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Trial registered on ANZCTR


Registration number
ACTRN12613001020774
Ethics application status
Approved
Date submitted
6/09/2013
Date registered
13/09/2013
Date last updated
13/09/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
To investigate the role of Intravitreal Aflibercept (Eylea) in the treatment of patients whose wet Age related Macular degeneration is not adequately controlled with conventional anti VEGF (intravitreal Avastin or Lucentis) treatment.
Scientific title
Intravitreal aflibercept for the treatment of previously treated exudative age related macular degeneration
Secondary ID [1] 283149 0
Nil
Universal Trial Number (UTN)
U1111-1140-9022
Trial acronym
AAA Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Exudative (Wet) Age related Macular Degeneration 290008 0
Condition category
Condition code
Eye 290393 290393 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The trial will study the effectiveness of intravireal AFLIBERCEPT in the treatment of exudative wet Macular degeneration which thus far has not responded to other anti VEGF agents (Bevacizumab and Ranibizumab).

The dose of aflibercept administered is 2 mg. The drug will delivered by intravitreal injection every 4 weeks for the first 12 weeks of the study. Thereafter the drug will be administered by intravitreal injection every 8 weeks until the close of the trial at week 52. The duration of the study is 12 months.

For the dutration of the study, participants will attend for review every 4 weeks but they will only require treatment every second visit. During each visit the patients response to treatment will be assessed with OCT (to measure the macula thickness) and their visual acuity will be assessed.
Intervention code [1] 287886 0
Treatment: Drugs
Comparator / control treatment
The patients previous lack of response to their existing anti VEGF treatment will be used as the comparitor in this trial.

This historical data will be derived from the fact that all participants in the trial will have had persiting subretinal fluid or cystic intraretinal oedema on OCT after treatment despite timely treatment with at least 4 anti-VEGF treatments delivered within minimum of 6 months. Thus all patients will have disease that has been non responsive to the conventional antiVEGF treatments for at least 6 months prior to entering the trial.
Control group
Historical

Outcomes
Primary outcome [1] 290413 0
Improvement in Best Corrected Visual Acuity (as measured with the EDTRS visual acuity chart) after 12 months of treatment with intravitreal Aflibercept compared with baseline.
Timepoint [1] 290413 0
12 months
Secondary outcome [1] 304470 0
Anatomical resolution of subretinal fluid as measured with OCT at 12 months compared with baseline.
Timepoint [1] 304470 0
12 months
Secondary outcome [2] 304471 0
Improved level of well being as measured using the Impact of Visual Impairment questionnaire
Timepoint [2] 304471 0
12 months
Secondary outcome [3] 304570 0
Anatomical resolution of intraretinal oedema as measured with OCT at 12 months compared with baseline.
Timepoint [3] 304570 0
12 months
Secondary outcome [4] 304571 0
Anatomical resolution of any associated Pigment epithelial detachment as measured with OCT at 12 months compared with baseline.
Timepoint [4] 304571 0
12 months

Eligibility
Key inclusion criteria
1. Ability to provide informed consent and complete study assessments
2. Age 50 years or older
3. CNV secondary to AMD
4. Best corrected baseline visual acuity between 6/6 to 6/60 on ETDRS chart
5. Presence of subretinal fluid or cystic intraretinal oedema on spectral domain OCT (SD-OCT) [Spectralis] after at least four anti-VEGF treatments within minimum of 6 months and maximum of 5 years before enrollment of the study.
6. Documentation of the presence of subretinal fluid or cystoid oedema less than 42 days since last treatment with an antiVegf agent.
Minimum age
50 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnancy or lactation
2. Premenopausal women not using contraception
3. Prior anti-VEGF injection in the study eye within 30 days of baseline
4. Prior treatment with photo dynamic therapy (PDT) within 90 days of baseline and more than 6 prior PDT treatments
5. Significant subretinal fibrosis or atrophy
6. Prior treatment with triamcinolone in the study eye within six months of baseline
7. Intraocular surgery in the study eye within 2 months of baseline
8. Prior vitrectomy or other surgical intervention for AMD in the study eye

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All patients whose wet Macular Degeneration is being treated in our unit and whose disease is not responding to their existing therapies will be invited to enroll in the study. All patients enrolled into the study will receive treatment with the study drug.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
This is a non randomised study
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The proportion of those patients whose visual acuity improved after 12 months will be compared to Base line. A similar analysis will be conducted to assess the proportion of patients whose disease activity (as measured by improved sub retinal fluid intra retinal oedema and Pigment epithelial detachment) improved compared to baseline.

