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Microplasmin Intravitreal Administration in Participants With Uveitic Macular Edema (MIME)

Primary Purpose

Uveitis

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Microplasmin

About this trial

This is an interventional treatment trial for Uveitis focused on measuring Microplasmin, Macular Edema, Uveitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

Participant must be 18 years of age or older.
Participant must understand and sign the protocol's informed consent document.
Participant has a diagnosis of uveitic macular edema that requires treatment in at least one eye (the study eye) and the uveitis in the study eye is deemed clinically quiet by the investigator.
Participant has no evidence of macular or complete PVD in the study eye by B-scan ultrasound and OCT.
Participant has visual acuity of 20/400 or better in the study eye.
Participant has a central macular thickness ≥ 270 microns in the study eye and loss of the normal foveal contour.
Participant does not have significant cataract or media opacity in the study eye that makes posterior segment visualization difficult as determined by investigator.
Female participants of childbearing potential must not be pregnant or breast-feeding and must have a negative serum pregnancy test at screening and throughout the study.
Both female participants of childbearing potential and male participants able to father a child must agree to practice two effective methods of birth control for six months following administration of study medication. Acceptable methods of birth control for this study include hormonal contraception (birth control pills, injected hormones, dermal patch or vaginal ring), intrauterine device, barrier methods (diaphragm, condom) with spermicide or surgical sterilization (hysterectomy, tubal ligation or vasectomy). Participants with a hysterectomy or vasectomy (or have a partner with a hysterectomy or vasectomy) are exempt from using two methods of birth control.
Participant is willing to comply with the study procedures and return for all study visits.

Exclusion Criteria

Participant has uncontrolled glaucoma, defined as intraocular pressure >30 mmHg despite treatment with anti-glaucoma medication, in the study eye.
Participant has lattice degeneration of the retina in the study eye deemed to be high risk by the investigator.
Participant has untreated retinal holes or tears, or a macular hole in the study eye.
Participant has a significant active ocular infection in the study eye.
Participant had intraocular surgery within the past 90 days or anticipates elective intraocular surgery in the study eye.
Participant had an injection of bevacizumab or ranibizumab within the past four weeks in the study eye.
Participant had an injection of triamcinolone within the past six weeks in the study eye.
Participant has a condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status that would pose a significant hazard if investigational therapy was started).
Participant has known anaphylaxis to sodium fluoride, or has urticaria, angioedema or an anaphylactoid response to sodium fluorescein dye that cannot be safely pre-medicated with an antihistamine and/or prednisone.

Sites / Locations

National Institutes of Health Clinical Center, 9000 Rockville Pike

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Microplasmin

Arm Description

Outcomes

Primary Outcome Measures

Number of Adverse Events

Number of Severe Adverse Events

Number of Ocular Adverse Events

The number of eye-related adverse events was calculated.

Number of Non-ocular Adverse Events

The number of adverse events that were not eye-related was calculated.

Secondary Outcome Measures

Change in Central Macular Thickness, as Measured by Optical Coherence Tomography (OCT), at 4 Weeks vs. Baseline

Retinal thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue. This protocol terminated early due to lack of recruitment; therefore, we chose not to report due to insufficient data.

Number of Participants Achieving Macular or Complete Posterior Vitreous Detachment (PVT) at 4 Weeks

This study terminated early due to lack of recruitment; therefore, we chose not to report due to insufficient data.

Change in ETDRS Best-corrected Visual Acuity (BCVA) at 4 Weeks vs. Baseline

Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. This study terminated early due to lack of recruitment; therefore, we chose not to report due to insufficient data.

Change in ETDRS Best-corrected Visual Acuity (BCVA) at 12 Weeks vs. Baseline

Change in Retino-vascular Leakage, as Seen on Fluorescein Angiography (FA), at 4 Weeks vs. Baseline

Retino-vascular leakage was calculated after manually outlining the inner and outer borders of the subretinal fluid packet in the optical coherence tomography (OCT) images using the "Edit Segmentation" function of the Cirrus HD-OCT software. For cases in which a pigment epithelial detachment was present, the volume of the pigment epithelial detachment was included in the calculation of leakage volume. This study terminated early due to lack of recruitment; therefore, we chose not to report due to insufficient data.

