OCT; presence of intraretinal or subretinal haemorrhage; new leakage shown on a FA; CNV enlargement on FA unless solely due to dry, fibrotic staining; visual acuity deterioration considered likely to represent CNV.
2. BCVA score at both Screening and Baseline must be 23 letters or more as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) logMAR charts (a Snellen visual acuity or equivalent of 20/320 or more may be used as an alternative at Screening).

Exclusion Criteria:

1. Any active periocular or ocular infection or inflammation (e.g., blepharitis, conjunctivitis, keratitis, scleritis, uveitis, endophthalmitis) at the time of Screening or Baseline.
2. Uncontrolled glaucoma (intraocular pressure \[IOP\] ≥30 mm Hg on medication) at the time of Screening or Baseline.
3. Neovascularisation of the iris or neovascular glaucoma at the time of Screening or Baseline.
4. Visually significant cataract, aphakia, severe vitreous haemorrhage, rhegmatogenous retinal detachment, proliferative diabetic retinopathy or CNV of any cause other than wet AMD at the time of screening and baseline.
5. Structural damage within 0.5 disc diameter of the centre of the macula (e.g., vitreomacular traction, epiretinal membrane, scar, laser burn, foveal atrophy) at the time of screening that in the investigator's opinion could preclude visual function improvement with treatment.
6. Treatment with any anti-angiogenic drugs (including any anti-VEGF agents) prior to Baseline in study eye (allowed in fellow eye).
7. Any intraocular procedure (including Ytrium-Aluminium- Garnet capsulotomy) within 2 months prior to Baseline or anticipated within the next 6 months following Baseline in th study eye (allowed in fellow eye).

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Mean Change in Best-corrected Visual Acuity (BCVA) From Baseline to 24 Months.
timeFrame: Baseline to month 24
Secondary outcomes:
measure: Mean Change in BCVA From Baseline to Month 12.
timeFrame: Baseline to month 12
measure: Mean Change in Central Retinal Thickness (CRT) From Baseline to Month 12 and 24.
timeFrame: Baseline to month 12 and month 24
measure: Mean Number of Injections From Baseline to Month 12 and 24
timeFrame: Baseline to month 12 to month 24.
measure: Mean Change in Area of New and Existing Geographic Atrophy From Baseline to Month 12 and 24.
timeFrame: Baseline to months 12 and 24.
measure: Proportion of Patients Showing Newly Developed Geographic Atrophy (GA) at Months 12 and 24
timeFrame: Months 12 and 24
measure: Proportion of Patients Showing no IRF and SRF at Months 2, 12 and 24.
timeFrame: Months 2, 12 and 24.
measure: Proportion of Patients Showing Greater Than or Equal to 15 Letters Early Treatment Diabetic Retinopathy (ETDRS) Gain From Baseline to Month 12 and 24.
timeFrame: Baseline to months 12 and 24.
measure: Proportion of Patients Showing Less Than 15 Letters ETDRS Loss From Baseline to Month 12 and 24.
timeFrame: Baseline to months 12 and 24
measure: Number of Participants With the Genotypes Associated With Age-Related Macular Degeneration (AMD) and Response to Treatment at Baseline; Correlation With Visual Acuity (VA) Outcome and Ability to Dry the Retina.
timeFrame: Baseline or following consent
measure: Proportion of Patients With Both SRF (Sub-retinal Fluid) and IRF (Intra-retinal Fluid) Who Despite Monthly Treatment do Not Resolve Their SRF
timeFrame: Month 12 and 24
measure: The Number of Times a Participant Needs to Return to Monthly Treatments During the 24 Months.
timeFrame: Month 24
Other outcomes:
Locations:
city: Albury
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Chatswood
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Eastwood
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Hurtsville
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Liverpool
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: North Ryde
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: Sydney
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Westmead
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Adelaide
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: Hobart
country: Australia
facility: Novartis Investigative Site
state: Tasmania
city: South Launceston
country: Australia
facility: Novartis Investigative Site
state: Tasmania
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Nedlands
country: Australia
facility: Novartis Investigative Site
state: Western Australia
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Arnold JJ, Markey CM, Kurstjens NP, Guymer RH. The role of sub-retinal fluid in determining treatment outcomes in patients with neovascular age-related macular degeneration--a phase IV randomised clinical trial with ranibizumab: the FLUID study. BMC Ophthalmol. 2016 Mar 24;16:31. doi: 10.1186/s12886-016-0207-3.