Evaluation of Intraoperative Use of Dexycu on the Signs and Symptoms of Dry Eye
Phase: PHASE4
Conditions: Dry Eye Syndromes
Sponsor: SR Cornea Consultants

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Evaluation of Intraoperative use of Dexycu on the Signs and Symptoms of Dry Eye 
 
Sponsor:  
 
 
SR Cornea Consultants 
 
 
 
 
16 Kimberley Circle, Oak Brook, IL 60523 
847 668 5498 
Name and title of person(s) authorized to sign the protocol for 
the sponsor:  Sanjay Rao, MD 
 
Monitor: 
 
 
Sanjay Rao, MD 
Medical Expert: 
 
Sanjay Rao, MD 
 
 
 
 
  
 
Investigators:  
 
Sanjay Rao, MD 
 
 
 
 
Clinical Laboratory(ies): 
 NA 
 
 
 
 
 
 
 
 
 
Study Product:  
 
DEXYCU (dexamethasone intraocular suspension) 9% 
 
Protocol Number: 
 
NCT04184999 
 
 
 
 
April 10, 2019 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
 
Study Summary 
 
1. Introduction 
1.1 Background 
1.2 Investigational or Study Product 
1.3 Preclinical Data 
1.4 Clinical Data to Date 
1.5 Dose Rationale  
1.6 Risks/Benefits 
2. Study Objectives 
3. Study Design 
3.1 General Design 
3.2 Primary/Secondary Study Endpoints 
4. Subject Selection and Withdrawal 
      4.1 Inclusion Criteria 
      4.2 Exclusion Criteria 
      4.3 Subject Recruitment and Screening 
      4.4 Early Withdrawal of Subjects 
       5. Investigational Product 
 
      5.1 Description 
 
      5.2 Treatment Regimen 
 
      5.3 Method for Assigning Subjects to Treatment Groups 
 
      5.4 Subject Compliance Monitoring  
 
      5.5 Prior and Concomitant Therapy  
 
      5.6 Packaging, Receiving, Storage, Dispensing and Return  
        6.   Study Procedures 
        7.   Statistical Plan 
 
     7.1 Sample Size Determination 
 
     7.2 Statistical Methods 
 
     7.3 Subject Population(s) for Analysis 
        8.  Safety and Adverse Events 
 
     8.1 Definitions 
 
     8.2 Assessment of Safety and Efficacy  
 
     8.3 Recording and Reporting of Adverse Events 
 
     8.4 Unblinding Procedures 
 
     8.5 Stopping Rules 
 
     8.6 Medical Monitoring 
        9.  Data Handling and Record Keeping 
 
     9.1 Confidentiality 
 
     9.2 Source Documents 
 
     9.3 Records Retention 
       10.  Study Monitoring, Auditing, and Inspecting 
       11.  Ethical Considerations 
 
 
 
 
    
 

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STUDY SUMMARY 
Title 
Evaluation of intraoperative use of Dexycu on the Signs and Symptoms of 
Dry Eye 
Protocol Number 
10 
Phase 
Phase IV 
Methodology 
Prospective Randomized Controlled Trial 
Study Duration 
3 weeks  
Study Center(s) 
Single-Center   
Objectives 
To evaluate the impact of intraoperative Dexycu during cataract surgery 
on the signs and symptoms of dry eye 
Number of subjects 
40 
Main Inclusion and 
Exclusion Criteria 
Inclusion:  Patients undergoing bilateral cataract surgery 
Exclusion:  Patients with severe ocular surface disease as defined by 
central corneal staining with fluorescein and/or a tear film osmolarity of 
greater than 340 in either eye 
Study product, Dose, 
Route, Regimen 
DEXYCU (dexamethasone intraocular suspension) 9%, administered as a 
single dose, intraocularly in the posterior chamber at the end of surgery.  
The dose is .005 mL of dexamethasone 9% (equivalent to 517 
micrograms) 
Duration of subjects 
participation  
Patients scheduled to undergo bilateral cataract surgery will be screened 
and have dry eye testing.  If enrolled in the study, patients will have dry 
eye testing at 1 week and 3 weeks after surgery. 
Reference product 
The control group will utilize a standard post-cataract surgery regimen 
of topical gatifloxacin and topical prednisolone acetate. 
 