Full Information

NCT ID

NCT01194674

First Posted

September 2, 2010

Last Updated

July 3, 2018

Sponsor

National Institutes of Health Clinical Center (CC)

Collaborators

National Eye Institute (NEI)

1. Study Identification

Unique Protocol Identification Number

NCT01194674

Brief Title

Microplasmin Intravitreal Administration in Participants With Uveitic Macular Edema

Acronym

MIME

Official Title

Microplasmin Intravitreal Administration in Participants With Uveitic Macular Edema

Study Type

Interventional

2. Study Status

Record Verification Date

July 2018

Overall Recruitment Status

Terminated

Why Stopped

Lack of enrollment.

Study Start Date

January 2011 (undefined)

Primary Completion Date

December 2011 (Actual)

Study Completion Date

December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

National Institutes of Health Clinical Center (CC)

Collaborators

National Eye Institute (NEI)

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The objective of this study is to investigate the safety and efficacy of microplasmin as a treatment for uveitic macular edema.

Detailed Description

Objective: Uveitis, an inflammatory condition that affects the uvea (iris, ciliary body and choroid) and adjacent structures of the eyes, is an important cause of visual loss. Most cases of uveitis, not related to an infectious agent, are thought to be autoimmune in origin and are effectively treated with medications to suppress the function of the immune system. Efforts to decrease morbidity, reduce the dose of more toxic immunosuppressive drugs, reduce the frequency of recurrences of inflammation and its sequelae are important goals in the treatment of uveitis. A frequent sequela of uveitis is macular edema. Treatment of macular edema in patients with uveitis has been a particular challenge. Current evidence from diabetic macular edema (DME) and vitreomacular traction (VMT) trials suggests that pharmacologically-induced vitreoretinal separation could be a potential treatment for macular edema associated with uveitis. Microplasmin, a truncated form of human plasmin and naturally occurring enzyme that dissolves blood clots, may be a reasonable candidate for the treatment of uveitic macular edema. The objective of this study is to investigate the safety and efficacy of microplasmin as a treatment for uveitic macular edema. Study Population: Five participants with uveitic macular edema, with or without VMT, will be enrolled. In addition, participants must have no evidence of macular or complete posterior vitreous detachment (PVD) by Optical Coherence Tomography (OCT) or ultrasound. Design: This Phase I-II, non-randomized, prospective, uncontrolled, single-center study will involve a one-time intravitreal injection of 125 µg in 100 µL of microplasmin. Eligible participants can receive the intravitreal injection on the same day of the baseline examination. Participants will be followed for 24 weeks post-injection. Outcome Measures: The primary outcome measure related to the safety and tolerability of microplasmin will be assessed by the number and severity of adverse events (AEs) and systemic and ocular toxicities during the study. The secondary outcome measures related to the potential efficacy of an intravitreal injection of microplasmin for macular edema secondary to uveitis will be assessed by a change in central macular thickness from baseline measured by OCT in response to microplasmin at 4 and 12 weeks post-injection, the number of participants achieving macular or complete PVD at 4 and 12 weeks post-injection, the change of ETDRS best-corrected visual acuity (BCVA) and the change of retino-vascular leakage from baseline seen on fluorescein angiography (FA).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Uveitis

Keywords

Microplasmin, Macular Edema, Uveitis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

2 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Microplasmin

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Microplasmin

Intervention Description

Participants received an intravitreal injection of 125 µg in 100 µL of microplasmin at baseline.

Primary Outcome Measure Information:

Title

Number of Adverse Events

Time Frame

24 weeks

Title

Number of Severe Adverse Events

Time Frame

24 weeks

Title

Number of Ocular Adverse Events

Description

The number of eye-related adverse events was calculated.

Time Frame

24 weeks

Title

Number of Non-ocular Adverse Events

Description

The number of adverse events that were not eye-related was calculated.

Time Frame

24 weeks

Secondary Outcome Measure Information:

Title

Change in Central Macular Thickness, as Measured by Optical Coherence Tomography (OCT), at 4 Weeks vs. Baseline

Description

Time Frame

Baseline and 4 weeks

Title

Number of Participants Achieving Macular or Complete Posterior Vitreous Detachment (PVT) at 4 Weeks

Description

This study terminated early due to lack of recruitment; therefore, we chose not to report due to insufficient data.

