ESBA1008 Microvolume Study

Conditions

Exudative Age-Related Macular Degeneration

Keywords

Exudative Age-Related Macular Degeneration, Wet AMD, Choroidal neovascularization (CNV), Vascular endothelial growth factor (VEGF)

Brief summary

The purpose of this study is to demonstrate a treatment effect of ESBA1008 applied as a microvolume injection or infusion on retinal function and morphology in subjects with exudative age-related macular degeneration (AMD).

Detailed description

This 4-cohort study was conducted in 2 stages. Stage 1 consisted out of 2 Cohorts. In each cohort subjects were randomized 10:3 to either receive ESBA1008 (Cohort 1 : 2 injections, Cohort 2 : 1 infusion and 1 injection) or 2 Lucentis injections. Stage 2 was conducted similarly with a different dosing level for ESBA1008 (Cohort 3 and 4). Subjects had follow-up visits at Day 7 and Day 14. All cohorts receiving ESBA1008 on Day 0 also received ESBA1008 6mg/50 μL via injection on Day 28. After the Day 28 visit (all cohorts), subjects returned for follow up visits at Day 42 and Day 56.

Related papers

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Interventions

DRUGESBA1008 solution

Intravitreal injection or infusion

DRUGRanibizumab

Intravitreal injection

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

50 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Sign informed consent document; * Able to make the required study visits and follow instructions; * Age-related macular degeneration in the study eye; * Visual acuity within protocol-specified range; * 340 μm minimal central subfield thickness (CSFT; Spectralis Equivalent) * Other protocol-defined inclusion criteria may apply.

Exclusion criteria

* Both eyes: Any active infection or inflammation; * Study eye: Any treatment for exudative age-related macular degeneration (AMD) other than vitamin supplements; * Study eye: Any current or history of macular or retinal disease; * Study eye: Any concurrent intraocular condition such as cataract or diabetic retinopathy that, in the opinion of the Investigator, could either require medical or surgical intervention during the course of the study to prevent or treat visual loss; * Study eye: Other ocular conditions or diseases that, in the opinion of the Investigator, could compromise visual acuity; * Study Eye: Uncontrolled glaucoma; * History of a medical condition that, in the opinion of the Investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product; * Women of childbearing potential who are lactating, pregnant, planning to become pregnant, or not using adequate birth control methods for the duration of the study; * Intraocular surgery within 3 months of baseline; * Study eye: Any history or current evidence of retinal angiomatous proliferation (RAP) lesions based on clinical exam; * Other protocol-defined

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Responders Based on CSFT and BCVA Outcomes at Day 14 and Day 28	Baseline, Day 14, Day 28	A subject was considered a responder if at least 3 out of the following 4 criteria were fulfilled in comparison to baseline: * Greater than or equal to 4 letter gain in BCVA at Day 14 * Greater than or equal to 4 letter gain in BCVA at Day 28 * Greater than or equal to 80 micron decrease in CSFT at Day 14 * Greater than or equal to 80 micron decrease in CSFT at Day 28. BCVA was measured by the number of letters read out of a possible 70 letters on the ETDRS chart. One eye (study eye) contributed to the analysis.

Secondary

Measure	Time frame	Description
Change From Baseline in BCVA, Cohort 2	Baseline, Day 7, Day 14, Day 28, Day 42, Day 56	BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly out of 70 letters on the chart. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis.
Change From Baseline in BCVA, Cohort 3	Baseline, Day 7, Day 14, Day 28, Day 42, Day 56	BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly out of 70 letters on the chart. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis.
Change From Baseline in BCVA, Cohort 4	Baseline, Day 7, Day 14, Day 28, Day 42, Day 56	BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly out of 70 letters on the chart. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis.
Change From Baseline in BCVA, Cohort 1	Baseline, Day 7, Day 14, Day 28, Day 42, Day 56	BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly out of 70 letters on the chart. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis.
Change From Baseline in CSFT, Cohort 2	Baseline, Day 7, Day 14, Day 28, Day 42, Day 56	CSFT was assessed by SD-OCT and measured in microns. A decrease in CSFT indicates improvement. One eye (study eye) contributed to the analysis.
Change From Baseline in CSFT, Cohort 3	Baseline, Day 7, Day 14, Day 28, Day 42, Day 56	CSFT was assessed by SD-OCT and measured in microns. A decrease in CSFT indicates improvement. One eye (study eye) contributed to the analysis.
Change From Baseline in CSFT, Cohort 4	Baseline, Day 7, Day 14, Day 28, Day 42, Day 56	CSFT was assessed by SD-OCT and measured in microns. A decrease in CSFT indicates improvement. One eye (study eye) contributed to the analysis.
Change From Baseline in CSFT, Cohort 1	Baseline, Day 7, Day 14, Day 28, Day 42, Day 56	CSFT was assessed by Spectral-Domain Optical Coherence Tomography (SD-OCT) and measured in microns. A decrease in CSFT indicates improvement. One eye (study eye) contributed to the analysis.

Participant flow

Recruitment details

Subjects were recruited from 12 investigational centers located in the US, Australia, and the Dominican Republic.

Pre-assignment details

Of the 107 enrolled, 55 subjects were exited as screen failures prior to randomization. This reporting group includes all randomized participants (52).

Participants by arm

Arm	Count
ESBA All subjects who were treated with ESBA1008.	40
LUCENTIS All subjects who were treated with LUCENTIS.	12
Total	52

Baseline characteristics

Characteristic	ESBA	LUCENTIS	Total
Age, Continuous Cohort 1, n=10, 3	77.5 years STANDARD_DEVIATION 3.6	78.3 years STANDARD_DEVIATION 7.2	77.7 years STANDARD_DEVIATION 4.3
Age, Continuous Cohort 2, n=10, 3	73.6 years STANDARD_DEVIATION 8.9	82.0 years STANDARD_DEVIATION 3.6	75.5 years STANDARD_DEVIATION 8.7
Age, Continuous Cohort 3, n=10, 3	76.5 years STANDARD_DEVIATION 9.7	81.7 years STANDARD_DEVIATION 11	77.7 years STANDARD_DEVIATION 9.8
Age, Continuous Cohort 4, n=10, 3	81.6 years STANDARD_DEVIATION 6.1	76.7 years STANDARD_DEVIATION 3.8	80.5 years STANDARD_DEVIATION 5.9
Best corrected visual acuity (BCVA) Cohort 1, n=10, 3	63.4 letters STANDARD_DEVIATION 6.8	55.0 letters STANDARD_DEVIATION 8.7	61.5 letters STANDARD_DEVIATION 7.8
Best corrected visual acuity (BCVA) Cohort 2, n=10, 3	61.0 letters STANDARD_DEVIATION 11.8	64.3 letters STANDARD_DEVIATION 6.8	61.8 letters STANDARD_DEVIATION 10.7
Best corrected visual acuity (BCVA) Cohort 3, n=10, 3	60.2 letters STANDARD_DEVIATION 14.7	59.3 letters STANDARD_DEVIATION 5.1	60.0 letters STANDARD_DEVIATION 12.9
Best corrected visual acuity (BCVA) Cohort 4, n=10, 3	54.8 letters STANDARD_DEVIATION 14.2	48.7 letters STANDARD_DEVIATION 16.9	53.4 letters STANDARD_DEVIATION 14.4
Central subfield thickness (CSFT) Cohort 1, n=10, 3	535.1 microns STANDARD_DEVIATION 194.7	482.3 microns STANDARD_DEVIATION 104.3	522.9 microns STANDARD_DEVIATION 175.5
Central subfield thickness (CSFT) Cohort 2, n=10, 3	423.0 microns STANDARD_DEVIATION 95.5	405.7 microns STANDARD_DEVIATION 19.9	419.0 microns STANDARD_DEVIATION 83.5
Central subfield thickness (CSFT) Cohort 3, n=10, 3	479.1 microns STANDARD_DEVIATION 93.7	403.3 microns STANDARD_DEVIATION 67.7	461.6 microns STANDARD_DEVIATION 91.9
Central subfield thickness (CSFT) Cohort 4, n=10, 3	534.8 microns STANDARD_DEVIATION 123.4	573.3 microns STANDARD_DEVIATION 160.6	543.7 microns STANDARD_DEVIATION 126.5
Sex/Gender, Customized Cohort 1, Female	3 participants	1 participants	4 participants
Sex/Gender, Customized Cohort 1, Male	7 participants	2 participants	9 participants
Sex/Gender, Customized Cohort 2, Female	6 participants	2 participants	8 participants
Sex/Gender, Customized Cohort 2, Male	4 participants	1 participants	5 participants
Sex/Gender, Customized Cohort 3, Female	5 participants	2 participants	7 participants
Sex/Gender, Customized Cohort 3, Male	5 participants	1 participants	6 participants
Sex/Gender, Customized Cohort 4, Female	4 participants	1 participants	5 participants
Sex/Gender, Customized Cohort 4, Male	6 participants	2 participants	8 participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	6 / 10	4 / 10	6 / 6	6 / 10	7 / 10	4 / 6	3 / 107
serious Total, serious adverse events	0 / 10	0 / 10	1 / 6	1 / 10	0 / 10	0 / 6	1 / 107

