Clinical Trial Results:
Assessment of Anatomical and Functional Outcomes in Patients Treated with Ocriplasmin for Vitreomacular Traction/Symptomatic Vitreomacular Adhesion
(VMT/sVMA)
Summary
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EudraCT number |
2013-005464-25 |
Trial protocol |
HU GB DE IT ES NL PT BE PL FR |
Global end of trial date |
02 Sep 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Aug 2016
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First version publication date |
30 Aug 2016
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
M-13-056
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02035748 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Alcon, A Novartis Division
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Sponsor organisation address |
6201 S. Freeway, Fort Worth, Texas, United States, 76134
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Public contact |
EMEA Medical Affairs Lead, Pharma, Alcon, A Novartis Division, +1 888-451-3937, alcon.medinfo@alcon.com
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Scientific contact |
EMEA Medical Affairs Lead, Pharma, Alcon, A Novartis Division, +1 888-451-3937, alcon.medinfo@alcon.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
02 Sep 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Sep 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The purpose of this study is to observe the anatomical and functional outcomes of ocriplasmin (JETREA®) over a 6-month follow-up period. After receiving a single intravitreal injection as per country's product label (Day 0), subjects were followed for a 6-month period (Day 180).
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Protection of trial subjects |
This study was performed in compliance with the ethical principles of the Declaration of Helsinki and Good Clinical Practice (GCP), including the archiving of essential documents.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
21 Apr 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 35
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Country: Number of subjects enrolled |
Poland: 30
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Country: Number of subjects enrolled |
Portugal: 9
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Country: Number of subjects enrolled |
Spain: 34
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Country: Number of subjects enrolled |
United Kingdom: 60
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Country: Number of subjects enrolled |
Belgium: 40
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Country: Number of subjects enrolled |
France: 99
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Country: Number of subjects enrolled |
Germany: 33
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Country: Number of subjects enrolled |
Hungary: 23
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Country: Number of subjects enrolled |
Italy: 38
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Country: Number of subjects enrolled |
Canada: 67
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Worldwide total number of subjects |
468
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EEA total number of subjects |
401
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
81
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From 65 to 84 years |
364
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85 years and over |
23
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Recruitment
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Recruitment details |
Subjects were recruited from 87 study centers located in Europe and Canada (10 Italy, 5 Netherlands, 4 Poland, 4 Portugal, 12 Spain, 15 United Kingdom, 3 Belgium, 12 France, 9 Germany, 5 Hungary, and 8 Canada). | ||||||||||||||||||||||
Pre-assignment
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Screening details |
Of the 628 enrolled, 160 subjects were exited prior to initiation of treatment. This reporting group includes all treated subjects (468). | ||||||||||||||||||||||
Period 1
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Period 1 title |
Overall study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||
Arms
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Arm title
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Ocriplasmin | ||||||||||||||||||||||
Arm description |
Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection | ||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||
Investigational medicinal product name |
Ocriplasmin
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Investigational medicinal product code |
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Other name |
JETREA
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Pharmaceutical forms |
Concentrate for solution for injection
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Routes of administration |
Intravitreal use
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Dosage and administration details |
0.5 mg/0.2 mL solution for injection
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Baseline characteristics reporting groups
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Reporting group title |
Overall study
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Reporting group description |
Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Ocriplasmin
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Reporting group description |
Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection |
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End point title |
Proportion of Subjects With Nonsurgical Resolution of Focal Vitreomacular Traction (VMT/VMA) at Day 28, as Determined by Central Reading Center (CRC) Spectral Domain Optical Coherence Tomography (SD-OCT) Evaluation [1] | ||||||||
End point description |
Vitreous separation was assessed by SD-OCT using scores ranging from 1 (vitreous attached from macula to ON; separated elsewhere cannot determine foveal) to 12 (unable to determine state of separation). Nonsurgical resolution was defined as a change from baseline score of 5/6/8 to 7/9/10 at Day 28. 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. Thus, the term VMA is used interchangeably with VMT/sVMA. Proportion of subjects is presented as a percentage, with percentage based on the number of subjects who have VMT/sVMA at baseline and SD-OCT value at Day 28. One eye (study eye) contributed to the analysis.
Subjects treated with IP with at least one post-treatment SD-OCT measurement (FAS). Missing data imputed using the last observation carried forward (LOCF) method. Subjects with vitrectomy after VMT/sVMA resolution were considered 'no resolution' after timepoint of vitrectomy.