 
 
 
 
 

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1 Introduction 
Evaluation of intraoperative use of Dexycu on the Signs and Symptoms of Dry Eye is a clinical 
research protocol and the study will be conducted in accordance with the protocol, Good 
Clinical Practice Standards, and applicable regulatory requirements.  
 
1.1 Background 
Multiple studies have established the relationship between dry eye and cataract surgery. 
First, a majority of patients undergoing cataract surgery have dry eye signs including 
decreased tear break up time (63%) and positive corneal staining (77%). Second, patients 
experience an increase in dry eye symptoms after cataract surgery compared to baseline. 
Third, Snellen visual acuity and contrast sensitivity are impacted by dry eye after cataract 
surgery.   
 
The objective of this clinical research is to evaluate whether the signs and symptoms of dry 
eye after cataract surgery improve with the addition of a DEXYCU intraocular injection. 
 
1.2 Investigational/Study Product 
DEXYCU contains dexamethasone 9% as a sterile suspension for intraocular ophthalmic 
administration.  DEXYCU is provided as a kit for administration of a single dose of 0.005 mL 
of 9% dexamethasone.  
 
 1.3 Preclinical Data 
 
 Not applicable. 
 
1.4 Clinical Data to Date 
 
Clinical efficacy was evaluated in a randomized, double masked, placebo controlled trial 
(NCT2006888) in which subjects received either DEXYCU or placebo (vehicle).  A dose of 5 
microliters of DEXYCU or vehicle was administered by the physician at the end of the 
surgical procedure.  The primary efficacy endpoint for the study was the proportion of 
patients with anterior chamber cell clearing on postoperative day 8.  The percentage of 
patients with anterior chamber clearing at Day 8 was 2-% in the placebo group, and 57%, 
and 60% in the 342 and 517 microgram treatment groups. 
 
1.5 Dose Rationale  
 
See section 1.4 
 
1.6 Risk/Benefits 
 
The following adverse events rates are derived from three clinical trials in which 339 
patients received the 517 microgram dose of DEXYCU.  The most commonly reported 
adverse reactions occurred in 5-15% of subjects and included increases in intraocular 
pressure, corneal edema, and iritis.  Other ocular adverse reactions occurring in 1-5% of 
subjects included, corneal endothelial cell loss, blepharitis, eye pain, cystoid macular edema, 
dry eye, ocular inflammation, posterior capsular opacification, blurred vision, reduced 
visual acuity, vitreous floaters, foreign body sensation, photophobia, and vitreous 
detachment.   
 
2  Study Objectives 
The objective of this clinical research is to evaluate whether the signs and symptoms of dry 
eye after cataract surgery improve with the addition of a DEXYCU intraocular injection.  
Multiple studies have established that dry eye worsens after cataract surgery.  There is also 

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a strong body of evidence that shows that dry eye is inflammatory.  The objective of this 
study is to evaluate whether the intraocular use of steroid impacts dry eye. 
  
 
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Study Design 
3.1  General Design 
• The type/design of the study:  
o  Prospective randomized controlled trial 
• A description of the measures taken to minimize/avoid bias:  
o Patients undergoing bilateral cataract surgery will be randomized to the 
DEXYCU group (standard postoperative cataract regimen + intraoperative 
DEXYCU) in one eye or the STANDARD group (standard postoperative 
cataract regimen).  Randomization will be done after screening visit, prior to 
surgery on the first eye and will be done by coin flip.  Standard cataract 
regimen to be used: topical prednisolone acetate 1% qid and topical 
gatifloxacin qid for 1 week, then tid for 1 week, then bid for 1 week.  
• Expected duration of subject participation  
o 3 weeks after cataract surgery 
o Patients undergoing cataract surgery will have dry eye testing prior to 
surgery, 1 week after surgery, and 3 weeks after surgery 
• A summary description of the sequence and duration of all trial periods including 
follow-up, if any 
o Patients undergoing cataract surgery will have dry eye testing prior to 
surgery, 1 week after surgery, and 3 weeks after surgery 
 
 
3.2 Primary/Secondary Endpoints 
 
Primary endpoints:  
1) Tear film Osmolarity as measured on Tear Lab system 
2) Corneal Staining (Oxford grading scale 0-15) 
 
 
Secondary endpoint: 
3) Satisfaction questionnaire – How satisfied are you with your surgery? (Graded 0-4) 
 
 
 
 

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Subject Selection and Withdrawal 
4.1 Inclusion Criteria 
1) Patients diagnosed with bilateral cataracts and scheduled to undergo bilateral cataract 
surgery 
2) Must be able to understand and sign an informed consent from that has been approved 
by an Institutional Review Board 
3) Patient is over the age of 18 
4) Patient must agree to comply with visit schedule and other requirements of the study 
5) Females who are not pregnant and are not lactating.  Females who are post-menopausal 
or surgically sterilized.    
 
If the answer to any of the inclusion criteria are NO, the subject is ineligible to continue 
study participation 
        4.2 Exclusion Criteria 
1) Patients with several ocular surface disease as defined by central corneal staining with 
fluorescein and/or a tear film osmolarity of greater than 340 in either eye 
 
        4.3 Subject Recruitment and Screening 
 Subjects will be recruited for the study from principal investigator’s clinical practice.  As 
part of the informed consent process, patients will be offered a DEXYCU injection and given 
a brochure/handout discussing DEXYCU.  As part of the standard cataract evaluation 
process, both tear film osmolarity and corneal staining will be performed. 
 
4.4 Early Withdrawal of Subjects 
 
Subjects will be carefully monitored after surgery, including visual acuity measurements, 
intraocular pressure measurements, anterior and posterior segment evaluation, as well as 
dry eye testing.  If patients have an intraocular pressure elevation over 35mm that requires 
additional medication, they will be withdrawn from the study.  Also, if patients require a 
deviation from the standard cataract postoperative regimen, they will be withdrawn from 
the study. 
 
5     Investigational Product  
5.1 Description  
Each kit of DEXYCU contains a single dose for a single patient.  The 2 mL glass vial is filled 
with 0.5 mL of 9% dexamethasone.  
 
5.2 Treatment/Dosing Regimen 
DEXYCU (dexamethasone intraocular suspension) 9%, administered as a single dose, 
intraocularly in the posterior chamber at the end of surgery.  The dose is .005 mL of 
dexamethasone 9% (equivalent to 517 micrograms)  
 
        5.3 Method for Assigning Subjects to Treatment/Dosing Groups 
 Patients undergoing bilateral cataract surgery will be randomized to the DEXYCU group 
(standard postoperative cataract regimen + intraoperative DEXYCU) in one eye or the 
STANDARD group (standard postoperative cataract regimen).  Randomization will be done 
after screening visit, prior to surgery on the first eye and will be done by coin flip.   Patients 
who are randomly assigned to the DEXYCU group will receive a sequentially numbered drug 
kit. 
 
        5.4 Subject Compliance Monitoring  

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The study team will assess and track compliance on each study visit (1 day, 1 week, 3 
weeks).  At all postoperative visits, the study team will monitor adherence to the eyedrop 
regimen.  If there is a significant deviation from the eyedrop regimen, the principal 
investigator will determine continuation in the study. 
 
A case report binder will be created for each subject in the study.  Binder tabs will include: 
Screening Visit 
Day 1 Visit 
Day 7 Visit 
Day 21 Visit 
Exit Form 
Early Exit Visit 
Nonserious Adverse Event Forms 
Serious Adverse Event Forms 
 
       
        5.5 Prior and Concomitant Therapy  
 All medications that subjects are taking prior to cataract surgery will be permitted.  
Subjects are also permitted to utilize artificial tears in addition to the therapeutic regimens.  
The use of artificial tears will be tracked by the study team. 
 
        5.6 Packaging, Receiving, Storage, Dispensing and Return 
Dexycu will be stored in a locked cabinet.  Usage of the medication will be logged.  
 
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Study Procedures 
Screening Visit 
Day 1 Postoperative Visit  
Day 7 Postoperative Visit 
Day 21 Postoperative Visit   
 
At all visits, visual acuity, eye pressure measurements, tear film osmolarity, and corneal 
staining will be measured and recorded.  At days 7 and 21, patient satisfaction scores will be 
measured. 
 
        7 Statistical Procedures 
        7.1 Sample Size Determination 
The determination of sample size was based on a review of similar cataract and dry eye 
studies.   As this is a single center, pilot study, it was determined that a sample size of 40 
patients would be feasible. 
 
 
   7.2 Statistical Methods 
An ANOVA analysis will be performed to compare the dry eye testing data between the 
DEXYCU group and the standard regimen group. 
 
 
   7.3 Subject Population(s) for Analysis 
All patient who met inclusion criteria and complete the study will be included in the 
selection of subjects to be included in the analyses. 
 
         8 Safety and Adverse Events 
         8.1 Definitions 

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An adverse event is any untoward medical occurrence in a patient who is administered a 
test article (DEXYCU).  The adverse event does not necessarily have a causal relationship 
with the treatment.  An adverse event can therefore be any unfavorable and unintended 
sign, symptom, or disease temporally associated with the use of the test article, whether or 
not related to the test article. 
 
A nonserious adverse event is defined as a change in a patient’s ophthalmic and or medical 
health that is not life-threatening, does not require hospitalization, does not prolong a 
current hospitalization and is not disabling.  Nonserious adverse events must be reported 
by use of a Nonserious Adverse Event Form and may also be reported by a telephone call.  
All nonserious advese events must be reported on a Nonserious Adverse Event Form 
whether they are considered related or unrelated to the test article. 
 
A serious adverse event is defined as any adverse experience occurring at any dose that 
results in any of the following outcomes: death; a life threatening adverse event, inpatient 
hospitalization, prolongation of existing hospitalization, or a persistent or significant 
disability/incapacity. 
 
 
    8.2 Recording and Reporting of Adverse Events 
An Adverse Event Form must be completed for all serious adverse events within 24 hours of 
the investigator’s knowledge of the event and to the Institutional Review Board according to 
their requirements.    
 
    
 
 
    8.4 Randomization Codes 
Patients undergoing bilateral cataract surgery will be randomized to the DEXYCU group 
(standard postoperative cataract regimen + intraoperative DEXYCU) in one eye or the 
STANDARD group (standard postoperative cataract regimen).  Randomization will be done 
after screening visit, prior to surgery on the first eye and will be done by coin flip.   Patients 
who are randomly assigned to the DEXYCU group will receive a sequentially numbered 
drug kit.   
 
 
 
 8.5 Stopping Rules 
Upon completion of the study, an “Exit Form” will be completed and signed by the 
Principal Investigator.  Patients who withdraw early from the study will complete an 
“Early Exit Visit” form detailing the last visit and reasons for early withdrawal. 
 
 
 8.6 Medical Monitoring 
The medical monitoring plan will be dictated by the protocol and recorded in the patient 
case report binder. 
 
         

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  9   Data Handling and Record Keeping 
 
  9.1 Confidentiality 
A confidential study binder will be maintained and secured in a locked cabinet by the 
principal investigator.   
 
All identifiable, sensitive information will be protected on a password protected, 
encrypted device. 
 
What information is being collected? 
Visit Date 
Date of Surgery 
Eye 
Concomitant Medication 
Ocular Symptoms (Graded 0-3) 
 
 
 
Foreign Body Sensation 
 
 
 
Tearing 
 
 
 
Photophobia 
Visual Acuity 
Intraocular Pressure 
Tear Film Osmolarity 
Corneal Staining 
Patient satisfaction score 
 
                 Will identifiers be removed? When? 
 
 
Identifiers will be removed 3 months after study completion 
                 How will the information be used? 
The information will be used to determine if Dexycu treatment impacts dry 
eye parameters after cataract surgery 
                 Will the information be sold to third parties? 
 
 
No 

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                 Will the information be used for future research? 
 
 
No 
                 Who has access? 
 
 
Only Principal Investigator 
                 When will the information be destroyed? 
 
 
12 months after study completion 
 
 
 
  9.2 Source Documents 
A case report binder will be created for each subject in the study.  Binder tabs will include: 
A.  Screening Visit 
B.  Day 1 Postoperative Visit 
C.  Day 7 Posteoperative Visit 
D.  Day 21 Postoperative Visit 
E.  Exit Form 
F.  Early Exit Visit 
G.  Nonserious Adverse Event Forms 
H.  Serious Adverse Event Forms 
 
A copy of the Source Documents are included.  
 
 
  9.4 Records Retention 
 
 
  Study records will be retained in a locked cabinet for 2 years.  
 
         10  Study Monitoring, Auditing, and Inspecting 
 
  The study and patients will be monitored on a weekly basis by the Principal Investigator.  
Patient will be followed as part of the study and will receive further follow-up per a        
standard cataract surgery protocol 3 months and 1 year after the study, as well as on as 
clinically needed basis.   
 
          11  Ethical Considerations 
There are no significant ethical considerations as the study is evaluating an FDA approved 
therapy.