Outcome results

Primary

Percentage of Responders Based on CSFT and BCVA Outcomes at Day 14 and Day 28

A subject was considered a responder if at least 3 out of the following 4 criteria were fulfilled in comparison to baseline: * Greater than or equal to 4 letter gain in BCVA at Day 14 * Greater than or equal to 4 letter gain in BCVA at Day 28 * Greater than or equal to 80 micron decrease in CSFT at Day 14 * Greater than or equal to 80 micron decrease in CSFT at Day 28. BCVA was measured by the number of letters read out of a possible 70 letters on the ETDRS chart. One eye (study eye) contributed to the analysis.

Time frame: Baseline, Day 14, Day 28

Population: This analysis population includes all subjects who were randomized, received the initial injection or infusion, and had a baseline value and at least 1 postbaseline measurement for the period up to Day 28 for the primary efficacy variables (BCVA and/or CSFT). Here, n is the number of subjects in each arm group.

Arm	Measure	Group	Value (NUMBER)
Cohort 1	Percentage of Responders Based on CSFT and BCVA Outcomes at Day 14 and Day 28	ESBA, n=10	70 percentage of responders
Cohort 1	Percentage of Responders Based on CSFT and BCVA Outcomes at Day 14 and Day 28	LUCENTIS, n=3	100 percentage of responders
Cohort 2	Percentage of Responders Based on CSFT and BCVA Outcomes at Day 14 and Day 28	LUCENTIS, n=3	100 percentage of responders
Cohort 2	Percentage of Responders Based on CSFT and BCVA Outcomes at Day 14 and Day 28	ESBA, n=10	60 percentage of responders
Cohort 3	Percentage of Responders Based on CSFT and BCVA Outcomes at Day 14 and Day 28	ESBA, n=10	80 percentage of responders
Cohort 3	Percentage of Responders Based on CSFT and BCVA Outcomes at Day 14 and Day 28	LUCENTIS, n=3	33.3 percentage of responders
Cohort 4	Percentage of Responders Based on CSFT and BCVA Outcomes at Day 14 and Day 28	ESBA, n=10	60 percentage of responders
Cohort 4	Percentage of Responders Based on CSFT and BCVA Outcomes at Day 14 and Day 28	LUCENTIS, n=3	66.7 percentage of responders

Secondary

Change From Baseline in BCVA, Cohort 1

BCVA (with spectacles or other visual corrective devices) using ETDRS testing was reported in letters read correctly out of 70 letters on the chart. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis.