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

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

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)

Study Overview

• Status: Unknown
• Conditions: Macular Degeneration
• Intervention / Treatment: Drug: Microplasmin; Drug: Placebo control

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • Jules Stein Eye Institute/UCLA
      • Principal Investigator: Steven D Schwartz, M.D.
      • Sub-Investigator: Jean-Pierre Hubschman, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: ThromboGenics
• Investigators: Principal Investigator: Steven D Schwartz, M.D., University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (ANTICIPATED): September 1, 2011
• Study Completion (ANTICIPATED): December 1, 2011

Study Registration Dates

• First Submitted: October 15, 2009
• First Submitted That Met QC Criteria: October 15, 2009
• First Posted (ESTIMATE): October 16, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): September 27, 2011
• Last Update Submitted That Met QC Criteria: September 26, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: Wet AMD; Wet age related macular degeneration (AMD); Vitreomacular adhesion (VMA); Vitreomacular traction (VMT); Neovascular age related macular degeneration
• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Retinal Degeneration; Retinal Diseases; Fibrosis; Cicatrix; Macular Degeneration; Tissue Adhesions; Wet Macular Degeneration; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Plasminogen
• Other Study ID Numbers: JSEI-TG-AMD-001