UveitisPhase 1/2MIMENCT01194674
Microplasmin Intravitreal Administration in Participants With Uveitic Macular Edema
A Phase 1/2 study testing Microplasmin in people with Uveitis, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
Trial summary
The objective of this study is to investigate the safety and efficacy of microplasmin as a treatment for uveitic macular edema. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Uveitis
- What is being tested?
- Microplasmin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2011to Dec 2011
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 10Show fewer
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
The objective of this study is to investigate the safety and efficacy of microplasmin as a treatment for uveitic macular edema.
Read the 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).
- Conditions
- Uveitis
- Being tested
- Microplasmin
- Keywords
- Microplasmin, Macular Edema, Uveitis
- Medical subject headings
- Uveitis, Macular Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MicroplasminDrug
Participants received an intravitreal injection of 125 µg in 100 µL of microplasmin at baseline.
| Study group | Role | What they receive |
|---|---|---|
| Microplasmin | Experimental | Not described Receives: Drug: Microplasmin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Adverse Events
Measured: 24 weeks
Number of Severe Adverse Events
Measured: 24 weeks
Number of Ocular Adverse Events
The number of eye-related adverse events was calculated.
Measured: 24 weeks
Number of Non-ocular Adverse Events
The number of adverse events that were not eye-related was calculated.
Measured: 24 weeks
Secondary outcomes (5)
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.
Measured: Baseline and 4 weeks
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.
Measured: Baseline and 4 weeks
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.
Measured: Baseline and 4 weeks
Change in ETDRS Best-corrected Visual Acuity (BCVA) at 12 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.
Measured: Baseline and 12 Weeks
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.
Measured: Baseline and 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2010 (estimated)
- Study startJan 2011
- Primary completionDec 2011
- Study completionDec 2011
Why it stopped: Lack of enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for UveitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Eye Institute (NEI)
- Responsible party
- Principal investigator, Nida Sen, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- Hatice Nida Sen, MD, MHSc, Principal investigator, National Institutes of Health (NIH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01194674
- Sponsor's protocol ID
- 100186
- Other IDs
- 10-EI-0186
- Acronym
- MIME
- Status last verified
- Jul 2018
- First submitted
- 2 Sep 2010
- Last updated
- 31 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 15019324Djalilian 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.
PubMed 12434489Whitcup 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.
PubMed 7641842
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Microplasmin Intravitreal Administration in Participants With Uveitic Macular Edema
- ClinicalTrials.gov ID
- NCT01194674
- Acronym / sponsor ID
- MIME / 100186
- Conditions
- Uveitis
- Keywords
- Microplasmin, Macular Edema, Uveitis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Collaborators
- National Eye Institute (NEI)
- Study start
- Jan 2011
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 3 Sep 2010 (estimated)
- Results
- Posted 14 Aug 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Microplasmin | Experimental | Drug: Microplasmin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MicroplasminParticipants received an intravitreal injection of 125 µg in 100 µL of microplasmin at baseline. | Drug | Microplasmin |
Primary outcome
Number of Adverse Events
Time frame: 24 weeks
Number of Severe Adverse Events
Time frame: 24 weeks
Number of Ocular Adverse Events
Time frame: 24 weeks
The number of eye-related adverse events was calculated.
Number of Non-ocular Adverse Events
Time frame: 24 weeks
The number of adverse events that were not eye-related was calculated.
5 secondary outcomes
Change in Central Macular Thickness, as Measured by Optical Coherence Tomography (OCT), at 4 Weeks vs. Baseline
Time frame: Baseline and 4 weeks
Number of Participants Achieving Macular or Complete Posterior Vitreous Detachment (PVT) at 4 Weeks
Time frame: Baseline and 4 weeks
Change in ETDRS Best-corrected Visual Acuity (BCVA) at 4 Weeks vs. Baseline
Time frame: Baseline and 4 weeks
Change in ETDRS Best-corrected Visual Acuity (BCVA) at 12 Weeks vs. Baseline
Time frame: Baseline and 12 Weeks
Change in Retino-vascular Leakage, as Seen on Fluorescein Angiography (FA), at 4 Weeks vs. Baseline
Time frame: Baseline and 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15019324Gritz 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.
- Background: PubMed 12434489Djalilian 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.
- Background: PubMed 7641842Whitcup 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hatice Nida Sen, MD, MHSc principal investigator
National Institutes of Health (NIH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Microplasmin in people with Uveitis, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Adverse Events (time frame: 24 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01194674, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2018.