Trial Outcomes & Findings for A Natural History of the Progression of Stargardt Disease: Retrospective and Prospective Studies (NCT NCT01977846)

NCT ID: NCT01977846

Last Updated: 2019-11-01

Results Overview

Yearly increase in area of decreased auto-fluorescence (DAF) which is defined as the sum of definite and questionable decreased auto-fluorescence

• Recruitment status: COMPLETED
• Target enrollment: 259 participants
• Primary outcome timeframe: 2-12 years
• Results posted on: 2019-11-01

Participant Flow

Participant milestones

Measure	Retrospective Cohort Patients with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Participant's data are from clinical examinations and central reading center (RC) grading of retinal imaging (fundus auto-fluorescence, and spectral domain optical coherence tomography (OCT).	Prospective Cohort Patients with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Participant's data are from standardized clinical examinations and central reading center (RC) grading of retinal imaging (fundus auto-fluorescence, spectral domain optical coherence tomography (OCT) and micro-perimetry (optional).
Total Study - Retrospective STARTED	251	0
Total Study - Retrospective COMPLETED	251	0
Total Study - Retrospective NOT COMPLETED	0	0
Total Study - Prospective STARTED	0	259
Total Study - Prospective COMPLETED	0	230
Total Study - Prospective NOT COMPLETED	0	29

Reasons for withdrawal

Measure	Retrospective Cohort Patients with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Participant's data are from clinical examinations and central reading center (RC) grading of retinal imaging (fundus auto-fluorescence, and spectral domain optical coherence tomography (OCT).	Prospective Cohort Patients with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Participant's data are from standardized clinical examinations and central reading center (RC) grading of retinal imaging (fundus auto-fluorescence, spectral domain optical coherence tomography (OCT) and micro-perimetry (optional).
Total Study - Prospective Death	0	1
Total Study - Prospective Lost to Follow-up	0	8
Total Study - Prospective Withdrawal by Subject	0	13
Total Study - Prospective Not available at time of visit	0	5
Total Study - Prospective No show	0	1
Total Study - Prospective Protocol Violation	0	1

Baseline Characteristics

A Natural History of the Progression of Stargardt Disease: Retrospective and Prospective Studies

Baseline characteristics by cohort

Measure	Retrospective Cohort n=251 Participants Subjects with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Clinical data from multiple centers extracted from medical records. Participants were to have at least two visits with at least one of the study image modalities (fundus auto-fluorescence, micro-perimetry, or spectral domain optical coherence tomography (OCT))	Prospective Cohort n=259 Participants Multicenter prospective longitudinal cohort. Patients with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Participants were to have standardized visits at baseline and every 6 months for 24 months. Participant's data are from clinical examinations and central RC grading of retinal imaging (fundus auto-fluorescence, spectral domain optical coherence tomography (OCT)) and micro-perimetry.	Total n=510 Participants Total of all reporting groups
Age, Categorical <=18 years	69 Participants n=5 Participants	51 Participants n=7 Participants	120 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	179 Participants n=5 Participants	201 Participants n=7 Participants	380 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Female	149 Participants n=5 Participants	141 Participants n=7 Participants	290 Participants n=5 Participants
Sex: Female, Male Male	102 Participants n=5 Participants	118 Participants n=7 Participants	220 Participants n=5 Participants
Race/Ethnicity, Customized Race · White/Middle Eastern	174 Participants n=5 Participants	222 Participants n=7 Participants	396 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	14 Participants n=5 Participants	20 Participants n=7 Participants	34 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian/Indian	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Race · More than one race	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race · Don't know/missing	46 Participants n=5 Participants	4 Participants n=7 Participants	50 Participants n=5 Participants
Region of Enrollment United States	90 participants n=5 Participants	137 participants n=7 Participants	227 participants n=5 Participants
Region of Enrollment United Kingdom	79 participants n=5 Participants	30 participants n=7 Participants	109 participants n=5 Participants
Region of Enrollment France	49 participants n=5 Participants	48 participants n=7 Participants	97 participants n=5 Participants
Region of Enrollment Germany	33 participants n=5 Participants	44 participants n=7 Participants	77 participants n=5 Participants

PRIMARY outcome

Timeframe: 2-12 years

Population: Eyes of participants with at least 2 visits with gradable fundus auto-fluorescence images with atrophic lesions present

Yearly increase in area of decreased auto-fluorescence (DAF) which is defined as the sum of definite and questionable decreased auto-fluorescence

