Proof of Concept Study of the Effectiveness of Ozurdex in Lieu of Oral Corticosteroids for the Control of Active Intermediate and Posterior Uveitis Requiring Immunosuppressive Drug Therapy
Phase: PHASE4
Conditions: Uveitis, Intermediate, Uveitis, Posterior
Sponsor: Johns Hopkins University

JHMIRB eFormA  01  
Date of last protocol update: December 11, 2015     
Principal Investigator: Jennifer E. Thorne, MD PhD  
 
  
  
  
  
 
 
  
  
Proof of Concept Study of the Effectiveness of Ozurdex in 
lieu of Oral Corticosteroids for the Control of Active 
Intermediate and Posterior Uveitis Requiring 
Immunosuppressive Drug Therapy 
 
 
 
 
NCT02049476 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
  
  
  
  
  

JHMIRB eFormA  01  
JHM IRB - eForm A – Protocol  
  
  
• 
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in each. If a section is not applicable, leave heading in and insert N/A.  
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1. 
Abstract (Provide no more than a one page research abstract briefly stating the problem, the research 
hypothesis, and the importance of the research.)  See background.  
  
2. 
Objectives:  
This is a single arm proof of concept study evaluating whether or not the dexamethasone pellet 
(Ozurdex®, Allergan, Irvine, CA) can replace oral corticosteroid (e.g. prednisone) in the treatment of 
active sight-threatening, noninfectious intermediate or posterior uveitis in which immunosuppressive 
drug therapy is indicated.    
  
3. 
Background:  Intermediate and posterior uveitis are thought to be severe intraocular inflammation 
that may lead to permanent visual loss.  It is estimated that these forms of uveitis comprise the fifth 
or sixth leading cause of blindness and tend to affect working class age patients, thus causing loss of 
work hours and diminished productivity and quality of life.  Because the posterior segment of the eye 
is not adequately treated by corticosteroid drops often systemic drug therapy is used including oral 
corticosteroids or prednisone.  Prednisone can have a myriad of side effects in approximately 
onequarter to one-third of cases treated in tertiary care centers such as ours, additional medications 
such as immunosuppressive drugs are required to control the disease and/or to allow for appropriate 
tapering of oral prednisone to subsequent levels that have a low side effect profile when delivered 
over a long period of time. Typically, chronic prednisone therapy in doses of 7.5 mg daily or less are 
thought to have a low enough side effect profile to be amenable to long-term therapy.  However 
frequently immunosuppressive drugs are required to get the dosing to this level.  There are occasions 
when patients are intolerant of any dose of oral corticosteroids or are intolerant of the higher doses of 
oral corticosteroids (30 – 60 mg daily) and therefore this treatment modality is avoided due to 
prednisone’s attendant side effects.  Although periocular and intravitreal corticosteroids injections 
may be performed, with these modalities the standard of care is to wait until the disease reactivates 
before instituting such therapy and therefore a chronic suppressive dose is not obtained.  The 
fluocinolone acetonide implant (Retisert®, Bausch and Lomb, Tampa, FL) is FDA-approved for the 
treatment of intermediate and posterior uveitis and it is equally effective in controlling uveitis as 
highdose oral corticosteroids but avoids the systemic side effects associated with the use of high doses 
of oral corticosteroids.  However, this form of local therapy has high rates of ocular side effects, 
including ocular hypertension causing glaucoma and/or requiring glaucoma surgery and cataracts.  
Furthermore, every two and half to three years the implant is exhausted of corticosteroid and therefore 
repeat surgical insertion of another implant may be required.  A useful potential therapy for the 
treatment of these patients would be a shorter-acting local corticosteroid that could be delivered in 
conjunction with systemic immunosuppressive drug therapy that would have a lower ocular side effect 
profile but still would be effective enough to replace the use of high-dose systemic corticosteroids in 
the treatment of active intermediate or posterior uveitis.  It is possible that the dexamethasone pellet 
could fill this unique role in the treatment of uveitis. We propose this proof of concept study to 
evaluate dexamethasone pellet for this specific use among patients with active intermediate and 
posterior uveitis.  
  

JHMIRB eFormA  01  
4.  
Study Procedures  
a. Study design, including the sequence and timing of study procedures   
(Distinguish research procedures from those that are part of routine care): - 
 
Single arm proof of concept interventional study.   
  
