Trial Outcomes & Findings for Assessment of Patients Treated With JETREA® for Vitreomacular Traction (NCT NCT02035748)

NCT ID: NCT02035748

Last Updated: 2016-10-12

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

628 participants

Primary outcome timeframe

Baseline, Day 28

Results posted on

2016-10-12

Participant Flow

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).

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

Participant milestones

Participant milestones
Measure	Ocriplasmin Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection
Overall Study STARTED	468
Overall Study COMPLETED	448
Overall Study NOT COMPLETED	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Ocriplasmin Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection
Overall Study Adverse Event	5
Overall Study Death	3
Overall Study Lost to Follow-up	2
Overall Study Physician Decision	3
Overall Study Withdrawal by Subject	6
Overall Study Progressive Disease	1

Baseline Characteristics

Assessment of Patients Treated With JETREA® for Vitreomacular Traction

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ocriplasmin n=468 Participants Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection
Age, Continuous	71.7 years STANDARD_DEVIATION 8.3 • n=5 Participants
Sex: Female, Male Female	345 Participants n=5 Participants
Sex: Female, Male Male	123 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Day 28

Population: 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.

Outcome measures

Outcome measures
Measure	Ocriplasmin n=466 Participants Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection
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	47.4 percentage of subjects

SECONDARY outcome

Timeframe: Baseline (Day 0), Day 28, Day 90, Day 180

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Ocriplasmin n=448 Participants Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection
Nonsurgical Change From Baseline in Best-corrected Visual Acuity (BCVA) at Distance Change from baseline at Day 28	1.7 letters Standard Deviation 6.70
Nonsurgical Change From Baseline in Best-corrected Visual Acuity (BCVA) at Distance Change from baseline at Day 90	3.0 letters Standard Deviation 7.07
Nonsurgical Change From Baseline in Best-corrected Visual Acuity (BCVA) at Distance Change from baseline at Day 180	3.5 letters Standard Deviation 7.77

SECONDARY outcome

Timeframe: Day 28, Day 90, Day 180

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Ocriplasmin n=86 Participants Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection
Proportion of Subjects With Nonsurgical Closure of Macular Hole (MH), if Present at Baseline Day 28	39.5 percentage of subjects
Proportion of Subjects With Nonsurgical Closure of Macular Hole (MH), if Present at Baseline Day 90	40.7 percentage of subjects
Proportion of Subjects With Nonsurgical Closure of Macular Hole (MH), if Present at Baseline Day 180	41.9 percentage of subjects

SECONDARY outcome

Timeframe: Baseline, Day 90, Day 180

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Ocriplasmin n=466 Participants Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection
Proportion of Subjects With Nonsurgical Resolution of VMT/sVMA Day 90	47.9 percentage of subjects
Proportion of Subjects With Nonsurgical Resolution of VMT/sVMA Day 180	49.4 percentage of subjects

SECONDARY outcome

Timeframe: Day 180

Population: Full Analysis Set

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.

Outcome measures

Outcome measures
Measure	Ocriplasmin n=466 Participants Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection
Proportion of Subjects Experiencing Pars Plana Vitrectomy (PPV) at Day 180	12.0 percentage of subjects

SECONDARY outcome

Timeframe: Baseline (Day 0), Day 28, Day 180

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Ocriplasmin n=466 Participants Ocriplasmin 0.125 mg in a 0.1 mL volume administered as a single dose by intravitreal injection
Mean Nonsurgical Change From Baseline in Central Foveal Thickness (CFT) Baseline (Day 0), n=466	276.1 micrometers Standard Deviation 166.4
Mean Nonsurgical Change From Baseline in Central Foveal Thickness (CFT) Change from baseline at Day 28, n=465	-43.2 micrometers Standard Deviation 113.47
Mean Nonsurgical Change From Baseline in Central Foveal Thickness (CFT) Change from baseline at Day 180, n=466	-45.4 micrometers Standard Deviation 131.84

Adverse Events

Pretreatment

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Ocriplasmin

Serious events: 46 serious events

Other events: 247 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Pretreatment n=628 participants at risk All subjects consented to participate in the study prior to the initiation of study treatment	Ocriplasmin n=468 participants at risk All subjects exposed to the investigational product
Eye disorders Visual acuity reduced	0.16% 1/628 • 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. 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.	27.1% 127/468 • 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. 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.
Eye disorders Photopsia	0.00% 0/628 • 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. 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.	22.2% 104/468 • 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. 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.
Eye disorders Vitreous floaters	0.00% 0/628 • 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. 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.	16.7% 78/468 • 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. 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.
Eye disorders Vision blurred	0.00% 0/628 • 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. 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.	11.5% 54/468 • 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. 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.
Eye disorders Macular oedema	0.00% 0/628 • 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. 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.	11.1% 52/468 • 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. 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.
Eye disorders Eye pain	0.00% 0/628 • 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. 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.	8.5% 40/468 • 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. 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.
Eye disorders Colour blindness acquired	0.00% 0/628 • 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. 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.	5.6% 26/468 • 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. 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.
Eye disorders Photophobia	0.00% 0/628 • 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. 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.	5.1% 24/468 • 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. 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.

Additional Information

EMEA Medical Affairs Lead, Pharma

Alcon, a Novartis company

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