Vitreomacular Adhesion, Vitreomacular Traction
Conditions
Keywords
VMT, sVMA, vitrectomy, ocriplasmin
Brief summary
The purpose of this study is to observe the anatomical and functional outcomes of ocriplasmin (JETREA™®) over a 6-month period.
Interventions
DRUGOcriplasmin 0.125 mg in a 0.1 mL volume
Sponsors
Alcon Research
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of VMT/sVMA, with evidence of focal VMT visible on Spectral Domain - Optical Coherence Tomography (SD-OCT). * Read, sign, and date an Institutional Review Board/Ethics Committee-approved informed consent form. * Willing and able to attend all study visits. * Other protocol-specified inclusion criteria may apply.
Exclusion criteria
* Women of childbearing potential if pregnant, test positive on a urine pregnancy test, intend to become pregnant during the study period, breastfeeding, or not in agreement to use adequate birth control methods to prevent pregnancy throughout the study. * Hypersensitivity to ocriplasmin or any of the JETREA™® excipients. * Active or suspected intraocular or periocular infection in either eye. * Participation in any interventional clinical trial within 30 days prior to baseline. * Presence of epiretinal membrane (ERM) over the macula at baseline in the study eye. * Broad VMT/VMA \> 1500 microns at baseline in the study eye. * History of vitrectomy in the study eye. * History of laser photocoagulation to the macula in the study eye. * Any relevant concomitant ocular condition in the study eye that, in the opinion of the Investigator, could be expected to worsen or require surgical intervention during the study period. * Macular hole of \> 400 microns diameter in the study eye. * High myopia in the study eye. * Pseudo-exfoliation, Marfan's syndrome, phacodonesis, or any other finding in the study eye that, in the Investigator's opinion, suggests lens/zonular instability. * Aphakia in the study eye. * History of retinal detachment in the study eye. * Recent ocular surgery or ocular injection in the study eye within the past 90 days (including laser therapy). * Proliferative diabetic retinopathy or ischemic retinopathies in the study eye. * Retinal vein occlusions in the study eye. * Exudative age-related macular degeneration (AMD) in the study eye. * Vitreous hemorrhage in the study eye. * Other protocol-specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Non-surgical Resolution of Focal VMT/sVMA at Day 28, as Determined by Central Reading Center (CRC) Spectral Domain Optical Coherence Tomography (SD-OCT) Evaluation | Day 28 | Vitreous separation was assessed, by SD-OCT according to CRC OCT image reading, into 1 of 12 categories, where the targeted status of VMA resolution was 7=Vitreous attached only at optic nerve (ON) or at ON and elsewhere, but not attached in macular, 9=Vitreous visible with complete separation and no attachment, and 10=No visible vitreous separation, which needed to be reached without prior vitrectomy. The assessment of resolution of VMT/sVMA was based upon the anatomical resolution of VMA only, i.e. no resolution of the related symptoms was considered. One eye (study eye) contributed to the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Best-corrected Visual Acuity (BCVA) at Distance at Days 7, 28, 90, and 180 | Baseline (Day 0), Day 7, Day 28, Day 90, Day 180 | BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) testing. BCVA was determined as follows: if tested at 4 meters, BCVA=the number of letters read correctly at 4 meters+30; if tested at 1 meter, BCVA=the number of letters read correctly at 1 meter, with 83-84 representing normal vision. BCVA change was defined as a change in letters read from the baseline assessment. A positive change value indicates improvement. One eye (study eye) contributed to the analysis. |
| Percentage of Subjects With Closure of Macular Hole (MH), at Days 7, 28, 90, and 180 (if Present at Baseline) | Day 7, Day 28, Day 90, Day 180 | The closure of macular hole (a full thickness defect of the retinal tissue involving the anatomical fovea) is defined as a flattened and reattached hole rim along the whole circumference of macular hole. Closure was determined by SD-OCT evaluation and the percentage of subjects tabulated. One eye (study eye) contributed to the analysis. |
| Percentage of Subjects With Non-surgical Resolution of VMT/sVMA at Days 7, 90, and 180 | Baseline (Day 0), Day 7, Day 90, Day 180 | As described in Primary Outcome Measure |
| Percentage of Subjects Experiencing Pars Plana Vitrectomy (PPV) at Day 180 | Day 180 | Pars plana vitrectomy (the surgical removal of vitreous gel from the eye) was captured in Concomitant Ocular Procedures. One eye (study eye) contributed to the analysis. |
| Change From Baseline in Central Foveal Thickness at Days 28 and 180 | Baseline (Day 0), Day 28, Day 180 | Central foveal thickness (CFT) was determined by subtracting the measurements in subretinal fluid (SRF) and retinal pigment epithelium (RPE) elevation and/or subretinal hyper-reflective material (SHRM) from the value in total retinal measurement. The change was defined as a change from baseline values of CFT. One eye (study eye) contributed to the analysis. |
Countries
Australia
Participant flow
Recruitment details
Subjects were recruited from 9 sites located in Australia and 1 site located in New Zealand.
