Primary: To demonstrate that intravitreal injection of 0.5 mg ranibizumab administered based on individual patient needs has superior efficacy compared to sham treatment in adult patients with visual impairment due to VEGF-driven ME. Secondary: Best…
ID
Source
Brief title
Condition
- Retina, choroid and vitreous haemorrhages and vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
BCVA change from baseline to month 2.
Secondary outcome
Time course of BCVA and OCT parameters, active ME leakage, rescue treatment
month 1, ranibizumab requirements over time. Adverse events.
Background summary
Vascular leakage leading to macular edema (ME) can result in irreversible
structural damage and permanent loss of vision. The pathogenesis of ME is
complex. The chronic tissue hypoxia and other metabolic causal risk factors
initiate a cascade of biochemical and physiopathological changes, such as
abnormal increased vascular endothelial growth factor (VEGF) levels in the
inner layers of the retina, generating the disruption of the blood-retinal
barrier followed by the increased accumulation of fluid within the intraretinal
layers of the macula, i.e. macular edema.
The VEGF-driven ME conditions other than diabetic macular edema (DME) and ME
associated with retinal vein occlusion (RVO) are considered to be less
frequent, the overall incidence and prevalence varies across countries or
regions worldwide. Some ocular conditions that cause ME in adults < 50 years of
age can also occur among adolescents between 12 and 18 years of age with VEGF
playing a major role in the pathogenesis.
Currently, there is no established standard of care therapy for persistent ME
due to these various etiologies. Treatments include topical NSAIDs, topical
steroids, intravitreal steroids, laser photocoagulation, etc. While the
efficacy of anti-VEGF medications in the treatment of DME and RVO has been
proven, published reports have shown in addition that intravitreal anti-VEGF
treatment could
also be beneficial in the management of ME due to various other underlying
conditions.
Ranibizumab (Lucentis) has been registered for the treatment of age-related
macular degeneration and visual impairment due to DME and ME associated with
RVO.
The purpose of this study is to determine whether intravitreal injections of
0.5 mg ranibizumab administered based on individual patient needs improve
visual acuity and reduce disease activity compared to sham treatment in adult
patients with visual impairment due to VEGF-driven ME conditions other than
diabetic macular edema DME and RVO.
Study objective
Primary: To demonstrate that intravitreal injection of 0.5 mg ranibizumab
administered based on individual patient needs has superior efficacy compared
to sham treatment in adult patients with visual impairment due to VEGF-driven
ME.
Secondary: Best-corrected visual acuity (BCVA) change from baseline by visit,
change in optical coherence tomography (OCT) parameters from baseline over
time, presence of active ME leakage assessed by fluorescein angiography (FA),
requirement for rescue treatment at Month 1, whether treatment with ranibizumab
was given by visit, number of ranibizumab treatments and re-treatments by Month
2, Month 6 and Month 12. Adverse events.
Study design
Multicenter randomized double-masked sham-controlled phase III parallel-group
study.
Randomisation (1:1) to one of the treatment regimens:
* 0.5 mg intravitreal injections of ranibizumab.
* Sham treatment. At Month 2, all adult patients assigned to the sham group
will switch to the ranibizumab treatment group.
NB: There is an open-label ranibizumab group of minors (12-18 years). However
no minors will not be included in NL.
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. 187 patients.
Intervention
Treatment withranibizumab or ni intervention till month 2. Thereafter everybody
monthly ranibizumab.
Study burden and risks
Risk: Adverse effects of study medication.
Burden: Study duration approx. 1 year. Screening, baseline, day 8, month 1,
thereafter monthly visits and end of study visit.
Intravitreal injection ranibizumab or sham on day 1. Retreatment with monthly
injections based on individual needs.
Blood tests (approx. 10 ml/occasion) at screening, month 2, 6, 9, 12.
All visits: ophthalmic examinations, incl. OCT.
Fluorescence angiography at screening, months 2, 6, 12.
Electroretinography (not in all centers) at screening, months 2, 6, 12.
Questionnaire, ophthalmic symptoms and signs, at screening, months 2, 6, 12.
Raapopseweg 1
Arnhem 6824 DP
NL
Raapopseweg 1
Arnhem 6824 DP
NL
Listed location countries
Age
Inclusion criteria
* Male or female patients at least 12 (in NL: 18) years of age.
* Naïve active ME secondary to any causes (for adult patients: except DME and RVO). See protocol page 25 for details.
* Visual impairment predominantly only due to the presence of any eligible types of ME, see protocol page 25 for details.
* BCVA score at Screening and Baseline * 24 and * 83 letters (see protocol page 25 for details).
Exclusion criteria
* Pregnant or nursing (lactating) women. Women of child-bearing potential, not practicing adequate contraception.
* Stroke less than 6 months prior to Screening.
* Systolic BP >160 mm Hg or diastolic BP >100 mm Hg at Screening or Baseline.
* Any active systemic inflammation or infection related directly to the underlying causal disease of ME at screening.
* Active diabetic retinopathy, active ocular/periocular infectious disease or active intraocular inflammation at screening.
* Intraocular pressure * 25 mmHg.
* Neovascularization of the iris or neovascular glaucoma.
* Exclusion criteria study eye and prior or current medications: see protocol page 27-28.
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 | clinicaltrials.gov; registratienummer n.n.b. |
| EudraCT | EUCTR2012-005418-20-NL |
| CCMO | NL45422.091.13 |