Assessment of Patients Treated With JETREA® for Vitreomacular Traction

• Sponsor: Alcon Research (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02035748
• Collaborator: (none)
• Enrollment: 628
• Arm: 1
• Duration (Months): 17

Study Details

Study Description

Brief Summary

The purpose of this study is to observe the anatomical and functional outcomes of ocriplasmin (JETREA®) over a 6-month follow-up period.

Condition or Disease	Intervention/Treatment	Phase
Vitreomacular Traction; Vitreomacular Adhesion	Drug: Ocriplasmin	Phase 4

Detailed Description

After receiving a single intravitreal injection as per country's product label (Day 0), subjects were followed for a 6-month period (Day 180).

Study Design

• Study Type: Interventional
• Actual Enrollment: 628 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Assessment of Anatomical and Functional Outcomes in Patients Treated With Ocriplasmin for Vitreomacular Traction/Symptomatic Vitreomacular Adhesion (VMT/sVMA)
• Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ocriplasmin Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection	Drug: Ocriplasmin; 0.5 mg/0.2 mL solution for injection; Other Names: JETREA®

Outcome Measures

Primary Outcome Measures

1. 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 [Baseline, Day 28]

   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.

Secondary Outcome Measures

1. Nonsurgical Change From Baseline in Best-corrected Visual Acuity (BCVA) at Distance [Baseline (Day 0), Day 28, Day 90, Day 180]

   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.

2. Proportion of Subjects With Nonsurgical Closure of Macular Hole (MH), if Present at Baseline [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. 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.

3. Proportion of Subjects With Nonsurgical Resolution of VMT/sVMA [Baseline, Day 90, Day 180]

   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.

4. Proportion 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. Proportion of subjects is reported as a percentage. One eye (study eye) contributed to the analysis.

5. Mean Nonsurgical Change From Baseline in Central Foveal Thickness (CFT) [Baseline (Day 0), Day 28, Day 180]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of vitreomacular traction/symptomatic vitreomacular adhesion (VMT/sVMA), with evidence of focal VMA visible on Spectral Domain Optical Coherence Tomography (SD-OCT).

• Read, sign, and date an Institutional Review Board/Ethics Committee-approved informed consent form.

• Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

• Women of childbearing potential if pregnant, 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.

• Presence of Epiretinal Membrane (ERM) over the macula at baseline.

• Broad VMT/VMA >1500 microns at baseline.

• History of vitrectomy in the study eye.

• History of laser photocoagulation to the macula in the study eye.

• Any relevant concomitant ocular condition that, in the opinion of the investigator, could be expected to worsen or require surgical intervention during the study period.

• Macular hole of >400µm diameter in the study eye.

• High myopia in the study eye.

• Pseudo-exfoliation, Marfan's syndrome, phacodonesis or any other finding in the Investigator's opinion suggesting lens/zonular instability.

• Aphakia.

• History of retinal detachment.

• Diabetic retinopathy, ischaemic retinopathies, retinal vein occlusions.

• Recent ocular surgery or ocular injection.

• Vitreous hemorrhage.

• Exudative age-related macular degeneration (AMD).

• Therapy with another investigational agent within 30 days prior to Visit 1.

• Active, simultaneous enrollment in another ophthalmology clinical study.

• Other protocol-defined exclusion criteria may apply.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Alcon Research

Investigators

• Study Director: Sr Clinical Manager, Ophtha-GCRA, Alcon, a Novartis Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alcon Research
• ClinicalTrials.gov Identifier: NCT02035748
• Other Study ID Numbers: M-13-056; 2013-005464-25
• First Posted: Jan 14, 2014
• Last Update Posted: Oct 12, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Alcon Research: Vitreomacular traction; Symptomatic vitreomacular adhesion; Ocriplasmin; JETREA
• Additional relevant MeSH terms: Tissue Adhesions

Study Results

Participant Flow

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 Detail	Of the 628 enrolled, 160 subjects were exited prior to initiation of treatment. This reporting group includes all treated subjects (468).

Arm/Group Title	Ocriplasmin
Arm/Group Description	Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection
Period Title: Overall Study
STARTED	468
COMPLETED	448
NOT COMPLETED	20

Baseline Characteristics

Arm/Group Title	Ocriplasmin
Arm/Group Description	Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection
Overall Participants	468
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.7 (8.3)
Sex: Female, Male (Count of Participants)
Female	345 73.7%
Male	123 26.3%

Outcome Measures

1. Primary Outcome

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
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.
Time Frame	Baseline, Day 28

Outcome Measure Data

Analysis Population Description

This analysis population includes all subjects who received treatment with IP and had at least one post-treatment measurement of SD-OCT (FAS). Missing data imputed using the last observation carried forward (LOCF) method. Subjects who had vitrectomy after VMT/sVMA resolution were considered as 'no resolution' after timepoint of vitrectomy.

