Primary: to compare the treatment effect of ranibizumab PRN (visual acuity loss and/or SD-OCT disease activity guided retreatment) versus aflibercept bimonthly regimen on central retinal thickness stability as measured by mean fluctuations between…
ID
Source
Brief title
Condition
- Retina, choroid and vitreous haemorrhages and vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Central retinal thickness up to month 6.
Secondary outcome
Visual acuity, retinal stress. Adverse events.
Background summary
Age-related macular degeneration (AMD) is the leading cause of severe loss of
vision in the elderly population. The depositions between the retinal
epithelium and Bruch*s membrane, known as drusen, is a main predictor of a
progressive and degenerative process, in which an advanced AMD,
neovascularization and atrophy, can be the final result.
In recent years earlier diagnosis, close monitoring (e.g. OCT) and efficacious
and safe medications (such as ranibizumab) of patients with neovascular (wet)
AMD (wAMD) have contributed to a decrease of cases of blindness as well as
improve the quality of life of the patients with this degenerative disease.
The current ranibizumab label in the EU recommends the monitoring of VA and the
interruption and re-initiation of treatment primarily based on VA assessments.
When stable VA (based on 3 consecutive monthly observations) is observed,
treatment can be interrupted. If, again, a loss of VA is observed, treatment is
re-initiated.
Since the approval of Lucentis (ranibizumab) there have been several clinical
studies that have evaluated a PRN (*if needed*) treatment algorithm including
guidance by OCT, but the results have been variable.
Despite the fact that OCT imaging is commonly used in clinical practice, there
is limited randomized clinical trial evidence on the use of OCT guided
treatment algorithms. Since OCT findings may play a key role in the treatment
decisions, there is need to generate additional data from large clinical
studies. Advances in OCT technology have led to the development and more
widespread use of spectral domain OCT (SD-OCT), and this study will use SD-OCT
to measure central retinal thickness.
This study will evaluate and compare the efficacy and safety of two approved
wAMD treatment drugs with their associated distinct regimens aiming to achieve
and maintain stable central subfield retinal thickness and prevent retinal
stress. Ranibizumab will be administered PRN with a best-corrected visual
acuity (BCVA) loss and/or OCT disease activity guided retreatment and
aflibercept according to its approved European label (continuous treatment for
the first year).
Study objective
Primary: to compare the treatment effect of ranibizumab PRN (visual acuity loss
and/or SD-OCT disease activity guided retreatment) versus aflibercept bimonthly
regimen on central retinal thickness stability as measured by mean fluctuations
between Month 3 and 6.
Secondary: to demonstrate correlation of functional outcome (visual acuity) at
month 12 with retinal stress, defined as significant fluctuations in central
retinal thickness, parameters as measured by SD-OCT up to month 6. Safety.
Study design
Multicenter randomized open-label phase IV parallel-group study.
Randomization (1:1) to one of the treatment regimens:
* 0.5 mg intravitreal injections of ranibizumab monthly until maximum stable
BCVA with retreatment based on BCVA loss and/or SD-OCT disease activity.
* 2 mg intravitreal injections of aflibercept monthly for the first 3 months,
followed by 2 mg intravitreal injections once every 2 months (current EU SmPC
label).
Treatment of one eye. If both eyes are affected: the *study eye* will be chosen
by the investigator. The treatment of the other eye will be selected by the
investigator.
Study duration 12 months.
Approx. 706 patients.
Intervention
Treatment with ranibizumab or aflibercept.
Study burden and risks
Risk: Adverse effects of study medication.
Burden: Study duration approx. 12 months. Screening, baseline, thereafter
monthly visits and end of study visit. Duration mostly 2-6 h.
Ranibizumab: monthly intravitreal injections (at least 3) until stable BCVA.
Retreatment with monthly injections based on BCVA plus/minus OCT paramaters.
Aflibercept: monthly injections during first 3 months, thereafter every 2
months.
Monthly ophthalmic examinations, incl. OCT.
Angiography at screening, months 3, 12.
At screening 4 ml blood in women of childbearing potential for pregnancy test
Questionnaire quality of life, at screening, months 3, 12.
In selected centres: electroretinography and assessment of contrast sensitivity.
Optional: biomarker research (3-8 times 20 ml blood and 2 extra visits for a
blood draw).
Raapopseweg 1
Arnhem 6824 DP
NL
Raapopseweg 1
Arnhem 6824 DP
NL
Listed location countries
Age
Inclusion criteria
* Male or female patients 18 years and above.
* Visual impairment predominantly due to neovascular AMD.
* Active, newly diagnosed, untreated, angiographically documented CNV lesion (see protocol page 21 for details) secondary to AMD.
Exclusion criteria
* Pregnant or lactating women. Women of child-bearing potential, not practicing adequate contraception.
* Stroke or myocardial infarction less than 3 months prior to screening.
* Systolic BP >160 mm Hg or diastolic BP >100 mm Hg at Screening or Baseline.
* Any active (peri)ocular infection or inflammation.
* Uncontrolled glaucoma (intraocular pressure*30 mm Hg on medication).
* Neovascularization of the iris or neovascular glaucoma.
* Exclusion criteria study eye and prior or current medications: see protocol page 22-23.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinical trials.gov; NCT01958918 |
| EudraCT | EUCTR2013-002431-15-NL |
| CCMO | NL48042.018.14 |