Macular EpiRetinal Brachytherapy Versus Lucentis® Only Treatment (MERLOT)

• Status: Completed
• Trial end date: 2016-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Wet age-related macular degeneration is the most common cause of blind registration in the United Kingdom (UK). Standard treatment involves regular eye injections of a drug called ranibizumab (Lucentis). For most patients, ranibizumab maintains their vision but the effect of the drug is temporary, and they therefore require monthly hospital visits and typically six injections into the eye every year, probably for life.

This study tests a new surgical device that delivers a focal dose of radiation (epimacular brachytherapy) to the macula (the part inside the back of the eye that gives fine central vision), to try and reduce or eliminate the need for ongoing, regular eye injections. The trial compares epimacular brachytherapy to ongoing standard treatment with ranibizumab.

Whereas most studies of this new surgical device target patients who have not yet commenced any treatment, this study targets those who are requiring frequent eye injections, as there are limited surgical resources and these resources are best directed to those who have not fully responded to ranibizumab therapy, or whose response is shortlived. These patients have the most to gain from a device that may reduce their burden of treatment. The findings in untreated disease cannot be extrapolated to this discrete subset of patients, hence the need for a study that targets refractory disease.

It is hypothesised that epimacular brachytherapy will reduce the frequency of Lucentis® (ranibizumab) re-treatment that patients require, whilst maintaining visual acuity.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: King's College Hospital NHS Trust
• Treatments: Bevacizumab; Ranibizumab

Criteria

Inclusion Criteria:

1. Subjects with subfoveal choroidal neovascularisation associated with wet age-related macular degeneration. Retinal Angiomatous Proliferation (RAP) lesions not directly involving the fovea must be associated with contiguous foveal leakage demonstrated on fundus examination, optical coherence tomography (OCT), or fluorescein angiography;

2. Subjects must have received anti-VEGF induction treatment, defined as the first three months of anti-VEGF therapy. Following this induction period, subjects must have received at least 4 additional injections of Lucentis® in no more than 12 months preceding enrolment, or 2 additional injections of Lucentis® in no more than 6 months preceding enrolment, given on an as needed basis;

3. At the time subjects commenced anti-VEGF therapy for wet age-related macular degeneration they were aged 50 years or older and met the NICE treatment criteria for Lucentis® therapy, as outlined in the Final Appraisal Determination (FAD). This states that all of the following circumstances must apply in the eye to be treated:

• the best-corrected visual acuity is between 6/12 and 6/96 (24 to 69 ETDRS letters)

• there is no permanent structural damage to the central fovea

• the lesion size is less than or equal to 12 disc areas in greatest linear dimension

• there is evidence of recent presumed disease progression (blood vessel growth, as indicated by fluorescein angiography, or recent visual acuity changes)

Exclusion Criteria:

1. Patients who have not been treated in accordance with NICE guidance;

2. Visual acuity worse than 6/96 at the time of study enrolment;

3. Subjects with prior or concurrent subfoveal CNV therapy with agents, surgery or devices (other than Macugen®, Avastin®, or Lucentis®) including thermal laser photocoagulation (with or without photographic evidence), photodynamic therapy, intravitreal or subretinal steroids, and transpupillary thermotherapy (TTT);

4. Subfoveal scarring;

5. Subjects with active concomitant disease in the study eye, including uveitis, presence of pigment epithelial tears or rips, acute ocular or periocular infection;

6. Subjects who have been previously diagnosed with Type 1 or Type 2 Diabetes Mellitus. Subjects who do not have a documented diagnosis, but have retinal findings consistent with Type 1 or Type 2 Diabetes Mellitus;

7. Subjects with advanced glaucoma (greater than 0.8 cup:disk) or intraocular pressure ≥ 30 mmHg in the study eye;

8. Previous glaucoma filtering surgery in the study eye;

9. Subjects with inadequate pupillary dilation or significant media opacities in the study eye, including cataract, which may interfere with visual acuity or the evaluation of the posterior segment;

10. Current vitreous haemorrhage in the study eye;

11. History of rhegmatogenous retinal detachment or macular hole in the study eye;

12. Subjects who present with CNV due to causes other than AMD, including subjects with known or suspected idiopathic polypoidal choroidal vasculopathy (IPCV), ocular histoplasmosis syndrome, angioid streaks, multifocal choroiditis, choroidal rupture, or pathologic myopia (spherical equivalent ≥ 8 Dioptre or axial length ≥ 25mm);

13. Subjects who have undergone any intraocular surgery in the study eye within 12 weeks prior to the screening visit, with the exception of cataract surgery as discussed in the Exclusion Criteria #14

14. Previous cataract surgery within 2 months prior to enrolment into the study;

15. Subjects with known serious allergies to fluorescein dye used in angiography;

16. Subjects with known sensitivity or allergy to Lucentis®;

17. Subjects who underwent previous radiation therapy to the eye, head or neck;

18. Subjects with an intravitreal device or drug in the study eye;

19. Subjects with any other condition, which in the judgment of the investigator would prevent the subject from completing the study (e.g. documented diagnosis of dementia or serious mental illness);

20. Current participation in another drug or device clinical trial, or participation in such a clinical trial within the last year;

21. History of use of drugs with known retinal toxicity, including: chloroquine (Aralen - an anti-malarial drug), hydroxychloroquine (Plaquenil), phenothiazines, chlorpromazine (Thorazine), thioridazine (Mellaril), fluphenazine (Prolixin), perphenazine (Trilafon), and trifluoperazine (Stelazine);

22. Subjects who are unwilling or unable to return for scheduled treatment and follow-up examinations for three years;

23. Women must be post-menopausal more than 1 year unless surgically sterilised