Re sample size:
From our local audit data we found that approximately 8-10% of patients with wet AMD did not respond to conventional antiVEGF agents. We look after a total cohort of 700 patients and thus judged that approximately 70 patients were therefore being inadequately treated with the existing treatments. We also know from anecodotal data; (data which has now been supported by published trial data from small cohort studies) that many of these patients do respond to Aflibercept. As this study is an investigator lead trial we took a proposal to the drug company who are supplying the drug to conduct a trial which would allow most of our patients access to this drug. This approach would ensure that we had as large a sample size as practically possible and at the same time allow as many patietns as possible to get access to the new treatment.


Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 5391 0
New Zealand
State/province [1] 5391 0

Funding & Sponsors
Funding source category [1] 287904 0
Hospital
Name [1] 287904 0
Auckland District Health Board
Address [1] 287904 0
Department of Ophthalmology,
Greenlane Clinical Centre,
Private bag 92189
Auckland Mail centre,
Auckland 1142
Country [1] 287904 0
New Zealand
Primary sponsor type
Hospital
Name
Greenlane Clinical Centre Auckland District Health Board
Address
Department of Ophthalmology,
Greenlane Clinical Centre,
Private bag 92189
Auckland Mail centre,
Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 286631 0
Commercial sector/Industry
Name [1] 286631 0
Bayer New Zealand
Address [1] 286631 0
Bayer New Zealand,
Bayer Healthcare Pharmaceuticals
3 Argus Place, Hillcrest,
Auckland , 0627,
New Zealand
Country [1] 286631 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289840 0
HDEC Ethics
Ethics committee address [1] 289840 0
Health and Disability Ethics Committe,
Ministry of Health,
1 The Terrace,
PO Box 5013
Wellington
6011
Ethics committee country [1] 289840 0
New Zealand
Date submitted for ethics approval [1] 289840 0
Approval date [1] 289840 0
15/07/2013
Ethics approval number [1] 289840 0
13/NTB/66

Summary
Brief summary
The aim of the study is to evaluate the effectiveness of intravitreal Aflibercept in the treatment of previously treated choroidal neovascularisation (CNV) secondary to age-related macular degeneration MD).

This is an open label study in patients who have been previously treated with intravitreal anti-VEGF drug (ranibizumab or bevacizumab) for AMD and have persisting disease activity despite previous monthly intravitreal injections. All subjects will initially receive 3 monthly doses of 2.0mg of intravitreal Aflibercept injection and then have 2.0mg of intravitreal Aflibercept at two monthly intervals for the next 9 months.
At the close of the trial the effectiveness of Aflibercept in the mangement of wet age related macular degeneration that has not responded to our existing therapies will be assessed.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 42706 0
Dr David Squirrell
Address 42706 0
Department of Ophthalmology,
Greenlane Clinical Centre,
Private bag 92189
Auckland Mail Centre,
Auckland 1142
Country 42706 0
New Zealand
Phone 42706 0
+ 64 9 3074949 ext 27624
Fax 42706 0
Email 42706 0
dsquirrell@adhb.govt.nz
Contact person for public queries
Name 42707 0
Dr David Squirrell
Address 42707 0
Department of Ophthalmology,
Greenlane Clinical Centre,
Private bag 92189
Auckland Mail centre,
Auckland 1142

Country 42707 0
New Zealand
Phone 42707 0
+ 64 9 3074949 ext 27624
Fax 42707 0
Email 42707 0
dsquirrell@adhb.govt.nz
Contact person for scientific queries
Name 42708 0
Dr David Squirrell
Address 42708 0
Department of Ophthalmology,
Greenlane Clinical Centre,
Private bag 92189
Auckland Mail centre,
Auckland 1142
Country 42708 0
New Zealand
Phone 42708 0
+ 64 9 3074949 ext 27624
Fax 42708 0
Email 42708 0
dsquirrell@adhb.govt.nz

No information has been provided regarding IPD availability
Summary results
No Results