Specifics of each clinical visit including data collected and procedures performed are as follows:   
• 
Baseline examination data collection consists of:  
o Signed informed consent obtained  
o Demographic data (age, gender, race, duration of uveitis, anatomic location of uveitis, 
smoking status, presence of systemic disease associated with uveitis)  
o Treatment history (current therapies for the treatment of uveitis, history of corticosteroid 
use including periocular corticosteroids, history of immunosuppressive drug use, need for 
IOP-lowering medications)  
o Past ocular history (any complications due to uveitis, any ocular surgeries or procedures, 
presence of amblyopia, history of glaucoma or ocular hypertension, treatment to lower 
intraocular pressure including laser procedures and/or surgeries  
o Ophthalmic examination including best-corrected visual acuity, IOP measurement, 
presence and degree of uveitis activity, presence of ocular complications including cystoid 
macular edema (CME), findings of slit lamp examination including presence and degree 
of cataract, findings of fundoscopic examination including cup to disc ratio.  
o Visual field assessment  
o Slit lamp photos to assess cataract if eye(s) are phakic o Optic nerve photos  
o Results of baseline OCT and fluorescein angiography testing if clinically indicated  o NEI 
VFQ and EuroQol administered  
• 
Dexamethasone pellet placement occurs within 14 days of baseline examination; for patients 
with bilaterally active uveitis, placement of a dexamethasone pellet in the second eye should 
occur within 14 days of the first implantation or within 30 day of the baseline examination.  
o Adverse events related to the procedure will be collected (e.g., vitreous hemorrhage, 
elevated IOP, retinal detachment) at time of placement  
• 
1-month examination o Interval treatment history (current therapies for the treatment of 
uveitis, history of corticosteroid use including periocular corticosteroids, history of 
immunosuppressive drug use, need for IOP-lowering medications)  
o Interval ocular history (any complications due to uveitis, any ocular surgeries or 
procedures, history of glaucoma or ocular hypertension, treatment to lower intraocular 
pressure including laser procedures and/or surgeries  
o Ophthalmic examination including best-corrected visual acuity, IOP measurement, 
presence and degree of uveitis activity, presence of ocular complications including cystoid 
macular edema (CME), findings of slit lamp examination including presence and degree 
of cataract, findings of fundoscopic examination including cup to disc ratio.  
o Results of OCT and fluorescein angiography testing if clinically indicated o NEI-VFQ 
and EuroQoL administered.  
o Adverse event reporting  
• 
2-month examination o Interval treatment history (current therapies for the treatment of 
uveitis, history of corticosteroid use including periocular corticosteroids, history of 
immunosuppressive drug use, need for IOP-lowering medications)  
o Interval ocular history (any complications due to uveitis, any ocular surgeries or 
procedures, history of glaucoma or ocular hypertension, treatment to lower intraocular 
pressure including laser procedures and/or surgeries  

JHMIRB eFormA  01  
o Ophthalmic examination including best-corrected visual acuity, IOP measurement, 
presence and degree of uveitis activity, presence of ocular complications including cystoid 
macular edema (CME), findings of slit lamp examination including presence and degree 
of cataract, findings of fundoscopic examination including cup to disc ratio.  
o Results of OCT and fluorescein angiography testing if clinically indicated o NEI-VFQ 
and EuroQoL administered.  
o Adverse event reporting  
• 
3-month examination o Interval treatment history (current therapies for the treatment of 
uveitis, history of corticosteroid use including periocular corticosteroids, history of 
immunosuppressive drug use, need for IOP-lowering medications)  
o Interval ocular history (any complications due to uveitis, any ocular surgeries or 
procedures, history of glaucoma or ocular hypertension, treatment to lower intraocular 
pressure including laser procedures and/or surgeries  
o Ophthalmic examination including best-corrected visual acuity, IOP measurement, 
presence and degree of uveitis activity, presence of ocular complications including cystoid 
macular edema (CME), findings of slit lamp examination including presence and degree 
of cataract, findings of fundoscopic examination including cup to disc ratio.  
o Results of OCT and fluorescein angiography testing if clinically indicated  o NEI-VFQ 
and EuroQoL administered.  
o Adverse event reporting  
• 
Possibility of repeat dexamethasone pellet insertion o Adverse events related to the procedure 
will be collected (e.g., vitreous hemorrhage, elevated IOP, retinal detachment)  
• 
6-month examination o Interval treatment history (current therapies for the treatment of 
uveitis, history of corticosteroid use including periocular corticosteroids, history of 
immunosuppressive drug use, need for IOP-lowering medications)  
o Interval ocular history (any complications due to uveitis, any ocular surgeries or 
procedures, history of glaucoma or ocular hypertension, treatment to lower intraocular 
pressure including laser procedures and/or surgeries  
o Ophthalmic examination including best-corrected visual acuity, IOP measurement, 
presence and degree of uveitis activity, presence of ocular complications including cystoid 
macular edema (CME), findings of slit lamp examination including presence and degree 
of cataract, findings of fundoscopic examination including cup to disc ratio.  
o Results of OCT and fluorescein angiography testing as clinically indicated o NEI-VFQ 
and EuroQoL administered.  
o Adverse event reporting  
• 
Possibility of repeat dexamethasone pellet insertion or treatment with best medical judgment o 
Adverse events related to the procedure will be collected (e.g., vitreous hemorrhage, elevated 
IOP, retinal detachment)  
• 
9-month examination o Interval treatment history (current therapies for the treatment of 
uveitis, history of corticosteroid use including periocular corticosteroids, history of 
immunosuppressive drug use, need for IOP-lowering medications)  
o Interval ocular history (any complications due to uveitis, any ocular surgeries or 
procedures, history of glaucoma or ocular hypertension, treatment to lower intraocular 
pressure including laser procedures and/or surgeries  
o Ophthalmic examination including best-corrected visual acuity, IOP measurement, 
presence and degree of uveitis activity, presence of ocular complications including cystoid 
macular edema (CME), findings of slit lamp examination including presence and degree 
of cataract, findings of fundoscopic examination including cup to disc ratio.  

JHMIRB eFormA  01  
o Results of OCT and fluorescein angiography testing as clinically indicated o NEI-VFQ 
and EuroQoL administered.  
o Adverse event reporting  
• 
Possibility of repeat dexamethasone pellet insertion or treatment with best medical judgment o 
Adverse events related to the procedure will be collected (e.g., vitreous hemorrhage, elevated 
IOP, retinal detachment)  
• 
12-month examination o Interval treatment history (current therapies for the treatment of 
uveitis, history of corticosteroid use including periocular corticosteroids, history of 
immunosuppressive drug use, need for IOP-lowering medications)  
o Interval ocular history (any complications due to uveitis, any ocular surgeries or 
procedures, history of glaucoma or ocular hypertension, treatment to lower intraocular 
pressure including laser procedures and/or surgeries  
o Ophthalmic examination including best-corrected visual acuity, IOP measurement, 
presence and degree of uveitis activity, presence of ocular complications including cystoid 
macular edema (CME), findings of slit lamp examination including presence and degree 
of cataract, findings of fundoscopic examination including cup to disc ratio.  
o Visual field assessment  
o Slit lamp photographs to assess cataract  
o Optic nerve photos  
o Results of OCT and fluorescein angiography testing as clinically indicated o NEI-VFQ 
and EuroQoL administered.  
o Adverse event reporting  
• 
Extended follow-ups o Patients will continue to be followed at 3 month intervals after M12 
according to standard of care until the common study close-out which will occur after the 2 year 
follow-up of the 20th enrolled patient  
• 
Possibility of repeat dexamethasone pellet insertion or treatment at each of the 3 month extended 
follow-ups with best medical judgment o Adverse events related to the procedure will be 
collected (e.g., vitreous hemorrhage, elevated IOP, retinal detachment)  
b. Study duration and number of study visits required of research participants.  
- 
Patients will be followed for a minimum period of 12 months.  
- 
A minimum of 9 visits (BL, Day 14, M1, M2, M3, M6, M9, and M12). If the PI/study 
ophthalmologist decides to insert another dexamethasone pellet, s/he may do so at M3, 
and/or M6, and/or M9, and/or at 3 month intervals thereafter (until the common study 
closeout) if indicated with best medical judgment  
c. Blinding, including justification for blinding or not blinding the trial, if applicable.  
- 
N/A  
d. Justification of why participants will not receive routine care or will have current therapy stopped.  
- 
N/A. Use of the dexamethasone pellet and immunosuppressive drug therapy are each part 
of standard clinical care in the treatment of active intermediate and posterior uveitis.  The 
dexamethasone pellet is FDA-approved for the treatment of intermediate and posterior 
uveitis.  
e. Justification for inclusion of a placebo or non-treatment group.  
- 
N/A. There is no placebo or non-treatment arm in this pilot study.  
f. Definition of treatment failure or participant removal criteria.  
 
-  N/A  
g. Description of what happens to participants receiving therapy when study ends or if a participant’s 
participation in the study ends prematurely.  

