Macular EpiRetinal Brachytherapy Versus Lucentis® Only Treatment (MERLOT)

NCT01006538 | Completed Phase 4 Results DMC

• 2 other identifiers: 09/HO206/202009-012509-20
• Study Type: interventional
• Target: 363
• Locations: 1 country
• Sites: 24

Brief 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.

Conditions

Macular Degeneration

Keywords

Wet Age-related Macular Degeneration; Predominantly classic; Minimally classic; Occult with no classic; Retinal Angiomatous Proliferation (RAP) lesions

Outcome Measures

Primary Outcomes (2)

• Mean Change in Early Treatment for Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) From Baseline to Month 12

  Manifest refraction and BCVA measurements were performed according to the standard procedure originally developed for Early Treatment for Diabetic Retinopathy Study (ETDRS) and adapted for the Age Related Eye Disease Study (AREDS) protocol. Visual acuity testing was measured at a distance of 4 meters and, for subjects with sufficiently reduced vision, at 1 meter. The ETDRS charts consist of 14 lines, each comprising a series of 5 letters of equal difficulty, with standardized spacing between letters and rows (total 70 letters). Minimum is 0 (no letters read at 1 m) and maximum possible is 100 (70 letters read at 4 m + 30). If visual acuity is so poor that the subject cannot read any of the largest letters at 1 meter count fingers (CF), hand movements (HM) and light perception (PL) are tested. The mean change in ETDRS BCVA was calculated from baseline to month 12.

  12 months

• Mean Number of Re-treatment Injections of Lucentis® Per Patient, Per Year.

  12 months

Secondary Outcomes (6)

• Percentage of Subjects Losing < 15 ETDRS Letters

  12 months

• Percentage of Subjects Gaining ≥ 0 ETDRS Letters

  12 months

• Percentage of Subjects Gaining ≥ 15 ETDRS Letters

  12 months

• Change in Total Lesion Size by Fluorescein Angiography From Baseline to Month 12

  12 months

• Change in Total Choroidal Neovascular Membrane (CNV) Size by Fluorescein Angiography From Baseline to Month 12

  12 months

Study Arms (2)

Arm A (treatment)

EXPERIMENTAL

Arm A: A single surgical procedure with epimacular brachytherapy using the VIDION® System, with Lucentis® (0.5 mg) administered on a monthly basis as required.

Device: Epimacular Brachytherapy; Drug: Ranibizumab

Arm B (control):

ACTIVE COMPARATOR

Arm B: Lucentis® (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria below.

Drug: Ranibizumab

Interventions

Epimacular Brachytherapy DEVICE

Strontium-90. The device delivers 24 Gray of beta radiation to the choroidal neovascular membrane (CNV) lesion. Each device is calibrated for a set duration.

Also known as: Vidion System, EpiRetinal Brachytherapy

Arm A (treatment)

Ranibizumab DRUG

intravitreal injection of Ranibizumab (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria

Also known as: Lucentis, Anti-VEGF therapy

Arm A (treatment); Arm B (control):

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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;
• 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)

You may not qualify if:

• Patients who have not been treated in accordance with NICE guidance;
• Visual acuity worse than 6/96 at the time of study enrolment;
• 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);
• Subfoveal scarring;
• Subjects with active concomitant disease in the study eye, including uveitis, presence of pigment epithelial tears or rips, acute ocular or periocular infection;
• 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;
• Subjects with advanced glaucoma (greater than 0.8 cup:disk) or intraocular pressure ≥ 30 mmHg in the study eye;
• Previous glaucoma filtering surgery in the study eye;
• 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;
• Current vitreous haemorrhage in the study eye;
• History of rhegmatogenous retinal detachment or macular hole in the study eye;
• 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);
• Previous cataract surgery within 2 months prior to enrolment into the study;
• Subjects with known serious allergies to fluorescein dye used in angiography;
• Subjects with known sensitivity or allergy to Lucentis®;

Sponsors & Collaborators

• King's College Hospital NHS Trust: lead

Study Sites (24)