Arm/Group Title	Ocriplasmin
Arm/Group Description	Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection
Measure Participants	466
Number [percentage of subjects]	47.4

2. Secondary Outcome

Title	Nonsurgical Change From Baseline in Best-corrected Visual Acuity (BCVA) at Distance
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.
Time Frame	Baseline (Day 0), Day 28, Day 90, Day 180

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ocriplasmin
Arm/Group Description	Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection
Measure Participants	448
Change from baseline at Day 28	1.7 (6.70)
Change from baseline at Day 90	3.0 (7.07)
Change from baseline at Day 180	3.5 (7.77)

3. Secondary Outcome

Title	Proportion of Subjects With Nonsurgical Closure of Macular Hole (MH), if Present at Baseline
Description	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. 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.
Time Frame	Day 28, Day 90, Day 180

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ocriplasmin
Arm/Group Description	Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection
Measure Participants	86
Day 28	39.5
Day 90	40.7
Day 180	41.9

4. Secondary Outcome

Title	Proportion of Subjects With Nonsurgical Resolution of VMT/sVMA
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.
Time Frame	Baseline, Day 90, Day 180

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ocriplasmin
Arm/Group Description	Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection
Measure Participants	466
Day 90	47.9
Day 180	49.4

5. Secondary Outcome

Title	Proportion of Subjects Experiencing Pars Plana Vitrectomy (PPV) at Day 180
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.
Time Frame	Day 180

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Ocriplasmin
Arm/Group Description	Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection
Measure Participants	466
Number [percentage of subjects]	12.0

6. Secondary Outcome

Title	Mean Nonsurgical Change From Baseline in Central Foveal Thickness (CFT)
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.
Time Frame	Baseline (Day 0), Day 28, Day 180

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Ocriplasmin
Arm/Group Description	Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection
Measure Participants	466
Baseline (Day 0), n=466	276.1 (166.4)
Change from baseline at Day 28, n=465	-43.2 (113.47)
Change from baseline at Day 180, n=466	-45.4 (131.84)

Adverse Events

Time Frame	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 pretreatment and treatment-emergent.
Adverse Event Reporting 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.
Arm/Group Title	Pretreatment		Ocriplasmin
Arm/Group Description	All subjects consented to participate in the study prior to the initiation of study treatment		All subjects exposed to the investigational product
All Cause Mortality
	Pretreatment		Ocriplasmin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pretreatment		Ocriplasmin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/628 (0.2%)		46/468 (9.8%)
Cardiac disorders
Arrhythmia	0/628 (0%)		1/468 (0.2%)
Atrial fibrillation	0/628 (0%)		1/468 (0.2%)
Cardiac failure	0/628 (0%)		1/468 (0.2%)
Left ventricular failure	0/628 (0%)		1/468 (0.2%)
Eye disorders
Macular Hole	0/628 (0%)		8/468 (1.7%)
Visual Acuity Reduced	0/628 (0%)		5/468 (1.1%)
Retinal detachment	0/628 (0%)		4/468 (0.9%)
Vitreous adhesions	0/628 (0%)		2/468 (0.4%)
Ciliary zonular dehiscence	0/628 (0%)		1/468 (0.2%)
Gastrointestinal disorders
Intestinal obstruction	0/628 (0%)		2/468 (0.4%)
Abdominal pain	0/628 (0%)		1/468 (0.2%)
Rectal prolapse	0/628 (0%)		1/468 (0.2%)
General disorders
Oedema peripheral	0/628 (0%)		1/468 (0.2%)
Infections and infestations
Bacterial sepsis	0/628 (0%)		1/468 (0.2%)
Lung infection	0/628 (0%)		1/468 (0.2%)
Sepsis	0/628 (0%)		1/468 (0.2%)
Injury, poisoning and procedural complications
Fall	0/628 (0%)		1/468 (0.2%)
Femoral neck fracture	0/628 (0%)		1/468 (0.2%)
Investigations
Colonoscopy	0/628 (0%)		1/468 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/628 (0%)		1/468 (0.2%)
Breast cancer metastatic	0/628 (0%)		1/468 (0.2%)
Bronchial carcinoma	0/628 (0%)		1/468 (0.2%)
Oesophageal carcinoma	0/628 (0%)		1/468 (0.2%)
Nervous system disorders
Cerebrovascular accident	0/628 (0%)		1/468 (0.2%)
Disturbance in attention	0/628 (0%)		1/468 (0.2%)
Syncope	0/628 (0%)		1/468 (0.2%)
Renal and urinary disorders
Nephrolithiasis	0/628 (0%)		1/468 (0.2%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/628 (0%)		1/468 (0.2%)
Pickwickian syndrome	0/628 (0%)		1/468 (0.2%)
Pulmonary embolism	0/628 (0%)		1/468 (0.2%)
Surgical and medical procedures
Eye operation	1/628 (0.2%)		0/468 (0%)
Hip arthroplasty	0/628 (0%)		2/468 (0.4%)
Cardioversion	0/628 (0%)		1/468 (0.2%)
Ear operation	0/628 (0%)		1/468 (0.2%)
Heart valve replacement	0/628 (0%)		1/468 (0.2%)
Hip surgery	0/628 (0%)		1/468 (0.2%)
Lithotripsy	0/628 (0%)		1/468 (0.2%)
Renal stone removal	0/628 (0%)		1/468 (0.2%)
Shoulder operation	0/628 (0%)		1/468 (0.2%)
Vitrectomy	0/628 (0%)		1/468 (0.2%)
Other (Not Including Serious) Adverse Events
	Pretreatment		Ocriplasmin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/628 (0.2%)		247/468 (52.8%)
Eye disorders
Visual acuity reduced	1/628 (0.2%)		127/468 (27.1%)
Photopsia	0/628 (0%)		104/468 (22.2%)
Vitreous floaters	0/628 (0%)		78/468 (16.7%)
Vision blurred	0/628 (0%)		54/468 (11.5%)
Macular oedema	0/628 (0%)		52/468 (11.1%)
Eye pain	0/628 (0%)		40/468 (8.5%)
Colour blindness acquired	0/628 (0%)		26/468 (5.6%)
Photophobia	0/628 (0%)		24/468 (5.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor reserves the right of prior review of any publication or presentation of information related to the study.