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End point type |
Primary
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End point timeframe |
Baseline, Day 28
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was performed |
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No statistical analyses for this end point |
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End point title |
Nonsurgical Change From Baseline in Best-corrected Visual Acuity (BCVA) at Distance | ||||||||||||||
End point description |
BCVA (with spectacles or other visual corrective devices) was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) testing at 4 meters. The charts contain 14 rows of letters. BCVA was calculated as the number of letters read correctly and improvement defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis.
Full Analysis Set. Missing data imputed using LOCF. BCVA values after a vitrectomy were imputed with the last non-missing value prior to the vitrectomy.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0), Day 28, Day 90, Day 180
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No statistical analyses for this end point |
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End point title |
Proportion of Subjects With Nonsurgical Closure of Macular Hole (MH), if Present at Baseline | ||||||||||||||
End point description |
The closure of macular hole (a full thickness defect of the retinal tissure 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. Proportion of subjects is presented as a percentage, with percentage based on the number of subjects who had macular hole at baseline and OCT value at each specific visit. One eye (study eye) contributed to the analysis.
Full Analysis Set. Missing data imputed using LOCF. Subjects who had vitrectomy after MH closure were considered as 'no MH closure' after the timepoint of vitrectomy.
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End point type |
Secondary
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End point timeframe |
Day 28, Day 90, Day 180
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No statistical analyses for this end point |
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End point title |
Proportion of Subjects With Nonsurgical Resolution of VMT/sVMA | ||||||||||||
End point description |
Vitreous separation was assessed by SD-OCT using scores ranging from 1 (vitreous attached from macula to ON; separated elsewhere cannot determine foveal) to 12 (unable to determine state of separation). Nonsurgical resolution was defined as a change from baseline score of 5/6/8 to 7/9/10 at Day 90 and Day 180. 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. Thus, the term VMA is used interchangeably with VMT/sVMA. Proportion of subjects is presented as a percentage, with percentage based on the number of subjects who have VMT/sVMA at baseline and SD-OCT value at Day 90/Day 180. One eye (study eye) contributed to the analysis.
Full Analysis Set. Missing data imputed using LOCF. Subjects who had vitrectomy after VMT/sVMA resolution were considered as 'no resolution' after the timepoint of vitrectomy.
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End point type |
Secondary
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End point timeframe |
Baseline, Day 90, Day 180
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No statistical analyses for this end point |
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End point title |
Proportion of Subjects Experiencing Pars Plana Vitrectomy (PPV) at Day 180 | ||||||||
End point description |
Pars plana vitrectomy (the surgical removal of vitreous gel from the eye) was captured in Concomitant Ocular Procedures. Proportion of subjects is reported as a percentage. One eye (study eye) contributed to the analysis.
Full Analysis Set
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End point type |
Secondary
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End point timeframe |
Day 180
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No statistical analyses for this end point |
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End point title |
Mean Nonsurgical Change From Baseline in Central Foveal Thickness (CFT) | ||||||||||||||
End point description |
Nonsurgical change in central foveal thickness (CFT values after a vitrectomy were imputed with the last non-missing value prior to the vitrectomy) was determined by subtracting the measurements in subretinal fluid and retinal pigment epithelium (RPE) elevations and/or SHRM (subretinal hyper-reflective material such as choroidal neovascularization (CNV)) from the value in total retinal measurement. A lower CFT indicates improvement. One eye (study eye) contributed to the analysis.
Full Analysis Set. Missing data is imputed using LOCF. CFT values after a vitrectomy were imputed with the last non-missing value prior to the vitrectomy.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0), Day 28, Day 180
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events (AEs) were collected for the duration of a subject's participation in the study (up to 7 months). Ocular AEs are presented for both study eye and non-study eye combined. AEs are reported as treatment-emergent.
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Adverse event reporting additional description |
An AE was defined as any untoward medical occurrence in a subject regardless of the causal relationship to the study medication. AEs could be volunteered or solicited by the Investigator or study personnel.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
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Reporting groups
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Reporting group title |
Ocriplasmin
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Reporting group description |
All subjects exposed to the investigational product | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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04 Mar 2014 |
The purpose of this amendment was to include additional exclusion criteria to ensure that patients for whom treatment was not recommended were not enrolled in this study. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |