Trial Outcomes & Findings for Ocriplasmin for Vitreomacular Traction/Symptomatic Vitreomacular Adhesion (NCT NCT02322229)
NCT ID: NCT02322229
Last Updated: 2018-08-21
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
62 participants
Primary outcome timeframe
Day 28
Results posted on
2018-08-21
Participant Flow
Subjects were recruited from 9 sites located in Australia and 1 site located in New Zealand.
Of the 62 enrolled, 10 subjects were exited as screen failures prior to initiation of treatment. This reporting group includes all eligible subjects (52).
Participant milestones
| Measure |
Ocriplasmin
Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal (IVT) injection
|
|---|---|
|
Overall Study
STARTED
|
52
|
|
Overall Study
COMPLETED
|
50
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Ocriplasmin
Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal (IVT) injection
|
|---|---|
|
Overall Study
Physician Decision
|
2
|
Baseline Characteristics
Ocriplasmin for Vitreomacular Traction/Symptomatic Vitreomacular Adhesion
Baseline characteristics by cohort
| Measure |
Ocriplasmin
n=52 Participants
Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by IVT injection
|
|---|---|
|
Age, Continuous
|
74.5 years
STANDARD_DEVIATION 7.0 • n=93 Participants
|
|
Sex: Female, Male
Female
|
39 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Day 28Population: 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.
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.
Outcome measures
| Measure |
Ocriplasmin
n=52 Participants
Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by IVT injection
|
|---|---|
|
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 outcome
Timeframe: Baseline (Day 0), Day 7, Day 28, Day 90, Day 180Population: 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.
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.
Outcome measures
| Measure |
Ocriplasmin
n=52 Participants
Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by IVT injection
|
|---|---|
|
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
|
|
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
|
|
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
|
|
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
|
|
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 outcome
Timeframe: Day 7, Day 28, Day 90, Day 180Population: 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.
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.
Outcome measures
| Measure |
Ocriplasmin
n=4 Participants
Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by IVT injection
|
|---|---|
|
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
|
|
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
|
|
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
|
|
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 outcome
Timeframe: Baseline (Day 0), Day 7, Day 90, Day 180Population: 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.
As described in Primary Outcome Measure
Outcome measures
| Measure |
Ocriplasmin
n=52 Participants
Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by IVT injection
|
|---|---|
|
Percentage of Subjects With Non-surgical Resolution of VMT/sVMA at Days 7, 90, and 180
Day 7
|
19.2 percentage of subjects
|
|
Percentage of Subjects With Non-surgical Resolution of VMT/sVMA at Days 7, 90, and 180
Day 90
|
38.5 percentage of subjects
|
|
Percentage of Subjects With Non-surgical Resolution of VMT/sVMA at Days 7, 90, and 180
Day 180
|
40.4 percentage of subjects
|
SECONDARY outcome
Timeframe: Day 180Population: Full Analysis Set
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.
Outcome measures
| Measure |
Ocriplasmin
n=52 Participants
Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by IVT injection
|
|---|---|
|
Percentage of Subjects Experiencing Pars Plana Vitrectomy (PPV) at Day 180
|
7.7 percentage of subjects
|
SECONDARY outcome
Timeframe: Baseline (Day 0), Day 28, Day 180Population: 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.
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.
Outcome measures
| Measure |
Ocriplasmin
n=52 Participants
Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by IVT injection
|
|---|---|
|
Change From Baseline in Central Foveal Thickness at Days 28 and 180
Baseline (BL)
|
302.3 Microns
Standard Deviation 161.23
|
|
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
|
|
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
|
Adverse Events
Pretreatment
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Jetrea
Serious events: 5 serious events
Other events: 41 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pretreatment
n=62 participants at risk
All subjects who consented to participate in the study prior to initiation of study treatment
|
Jetrea
n=52 participants at risk
Subjects exposed to Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by IVT injection
|
|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/62 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
1.9%
1/52 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
|
Eye disorders
Macular hole
|
0.00%
0/62 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
1.9%
1/52 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
|
Gastrointestinal disorders
Intestinal haemorrhage
|
0.00%
0/62 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
1.9%
1/52 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
|
Infections and infestations
Lung infection
|
0.00%
0/62 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
1.9%
1/52 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.00%
0/62 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
1.9%
1/52 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
Other adverse events
| Measure |
Pretreatment
n=62 participants at risk
All subjects who consented to participate in the study prior to initiation of study treatment
|
Jetrea
n=52 participants at risk
Subjects exposed to Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by IVT injection
|
|---|---|---|
|
Eye disorders
Eye pain
|
0.00%
0/62 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
7.7%
4/52 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
|
Eye disorders
Lacrimation increased
|
0.00%
0/62 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
5.8%
3/52 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
|
Eye disorders
Metamorphopsia
|
0.00%
0/62 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
15.4%
8/52 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
|
Eye disorders
Photopsia
|
0.00%
0/62 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
51.9%
27/52 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
|
Eye disorders
Vision blurred
|
0.00%
0/62 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
23.1%
12/52 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
|
Eye disorders
Visual acuity reduced
|
0.00%
0/62 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
21.2%
11/52 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
|
Eye disorders
Visual impairment
|
0.00%
0/62 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
17.3%
9/52 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
|
Eye disorders
Vitreous floaters
|
1.6%
1/62 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
11.5%
6/52 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
|
Infections and infestations
Influenza
|
0.00%
0/62 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
5.8%
3/52 • Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 7 months). AEs are reported as pretreatment and treatment-emergent.
An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment (ie, initiation of treatment with test article) regardless of whether or not the event has a causal relationship with the treatment. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator as outlined in the study protocol.
|
Additional Information
Worldwide Medical Affairs Director, GMA Retina Lucentis
Alcon, A Novartis Division
Phone: 1-888-451-3937
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor reserves the right of prior review of any publication or presentation of information related to the study.
- Publication restrictions are in place
Restriction type: OTHER