Time Frame

Baseline and 4 weeks

Title

Change in ETDRS Best-corrected Visual Acuity (BCVA) at 4 Weeks vs. Baseline

Description

Time Frame

Baseline and 4 weeks

Title

Change in ETDRS Best-corrected Visual Acuity (BCVA) at 12 Weeks vs. Baseline

Description

Time Frame

Baseline and 12 Weeks

Title

Change in Retino-vascular Leakage, as Seen on Fluorescein Angiography (FA), at 4 Weeks vs. Baseline

Description

Time Frame

Baseline and 4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria Participant must be 18 years of age or older. Participant must understand and sign the protocol's informed consent document. Participant has a diagnosis of uveitic macular edema that requires treatment in at least one eye (the study eye) and the uveitis in the study eye is deemed clinically quiet by the investigator. Participant has no evidence of macular or complete PVD in the study eye by B-scan ultrasound and OCT. Participant has visual acuity of 20/400 or better in the study eye. Participant has a central macular thickness ≥ 270 microns in the study eye and loss of the normal foveal contour. Participant does not have significant cataract or media opacity in the study eye that makes posterior segment visualization difficult as determined by investigator. Female participants of childbearing potential must not be pregnant or breast-feeding and must have a negative serum pregnancy test at screening and throughout the study. Both female participants of childbearing potential and male participants able to father a child must agree to practice two effective methods of birth control for six months following administration of study medication. Acceptable methods of birth control for this study include hormonal contraception (birth control pills, injected hormones, dermal patch or vaginal ring), intrauterine device, barrier methods (diaphragm, condom) with spermicide or surgical sterilization (hysterectomy, tubal ligation or vasectomy). Participants with a hysterectomy or vasectomy (or have a partner with a hysterectomy or vasectomy) are exempt from using two methods of birth control. Participant is willing to comply with the study procedures and return for all study visits. Exclusion Criteria Participant has uncontrolled glaucoma, defined as intraocular pressure >30 mmHg despite treatment with anti-glaucoma medication, in the study eye. Participant has lattice degeneration of the retina in the study eye deemed to be high risk by the investigator. Participant has untreated retinal holes or tears, or a macular hole in the study eye. Participant has a significant active ocular infection in the study eye. Participant had intraocular surgery within the past 90 days or anticipates elective intraocular surgery in the study eye. Participant had an injection of bevacizumab or ranibizumab within the past four weeks in the study eye. Participant had an injection of triamcinolone within the past six weeks in the study eye. Participant has a condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status that would pose a significant hazard if investigational therapy was started). Participant has known anaphylaxis to sodium fluoride, or has urticaria, angioedema or an anaphylactoid response to sodium fluorescein dye that cannot be safely pre-medicated with an antihistamine and/or prednisone.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hatice Nida Sen, MD, MHSc

Organizational Affiliation

National Institutes of Health (NIH)

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Institutes of Health Clinical Center, 9000 Rockville Pike

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

15019324

Citation

Gritz DC, Wong IG. Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study. Ophthalmology. 2004 Mar;111(3):491-500; discussion 500. doi: 10.1016/j.ophtha.2003.06.014.

Results Reference

background

PubMed Identifier

12434489

Citation

Djalilian AR, Nussenblatt RB. Immunosuppression in uveitis. Ophthalmol Clin North Am. 2002 Sep;15(3):395-404, viii. doi: 10.1016/s0896-1549(02)00036-6.

Results Reference

background

PubMed Identifier

7641842

Citation

Whitcup SM, Hikita N, Shirao M, Miyasaka M, Tamatani T, Mochizuki M, Nussenblatt RB, Chan CC. Monoclonal antibodies against CD54 (ICAM-1) and CD11a (LFA-1) prevent and inhibit endotoxin-induced uveitis. Exp Eye Res. 1995 Jun;60(6):597-601. doi: 10.1016/s0014-4835(05)80001-6.

Results Reference

background

Links:

URL

http://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2010-EI-0186.html

Description

NIH Clinical Center Detailed Web Page

Learn more about this trial

Microplasmin Intravitreal Administration in Participants With Uveitic Macular Edema

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