Royal Devon and Exeter Hospital

Exeter, Devon, EX2 5DW, United Kingdom

Location

Plymouth Royal Eye Infirmary

Plymouth, Devon, PL4 6PL, United Kingdom

Location

Torbay Hospital

Torquay, Devon, TQ2 7AA, United Kingdom

Location

Royal Bournemouth Hospital

Bournemouth, Dorset, BH7 7DW, United Kingdom

Location

Sussex Eye Hospital

Brighton, East Sussex, BN2 5BF, United Kingdom

Location

Hull and East Yorks Hospital

Hull, East Yorkshire, HU3 2JZ, United Kingdom

Location

Essex County Hospital

Colchester, Essex, CO3 3SP, United Kingdom

Location

Southend Hospital

Westcliff-on-Sea, Essex, SS0 0RY, United Kingdom

Location

Manchester Royal Eye Hospital

Manchester, Greater Manchester, M13 9WH, United Kingdom

Location

Queen Alexandra Hospital

Portsmouth, Hampshire, PO6 3LY, United Kingdom

Location

Maidstone Hospital

Maidstone, Kent, ME16 9QQ, United Kingdom

Location

Ashford William Harvey Hospital

Willesborough, Kent, TN24 0LZ, United Kingdom

Location

Royal Liverpool Hospital

Liverpool, Merseyside, L7 8XP, United Kingdom

Location

Arrowe Park Hospital

Upton, Merseyside, CH49 5PE, United Kingdom

Location

James Cook Hospital

Middlesbrough, North Yorkshire, TS4 3BW, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, South Yorkshire, S10 2JF, United Kingdom

Location

Southampton Hospital

Shirley, Southampton, SO16 6YD, United Kingdom

Location

Royal Victoria Infirmary

Newcastle, Tyne and Wear, NE1 4LP, United Kingdom

Location

Sunderland Eye Infimary

Sunderland, Tyne and Wear, SR2 9HP, United Kingdom

Location

Warwick Hospital Eye Unit

Warwick, Warwickshire, CV34 5BW, United Kingdom

Location

St James University Hospital

Leeds, West Yorkshire, LS9 7TF, United Kingdom

Location

Bristol Eye Hospital

Bristol, BS1 2LX, United Kingdom

Location

Darlington Memorial Hospital

Darlington, DL3 6HX, United Kingdom

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

Related Publications (4)

• Jackson TL, Soare C, Petrarca C, Simpson A, Neffendorf JE, Petrarca R, Muldrew KA, Peto T, Chakravarthy U, Membrey L, Haynes R, Costen M, Steel DHW, Desai R; MERLOT Study Group. Epimacular brachytherapy for previously treated neovascular age-related macular degeneration: month 36 results of the MERLOT randomised controlled trial. Br J Ophthalmol. 2023 Jul;107(7):987-992. doi: 10.1136/bjophthalmol-2021-320620. Epub 2022 Feb 25.

  PMID: 35217515 DERIVED

• Evans JR, Igwe C, Jackson TL, Chong V. Radiotherapy for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2020 Aug 26;8(8):CD004004. doi: 10.1002/14651858.CD004004.pub4.

  PMID: 32844399 DERIVED

• Jackson TL, Soare C, Petrarca C, Simpson A, Neffendorf JE, Petrarca R, Muldrew A, Peto T, Chakravarthy U, Membrey L, Haynes R, Costen M, Steel D, Desai R; MERLOT Study Group. Evaluation of Month-24 Efficacy and Safety of Epimacular Brachytherapy for Previously Treated Neovascular Age-Related Macular Degeneration: The MERLOT Randomized Clinical Trial. JAMA Ophthalmol. 2020 Aug 1;138(8):835-842. doi: 10.1001/jamaophthalmol.2020.2309.

  PMID: 32644148 DERIVED

• Jackson TL, Dugel PU, Bebchuk JD, Smith KR, Petrarca R, Slakter JS, Jaffe GJ, Nau JA; CABERNET Study Group. Epimacular brachytherapy for neovascular age-related macular degeneration (CABERNET): fluorescein angiography and optical coherence tomography. Ophthalmology. 2013 Aug;120(8):1597-603. doi: 10.1016/j.ophtha.2013.01.074. Epub 2013 Mar 13.

  PMID: 23490325 DERIVED

Related Links

• MERLOT Study website with information for Patients and Investigators
• Website for King's College Hospital (Study Sponsor Site)

MeSH Terms

Conditions

Macular Degeneration

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Radiation-related microvascular retinal changes may occur beyond the 12 month reporting window (three years' follow up is planned)

Results Point of Contact

• Title: Mr Tim Jackson
• Organization: King's College Hospital, London

t.jackson1@nhs.net

+44 2032999000

Study Officials

• Timothy L Jackson, PhD FRCOphth

  King's College Hospital NHS Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2009
• First Posted: November 3, 2009
• Study Start: November 1, 2009
• Primary Completion: March 1, 2015
• Study Completion: December 1, 2016
• Last Updated: December 7, 2020
• Results First Posted: July 22, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (24)