Pre-assignment details
Of the 62 enrolled, 10 subjects were exited as screen failures prior to initiation of treatment. This reporting group includes all eligible subjects (52).
Participants by arm
| Arm | Count |
|---|---|
| Ocriplasmin Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by IVT injection | 52 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 2 |
Baseline characteristics
| Characteristic | Ocriplasmin |
|---|---|
| Age, Continuous | 74.5 years STANDARD_DEVIATION 7 |
| Sex: Female, Male Female | 39 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 62 | 0 / 52 |
| other Total, other adverse events | 1 / 62 | 41 / 52 |
| serious Total, serious adverse events | 0 / 62 | 5 / 52 |
Outcome results
Primary
Percentage of Subjects With Non-surgical Resolution of Focal VMT/sVMA at Day 28, as Determined by Central Reading Center (CRC) Spectral Domain Optical Coherence Tomography (SD-OCT) Evaluation
Vitreous separation was assessed, by SD-OCT according to CRC OCT image reading, into 1 of 12 categories, where the targeted status of VMA resolution was 7=Vitreous attached only at optic nerve (ON) or at ON and elsewhere, but not attached in macular, 9=Vitreous visible with complete separation and no attachment, and 10=No visible vitreous separation, which needed to be reached without prior vitrectomy. The assessment of resolution of VMT/sVMA was based upon the anatomical resolution of VMA only, i.e. no resolution of the related symptoms was considered. One eye (study eye) contributed to the analysis.
Time frame: Day 28
Population: Full Analysis Set. Missing data imputed using the last observation carried forward (LOCF) method. Subjects who had vitrectomy after VMA resolution are considered as 'no VMA resolution' after timepoint of vitrectomy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ocriplasmin | Percentage of Subjects With Non-surgical Resolution of Focal VMT/sVMA at Day 28, as Determined by Central Reading Center (CRC) Spectral Domain Optical Coherence Tomography (SD-OCT) Evaluation | 26.9 percentage of subjects |
Secondary
Change From Baseline in Best-corrected Visual Acuity (BCVA) at Distance at Days 7, 28, 90, and 180
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) testing. BCVA was determined as follows: if tested at 4 meters, BCVA=the number of letters read correctly at 4 meters+30; if tested at 1 meter, BCVA=the number of letters read correctly at 1 meter, with 83-84 representing normal vision. BCVA change was defined as a change in letters read from the baseline assessment. A positive change value indicates improvement. One eye (study eye) contributed to the analysis.
Time frame: Baseline (Day 0), Day 7, Day 28, Day 90, Day 180
Population: Full Analysis Set. Missing data imputed using the LOCF method. BCVA values after a vitrectomy are imputed with the last non-missing value prior to the vitrectomy.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocriplasmin | Change From Baseline in Best-corrected Visual Acuity (BCVA) at Distance at Days 7, 28, 90, and 180 | Baseline (BL) | 70.6 letters | Standard Deviation 10.62 |
| Ocriplasmin | Change From Baseline in Best-corrected Visual Acuity (BCVA) at Distance at Days 7, 28, 90, and 180 | Change from BL at Day 7 | -1.8 letters | Standard Deviation 7.09 |
| Ocriplasmin | Change From Baseline in Best-corrected Visual Acuity (BCVA) at Distance at Days 7, 28, 90, and 180 | Change from BL at Day 28 | 1.0 letters | Standard Deviation 7.67 |
| Ocriplasmin | Change From Baseline in Best-corrected Visual Acuity (BCVA) at Distance at Days 7, 28, 90, and 180 | Change from BL at Day 90 | 2.1 letters | Standard Deviation 8.07 |
| Ocriplasmin | Change From Baseline in Best-corrected Visual Acuity (BCVA) at Distance at Days 7, 28, 90, and 180 | Change from BL at Day 180 | 3.3 letters | Standard Deviation 9.16 |
Secondary
Change From Baseline in Central Foveal Thickness at Days 28 and 180
Central foveal thickness (CFT) was determined by subtracting the measurements in subretinal fluid (SRF) and retinal pigment epithelium (RPE) elevation and/or subretinal hyper-reflective material (SHRM) from the value in total retinal measurement. The change was defined as a change from baseline values of CFT. One eye (study eye) contributed to the analysis.
