Conditions: Chronic Ocular Graft-versus-host Disease
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 33
Healthy volunteers: no

Brief summary:
To evaluate the safety and efficacy of Pro-ocular™ 1% topical gel administered twice daily for 70 days in reducing or eliminating symptoms and signs of chronic ocular GvHD.

Detailed description:
Ocular graft versus host disease presents a most severe form of ocular surface disease that compromises quality of life of afflicted allogeneic hematopoietic transplantation patients.

A controlled study is necessary to verify findings obtained to date in isolated patients. Currently available ophthalmic solutions and suspensions, drugs and devices largely have not been effective in alleviating the suffering of chronic ocular GvHD patients. Thus, this is an unmet need that Pro-ocular™ topical gel can fulfill.

Potential benefits: Decrease or cessation of adverse ocular symptoms and signs of chronic ocular GvHD, reduction or elimination of the need for other topical ocular therapeutic treatments for chronic ocular GvHD, and restoration of quality of life.

Arms:
arm 1: Pro-ocular™ 1% topical gel applied dermally to forehead twice daily, morning and before bedtime. arm 2: Vehicle topical gel without active ingredient applied dermally to forehead twice daily, morning and before bedtime.

Interventions: intervention 1: Pro-ocular™ topical gel intervention 2: Placebo topical gel
Intervention descriptions: intervention 1: Topical gel for forehead dermal application intervention 2: Topical gel for forehead dermal application

Protocol document:
Prot_000.pdf: 
ClinicalTrials.gov ID NCT03990051 
 
 
Treatment Safety and Efficacy of Pro-ocular™ 1% for Chronic 
Ocular Graft Following Allogeneic HSCT 
 
 
Sponsor:  Glia, LLC 
 
 
Protocol  
March 17, 2020 


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TREATMENT FOR CHRONIC OCULAR GRAFT-VERSUS-HOST DISEASE 
 - CLINICAL STUDY PROTOCOL - 
Protocol Title: 
Treatment safety and efficacy using Pro-ocular™ for 
chronic ocular graft versus host disease (GvHD) 
following allogeneic hematopoietic stem cell 
transplantation. 
Study Objective: 
To evaluate the safety and efficacy of Pro-ocular™ 1% 
topical gel administered twice daily for 70 days in 
ameliorating symptoms and signs of chronic ocular 
GvHD. 
Version / Date: 
V 5.1 March 17, 2020 
Protocol Number: 
oGvHD-1 
Study Phase: 
2 
Study Drug and Placebo: 
Pro-ocular™ 1% topical gel (progesterone) and placebo 
IND Number: 
143010 
Indication: 
Reduce or eliminate ocular symptoms and signs of 
chronic ocular graft-versus-host disease 
Study Site: 
Massachusetts Eye and Ear Longwood 
 
 
800 Huntington Avenue 
Boston, MA 02115 
Principal Investigator: 
Zhonghui Katie Luo, MD, PhD 
 
 
 
 
 
 
Co-Investigators: 
Edwin P. Alyea III , MD 
Joseph H. Antin, MD 
Philippe Armand, MD, PhD 
Corey S. Cutler, MDCM, MPH 
Mahasweta Gooptu, MD 
Vincent Trien-Vinh Ho, MD 
John Koreth, MBBS, DPhil 
Sarah Nikiforow, MD, PhD 
Rizwan Romee, MD 
Robert J. Soiffer, MD 
Sponsor: 
Glia, LLC 
134 Saint Botolph Street 
Boston, MA 02115 
IRB: 
Partners Human Research Committee 
 
Confidentiality Statement 
This protocol contains confidential, proprietary information of Glia, LLC. 
Further dissemination, distribution or copying of this protocol or its contents is strictly prohibited 
 


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Approved: 
 
Zhonghui Katie Luo, MD, PhD, Principal Investigator 
Robert J. Soiffer, MD, Co-Investigator 
Wei-wei Chang, PhD, GLIA LLC 
Kenneth Sawyer, JD, GLIA, LLC 
 
 
 