JHMIRB eFormA  01  
- Since all treatments are currently used in the clinical care of uveitis patients, all patients 
enrolled in this study will be able to continue receiving therapy according to best medical 
judgment once the study ends.   
5.  
Inclusion/Exclusion Criteria Inclusion 
Criteria:    
- 
Active sight-threatening intermediate or posterior uveitis for which immunosuppressive drug 
therapy is planned and the physician is considering treatment with high-dose corticosteroid to 
control the uveitis whilst immunosuppressive drugs are being instituted or adjusted.    
o Note: it is acceptable for the patient to already be on an immunosuppressive drug as long as 
high dose corticosteroids are indicated.    
- 
Patients must be age 18 years or older (the dexamethasone pellet is not FDA-approved for 
pediatric use) and sign an informed consent.    
- 
The ocular media must be clear enough to obtain OCT and fundus photographs.    
- 
No elective intraocular surgery should be planned for the first 3 months after enrollment.  
Exclusion Criteria:    
- 
Infectious uveitis  
- 
History of scleritis  
- 
Active or suspected viral infection of the cornea or conjunctiva  
- 
History of mycobacterial or fungal disease  
- 
HIV positivity  
- 
Age <18 years old  
- 
Allergy to dexamethasone  
- 
Uncontrolled IOP  
- 
Advanced glaucoma  
- 
Aphakia with rupture of the posterior lens capsule  
- 
ACIOL with rupture of the posterior lens capsule  
- 
Media opacity that would preclude evaluation of the posterior pole via fundus photography or 
OCT assessment  
- 
Planned elective ocular surgery within 3 months of enrollment -  
Any systemic disease 
requiring systemic corticosteroids.   
6.  
Drugs/ Substances/ Devices  
a. The rationale for choosing the drug and dose or for choosing the device to be used.  
The fluocinolone acetonide implant is FDA-approved for the treatment of intermediate and posterior 
uveitis and it is equally effective in controlling uveitis as high-dose oral corticosteroids but avoids 
the systemic side effects associated with the use of high doses of oral corticosteroids.  However, this 
form of local therapy has high rates of ocular side effects, including ocular hypertension causing 
glaucoma and/or requiring glaucoma surgery and cataracts.  Furthermore, every two and half to three 
years the implant is exhausted of corticosteroid and therefore repeat surgical insertion of another 
implant may be required.  A useful potential therapy for the treatment of these patients would be a 
shorter-acting local corticosteroid that could be delivered in conjunction with systemic 
immunosuppressive drug therapy that would have a lower ocular side effect profile but still would 
be effective enough to replace the use of high-dose systemic corticosteroids in the treatment of active 
intermediate and posterior uveitis.  It is possible that the dexamethasone pellet could fill this unique 
role in the treatment of uveitis. We propose this proof of concept study to evaluate the 
dexamethasone pellet for this specific use among patients with active intermediate and posterior 
uveitis.  
b. Justification and safety information if FDA approved drugs will be administered for non-FDA 
approved indications or if doses or routes of administration or participant populations are changed.  

