Diabetic Retinopathy, Disease Progression, Posterior Vitreous Detachment
Conditions
Brief summary
The purpose of this study is to assess the efficacy and safety of up to 3 intravitreal injections of ocriplasmin (0.0625mg or 0.125mg), in subjects with moderate to very severe non-proliferative diabetic retinopathy (NPDR), to induce total posterior vitreous detachment (PVD) in order to reduce the risk of disease progression to proliferative diabetic retinopathy (PDR).
Interventions
DRUGocriplasmin 0.0625mg
Up to 3 intravitreal injections of ocriplasmin 0.0625mg approximately 1 month apart
DRUGocriplasmin 0.125mg
Up to 3 intravitreal injections of ocriplasmin 0.125mg approximately 1 month apart
DRUGSham injection
3 sham injections approximately 1 month apart. No actual injections. No medication is used.
Sponsors
ThromboGenics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female aged 18 years or older * Best-corrected visual acuity (BCVA) of 65 letters read or greater (Snellen equivalent of 20/50 or better) in the study eye * HbA1c ≤ 12%, as assessed by the central laboratory * Moderate to very severe NPDR as per ETDRS Severity Scale, based on 7 standard field stereo colour fundus photograph * Central subfield thickness of ≤ 340µm on Spectralis SD-OCT or ≤ 320µm on non-Spectralis SD OCT in the study eye, with or without mild centre-involved diabetic macular oedema * No evidence of total PVD in the study eye * Written informed consent obtained from the subject prior to screening procedures
Exclusion criteria
* History of or current ocular condition in the study eye that may interfere with the assessment of the progression to PDR * Presence of epiretinal membrane in the study eye * Presence of foveal ischemia in the study eye * Presence of pre-retinal or vitreous haemorrhage in the study eye * Presence of iris or angle neovascularisation in the study eye * Any active ocular / intraocular infection or inflammation in either eye * Aphakic study eye * Uncontrolled hypertension in the opinion of the Investigator * Pseudoexfoliation, Marfan's syndrome, phacodonesis or any other finding in the Investigator's opinion suggesting lens / zonular instability
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Total PVD by the Month 3 Visit | Month 3 | Total PVD should be confirmed on both B-scan ultrasound and spectral domain optical coherence tomography (SD-OCT), as assessed by the masked central reading centres |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Ocular Treatment-emergent Adverse Events in the Study Eye | From first injection until the end of the study (Month 24) | Adverse events were identified by ophthalmic assessments (including BCVA assessment, full ophthalmic examination and ocular imaging) and by subject reporting |
Countries
Czechia, France, Germany, Hungary, Israel, Italy, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ocriplasmin 0.0625mg Subjects received up to 3 intravitreal injections of ocriplasmin 0.0625mg approximately 1 month apart | 20 |
| Ocriplasmin 0.125mg Subjects received up to 3 intravitreal injections of ocriplasmin 0.125mg approximately 1 month apart | 19 |
| Sham Injection Subjects received 3 sham injections approximately 1 month apart. No actual injections. No medication was used. | 9 |
| Total | 48 |
Baseline characteristics
| Characteristic | Ocriplasmin 0.0625mg | Ocriplasmin 0.125mg | Sham Injection | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 5 Participants | 3 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 14 Participants | 6 Participants | 32 Participants |
| Age, Continuous | 57.7 years STANDARD_DEVIATION 12.14 | 55.4 years STANDARD_DEVIATION 10.15 | 54.3 years STANDARD_DEVIATION 13.01 | 56.2 years STANDARD_DEVIATION 11.39 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 4 Participants | 2 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 15 Participants | 7 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 18 Participants | 7 Participants | 45 Participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 2 Participants | 13 Participants |
| Sex: Female, Male Male | 14 Participants | 14 Participants | 7 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 19 | 0 / 9 |
| other Total, other adverse events | 16 / 20 | 17 / 19 | 7 / 9 |
| serious Total, serious adverse events | 5 / 20 | 8 / 19 | 1 / 9 |
Outcome results
Primary
Number of Subjects With Total PVD by the Month 3 Visit
Total PVD should be confirmed on both B-scan ultrasound and spectral domain optical coherence tomography (SD-OCT), as assessed by the masked central reading centres
Time frame: Month 3
Population: All Treated Subjects with B-scan ultrasound and SD-OCT assessments at Month 3
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ocriplasmin 0.0625mg | Number of Subjects With Total PVD by the Month 3 Visit | 0 Participants |
| Ocriplasmin 0.125mg | Number of Subjects With Total PVD by the Month 3 Visit | 0 Participants |
| Sham Injection | Number of Subjects With Total PVD by the Month 3 Visit | 0 Participants |
Secondary
Number of Subjects With Ocular Treatment-emergent Adverse Events in the Study Eye
Adverse events were identified by ophthalmic assessments (including BCVA assessment, full ophthalmic examination and ocular imaging) and by subject reporting
Time frame: From first injection until the end of the study (Month 24)
Population: All Treated Subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ocriplasmin 0.0625mg | Number of Subjects With Ocular Treatment-emergent Adverse Events in the Study Eye | 15 Participants |
| Ocriplasmin 0.125mg | Number of Subjects With Ocular Treatment-emergent Adverse Events in the Study Eye | 14 Participants |
| Sham Injection | Number of Subjects With Ocular Treatment-emergent Adverse Events in the Study Eye | 4 Participants |