Outcome measures

Measure	Retrospective Cohort n=386 eyes Subjects with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Clinical data from multiple centers extracted from medical records. Participants were to have at least two visits with at least one of the study image modalities (fundus auto-fluorescence, micro-perimetry, or spectral domain optical coherence tomography (OCT))	Prospective Cohort n=489 eyes Multicenter prospective longitudinal cohort. Patients with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Participants were to have standardized visits at baseline and every 6 months for 24 months. Participant's data are from clinical examinations and central RC grading of retinal imaging (fundus auto-fluorescence, spectral domain optical coherence tomography (OCT)) and micro-perimetry.
Yearly Progression Rate of Atrophic Lesions Using Fundus Autofluorescence (FAF) Images	0.35 mm^2/year Interval 0.28 to 0.43	0.64 mm^2/year Interval 0.57 to 0.71

SECONDARY outcome

Timeframe: 2 years

Population: Microperimetry data are available for only the Prospective cohort at centers with required equipment

The yearly rate of change in retinal sensitivity. Sensitivity tested with a Nidek MP-1 machine using a modified Humphrey 10-2 grid. The sensitivity was the average sensitivity from a 68-points test pattern (Prospective cohort only)

Outcome measures

Measure	Retrospective Cohort Subjects with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Clinical data from multiple centers extracted from medical records. Participants were to have at least two visits with at least one of the study image modalities (fundus auto-fluorescence, micro-perimetry, or spectral domain optical coherence tomography (OCT))	Prospective Cohort n=449 eyes Multicenter prospective longitudinal cohort. Patients with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Participants were to have standardized visits at baseline and every 6 months for 24 months. Participant's data are from clinical examinations and central RC grading of retinal imaging (fundus auto-fluorescence, spectral domain optical coherence tomography (OCT)) and micro-perimetry.
Yearly Rate of Loss of Retinal Sensitivity as Measured by Scotopic Microperimetry (MP)	—	-0.76 dB/year Interval -0.87 to -0.66

SECONDARY outcome

Timeframe: 2-12 years

Yearly change of visual acuity. Visual acuity measures of best-corrected or presenting VA extracted from medical record charts. Prospective cohort is best-corrected visual acuity using Early-Treatment Diabetic Retinopathy study methods

Outcome measures

Measure	Retrospective Cohort n=332 eyes Subjects with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Clinical data from multiple centers extracted from medical records. Participants were to have at least two visits with at least one of the study image modalities (fundus auto-fluorescence, micro-perimetry, or spectral domain optical coherence tomography (OCT))	Prospective Cohort n=489 eyes Multicenter prospective longitudinal cohort. Patients with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Participants were to have standardized visits at baseline and every 6 months for 24 months. Participant's data are from clinical examinations and central RC grading of retinal imaging (fundus auto-fluorescence, spectral domain optical coherence tomography (OCT)) and micro-perimetry.
Yearly Rate of Visual Acuity Loss	0.030 logMAR/year Interval 0.026 to 0.043	0.011 logMAR/year Interval 0.004 to 0.018

SECONDARY outcome

Timeframe: 2 years

Population: Photopic microperimetry was obtained in a subset of patients, in a single designated study eye

Difference in the yearly rate of change in retinal sensitivity under photopic and scotopic conditions. Sensitivity tested with a Nidek MP-1. Scotopic sensitivity was obtained using a 40 points test pattern, and photopic sensitivity was obtained using a 68 points test pattern in a subset of Prospective cohort patients

Outcome measures

Measure	Retrospective Cohort Subjects with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Clinical data from multiple centers extracted from medical records. Participants were to have at least two visits with at least one of the study image modalities (fundus auto-fluorescence, micro-perimetry, or spectral domain optical coherence tomography (OCT))	Prospective Cohort n=118 eyes Multicenter prospective longitudinal cohort. Patients with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Participants were to have standardized visits at baseline and every 6 months for 24 months. Participant's data are from clinical examinations and central RC grading of retinal imaging (fundus auto-fluorescence, spectral domain optical coherence tomography (OCT)) and micro-perimetry.
Difference in the Rate of Retinal Sensitivity Change Per Year Between Photopic and Scotopic Micro-perimetry Testing	—	-0.78 dB/year Interval -1.16 to -0.41

SECONDARY outcome

Timeframe: Participants followed at Baseline, 6 months, 12 months and 24 months

Population: All visits of eligible eyes of the 258 participants with gradable overall thickness. Only OCT scans with adequate and fair quality are included

Yearly decrease of overall retinal thickness using spectral domain optical coherence tomography (SD-OCT) scans from a 20° x 20° scan area centered on the fovea. Data are only available for the Prospective cohort.