CONTACT INFORMATION FOR THE STUDY 
 
Principal Investigator: 
Zhonghui Katie Luo, MD, PhD 
 
 
MEE Longwood 
800 Huntington Avenue 
Boston, MA 02115 
Email: Zhonghui_Luo@MEEI.Harvard.edu 
Administrative Contact: 
Patricia Li  
Tel. 617-936-6092 (7:30 am – 3:30 pm) 
 
IRB: 
Partners Human Research Committee 
399 Revolution Drive 
Suite # 710 
Somerville MA, 02145 
857-282-1900 
Sponsor Contact: 
Wei-wei Chang, PhD 
Direct: 617-794-8922; email chang@gliacell.com 
 
Kenneth Sawyer, JD 
Direct: 201-621-1036; email sawyer@gliacell.com 
 
Glia, LLC 
134 Saint Botolph Street 
Boston, MA 02115 
Tel: 617-859-0800 
Fax: 617-859-0818 
 
 
 
 
 


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SYNOPSIS 
Protocol Title: 
Treatment safety and efficacy using Pro-ocular™ for 
chronic ocular graft versus host disease (GvHD) 
following allogeneic hematopoietic stem cell 
transplantation 
Version / Date: 
V 5.1 March 17, 2020 
Protocol Number: 
oGvHD-1 
Study Phase: 
2 
Study Drug and Placebo: 
Pro-ocular™ 1% topical gel (progesterone USP) and 
placebo 
IND Number: 
143010 
Indication: 
Reduce or eliminate ocular symptoms and signs of 
chronic ocular graft-versus-host disease 
Study Objective: 
To evaluate the safety and efficacy of Pro-ocular™ 1% 
topical gel administered twice daily for 70 days in 
ameliorating symptoms and signs of chronic ocular 
GvHD. 
Design Structure: 
Single center, randomized, parallel, double-masked, 
placebo-controlled study 
Institutional Review Board: 
Partners Human Research Committee 
 
Duration: 
10-week treatment period (active and placebo) 
6-week crossover period (placebo to active) 
open label phase long term phase to extend the entire 
treatment period for 27 months 
Dosage/Dose Regimen: 
Approximately 0.07 g Pro-ocular™ 1% topical gel 
applied and massaged into the forehead skin twice daily, 
morning and before bedtime. 
Route of Administration: 
 
 
Visit Schedule, Double-Masked 
Phase: 
5 visits over 70 days including: 
• Visit 1, Screening (Day -14 to -1) 
• Visit 2, Baseline and 1st drug application 
• Visit 3, 2-week follow-up (Day 14 ± 2) 
• Visit 4, 6-week follow-up (Day 42 ± 3) 
• Visit 5, 10-week follow-up (Day 70 ± 3) 
Crossover Phase for Subjects on 
Placebo: 
Subjects in placebo group will receive Pro-ocular 1% 
topical gel for twice daily administration for over 6 weeks 
starting at Visit 5: 


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•
Visit 6, 13-week follow-up (3 weeks on active
drug), placebo cross-over subjects only
•
Visit 7, 16-week follow-up (6 weeks on active
drug), placebo cross-over subjects only
Long Term Follow Up for 
Subjects in Open Label Phase 
(for Eligible & Interested 
Subjects) 
Drug will be supplied after the study period for a total of 
27 months’ treatment period beginning with Visit 2, with 
safety monitoring and reporting by the PI and co-
investigators under protocol during clinic: 
Visit 8, 66 ± 6 weeks (15 months) 
Visit 9, 117 ± 6 weeks (27 months) 
Measures Taken to Reduce Bias: 
Randomized treatment assignment; double-masked 
parallel study design,  
2:1, study drug: placebo, 22 subjects:11 subjects 
Number of Subjects: 
33 patients diagnosed with chronic ocular GvHD in at 
least one eye, not wearing scleral or contact lens for at 
least one month in any eye prior to screening 
Number of Study Sites: 
1 
Inclusion Criteria: 
1. Male or female of any race, at least 18 years of age at
Visit 1 Screening.
2. Has the diagnosis of chronic ocular GvHD.
3. Has the NIH Consensus Eye Score of at least 2.
4. On the GLIA Ocular Surface Disease Symptoms
Questionnaire at Screening, has ocular discomfort at a
severity score of moderate or more, and at least one
other symptom at a severity of moderate or more.
5. One or more signs from the list of chronic ocular
GvHD signs below.
6. Has provided verbal and written informed consent.
7. Be able and willing to follow oral and written
instructions, including participation in all study
assessments and visits.
Exclusion Criteria: 
1. Wearing scleral lens within the last month, or those
who plan to start wearing scleral lens during the
study.
2. Anticipate major changes in systemic GvHD
management during study period.
3. Comorbidity with other severe or chronic eye
conditions that in the judgment of the investigator will
interfere with study assessments, such as but not
limited to retinal detachment, recent ocular surgery,
Bell’s palsy, active trigeminal neuritis or neuralgia.


