Trial Outcomes & Findings for A Phase III Study of A01016 in Subjects With Symptomatic Vitreomacular Adhesion (NCT NCT01889251)

Last Updated: 2015-11-30

Results Overview

VMA (adhesion of the vitreous gel to the retina in an abnormally strong manner) was determined by masked Central Reading Center (CRC) Spectral Domain Optical Coherence Tomography (SD-OCT) evaluation. Only one eye (study eye) was analyzed. Proportion of subjects is reported as a percentage.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

251 participants

Primary outcome timeframe

Day 28

Results posted on

2015-11-30

Participant Flow

Subjects were recruited from 40 study centers located in Japan.

Of the 251 enrolled, 79 subjects were exited as screen failures prior to randomization. This reporting group includes all randomized subjects (172).

Participant milestones

Participant milestones
Measure	Ocriplasmin Single intravitreal injection to the study eye at baseline	Sham Injection Single sham injection to the study eye at baseline
Overall Study STARTED	115	57
Overall Study COMPLETED	114	57
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Ocriplasmin Single intravitreal injection to the study eye at baseline	Sham Injection Single sham injection to the study eye at baseline
Overall Study Adverse Event	1	0

Baseline Characteristics

A Phase III Study of A01016 in Subjects With Symptomatic Vitreomacular Adhesion

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ocriplasmin n=115 Participants Single intravitreal injection to the study eye at baseline	Sham Injection n=57 Participants Single sham injection to the study eye at baseline	Total n=172 Participants Total of all reporting groups
Age, Continuous	68.1 years STANDARD_DEVIATION 7.3 • n=5 Participants	68.6 years STANDARD_DEVIATION 9.2 • n=7 Participants	68.2 years STANDARD_DEVIATION 8.0 • n=5 Participants
Sex: Female, Male Female	59 Participants n=5 Participants	32 Participants n=7 Participants	91 Participants n=5 Participants
Sex: Female, Male Male	56 Participants n=5 Participants	25 Participants n=7 Participants	81 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 28

Population: This analysis population includes all subjects who received study medication, completed at least 1 on-therapy study visit and had symptomatic VMA at baseline, as randomized, based on an intent to treat approach.

Outcome measures

Outcome measures
Measure	Ocriplasmin n=115 Participants Single intravitreal injection to the study eye at baseline	Sham Injection n=57 Participants Single sham injection to the study eye at baseline
Proportion of Subjects With Non-Surgical Resolution of Vitreomacular Adhesion (VMA)	52.2 percentage of subjects	1.8 percentage of subjects

Adverse Events

Ocriplasmin

Serious events: 23 serious events

Other events: 63 other events

Deaths: 0 deaths

Sham Injection

Serious events: 4 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ocriplasmin n=114 participants at risk Single intravitreal injection to the study eye at baseline	Sham Injection n=58 participants at risk Single sham injection to the study eye at baseline
Eye disorders Macular hole	9.6% 11/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	5.2% 3/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.88% 1/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	0.00% 0/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Eye disorders Vitreous adhesions	1.8% 2/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	1.7% 1/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Infections and infestations Pneumonia	1.8% 2/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	0.00% 0/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Eye disorders Retinal detachment	2.6% 3/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	0.00% 0/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Injury, poisoning and procedural complications Spinal compression fracture	0.88% 1/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	0.00% 0/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Respiratory, thoracic and mediastinal disorders Asthma	0.88% 1/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	0.00% 0/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Eye disorders Ocular hypertension	0.88% 1/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	0.00% 0/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Eye disorders Angle closure glaucoma	0.88% 1/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	0.00% 0/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Investigations Intraocular pressure increased	0.88% 1/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	0.00% 0/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.88% 1/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	0.00% 0/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Eye disorders Macular pseudohole	0.88% 1/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	0.00% 0/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.

Other adverse events

Other adverse events
Measure	Ocriplasmin n=114 participants at risk Single intravitreal injection to the study eye at baseline	Sham Injection n=58 participants at risk Single sham injection to the study eye at baseline
Eye disorders Conjunctival haemorrhage	19.3% 22/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	8.6% 5/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Eye disorders Vitreous floaters	12.3% 14/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	3.4% 2/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Eye disorders Anterior chamber cell	11.4% 13/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	5.2% 3/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Eye disorders Eye pain	11.4% 13/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	1.7% 1/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Musculoskeletal and connective tissue disorders Back pain	9.6% 11/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	6.9% 4/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Eye disorders Conjunctival hyperaemia	7.9% 9/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	0.00% 0/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Eye disorders Visual impairment	7.0% 8/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	1.7% 1/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Eye disorders Corneal disorder	7.0% 8/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	0.00% 0/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Eye disorders Punctate keratitis	6.1% 7/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	1.7% 1/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Eye disorders Retinal detachment	6.1% 7/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	0.00% 0/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Investigations Intraocular pressure increased	6.1% 7/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	6.9% 4/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.
Gastrointestinal disorders Constipation	1.8% 2/114 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.	6.9% 4/58 • Adverse events (AEs) were collected for the duration of the study (1 year, 2 months). This analysis group includes all subjects who received study medication, as treated. Note: One subject randomized to Ocriplasmin was inadvertently treated with Sham. An AE was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. Ocular adverse events are presented for both study eye and non-study eye.

Additional Information

Group Manager, Clinical Development

Alcon Japan, Ltd.

Phone: +81368995277

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