Global Atrophie Biomarker Evaluation Study (GABiE)

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03935126
• Collaborator: (none)
• Enrollment: 3
• Locations: 2
• Actual Duration (Months): 12.3
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To investigate the use of microperimetry and SS-OCT in assessing the natural changes of retinal sensitivity and anatomy in the perilesional zone of geographic atrophy areas in patients with dry age-related macular degeneration.

Condition or Disease	Intervention/Treatment	Phase
Age-related Macular Degeneration	Diagnostic Test: Diagnostics

Study Design

• Study Type: Observational
• Actual Enrollment: 3 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: A Biomarker Evaluation Study in Patients With Geographic Atrophy Secondary to Age-related Macular Degeneration (AMD) Evaluating the Use of Microperimetry (Fundus-controlled Perimetry) and Swept Source-OCT in Assessing Changes in Retinal Sensitivity and Anatomy Over Time.
• Actual Study Start Date: May 7, 2019
• Actual Primary Completion Date: May 6, 2020
• Actual Study Completion Date: May 14, 2020

Arms and Interventions

Arm	Intervention/Treatment
All patients	Diagnostic Test: Diagnostics; Diagnostics

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Retinal Sensitivity in the Junctional Zone and in the Perilesional Zone of the Largest Atrophic Loci as Assessed by Microperimetry for the Evaluation of Macular Functional Response at Week 12 [At baseline and at week 12.]

2. Change From Baseline in Retinal Pigment Epithelium (RPE) Layer Thickness in the Junctional Zone and in the Perilesional Zone as Measured by Swept Source - Optical Coherence Tomography (SS-OCT) at Week 12 [At baseline and at week 12.]

3. Change From Baseline in Photoreceptor Layer Thickness in the Junctional Zone and in the Perilesional Zone as Measured by Swept Source - Optical Coherence Tomography (SS-OCT) at Week 12 [At baseline and at week 12.]

Secondary Outcome Measures

1. Change From Baseline in Retinal Sensitivity in the Junctional Zone and in the Perilesional Zone of the Largest Atrophic Loci as Assessed by Microperimetry at Week 24 and 48 [At baseline and at week 24 and 48.]

2. Change From Baseline in Retinal Pigment Epithelium (RPE) Layer Thickness in the Junctional Zone and in the Perilesional Zone as Measured by Swept Source - Optical Coherence Tomography (SS-OCT) at Week 24 and 48 [At baseline and at week 24 and 48.]

3. Change From Baseline in Photoreceptor Layer Thickness in the Junctional Zone and in the Perilesional Zone as Measured by Swept Source - Optical Coherence Tomography (SS-OCT) at Week 24 and 48 [At baseline and at week 24 and 48.]

4. Change From Baseline in the GA Area as Measured by Fundus Autofluorescence (FAF) at Week 12, 24 and 48 [At baseline and at week 12, 24 and 48]

5. Change From Baseline in Best Corrected Visual Acuity (BCVA) Score as Assessed by Early Treatment Diabetic Retinopathy Scale (ETDRS) Chart at a Starting Distance of 4 Meters at Week 12, 24 and 48 [At baseline and at week 12, 24 and 48.]

6. Change From Baseline in Low Luminance Visual Acuity (LLVA) Score as Assessed by ETDRS Chart Under Low Luminance Conditions at a Starting Distance of 4 Meters at Week 12, 24 and 48 [At baseline and at week 12, 24 and 48.]

7. Number of Scotomatous Points Assessed by Microperimetry at Week 12, 24 and 48 [At week 12, 24 and 48]

8. Change From Baseline in the Area of Choroidal Non-perfusion as Measured Via Optical Coherence Tomography Angiography (OCT-A) at Week 12, 24 and 48 [At baseline and at week 12, 24 and 48.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the study

• Age >=60 years

• Ability (including a sufficient general health status according to investigators judgement) and willingness to undertake all scheduled visits and assessments including predefined methodology and standards utilizing microperimetry GA secondary to AMD with no evidence of prior or active choroidal neovascularization (CNV) in the study eye

• GA lesion in the study eye must reside completely within the FAF imaging field (Field 2- 30 degree image centered on the fovea)

• BCVA of 20/63 or better (Snellen equivalent) using ETDRS charts at starting distance of 4 m in the study eye

• Well demarcated area(s) of GA secondary to AMD with no evidence of prior or active CNV in the study eye

• The total GA lesion size >=1.2 mm^{2 (approximately >=0.5 disc area [DA]) and <=17.78 mm}2 (approximately <=7 DA) and must reside completely within the FAF imaging field (Field 2-30 degree image centered on the fovea)

• If GA is multifocal, at least 1 focal lesion must be >=1.2 mm^2 (approximately

=0.5 DA)

• Sufficiently clear ocular media, adequate pupillary dilation, and fixation to permit quality fundus imaging in the study eye

Exclusion Criteria:

• GA in either eye due to causes other than AMD (for example, monogenetic macular dystrophies [e.g., Stargardt disease, cone rod dystrophy] or toxic maculopathies [e.g., chloroquine/hydroxychloroquine maculopathy])

• Receiving active treatment in any studies of investigational drugs for GA/dry AMD in the study eye

• Mean sensitivity difference > 3 dB between the two microperimetry examinations in the screening visit.

• History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in the study eye

• Previous laser photocoagulation for CNV, diabetic macular edema, retinal vein occlusion, and proliferative diabetic retinopathy in the study eye

• Prior treatment with Visudyne ®, external-beam radiation therapy, or transpupillary thermotherapy in the study eye

• History of prophylactic subthreshold laser treatment for AMD in the study eye

• Further criteria apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tufts Medical Center	Boston	Massachusetts	United States	02111
2	University Hospital Basel	Basel		Switzerland	4031

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 21, 2019

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT03935126
• Other Study ID Numbers: 0352-2110
• First Posted: May 2, 2019
• Last Update Posted: May 21, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Macular Degeneration; Atrophy

Study Results

Participant Flow

Recruitment Details	A biomarker evaluation study in patients with geographic atrophy secondary to age-related macular degeneration (AMD) evaluating the use of microperimetry (fundus-controlled perimetry) and Swept Source-Optical Coherence Tomography in assessing changes in retinal sensitivity and anatomy over observation period of 48 weeks.
Pre-assignment Detail	All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Arm/Group Title	All Enrolled
Arm/Group Description	All enrolled participants who had geographic atrophy secondary to age-related macular degeneration, signed informed consent for this trial, and met all inclusion criteria and none of the exclusion criteria, for evaluating the usage of microperimetry and Swept Source - Optical Coherence Tomography (SS-OCT) in assessing the natural changes of retinal sensitivity and anatomy in the retina. Each participant was planned to be observed for an observation period of 48 weeks after screening visit. During the observation period, 4 visits were planned to be taken at Week 0, 12, 24, and 48 of the observation period.
Period Title: Overall Study
STARTED	3
COMPLETED	0
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	All Enrolled
Arm/Group Description	All enrolled participants who had geographic atrophy secondary to age-related macular degeneration, signed informed consent for this trial, and met all inclusion criteria and none of the exclusion criteria, for evaluating the usage of microperimetry and Swept Source - Optical Coherence Tomography (SS-OCT) in assessing the natural changes of retinal sensitivity and anatomy in the retina. Each participant was planned to be observed for an observation period of 48 weeks after screening visit. During the observation period, 4 visits were planned to be taken at Week 0, 12, 24, and 48 of the observation period.
Overall Participants	3
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	83.7 (4.2)
Sex: Female, Male (Count of Participants)
Female	1 33.3%
Male	2 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 33.3%
Not Hispanic or Latino	2 66.7%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	3 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Retinal Sensitivity in the Junctional Zone and in the Perilesional Zone of the Largest Atrophic Loci as Assessed by Microperimetry for the Evaluation of Macular Functional Response at Week 12
Time Frame	At baseline and at week 12.

