Intravitreal Microplasmin in Patients Undergoing Surgical Vitrectomy

A Dose-escalation Clinical Trial of Intravitreal Microplasmin in Patients Undergoing Surgical Vitrectomy for Vitreomacular Traction Maculopathy

The purpose of this trial is to evaluate the safety and preliminary efficacy of different doses and several exposure times of intravitreal microplasmin in the setting of pars plana vitrectomy for vitreomacular traction maculopathy.

Study Overview

• Status: Completed
• Conditions: Eye Diseases; Vitreomacular Traction Maculopathy
• Intervention / Treatment: Drug: Microplasmin

Detailed Description

Study drug will be administered in the mid-vitreous by injection. Patients will be enrolled into the cohorts in a sequential dose/time-escalating fashion. To ensure that enrolment is evenly balanced across eligible conditions, enrolment of any specific underlying disease type into any cohort will be capped at five (5) patients.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, B-3000
    • University Hospital Gasthuisberg
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academic Medical Center, University of Amsterdam
  • Rotterdam, Netherlands, 3011 BH
    • Oogziekenhuis Rotterdam

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with vitreomacular traction maculopathy for whom vitrectomy is indicated, according to the principal investigator, including:

  • Macular edema associated with vitreomacular traction (DME, VMTS);
  • Stage II-III macular hole of < 6 months duration since symptom onset;
  • Demonstration of vitreomacular adhesion (based on preoperative optic coherence tomography [OCT]) in the study eye;
  • OCT - presence of posterior hyaloid membrane inserting on to the macula, but with some area of clear separation visible between the retina and the posterior hyaloid.

Exclusion Criteria:

• Evidence of fibrocellular proliferation characterized by whitish epimacular tissue (surface wrinkling is not an exclusion criterion).
• Patients with vitreous hemorrhage which precludes either of the following: visualization of the posterior pole by visual inspection OR adequate assessment of the macula by either OCT and/or fluorescein angiogram in the study eye.
• Patients with rhegmatogenous retinal detachment, proliferative vitreoretinopathy (PVR), or retinal degenerative changes in the study eye.
• Patients with high myopia or aphakia in the study eye
• Patients with history of rhegmatogenous retinal detachment in the fellow eye or family history of retinal detachment
• Patients who are considered likely to require intraocular surgery in the study eye for any reason other than vitreomacular traction maculopathy/macular edema in the coming three months.
• Patients who have had ocular surgery in the study eye in the prior three months.
• Patients who have had a vitrectomy in the study eye at any time.
• Patients with a history of uveitis or significant trauma in the study eye.
• Patients who are currently being treated for glaucoma in the study eye.
• Patients who have had laser photocoagulation treatment in the study eye in the previous 3 months.
• Intravitreal injection of any drug in the study eye in the previous 6 months or during the study.
• Patients who are pregnant or of child-bearing potential not utilizing a form of contraception acceptable to the investigator.
• Patients who, in the investigator's view, will not complete all visits and investigations, including the exit visit at 6 months.
• Patients who have participated in an investigational drug study within the past 30 days.
• HgA1c > 9%.
• Patients with hypertension (either systolic blood pressure [SBP] > 170 or diastolic blood pressure [DBP] > 100 mm Hg).
• Patients with a life-expectancy less than 6 months.
• Patients who have previously participated in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Microplasmin; 25ug injected 1 hr prior to PPV, 24 hr and 7 days prior to PPV, 50ug injected 24 hr prior to PPV, 75ug injected 24 hr prior to PPV and 125ug injected 24 hr prior to PPV.
Experimental: 2	Drug: Microplasmin; 25ug injected 1 hr prior to PPV, 24 hr and 7 days prior to PPV, 50ug injected 24 hr prior to PPV, 75ug injected 24 hr prior to PPV and 125ug injected 24 hr prior to PPV.
Experimental: 3	Drug: Microplasmin; 25ug injected 1 hr prior to PPV, 24 hr and 7 days prior to PPV, 50ug injected 24 hr prior to PPV, 75ug injected 24 hr prior to PPV and 125ug injected 24 hr prior to PPV.
Experimental: 4	Drug: Microplasmin; 25ug injected 1 hr prior to PPV, 24 hr and 7 days prior to PPV, 50ug injected 24 hr prior to PPV, 75ug injected 24 hr prior to PPV and 125ug injected 24 hr prior to PPV.
Experimental: 5	Drug: Microplasmin; 25ug injected 1 hr prior to PPV, 24 hr and 7 days prior to PPV, 50ug injected 24 hr prior to PPV, 75ug injected 24 hr prior to PPV and 125ug injected 24 hr prior to PPV.
Experimental: 6	Drug: Microplasmin; 25ug injected 1 hr prior to PPV, 24 hr and 7 days prior to PPV, 50ug injected 24 hr prior to PPV, 75ug injected 24 hr prior to PPV and 125ug injected 24 hr prior to PPV.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Grade of Posterior Vitreous Detachment (PVD) preoperatively and release of vitreomacular traction	Baseline, 1,2 and 3hr, 1, 3, 14, 28, 90 and 180 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
The occurrence of any (serious) adverse event	Throught-out the study

Collaborators and Investigators

• Sponsor: ThromboGenics
• Investigators: Principal Investigator: Marc deSmet, Prof. Dr, Amsterdam UMC, location VUmc

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (Actual): February 1, 2007
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: July 21, 2005
• First Submitted That Met QC Criteria: July 21, 2005
• First Posted (Estimate): July 22, 2005

Study Record Updates

• Last Update Posted (Estimate): April 7, 2014
• Last Update Submitted That Met QC Criteria: April 4, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: diabetic macular edema; macular hole; vitreomacular traction syndrome
• Additional Relevant MeSH Terms: Retinal Degeneration; Retinal Diseases; Macular Degeneration; Eye Diseases; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Plasminogen
• Other Study ID Numbers: TG-MV-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No