Outcome measures

Measure	Retrospective Cohort n=487 eyes Subjects with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Clinical data from multiple centers extracted from medical records. Participants were to have at least two visits with at least one of the study image modalities (fundus auto-fluorescence, micro-perimetry, or spectral domain optical coherence tomography (OCT))	Prospective Cohort Multicenter prospective longitudinal cohort. Patients with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Participants were to have standardized visits at baseline and every 6 months for 24 months. Participant's data are from clinical examinations and central RC grading of retinal imaging (fundus auto-fluorescence, spectral domain optical coherence tomography (OCT)) and micro-perimetry.
Yearly Rate of Loss of Overall Retinal Thickness	-2.85 microns/year Interval -3.19 to -2.52	—

SECONDARY outcome

Timeframe: Participants followed at Baseline, 6 months, 12 months and 24 months

Population: All visits of eligible eyes of the 258 participants with gradable thickness in the outer ring. Only OCT scans with adequate and fair quality are included

Yearly decrease of outer ring retinal thickness using SD-OCT scans from a 20° x 20° scan area centered on the fovea. Outer ring defined as ETDRS fields 1-4.

Outcome measures

Measure	Retrospective Cohort n=487 eyes Subjects with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Clinical data from multiple centers extracted from medical records. Participants were to have at least two visits with at least one of the study image modalities (fundus auto-fluorescence, micro-perimetry, or spectral domain optical coherence tomography (OCT))	Prospective Cohort Multicenter prospective longitudinal cohort. Patients with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Participants were to have standardized visits at baseline and every 6 months for 24 months. Participant's data are from clinical examinations and central RC grading of retinal imaging (fundus auto-fluorescence, spectral domain optical coherence tomography (OCT)) and micro-perimetry.
Yearly Rate of Loss of Outer Ring Retinal Thickness	-2.84 microns/year Interval -3.19 to -2.5	—

SECONDARY outcome

Timeframe: Participants followed at Baseline, 6 months, 12 months and 24 months

Population: All visits of eligible eyes of the 258 participants with gradable thickness in the inner ring. Only OCT scans with adequate and fair quality are included

Yearly decrease of the inner ring retinal thickness using SD-OCT scans from a 20° x 20° scan area centered on the fovea. Inner ring defined as ETDRS fields 5-8. Data are only available for the Prospective cohort.

Outcome measures

Measure	Retrospective Cohort n=487 eyes Subjects with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Clinical data from multiple centers extracted from medical records. Participants were to have at least two visits with at least one of the study image modalities (fundus auto-fluorescence, micro-perimetry, or spectral domain optical coherence tomography (OCT))	Prospective Cohort Multicenter prospective longitudinal cohort. Patients with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Participants were to have standardized visits at baseline and every 6 months for 24 months. Participant's data are from clinical examinations and central RC grading of retinal imaging (fundus auto-fluorescence, spectral domain optical coherence tomography (OCT)) and micro-perimetry.
Yearly Rate of Loss of the Inner Ring Retinal Thickness	-3.20 microns/year Interval -3.68 to -2.72	—

SECONDARY outcome

Timeframe: Participants followed at Baseline, 6 months, 12 months and 24 months

Population: All visits of eligible eyes of the 258 participants with gradable thickness in the inner ring. Only OCT scans with adequate and fair quality are included

Yearly decrease of the central ring retinal thickness using SD-OCT scans from a 20° x 20° scan area centered on the fovea. Central area defined as ETDRS fields 9. Data are only available for the Prospective cohort.

Outcome measures

Measure	Retrospective Cohort n=487 eyes Subjects with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Clinical data from multiple centers extracted from medical records. Participants were to have at least two visits with at least one of the study image modalities (fundus auto-fluorescence, micro-perimetry, or spectral domain optical coherence tomography (OCT))	Prospective Cohort Multicenter prospective longitudinal cohort. Patients with at least two pathogenic mutations in the ABCA4 gene (or one mutation, but the clinical phenotype of flecks at the level of the RPE typical for STGD1). Participants were to have standardized visits at baseline and every 6 months for 24 months. Participant's data are from clinical examinations and central RC grading of retinal imaging (fundus auto-fluorescence, spectral domain optical coherence tomography (OCT)) and micro-perimetry.
Yearly Rate of Loss of the Central Ring Retinal Thickness	-2.24 microns/year Interval -3.06 to -1.42	—

Adverse Events

Retrospective Cohort

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Prospective Cohort

Serious events: 0 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Chief Scientific Officer

Foundation Fighting Blindness

Phone: 410-423-0600

Email: info@FightBlindness.org

Results disclosure agreements

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