Trial Outcomes & Findings for Macular EpiRetinal Brachytherapy Versus Lucentis® Only Treatment (MERLOT) (NCT NCT01006538)

NCT ID: NCT01006538

Last Updated: 2020-12-07

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 363 participants
• Primary outcome timeframe: 12 months
• Results posted on: 2020-12-07

Participant Flow

Participant milestones

Measure	Arm A: Epimacular Bracytherapy + Lucentis® 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. Epimacular Brachytherapy: Strontium-90. The device delivers 24 Gray of beta radiation to the CNV lesion. Each device is calibrated for a set duration.	Arm B: Lucentis® Only Arm B: Lucentis® (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria below. Ranibizumab: intravitreal injection (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria
Overall Study STARTED	244	119
Overall Study COMPLETED	233	115
Overall Study NOT COMPLETED	11	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Macular EpiRetinal Brachytherapy Versus Lucentis® Only Treatment (MERLOT)

Baseline characteristics by cohort

Measure	Arm A (Treatment) n=244 Participants 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. Epimacular Brachytherapy: Strontium-90. The device delivers 24 Gray of beta radiation to the CNV lesion. Each device is calibrated for a set duration.	Arm B (Control): n=119 Participants Arm B: Lucentis® (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria below. Ranibizumab: intravitreal injection (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria	Total n=363 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=5 Participants	11 Participants n=7 Participants	28 Participants n=5 Participants
Age, Categorical >=65 years	227 Participants n=5 Participants	108 Participants n=7 Participants	335 Participants n=5 Participants
Age, Continuous	76.9 years STANDARD_DEVIATION 7.2 • n=5 Participants	75.8 years STANDARD_DEVIATION 7.6 • n=7 Participants	76.5 years STANDARD_DEVIATION 7.2 • n=5 Participants
Sex: Female, Male Female	155 Participants n=5 Participants	62 Participants n=7 Participants	217 Participants n=5 Participants
Sex: Female, Male Male	89 Participants n=5 Participants	57 Participants n=7 Participants	146 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	244 Participants n=5 Participants	119 Participants n=7 Participants	363 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United Kingdom	244 participants n=5 Participants	119 participants n=7 Participants	363 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

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.

Outcome measures

Measure	Arm A: Epimacular Bracytherapy + Lucentis® n=244 Participants 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. Epimacular Brachytherapy: Strontium-90. The device delivers 24 Gray of beta radiation to the CNV lesion. Each device is calibrated for a set duration.	Arm B: Lucentis® Only n=119 Participants Arm B: Lucentis® (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria below. Ranibizumab: intravitreal injection (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria
Mean Change in Early Treatment for Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) From Baseline to Month 12	-4.8 ETDRS Letters Standard Deviation 10.8	-0.9 ETDRS Letters Standard Deviation 9.7

PRIMARY outcome

Timeframe: 12 months

Outcome measures

Measure	Arm A: Epimacular Bracytherapy + Lucentis® n=244 Participants 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. Epimacular Brachytherapy: Strontium-90. The device delivers 24 Gray of beta radiation to the CNV lesion. Each device is calibrated for a set duration.	Arm B: Lucentis® Only n=119 Participants Arm B: Lucentis® (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria below. Ranibizumab: intravitreal injection (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria
Mean Number of Re-treatment Injections of Lucentis® Per Patient, Per Year.	4.8 injections per patient per year Standard Deviation 3.2	4.1 injections per patient per year Standard Deviation 2.4

SECONDARY outcome

Timeframe: 12 months

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.

Participants with worsening in BCVA by less than 15 EDTRS letters at month 12 compared with baseline were considered for this outcome measure.

Outcome measures

Measure	Arm A: Epimacular Bracytherapy + Lucentis® n=244 Participants 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. Epimacular Brachytherapy: Strontium-90. The device delivers 24 Gray of beta radiation to the CNV lesion. Each device is calibrated for a set duration.	Arm B: Lucentis® Only n=119 Participants Arm B: Lucentis® (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria below. Ranibizumab: intravitreal injection (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria
Percentage of Subjects Losing < 15 ETDRS Letters	204 Participants	110 Participants

SECONDARY outcome

Timeframe: 12 months

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.

Participants with an improvement in BCVA by more than 0 EDTRS letters at month 12 compared with baseline were considered for this outcome measure.

Outcome measures

Measure	Arm A: Epimacular Bracytherapy + Lucentis® n=244 Participants 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. Epimacular Brachytherapy: Strontium-90. The device delivers 24 Gray of beta radiation to the CNV lesion. Each device is calibrated for a set duration.	Arm B: Lucentis® Only n=119 Participants Arm B: Lucentis® (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria below. Ranibizumab: intravitreal injection (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria
Percentage of Subjects Gaining ≥ 0 ETDRS Letters	91 Participants	55 Participants

SECONDARY outcome

Timeframe: 12 months

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.

Participants with an improvement in BCVA by more than 15 EDTRS letters at month 12 compared with baseline were considered for this outcome measure.

