Safety and Efficacy of Brimonidine Intravitreal Implant in Patients With Geographic Atrophy Due to Age-related Macular Degeneration (AMD)

Safety and Efficacy of Brimonidine Intravitreal Implant in Patients With Geographic Atrophy Due to AMD

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00658619

Enrollment

119

Registered

2008-04-15

Start date

2008-05-01

Completion date

2011-04-08

Last updated

2018-08-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Macular Degeneration

Brief summary

Stage 1 is a patient-masked, dose-escalation, safety evaluation of brimonidine intravitreal implant. Patients will receive implant in one eye and sham treatment (meaning no treatment) in the fellow eye. Stage 2 will begin after 1 month of safety has been evaluated for Stage 1. Stage 2 is a randomized, double-masked, dose-response, sham-controlled evaluation of the safety and efficacy of brimonidine intravitreal implant in patients with geographic atrophy from age-related macular degeneration. Patients will be followed for up to 2 years.

Interventions

OTHERSham (no implant)

Sham in one or both eyes on Day 1 and Month 6.

DRUG400 µg Brimonidine Tartrate Implant

400 µg brimonidine tartrate implant in the study eye on Day 1 and Month 6.

DRUG200 µg Brimonidine Tartrate Implant

200 µg brimonidine tartrate implant in the study eye on Day 1 and Month 6.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

50 Years to No maximum

Healthy volunteers

Inclusion criteria

* Geographic atrophy in both eyes due to age-related macular degeneration * Visual acuity between 20/40 to 20/320

Exclusion criteria

* Known allergy to brimonidine * Uncontrolled systemic disease or infection of the eye * Recent eye surgery or injections in the eye * Female patients who are pregnant, nursing or planning a pregnancy

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Size of Geographic Atrophy Lesion Area in the Study Eye	Baseline, Month 12	Change from baseline in size of geographic atrophy lesion area in the study eye is based on fundus photography as read by an independent Reading Center. Photographs are taken with a specialized microscope with an attached camera to photograph the interior of the eye, including the retina and optic disc. A positive change from baseline indicates an increase in size of geographic atrophy lesion area (worsening; disease progression). Data are reported in disc area where 1 disc area = 1.767 millimeters squared (mm\^2).

Secondary

Measure	Time frame	Description
Change From Baseline in Size of Geographic Atrophy Lesion Area in the Study Eye	Baseline, Month 3, Month 6, Month 9, Month 18, Month 24	Change from baseline in size of geographic atrophy lesion area in the study eye is based on fundus photography as read by an independent Reading Center. Photographs are taken with a specialized microscope with an attached camera to photograph the interior of the eye, including the retina and optic disc. A positive change from baseline indicates an increase in size of geographic atrophy lesion area (worsening; disease progression). Data are reported in disc area where 1 disc area = 1.767 millimeters squared (mm\^2).
Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye	Baseline, 24 Months	BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening.
Change From Baseline in Contrast Sensitivity in the Study Eye	Baseline, 24 Months	Change from baseline in contrast sensitivity in the study eye is measured using a Pelli-Robson contrast sensitivity chart at 1 meter. The contrast sensitivity chart contains letters that are darkest at the top and then get progressively lighter. Scores range from 0 to 48 and are based on the number of letters read correctly. A negative change from baseline indicates a worsening in contrast sensitivity and a positive change from baseline indicates an improvement.
Change From Baseline in Reading Speed in the Study Eye	Baseline, 24 Months	Change from baseline in reading speed in the study eye is assessed using modified Bailey-Lovie word charts. Patients read the chart for 2 minutes and the numbers of words read correctly per minute are totaled. An increase in the number of words read correctly indicates an improvement and a decrease in the number of words read correctly indicates a worsening.

Countries

Australia, Germany, Italy, Philippines, Portugal, South Korea, United States

Participant flow

Pre-assignment details

Stage 1 of the study was a patient-masked, dose-escalation, paired-eye comparison and the Investigator was not masked. Stage 2 was a parallel-group, sham-controlled, paired-eye comparison. Investigators were masked as to dose received for patients in the active treatment groups. No patients from Stage 1 were enrolled in Stage 2.

Participants by arm

Arm	Count
400 µg Brimonidine Tartrate Implant Stage 1 Stage 1: 400 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1 and Month 6.	3
200 µg Brimonidine Tartrate Implant Stage 1 Stage 1: 200 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1 and Month 6.	3
400 µg Brimonidine Tartrate Implant Stage 2 Stage 2: 400 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1 and Month 6.	41
200 µg Brimonidine Tartrate Implant Stage 2 Stage 2: 200 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1 and Month 6.	49
Sham (no Implant) Stage 2 Stage 2: sham in both eyes on Day 1 and Month 6.	23
Total	119

Baseline characteristics

Characteristic	400 µg Brimonidine Tartrate Implant Stage 1	200 µg Brimonidine Tartrate Implant Stage 1	400 µg Brimonidine Tartrate Implant Stage 2	200 µg Brimonidine Tartrate Implant Stage 2	Sham (no Implant) Stage 2	Total
Age, Continuous	85.0 Years STANDARD_DEVIATION 3.61	79.0 Years STANDARD_DEVIATION 3	75.6 Years STANDARD_DEVIATION 8.78	77.0 Years STANDARD_DEVIATION 9.13	78.4 Years STANDARD_DEVIATION 5.8	77.0 Years STANDARD_DEVIATION 8.33
Sex: Female, Male Female	3 Participants	2 Participants	27 Participants	28 Participants	12 Participants	72 Participants
Sex: Female, Male Male	0 Participants	1 Participants	14 Participants	21 Participants	11 Participants	47 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	38 / 43	47 / 51	20 / 23
serious Total, serious adverse events	14 / 43	20 / 51	9 / 23

Outcome results

Primary

Change From Baseline in Size of Geographic Atrophy Lesion Area in the Study Eye

Change from baseline in size of geographic atrophy lesion area in the study eye is based on fundus photography as read by an independent Reading Center. Photographs are taken with a specialized microscope with an attached camera to photograph the interior of the eye, including the retina and optic disc. A positive change from baseline indicates an increase in size of geographic atrophy lesion area (worsening; disease progression). Data are reported in disc area where 1 disc area = 1.767 millimeters squared (mm\^2).

Time frame: Baseline, Month 12