Overview

This trial is active, not recruiting.

Condition subfoveal choroidal neovascularization (cnv) secondary to wet age-related macular degeneration (amd)
Treatment ranibizumab
Phase phase 4
Target VEGF
Sponsor Novartis Pharmaceuticals
Start date October 2013
End date November 2016
Trial size 347 participants
Trial identifier NCT01972789, CRFB002AAU15

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 further recommendations about intensive versus relaxed treatment approaches and how they can be utilised within an 'inject and extend' approach to maximise patient outcomes, while reducing the need for potentially unnecessary intravitreal injections. This study will also investigate genotypic expression and response to intravitreal injections of ranibizumab between the two treatment arms.

The study hypothesis is that intravitreal ranibizumab when administered to resolve IRF only 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking single blind (subject)
Primary purpose treatment
Arm
(Experimental)
Ranibizumab 0.5mg is given monthly for the first 3 months followed by an individualised treatment regimen as determined by disease activity defined by a loss of ≥5 letters, new retinal haemorrhage, presence of any IRF or SRF on OCT.
ranibizumab LUCENTIS
Ranibizumab solution for injection is commercially supplied in vials with each vial containing ranibizumab in the concentration of 10 mg/ml (0.5 mg/0.05 ml, corresponding to a 0.5 mg dose level). It will be prescribed and administered by the investigator or designee.
(Experimental)
Ranibizumab 0.5mg is given monthly for the first 3 months followed by an individualised treatment regimen as determined by disease activity defined by a loss of ≥5 letters, new retinal haemorrhage, presence of IRF or SRF >200 um on OCT.
ranibizumab LUCENTIS
Ranibizumab solution for injection is commercially supplied in vials with each vial containing ranibizumab in the concentration of 10 mg/ml (0.5 mg/0.05 ml, corresponding to a 0.5 mg dose level). It will be prescribed and administered by the investigator or designee.

Primary Outcomes

Measure
Mean change in best-corrected visual acuity (BCVA) from baseline to 24 months.
time frame: Baseline to month 24

Secondary Outcomes

Measure
Mean change in BCVA from baseline to month 12.
time frame: Baseline to month 12
Mean change in central retinal thickness (CRT) from baseline to month 12 and 24.
time frame: Baseline to month 12 and month 24
Mean number of injections from baseline to month 12 and 24
time frame: Baseline to month 12 to month 24.
Mean change in area of new and existing geographic atrophy from baseline to month 12 and 24.
time frame: Baseline to months 12 and 24.
Proportion of patients showing newly developed geographic atrophy at months 12 and 24
time frame: Months 12 and 24
Proportion of patients showing no IRF and SRF at months 2, 12 and 24.
time frame: Months 2, 12 and 24.
Proportion of patients showing greater than 15 letters Early Treatment Diabetic Retinopathy (ETDRS) gain from baseline to month 12 and 24.
time frame: Baseline to months 12 and 24.
Proportion of patients showing less than 15 letters ETDRS loss from baseline to month 12 and 24.
time frame: Baseline to months 12 and 24
Determination of genotypes associated with AMD and response to treatment at baseline; correlation with visual acuity (VA) outcome and ability to dry the retina.
time frame: Baseline or following consent
Proportion of patients with both SRF and IRF who despite monthly treatment do not resolve their SRF
time frame: Monthly
The number of times a participant needs to return to monthly treatments during the 24 months.
time frame: Monthly
Ocular and systemic adverse events
time frame: Baseline to end of study (month 24)

Eligibility Criteria

Male or female participants at least 50 years old.

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.

Additional Information

Official title A Phase IV, Randomised, Controlled, 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)
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Novartis.