AMD: Study of Intravitreal Microplasmin in Relieving Vitreo-Macular Adhesion in Neovascular Age-related Macular Degeneration

Sponsor

University of California, Los Angeles (Other)

Overall Status

Unknown status

CT.gov ID

NCT00996684

Collaborator

ThromboGenics (Industry)

Enrollment

Location

Arms

Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether microplasmin given by intravitreal injection is effective and safe for the treatment of wet age-related macular degeneration (AMD) in patients who have focal vitreomacular adhesion (VMA)

Condition or Disease	Intervention/Treatment	Phase
Macular Degeneration	Drug: Microplasmin Drug: Placebo control	Phase 2

Detailed Description

The human vitreous gel undergoes progressive liquefaction with age. Concurrent with the process of vitreous liquefaction, there is a weakening of the adhesion at the vitreoretinal interface between the cortical vitreous gel and the inner limiting lamina. Posterior vitreous detachment (PVD) is a separation of the cortical vitreous get from the inner limiting lamina. PVD is usually a sudden event during which liquefied vitreous from the center of the vitreous body bursts through a hole in the posterior vitreous cortex and then dissects the residual cortex gel away from the inner limiting lamina. If there is residual vitreoretinal traction around the break, this process may induce a tear in the retina that can in turn result in rhegmatogenous retinal detachment, macular hole, or cystoid macular edema. The importance of the vitreous in the progression of diabetic retinopathy may also extend beyond tractional considerations. For example, it is believed that the vitreous serves as scaffolding for new vessel formation and may also contribute to molecular imbalances that lead to retinopathy progression. Therefore, total PVD, by releasing vitreoretinal traction as well as other potential mechanisms, may be beneficial in various vitreoretinal diseases such as neovascular AMD.

Vitreomacular adhesion (VMA) in exudative (wet) AMD may be associated with poor prognosis in patients with AMD. This trial is primarily aimed at showing that release of VMA can be induced by microplasmin, a proteolytic enzyme, in patients with wet AMD, and that microplasmin is safe in patients w/ neovascular (wet) AMD. Secondary endpoint will be assessment of improved AMD outcomes.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Resolution of Vitreomacular Adhesion (VMA) Associated With Neovascular Age Related Macular Degeneration (AMD) With Intravitreal Microplasmin

Study Start Date :

Oct 1, 2009

Anticipated Primary Completion Date :

Sep 1, 2011

Anticipated Study Completion Date :

Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: microplasmin, intravitreal injection Subjects will receive one intravitreal injection of microplasmin on Day 0.	Drug: Microplasmin Microplasmin, 1.875 mg, will be given by intravitreal injection,on Day 0.
Placebo Comparator: Placebo Subjects will receive one intravitreal injection of the placebo on Day 0.	Drug: Placebo control The placebo control will be the microplasmin vehicle without the microplasmin.

Arm

Intervention/Treatment

Experimental: microplasmin, intravitreal injection

Subjects will receive one intravitreal injection of microplasmin on Day 0.

Drug: Microplasmin

Microplasmin, 1.875 mg, will be given by intravitreal injection,on Day 0.

Placebo Comparator: Placebo

Subjects will receive one intravitreal injection of the placebo on Day 0.

Drug: Placebo control

The placebo control will be the microplasmin vehicle without the microplasmin.

Outcome Measures

Primary Outcome Measures

The primary outcome is the proportion of patients in whom there is release of vitreomacular traction as assessed by ultrasonography, optical coherence tomography and physical examination [Day 28]

Secondary Outcome Measures

Total number of ranibizumab injections following microplasmin in those with PVD compared with those without PVD [12 months]
Change in mean macular thickness [Day 28 and month 12]
Mean change in ETDRS visual acuity [Day 28 and Month 12]
Incidence and severity of ocular adverse events [Day 28 and Month 12]
Incidence and severity of nonocular adverse events [Day 28 and Month 12]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female subjects aged 50 years or older
Presence of focal vitreomacular adhesion as seen by OCT
BCVA of 20/800 or better in non-study eye
Presence of active choroidal neovascular membrane
Written informed consent obtained from subject prior to inclusion in the trial

Exclusion Criteria:

Subjects who have previously received microplasmin
Subjects with any vitreous hemorrhage or any other vitreous opacification which precludes adequate examination or investigation of study eye
Patient with uncontrolled glaucoma including IOP >25 mm Hg
Subjects who have had vitrectomy or retinal detachment or who are aphakic or highly myopic (>8.0 D) in the study eye
Subjects who are pregnant or of child-bearing potential not utilizing an acceptable form of contraception. Acceptable methods include intrauterine device, oral, implanted or injected contraceptives, and barrier methods with spermicide.
Subjects who, in the Investigator's view, will not complete all visits and investigations
Patient who have PDT or any intravitreal injection in the last 10 days. Patients who in the examiners opinion will need intravitreal injection in the next 10 days (apart from microplasmin).
Patients who have participated in an investigational drug trial in the past 30 days.