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4. Anticipate change of vision correction or anticipate 
any ocular procedure during study period. 
5. A woman who is pregnant, nursing an infant, or 
planning a pregnancy. 
6. A woman of childbearing potential who has a positive 
urine pregnancy test at Visit 1, or who does not use an 
adequate method of birth control throughout the study 
period. 
7. Has a known adverse reaction and/or sensitivity to the 
study drug or its components. 
8. Unwilling to cease the use of sunscreen on the 
forehead or eye area. 
9. Intraocular pressure >22 mm Hg at screening visit 
with or without ongoing glaucoma treatment. 
10. Currently enrolled in an investigational drug or device 
study for ocular GvHD. 
Evaluation Criteria: 
Efficacy Measures: 
Glia Ocular Surface Disease Symptoms Questionnaire, 
Clinic and Daily Diary 
- 
Ocular discomfort 
- 
Dryness 
- 
Grittiness 
- 
Burning 
- 
Stinging 
- 
Foreign body sensation 
- 
Ocular pain 
- 
Conjunctival redness 
- 
Itching 
- 
Photophobia 
- 
Mucus discharge 
- 
Blurred or cloudy vision 
- 
Air flow sensitivity 
- 
Lid redness 
- 
Lid sticking 
Daily use of eye drops (Restasis®, Xiidra®, artificial 
tears and/or gels, autologous tears (# times administered 
per wake-time hours and sleep-time hours) 
SANDE – Symptom Assessment iN Dry Eye 
Questionnaire 
National Institutes of Health Eye Score 
Chronic ocular GvHD Signs (Ophthalmologist 
examination at each visit) 
- 
TearScan examination:  Tear film, lid margins, 
and meibum expression 


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- 
Visual acuity with current correction. 
- 
Slit lamp without staining:  Lids (lid margin 
erythema, edema, ulceration, notches, entropion/ 
ectropion, trichiasis/madarosis, floppy eyelids, 
hordeolum); Conjunctiva (hyperemia, cicatricial 
changes, pseudomembranes, chalasis); Cornea 
(edema, ulcers, filamentous keratitis, thinning, 
corneal neovascularization, scars, conjunctival 
epithelium invasion, limbal thickening). 
- 
Corneal and conjunctival fluorescein staining 
Non-Ocular GvHD Signs (recorded by patient and 
physician): 
- 
Systemic assessment by BMT physician such as 
dry mouth 
 
Safety Measures: 
 
- 
Adverse events 
- 
Visual acuity 
- 
Slit lamp biomicroscopy 
- 
Undilated fundoscopy examination 
- 
Intraocular pressure  
- 
Systemic assessment by BMT physician at Dana 
Farber Cancer Institute 
Laboratory Tests Routine and 
Afor Assessment of HPA 
(hypothalamic-pituitary-
adrenal axis) Function  
 
Tests to be run at Visits 1, 4, 5, 7, 8 and 9:  Standard 
panel to include CBC with differential, metabolic panel, 
tacrolimus/sirolimus levels, Vitamin D Total 25-hydroxy 
(D2 and D3), T4 (T total and free), T3, ACTH, TSH,   
DHEA-S, estradiol, FSH, LH, progesterone, testosterone 
(total and free). 
 
