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Comparison of Treatment Regimens Using Ranibizumab: Intensive (Resolution of Intra- and Sub-retinal Fluid) vs Relaxed (Resolution of Primarily Intra-retinal Fluid) Treatment. (FLUID)

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ClinicalTrials.gov Identifier: NCT01972789
Recruitment Status : Completed
First Posted : October 30, 2013
Last Update Posted : July 25, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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 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.


Condition or disease Intervention/treatment Phase
Subfoveal Choroidal Neovascularization CNV Secondary to Wet Age-related Macular Degeneration AMD Drug: Ranibizumab Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 346 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
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)
Actual Study Start Date : October 31, 2013
Actual Primary Completion Date : February 28, 2017
Actual Study Completion Date : February 28, 2017


Arm Intervention/treatment
Experimental: Intensive retinal fluid regimen
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.
Drug: Ranibizumab
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.
Other Name: LUCENTIS

Experimental: Relaxed retinal fluid regimen
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.
Drug: Ranibizumab
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.
Other Name: LUCENTIS




Primary Outcome Measures :
  1. Mean change in best-corrected visual acuity (BCVA) from baseline to 24 months. [ Time Frame: Baseline to month 24 ]
    Best-corrected visual acuity (BCVA) with refraction will be taken using a logMAR chart at a distance of 3 metres in the study eye at baseline and month 24.


Secondary Outcome Measures :
  1. Mean change in BCVA from baseline to month 12. [ Time Frame: Baseline to month 12 ]
    Best-corrected visual acuity (BCVA) with refraction will be taken using a logMAR chart at a distance of 3 metres in the study eye at baseline and month 12.

  2. Mean change in central retinal thickness (CRT) from baseline to month 12 and 24. [ Time Frame: Baseline to month 12 and month 24 ]
    Central retinal thickness will be measured by Optical Coherence Tomography (OCT) at every visit.

  3. Mean number of injections from baseline to month 12 and 24 [ Time Frame: Baseline to month 12 to month 24. ]
    The number of injections will be determined by the individual patient response to ranibizumab therapy and potential for extension between injections based on specific criteria: loss of visual acuity, new retinal haemorrhage, and presence of IRF or SRF on OCT.

  4. 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. ]
    Autofluorescence will be measured by multimodal imaging to assess the presence and development of geographic atrophy in the study at baseline, and month 12 and 24.

  5. Proportion of patients showing newly developed geographic atrophy at months 12 and 24 [ Time Frame: Months 12 and 24 ]
    Autofluorescence will be performed using multimodal imaging to assess the presence of new geographic atrophy in the study eye at baseline, and month 12 and 24.

  6. Proportion of patients showing no IRF and SRF at months 2, 12 and 24. [ Time Frame: Months 2, 12 and 24. ]
    Assessed by Optical Coherence Tomography (OCT) and confirmed by a central reading centre.

  7. 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. ]
    Best-corrected visual acuity (BCVA) with refraction will be taken using a logMAR chart at a distance of 3 metres in the study eye at baseline and months 2, 12 and 24.

  8. 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 ]
    Best-corrected visual acuity with refraction will be taken using a logMAR chart at a distance of 3 metres in the study eye at baseline and months 2, 12 and 24.

  9. 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 ]
    DNA will be extracted from saliva and genotyping performed on the significantly associated single nucleotide polymorphisms (SNPs) identified by the AMD Gene Consortium (Nature Genetics, March 2013). Genotypes will be derived through the use of a Sequenom Iplex protocol.

  10. Proportion of patients with both SRF and IRF who despite monthly treatment do not resolve their SRF [ Time Frame: Monthly ]
    Assessed by Optical Coherence Tomography (OCT) and confirmed by a central reading centre.

  11. The number of times a participant needs to return to monthly treatments during the 24 months. [ Time Frame: Monthly ]
    Treatment requirements will be determined by the individual patient disease activity as measured by OCT, BCVA, colour fundus photography and fluorescein angiography (FA).

  12. Ocular and systemic adverse events [ Time Frame: Baseline to end of study (month 24) ]
    The investigator or designee will discuss this on an ongoing basis with the study participant.



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:

  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.


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): NCT01972789


Locations
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Australia, New South Wales
Novartis Investigative Site
Albury, New South Wales, Australia, 2640
Novartis Investigative Site
Chatswood, New South Wales, Australia, 2067
Novartis Investigative Site
Eastwood, New South Wales, Australia, 2122
Novartis Investigative Site
Hurtsville, New South Wales, Australia, 2220
Novartis Investigative Site
Liverpool, New South Wales, Australia, 2170
Novartis Investigative Site
North Ryde, New South Wales, Australia, 2109
Novartis Investigative Site
Parramatta, New South Wales, Australia, 2150
Novartis Investigative Site
Strathfield, New South Wales, Australia, 2135
Novartis Investigative Site
Sydney, New South Wales, Australia, 2000
Novartis Investigative Site
Westmead, New South Wales, Australia, 2145
Australia, South Australia
Novartis Investigative Site
Adelaide, South Australia, Australia, 5000
Australia, Tasmania
Novartis Investigative Site
Hobart, Tasmania, Australia, 7000
Novartis Investigative Site
South Launceston, Tasmania, Australia, 7249
Australia, Victoria
Novartis Investigative Site
Melbourne, Victoria, Australia, 3000
Novartis Investigative Site
Melbourne, Victoria, Australia, 3002
Australia, Western Australia
Novartis Investigative Site
Nedlands, Western Australia, Australia, 6009
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01972789     History of Changes
Other Study ID Numbers: CRFB002AAU15
First Posted: October 30, 2013    Key Record Dates
Last Update Posted: July 25, 2017
Last Verified: July 2017
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 ):
Subfoveal choroidal neovascularization (CNV)
wet age-related macular degeneration(AMD)
inject and extend
retinal fluid

Additional relevant MeSH terms:
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Macular Degeneration
Neovascularization, Pathologic
Choroidal Neovascularization
Retinal Degeneration
Retinal Diseases
Eye Diseases
Metaplasia
Pathologic Processes
Choroid Diseases
Uveal Diseases
Ranibizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents