Exudative Age-Related Macular Degeneration
Conditions
Keywords
AMD, Wet AMD, Exudative, CNV
Brief summary
The purpose of this study was to assess the safety, tolerability, and the effects of treatment on ocular outcomes following a single intravitreal administration of ESBA1008 compared with LUCENTIS® in patients with exudative age-related macular degeneration (AMD).
Detailed description
This study was conducted in two parts. In Part 1, patients were initially randomized (5:2) to receive either ESBA1008 at the lowest dose (Dose A) or LUCENTIS. After Safety Committee review, a second cohort was enrolled and randomized (5:2) to the next higher dose of ESBA1008 (Dose B). Safety review and enrollment of patients into the third cohort (Dose C) and fourth cohort (Dose D) was conducted in the same manner. Part 2, the expansion period, consisted of 2 arms. In the first arm patients were randomized to receive ESBA1008 Dose C or LUCENTIS (43:44) . In the second arm, patients were randomized to ESBA1008 Doses A:B:D:Lucentis (5:30:35:9). All enrolled patients (Part 1 and Part 2) were evaluated for safety and efficacy across 13 study visits, including Screening, Randomization, and 11 post- treatment follow-up visits (Day 1 through Month 6).
Interventions
BIOLOGICALESBA1008 solution
Administered as a single intravitreal injection (Dose A, Dose B, Dose C, Dose D)
BIOLOGICALRanibizumab 0.5 mg
Administered as a single intravitreal injection
Sponsors
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provide written informed consent. * Primary subfoveal choroidal neovascularization (CNV) secondary to AMD, including predominantly classic, minimally classic or occult lesions, in the study eye. * New diagnosis of wet AMD or evidence of recent disease progression within the last 3 months in study eye. * Evidence of subretinal fluid or retinal cystic changes with a CSFT of \> 340 μm using a Spectralis SD-OCT (Heidelberg Engineering) imaging system. * Best-corrected visual acuity (BCVA) of Snellen equivalent 20/200 or better in the non-study eye. * Other protocol-defined inclusion criteria may apply.
Exclusion criteria
* Previously administered therapy, approved or investigational, for wet AMD in the study eye. * Any current or history of macular or retinal disease in the stuy eye other than wet AMD. * Lasik or cataract surgery within the last 3 months in the study eye or expected to have cataract removal surgery during the study. * Uncontrolled or advanced glaucoma in the study eye. * Use of systemic or topical ocular corticosteroids. * History of a medical condition that, in the opinion of the Investigator, would preclude scheduled visits, completion of the study, or safe administration of study medication. * Abnormal or unsuitable laboratory results at Screening visit. * Lactating or pregnant. Women of childbearing potential must use adequate birth control for the duration of the study. * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Month 1 in Central Subfield Thickness (CSFT) as Measured by Spectral Domain Ocular Coherence Tomography (SD-OCT) | Baseline, Month 1 | CSFT is a retinal thickness measurement and was measured with SD-OCT. A thickening of the retina is characteristic of wet AMD, and a reduction in CSFT may indicate an improvement in ocular health. One eye (ie, study eye) contributed to the mean. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Effect Measured by the Time From Randomization to Receipt of Standard of Care as Determined by the Investigator Based on Protocol Criteria | Time to event, up to Month 6 | Standard of care (SOC) therapy for exudative AMD was implemented if any protocol-specified criteria relating to CSFT, best-corrected visual acuity, or clinically significant intraocular hemorrhages in the study eye were met, in the opinion of the Investigator. |
Participant flow
Recruitment details
Subjects were recruited from 51 investigational centers located in the United States, Europe, Israel, and Australia.
Pre-assignment details
Of the 376 enrolled, 182 were exited as screen failures prior to exposure to randomization and exposure to the study drug. This reporting group includes all patients who were randomized, received study drug, and completed at least 1 scheduled on-therapy study visit (ITT) (194).
Participants by arm
| Arm | Count |
|---|---|
| ESBA1008 Dose A Single intravitreal injection with 6-month follow-up | 10 |
| ESBA1008 Dose B Single intravitreal injection with 6-month follow-up | 35 |
| ESBA1008 Dose C Single intravitreal injection with 6-month follow-up | 48 |
| ESBA1008 Dose D Single intravitreal injection with 6-month follow-up | 40 |
| Lucentis Single intravitreal injection with 6-month follow-up | 61 |
| Total | 194 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Decision Unrelated to an Adverse Event | 0 | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | ESBA1008 Dose A | ESBA1008 Dose B | ESBA1008 Dose C | ESBA1008 Dose D | Lucentis | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 75.9 years STANDARD_DEVIATION 6.9 | 78.5 years STANDARD_DEVIATION 8.3 | 75.2 years STANDARD_DEVIATION 7.7 | 74.5 years STANDARD_DEVIATION 9.8 | 77.8 years STANDARD_DEVIATION 8.1 | 76.5 years STANDARD_DEVIATION 8.4 |
| Sex: Female, Male Female | 6 Participants | 15 Participants | 27 Participants | 25 Participants | 33 Participants | 106 Participants |
| Sex: Female, Male Male | 4 Participants | 20 Participants | 21 Participants | 15 Participants | 28 Participants | 88 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 11 | 10 / 31 | 17 / 47 | 16 / 44 | 13 / 61 |
| serious Total, serious adverse events | 0 / 11 | 4 / 31 | 3 / 47 | 3 / 44 | 7 / 61 |
Outcome results
Primary
Change From Baseline at Month 1 in Central Subfield Thickness (CSFT) as Measured by Spectral Domain Ocular Coherence Tomography (SD-OCT)
CSFT is a retinal thickness measurement and was measured with SD-OCT. A thickening of the retina is characteristic of wet AMD, and a reduction in CSFT may indicate an improvement in ocular health. One eye (ie, study eye) contributed to the mean.
Time frame: Baseline, Month 1
Population: This analysis population includes all patients who were randomized, received study drug, and completed at least 1 scheduled on-therapy study visit (ITT). Efficacy data from visits occurring after standard of care (SoC) were censored and replaced based on LOCF,i.e. by the data observed at the time of the SoC decision.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ESBA1008 Dose A | Change From Baseline at Month 1 in Central Subfield Thickness (CSFT) as Measured by Spectral Domain Ocular Coherence Tomography (SD-OCT) | -142.3 microns | Standard Deviation 78.8 |
| ESBA1008 Dose B | Change From Baseline at Month 1 in Central Subfield Thickness (CSFT) as Measured by Spectral Domain Ocular Coherence Tomography (SD-OCT) | -181.6 microns | Standard Deviation 107.2 |
| ESBA1008 Dose C | Change From Baseline at Month 1 in Central Subfield Thickness (CSFT) as Measured by Spectral Domain Ocular Coherence Tomography (SD-OCT) | -175.6 microns | Standard Deviation 138.9 |
| ESBA1008 Dose D | Change From Baseline at Month 1 in Central Subfield Thickness (CSFT) as Measured by Spectral Domain Ocular Coherence Tomography (SD-OCT) | -174.9 microns | Standard Deviation 101.3 |
| Lucentis | Change From Baseline at Month 1 in Central Subfield Thickness (CSFT) as Measured by Spectral Domain Ocular Coherence Tomography (SD-OCT) | -159.4 microns | Standard Deviation 110.1 |
Secondary
Duration of Effect Measured by the Time From Randomization to Receipt of Standard of Care as Determined by the Investigator Based on Protocol Criteria
Standard of care (SOC) therapy for exudative AMD was implemented if any protocol-specified criteria relating to CSFT, best-corrected visual acuity, or clinically significant intraocular hemorrhages in the study eye were met, in the opinion of the Investigator.
Time frame: Time to event, up to Month 6
Population: ITT: All patients who were randomized, received study drug, and completed at least 1 scheduled on-therapy study visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ESBA1008 Dose A | Duration of Effect Measured by the Time From Randomization to Receipt of Standard of Care as Determined by the Investigator Based on Protocol Criteria | 45 Days |
| ESBA1008 Dose B | Duration of Effect Measured by the Time From Randomization to Receipt of Standard of Care as Determined by the Investigator Based on Protocol Criteria | 75 Days |
| ESBA1008 Dose C | Duration of Effect Measured by the Time From Randomization to Receipt of Standard of Care as Determined by the Investigator Based on Protocol Criteria | 67.5 Days |
| ESBA1008 Dose D | Duration of Effect Measured by the Time From Randomization to Receipt of Standard of Care as Determined by the Investigator Based on Protocol Criteria | 75 Days |
| Lucentis | Duration of Effect Measured by the Time From Randomization to Receipt of Standard of Care as Determined by the Investigator Based on Protocol Criteria | 45 Days |