Time frame: Baseline (Day 0), Day 28, Day 180
Population: Missing data is imputed using the LOCF method. CFT values after a vitrectomy are imputed with the last non-missing value prior to the vitrectomy.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocriplasmin | Change From Baseline in Central Foveal Thickness at Days 28 and 180 | Baseline (BL) | 302.3 Microns | Standard Deviation 161.23 |
| Ocriplasmin | Change From Baseline in Central Foveal Thickness at Days 28 and 180 | Change from BL at Day 28 | -35.5 Microns | Standard Deviation 95.53 |
| Ocriplasmin | Change From Baseline in Central Foveal Thickness at Days 28 and 180 | Change from BL at Day 180 | -17.6 Microns | Standard Deviation 143.63 |
Secondary
Percentage of Subjects Experiencing Pars Plana Vitrectomy (PPV) at Day 180
Pars plana vitrectomy (the surgical removal of vitreous gel from the eye) was captured in Concomitant Ocular Procedures. One eye (study eye) contributed to the analysis.
Time frame: Day 180
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ocriplasmin | Percentage of Subjects Experiencing Pars Plana Vitrectomy (PPV) at Day 180 | 7.7 percentage of subjects |
Secondary
Percentage of Subjects With Closure of Macular Hole (MH), at Days 7, 28, 90, and 180 (if Present at Baseline)
The closure of macular hole (a full thickness defect of the retinal tissue involving the anatomical fovea) is defined as a flattened and reattached hole rim along the whole circumference of macular hole. Closure was determined by SD-OCT evaluation and the percentage of subjects tabulated. One eye (study eye) contributed to the analysis.
Time frame: Day 7, Day 28, Day 90, Day 180
Population: This analysis population includes all subjects in Full Analysis Set with MH at baseline (n=4). Subjects who had vitrectomy after MH closure are considered as 'no MH closure' after the timepoint of vitrectomy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocriplasmin | Percentage of Subjects With Closure of Macular Hole (MH), at Days 7, 28, 90, and 180 (if Present at Baseline) | Day 7 | 25.0 percentage of subjects |
| Ocriplasmin | Percentage of Subjects With Closure of Macular Hole (MH), at Days 7, 28, 90, and 180 (if Present at Baseline) | Day 28 | 50.0 percentage of subjects |
| Ocriplasmin | Percentage of Subjects With Closure of Macular Hole (MH), at Days 7, 28, 90, and 180 (if Present at Baseline) | Day 90 | 50.0 percentage of subjects |
| Ocriplasmin | Percentage of Subjects With Closure of Macular Hole (MH), at Days 7, 28, 90, and 180 (if Present at Baseline) | Day 180 | 50.0 percentage of subjects |
Secondary
Percentage of Subjects With Non-surgical Resolution of VMT/sVMA at Days 7, 90, and 180
As described in Primary Outcome Measure
Time frame: Baseline (Day 0), Day 7, Day 90, Day 180
Population: Full Analysis Set. Missing data imputed for Days 90 and 180 using the LOCF method. Subjects who had vitrectomy are considered as 'no VMA resolution' after the timepoint of vitrectomy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocriplasmin | Percentage of Subjects With Non-surgical Resolution of VMT/sVMA at Days 7, 90, and 180 | Day 7 | 19.2 percentage of subjects |
| Ocriplasmin | Percentage of Subjects With Non-surgical Resolution of VMT/sVMA at Days 7, 90, and 180 | Day 90 | 38.5 percentage of subjects |
| Ocriplasmin | Percentage of Subjects With Non-surgical Resolution of VMT/sVMA at Days 7, 90, and 180 | Day 180 | 40.4 percentage of subjects |