Outcome Measure Data

Analysis Population Description

Study was terminated early. 3 subjects were enrolled but no subject was entered. No outcome measures data was collected.

Arm/Group Title	All Enrolled
Arm/Group Description	All enrolled participants who had geographic atrophy secondary to age-related macular degeneration, signed informed consent for this trial, and met all inclusion criteria and none of the exclusion criteria, for evaluating the usage of microperimetry and Swept Source - Optical Coherence Tomography (SS-OCT) in assessing the natural changes of retinal sensitivity and anatomy in the retina. Each participant was planned to be observed for an observation period of 48 weeks after screening visit. During the observation period, 4 visits were planned to be taken at Week 0, 12, 24, and 48 of the observation period.
Measure Participants	0

2. Primary Outcome

Title	Change From Baseline in Retinal Pigment Epithelium (RPE) Layer Thickness in the Junctional Zone and in the Perilesional Zone as Measured by Swept Source - Optical Coherence Tomography (SS-OCT) at Week 12
Time Frame	At baseline and at week 12.

Outcome Measure Data

Analysis Population Description

Study was terminated early. 3 subjects were enrolled but no subject was entered. No outcome measures data was collected.

Arm/Group Title	All Enrolled
Arm/Group Description	All enrolled participants who had geographic atrophy secondary to age-related macular degeneration, signed informed consent for this trial, and met all inclusion criteria and none of the exclusion criteria, for evaluating the usage of microperimetry and Swept Source - Optical Coherence Tomography (SS-OCT) in assessing the natural changes of retinal sensitivity and anatomy in the retina. Each participant was planned to be observed for an observation period of 48 weeks after screening visit. During the observation period, 4 visits were planned to be taken at Week 0, 12, 24, and 48 of the observation period.
Measure Participants	0

3. Primary Outcome

Title	Change From Baseline in Photoreceptor Layer Thickness in the Junctional Zone and in the Perilesional Zone as Measured by Swept Source - Optical Coherence Tomography (SS-OCT) at Week 12
Time Frame	At baseline and at week 12.

Outcome Measure Data

Analysis Population Description

Study was terminated early. 3 subjects were enrolled but no subject was entered. No outcome measures data was collected.

Arm/Group Title	All Enrolled
Arm/Group Description	All enrolled participants who had geographic atrophy secondary to age-related macular degeneration, signed informed consent for this trial, and met all inclusion criteria and none of the exclusion criteria, for evaluating the usage of microperimetry and Swept Source - Optical Coherence Tomography (SS-OCT) in assessing the natural changes of retinal sensitivity and anatomy in the retina. Each participant was planned to be observed for an observation period of 48 weeks after screening visit. During the observation period, 4 visits were planned to be taken at Week 0, 12, 24, and 48 of the observation period.
Measure Participants	0

4. Secondary Outcome

Title	Change From Baseline in Retinal Sensitivity in the Junctional Zone and in the Perilesional Zone of the Largest Atrophic Loci as Assessed by Microperimetry at Week 24 and 48
Time Frame	At baseline and at week 24 and 48.

Outcome Measure Data

Analysis Population Description

Study was terminated early. 3 subjects were enrolled but no subject was entered. No outcome measures data was collected.

Arm/Group Title	All Enrolled
Arm/Group Description	All enrolled participants who had geographic atrophy secondary to age-related macular degeneration, signed informed consent for this trial, and met all inclusion criteria and none of the exclusion criteria, for evaluating the usage of microperimetry and Swept Source - Optical Coherence Tomography (SS-OCT) in assessing the natural changes of retinal sensitivity and anatomy in the retina. Each participant was planned to be observed for an observation period of 48 weeks after screening visit. During the observation period, 4 visits were planned to be taken at Week 0, 12, 24, and 48 of the observation period.
Measure Participants	0

5. Secondary Outcome

Title	Change From Baseline in Retinal Pigment Epithelium (RPE) Layer Thickness in the Junctional Zone and in the Perilesional Zone as Measured by Swept Source - Optical Coherence Tomography (SS-OCT) at Week 24 and 48
Time Frame	At baseline and at week 24 and 48.

