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)
Condition: Subfoveal Choroidal Neovascularization CNV Secondary to Wet Age-related Macular Degeneration AMD
MeSH terms: Macular Degeneration; Choroidal Neovascularization; Neovascularization, Pathologic
Intervention: Ranibizumab
Intervention description: Ranibizumab solution for injection is commercially supplied in two presentations: as a pre-filled syringe (containing 1.65 mg of ranibizumab in 0.165 mL solution) and as a vial (containing 2.3 mg of ranibizumab in 0.23 mL solution) corresponding to a recommended dose of 0.5 mg (0.05 mL) given as a single intravitreal injection. It will be prescribed and administered by the investigator or designee
Intervention MeSH terms: Ranibizumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 349.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: Subfoveal choroidal neovascularization (CNV); wet age-related macular degeneration(AMD); inject and extend; retinal fluid

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.