Outcome measures

Measure	Arm A: Epimacular Bracytherapy + Lucentis® n=244 Participants 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. Epimacular Brachytherapy: Strontium-90. The device delivers 24 Gray of beta radiation to the CNV lesion. Each device is calibrated for a set duration.	Arm B: Lucentis® Only n=119 Participants Arm B: Lucentis® (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria below. Ranibizumab: intravitreal injection (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria
Percentage of Subjects Gaining ≥ 15 ETDRS Letters	3 Participants	6 Participants

SECONDARY outcome

Timeframe: 12 months

Outcome measures

Measure	Arm A: Epimacular Bracytherapy + Lucentis® n=219 Participants 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. Epimacular Brachytherapy: Strontium-90. The device delivers 24 Gray of beta radiation to the CNV lesion. Each device is calibrated for a set duration.	Arm B: Lucentis® Only n=110 Participants Arm B: Lucentis® (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria below. Ranibizumab: intravitreal injection (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria
Change in Total Lesion Size by Fluorescein Angiography From Baseline to Month 12	1.2 mm2 Standard Deviation 8.3	0.4 mm2 Standard Deviation 7.6

SECONDARY outcome

Timeframe: 12 months

Outcome measures

Measure	Arm A: Epimacular Bracytherapy + Lucentis® n=219 Participants 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. Epimacular Brachytherapy: Strontium-90. The device delivers 24 Gray of beta radiation to the CNV lesion. Each device is calibrated for a set duration.	Arm B: Lucentis® Only n=110 Participants Arm B: Lucentis® (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria below. Ranibizumab: intravitreal injection (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria
Change in Total Choroidal Neovascular Membrane (CNV) Size by Fluorescein Angiography From Baseline to Month 12	0.5 mm2 Standard Deviation 7.6	1.3 mm2 Standard Deviation 7.0

SECONDARY outcome

Timeframe: 12 months

Outcome measures

Measure	Arm A: Epimacular Bracytherapy + Lucentis® n=225 Participants 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. Epimacular Brachytherapy: Strontium-90. The device delivers 24 Gray of beta radiation to the CNV lesion. Each device is calibrated for a set duration.	Arm B: Lucentis® Only n=111 Participants Arm B: Lucentis® (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria below. Ranibizumab: intravitreal injection (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria
Foveal Thickness Measured Using Optical Coherence Tomography (OCT) From Baseline to Month 12	-1.0 μm Standard Deviation 215	15.7 μm Standard Deviation 196

Adverse Events

Arm A: Epimacular Brachytherapy + Lucentis®

Serious events: 7 serious events

Other events: 244 other events

Deaths: 3 deaths

Arm B (Control): Lucentis ® Only

Serious events: 0 serious events

Other events: 50 other events

Deaths: 5 deaths

Serious adverse events

Measure	Arm A: Epimacular Brachytherapy + Lucentis® n=244 participants at risk 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. Epimacular Brachytherapy: Strontium-90. The device delivers 24 Gray of beta radiation to the CNV lesion. Each device is calibrated for a set duration. Ranibizumab: intravitreal injection of Ranibizumab (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria	Arm B (Control): Lucentis ® Only n=119 participants at risk Arm B: Lucentis® (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria below. Ranibizumab: intravitreal injection of Ranibizumab (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria
Eye disorders Endophthalmitis	0.41% 1/244 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) are reported between baseline and month 12.	0.00% 0/119 • Adverse events (AEs) and serious adverse events (SAEs) are reported between baseline and month 12.
Eye disorders Postoperative uveitis	0.82% 2/244 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) are reported between baseline and month 12.	0.00% 0/119 • Adverse events (AEs) and serious adverse events (SAEs) are reported between baseline and month 12.
Eye disorders Retinal detachment	1.2% 3/244 • Number of events 3 • Adverse events (AEs) and serious adverse events (SAEs) are reported between baseline and month 12.	0.00% 0/119 • Adverse events (AEs) and serious adverse events (SAEs) are reported between baseline and month 12.
Eye disorders Visual hallucinations	0.41% 1/244 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) are reported between baseline and month 12.	0.00% 0/119 • Adverse events (AEs) and serious adverse events (SAEs) are reported between baseline and month 12.

Other adverse events

Measure	Arm A: Epimacular Brachytherapy + Lucentis® n=244 participants at risk 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. Epimacular Brachytherapy: Strontium-90. The device delivers 24 Gray of beta radiation to the CNV lesion. Each device is calibrated for a set duration. Ranibizumab: intravitreal injection of Ranibizumab (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria	Arm B (Control): Lucentis ® Only n=119 participants at risk Arm B: Lucentis® (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria below. Ranibizumab: intravitreal injection of Ranibizumab (0.5 mg) administered on a monthly basis as required, using the re-treatment criteria
Eye disorders Cataract	33.6% 82/244 • Number of events 82 • Adverse events (AEs) and serious adverse events (SAEs) are reported between baseline and month 12.	9.2% 11/119 • Number of events 11 • Adverse events (AEs) and serious adverse events (SAEs) are reported between baseline and month 12.
Eye disorders Visual acuity reduced	16.0% 39/244 • Number of events 39 • Adverse events (AEs) and serious adverse events (SAEs) are reported between baseline and month 12.	6.7% 8/119 • Number of events 8 • Adverse events (AEs) and serious adverse events (SAEs) are reported between baseline and month 12.
Eye disorders Ocular Adverse Events in Study Eye	52.0% 127/244 • Number of events 127 • Adverse events (AEs) and serious adverse events (SAEs) are reported between baseline and month 12.	26.1% 31/119 • Number of events 31 • Adverse events (AEs) and serious adverse events (SAEs) are reported between baseline and month 12.

Additional Information

Mr Tim Jackson

King's College Hospital, London

Phone: +44 2032999000

Email: t.jackson1@nhs.net

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place