Outcome Measure Data

Analysis Population Description

Study was terminated early. 3 subjects were enrolled but no subject was entered. No outcome measures data was collected.

Arm/Group Title	All Enrolled
Arm/Group Description	All enrolled participants who had geographic atrophy secondary to age-related macular degeneration, signed informed consent for this trial, and met all inclusion criteria and none of the exclusion criteria, for evaluating the usage of microperimetry and Swept Source - Optical Coherence Tomography (SS-OCT) in assessing the natural changes of retinal sensitivity and anatomy in the retina. Each participant was planned to be observed for an observation period of 48 weeks after screening visit. During the observation period, 4 visits were planned to be taken at Week 0, 12, 24, and 48 of the observation period.
Measure Participants	0

6. Secondary Outcome

Title	Change From Baseline in Photoreceptor Layer Thickness in the Junctional Zone and in the Perilesional Zone as Measured by Swept Source - Optical Coherence Tomography (SS-OCT) at Week 24 and 48
Time Frame	At baseline and at week 24 and 48.

Outcome Measure Data

Analysis Population Description

Study was terminated early. 3 subjects were enrolled but no subject was entered. No outcome measures data was collected.

Arm/Group Title	All Enrolled
Arm/Group Description	All enrolled participants who had geographic atrophy secondary to age-related macular degeneration, signed informed consent for this trial, and met all inclusion criteria and none of the exclusion criteria, for evaluating the usage of microperimetry and Swept Source - Optical Coherence Tomography (SS-OCT) in assessing the natural changes of retinal sensitivity and anatomy in the retina. Each participant was planned to be observed for an observation period of 48 weeks after screening visit. During the observation period, 4 visits were planned to be taken at Week 0, 12, 24, and 48 of the observation period.
Measure Participants	0

7. Secondary Outcome

Title	Change From Baseline in the GA Area as Measured by Fundus Autofluorescence (FAF) at Week 12, 24 and 48
Time Frame	At baseline and at week 12, 24 and 48

Outcome Measure Data

Analysis Population Description

Study was terminated early. 3 subjects were enrolled but no subject was entered. No outcome measures data was collected.

Arm/Group Title	All Enrolled
Arm/Group Description	All enrolled participants who had geographic atrophy secondary to age-related macular degeneration, signed informed consent for this trial, and met all inclusion criteria and none of the exclusion criteria, for evaluating the usage of microperimetry and Swept Source - Optical Coherence Tomography (SS-OCT) in assessing the natural changes of retinal sensitivity and anatomy in the retina. Each participant was planned to be observed for an observation period of 48 weeks after screening visit. During the observation period, 4 visits were planned to be taken at Week 0, 12, 24, and 48 of the observation period.
Measure Participants	0

8. Secondary Outcome

Title	Change From Baseline in Best Corrected Visual Acuity (BCVA) Score as Assessed by Early Treatment Diabetic Retinopathy Scale (ETDRS) Chart at a Starting Distance of 4 Meters at Week 12, 24 and 48
Time Frame	At baseline and at week 12, 24 and 48.

Outcome Measure Data

Analysis Population Description

Study was terminated early. 3 subjects were enrolled but no subject was entered. No outcome measures data was collected.

Arm/Group Title	All Enrolled
Arm/Group Description	All enrolled participants who had geographic atrophy secondary to age-related macular degeneration, signed informed consent for this trial, and met all inclusion criteria and none of the exclusion criteria, for evaluating the usage of microperimetry and Swept Source - Optical Coherence Tomography (SS-OCT) in assessing the natural changes of retinal sensitivity and anatomy in the retina. Each participant was planned to be observed for an observation period of 48 weeks after screening visit. During the observation period, 4 visits were planned to be taken at Week 0, 12, 24, and 48 of the observation period.
Measure Participants	0

9. Secondary Outcome

Title	Change From Baseline in Low Luminance Visual Acuity (LLVA) Score as Assessed by ETDRS Chart Under Low Luminance Conditions at a Starting Distance of 4 Meters at Week 12, 24 and 48
Time Frame	At baseline and at week 12, 24 and 48.

Outcome Measure Data

Analysis Population Description

Study was terminated early. 3 subjects were enrolled but no subject was entered. No outcome measures data was collected.

Arm/Group Title	All Enrolled
Arm/Group Description	All enrolled participants who had geographic atrophy secondary to age-related macular degeneration, signed informed consent for this trial, and met all inclusion criteria and none of the exclusion criteria, for evaluating the usage of microperimetry and Swept Source - Optical Coherence Tomography (SS-OCT) in assessing the natural changes of retinal sensitivity and anatomy in the retina. Each participant was planned to be observed for an observation period of 48 weeks after screening visit. During the observation period, 4 visits were planned to be taken at Week 0, 12, 24, and 48 of the observation period.
Measure Participants	0

10. Secondary Outcome

Title	Number of Scotomatous Points Assessed by Microperimetry at Week 12, 24 and 48
Time Frame	At week 12, 24 and 48

Outcome Measure Data

Analysis Population Description

Study was terminated early. 3 subjects were enrolled but no subject was entered. No outcome measures data was collected.

Arm/Group Title	All Enrolled
Arm/Group Description	All enrolled participants who had geographic atrophy secondary to age-related macular degeneration, signed informed consent for this trial, and met all inclusion criteria and none of the exclusion criteria, for evaluating the usage of microperimetry and Swept Source - Optical Coherence Tomography (SS-OCT) in assessing the natural changes of retinal sensitivity and anatomy in the retina. Each participant was planned to be observed for an observation period of 48 weeks after screening visit. During the observation period, 4 visits were planned to be taken at Week 0, 12, 24, and 48 of the observation period.
Measure Participants	0

11. Secondary Outcome

Title	Change From Baseline in the Area of Choroidal Non-perfusion as Measured Via Optical Coherence Tomography Angiography (OCT-A) at Week 12, 24 and 48
Time Frame	At baseline and at week 12, 24 and 48.

Outcome Measure Data

Analysis Population Description

Study was terminated early. 3 subjects were enrolled but no subject was entered. No outcome measures data was collected.

Arm/Group Title	All Enrolled
Arm/Group Description	All enrolled participants who had geographic atrophy secondary to age-related macular degeneration, signed informed consent for this trial, and met all inclusion criteria and none of the exclusion criteria, for evaluating the usage of microperimetry and Swept Source - Optical Coherence Tomography (SS-OCT) in assessing the natural changes of retinal sensitivity and anatomy in the retina. Each participant was planned to be observed for an observation period of 48 weeks after screening visit. During the observation period, 4 visits were planned to be taken at Week 0, 12, 24, and 48 of the observation period.
Measure Participants	0

Adverse Events

Time Frame	From screening visit 1 until early termination of the study, up to 6 month + 5 days.
Adverse Event Reporting Description	Enrolled set: This subject set includes all subjects that signed informed consent for this trial.
Arm/Group Title	All Enrolled
Arm/Group Description	All enrolled participants who had geographic atrophy secondary to age-related macular degeneration, signed informed consent for this trial, and met all inclusion criteria and none of the exclusion criteria, for evaluating the usage of microperimetry and Swept Source - Optical Coherence Tomography (SS-OCT) in assessing the natural changes of retinal sensitivity and anatomy in the retina. Each participant was planned to be observed for an observation period of 48 weeks after screening visit. During the observation period, 4 visits were planned to be taken at Week 0, 12, 24, and 48 of the observation period.
All Cause Mortality
	All Enrolled
	Affected / at Risk (%)	# Events
Total	0/3 (0%)
Serious Adverse Events
	All Enrolled
	Affected / at Risk (%)	# Events
Total	0/3 (0%)
Other (Not Including Serious) Adverse Events
	All Enrolled
	Affected / at Risk (%)	# Events
Total	0/3 (0%)

Limitations/Caveats

Study was terminated early by the sponsor. No outcome measures data was collected.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.