JHMIRB eFormA  01  
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N/A  
c. Justification and safety information if non-FDA approved drugs without an IND will be 
administered.   
- 
N/A.  The dexamethasone pellet is FDA-approved for the treatment of intermediate and posterior 
uveitis.   
7.  
Study Statistics  
a. Primary outcome variable.  
- 
Control of uveitis at the 1 month, 2 month, 3 month, 6 month and 12 month time points.  
Cumulative incidences of uveitis control will be compared to historical data from the Johns 
Hopkins cohort and from the Systemic Immunosuppressive Treatment of Eye Diseases (SITE) 
Research Group.  
b. Secondary outcome variables.  
- 
The cumulative incidence of control of inflammation (0.5+ or less vitreous cells in the liquid 
vitreous; trace or less anterior chamber cells; and inactive chorioretinal lesions) at the 3month 
visit and the 6-month visit will be compared to the published data (from Johns Hopkins and 
from the SITE database) of the cumulative incidence of steroid-sparing success (prednisone 
<=7.5 mg daily and controlled disease) and of oral steroid discontinuation with the goal of 
proving NON-INFERIORITY of the dexamethasone pellet.  Cumulative incidences of ocular 
and systemic side effects of the dexamethasone pellet will be compared to those of oral 
prednisone via rates and cumulative incidences at 12 months.      
c. Statistical plan including sample size justification and interim data analysis.  
- 
20 patients will be enrolled and the data regarding success of control of uveitis at the 6 and 12 
month examinations will be compared with historical published data.  Comparative data from 
the Johns Hopkins cohort, SITE database, and published MUST data will be utilized. d. Early 
stopping rules.  
- 
None   
8.  
Risks  
a. Medical risks, listing all procedures, their major and minor risks and expected frequency.  
- 
Dexamethasone pellet insertion within 14 days of the baseline visit and potential insertion at 
months 3, 6, 9, and every 3 months thereafter based on the study protocol and clinical 
judgment of the PI/study ophthalmologist.  
- 
Dexamethasone pellet should not be used if patient is allergic to any of its ingredients.  
- 
Injections into the vitreous in the eye may be associated with eye inflammation, 
subconjunctival hemorrhage, and transient increased eye pressure.  Rarely, intravitreal 
injections may be associated with vitreous hemorrhage, retinal detachment, or 
endophthalmitis.  The risk of performing an intravitreal injection as part of this study is no 
greater than that associated with clinical care in the treatment of uveitis. The study 
ophthalmologist will monitor the patient regularly after each injection.   
- 
Use of corticosteroids (including dexamethasone) may produce posterior subcapsular 
cataracts, increased intraocular pressure, glaucoma, and may increase the establishment of 
secondary eye infections due to bacteria, fungi, or viruses.  However, these side effects have 
been reported to occur less frequently with the dexamethasone pellet than with other forms of 
intravitreal corticosteroids such as triamcinolone acetonide or fluocinolone acetonide.  There 
may be a risk of the dexamethasone pellet moving into the anterior chamber of the  
eye in eyes in which cataract surgery has been performed.  However, the risk is greatest in 
aphakic eyes or eyes with anterior chamber intraocular lens (ACIOL) in which the posterior 
capsule has been ruptured.  Because of this, these eyes are excluded from this study.   

JHMIRB eFormA  01  
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There are no major risks or discomforts associated with SD-OCT imaging, Humphrey Visual 
Field, visual acuity.  
- 
Photographing of the eyes is low risk but may be uncomfortable because of the bright flashes 
of light used to take the pictures. The test takes about 5 to 10 minutes.  
- 
Fluorescein angiography might cause nausea and vomiting in some patients.   
- 
Overall, the mentioned risks above are not greater than those of standard clinical care with 
these patients.  
b. Steps taken to minimize the risks.  
- 
N/A.  The risks associated with the treatment of uveitis in this study are no greater than those 
associated with routine care of a patient with these types of uveitis.  
c. Plan for reporting unanticipated problems or study deviations.  
- 
Adverse Event Reporting at each visit after the baseline visit. Which includes:  Loss of three 
lines or greater of visual acuity, new onset cataract, new onset intraocular pressure (IOP) 
greater than 21 mm Hg, new onset intraocular pressure greater than 30 mm Hg, rise of IOP of 
10 mm Hg or greater, need for cataract surgery, need for glaucoma surgery, complications of 
dexamethasone pellet insertion including, but not limited to: vitreous hemorrhage, retinal 
detachment and endophthalmitis.    
d. Legal risks such as the risks that would be associated with breach of confidentiality.  
- 
Risks to one’s privacy will be addressed by collecting the data in a de-identified manner and 
stored in a locked office. The whole study will be conducted by JHU IRB certified research 
personnel based on HIPPA regulations.  
e. Financial risks to the participants.  
- 
The clinical visits will be charged to the patient’s insurance as they are part of the clinical 
standard of care.  The use of immunosuppressive drug therapy and its laboratory monitoring 
also will be charged to the patient’s insurance.   
- 
The dexamethasone implants are being provided by the study sponsor and therefore the patient 
will not incur a charge for this drug or procedure.   
- 
All other study specific procedures such as (lens photos, visual field testing, optic disc photos 
will be covered by study sponsor.    
9.  
Benefits  
a. Description of the probable benefits for the participant and for society.  
- The study participants may benefit from the treatment as all participants will be treated.  We 
may learn of a new way to treat these type of patients that is as effective as oral prednisone 
but without the systemic side effects.   
10.  
Payment and Remuneration  
a. Detail compensation for participants including possible total compensation, proposed bonus, and 
any proposed reductions or penalties for not completing the protocol.  
 
-  Participants will receive $15.00 at each visit, to compensate their parking charge.   
  
11.  
Costs  
a. Detail costs of study procedure(s) or drug (s) or substance(s) to participants and identify who will 
pay for them.  
- Costs of procedures done only for the study are covered by the research funding from the study 
sponsor. The study participant and/or their insurance company will be responsible for the cost 
of the regular medical care, in the same manner as if the participant was not participating in 
this study.