 
 
 
 
 


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TREATMENT FOR CHRONIC OCULAR GRAFT-VERSUS-HOST DISEASE 
CLINICAL STUDY PROTOCOL 
Table of Contents 
SYNOPSIS ....................................................................................................................................................... 3 
List of Abbreviations ..................................................................................................................................... 8 
TREATMENT FOR CHRONIC OCULAR GRAFT-VERSUS-HOST DISEASE - CLINICAL STUDY PROTOCOL ........... 9 
I. 
BACKGROUND AND SIGNIFICANCE ....................................................................................................... 9 
II. 
SPECIFIC AIMS ..................................................................................................................................... 10 
III. 
SUBJECT SELECTION ........................................................................................................................ 10 
IV. 
SUBJECT ENROLLMENT ................................................................................................................... 12 
V. 
STUDY PROCEDURES ........................................................................................................................... 12 
VI. 
BIOSTATISTICAL ANALYSIS ............................................................................................................... 18 
VII. 
RISKS AND DISCOMFORTS ............................................................................................................... 19 
VIII. 
POTENTIAL BENEFITS ...................................................................................................................... 19 
IX. 
MONITORING AND QUALITY ASSURANCE ...................................................................................... 20 
X. 
REFERENCES ........................................................................................................................................ 21 
APPENDICES ................................................................................................................................................ 26 
SCHEDULE OF VISITS AND ASSESSMENTS ................................................................................................... 27 
Visits 1-7 ...................................................................................................................................................... 27 
SCHEDULE OF VISITS AND ASSESSMENTS ................................................................................................... 28 
Visits 8-10 Long Term Open Label .............................................................................................................. 28 
 
 
 
 
 
 
 
 


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List of Abbreviations 
ADL 
Activities of daily living 
AE 
Adverse event 
BID 
Twice a day 
BMT 
Bone marrow transplantation 
CN V 
Cranial Nerve Five 
CN VII 
Cranial Nerve Seven 
CS 
Clinically significant 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
Curriculum vitae 
FDA 
Food and Drug Administration 
g 
gram 
GvHD 
Graft-versus-host disease 
HSCT 
Hematopoietic stem cell transplantation 
ICF 
Informed consent form 
IND 
Investigational new drug application 
IOP 
Intraocular pressure 
IRB 
Institutional review board 
ITT 
Intent to treat 
kg 
kilogram 
LOCF 
Last observation carried forward 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
µg 
microgram 
mL 
milliliter 
µL  
microliter  
mm 
millimeter 
µm 
micrometer 
mmHg 
millimeters of mercury 
NCS 
Not clinically significant 
nd  
not done  
OD 
Right eye 
oGvHD 
Ocular graft-versus-host disease 
OS 
Left eye 
OU 
Both eyes 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
USP 
United States Pharmacopeia 
VA 
Visual acuity 
 


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TREATMENT FOR CHRONIC OCULAR GRAFT-VERSUS-HOST DISEASE - 
CLINICAL STUDY PROTOCOL 
I. 
BACKGROUND AND SIGNIFICANCE 
  
 
a. Historical background 
 
Pro-Ocular™ topical gel has been studied in controlled clinical studies for dry eye, 
ocular discomfort and in compassionate use since 2013.  Each metered dose of Pro-
Ocular 1% will be about 0.07 g containing about 0.7 mg progesterone.  One skin 
penetration study showed that less than 5% of the applied dose was able to cross the 
outer skin layer or stratum corneum. 
   
b.  Scientific evidence 
The animal study done by Ian Meng et.al has just been published on Investigative 
Ophthalmology & Vision Science 2019; 60 (1706-1713). The study has shown that 
Progesterone 1% gel application to the forehead, but not the contralateral cheek of the rats, 
decreased pain sensation from capsaicin and hypertonic saline application. Local anesthesia of 
the forehead skin blocks the response. The work has indicated that the mechanism of action is 
not via systemic absorption; and a local neuro-pathway is likely activated to alter corneal 
nociception, likely via the cranial nerve V1 branch.  
c. Previous pre-clinical or clinical studies leading up to, and supporting the proposed research 
A product with a similar formulation, PG101 1% topical gel, was given to 24 subjects in a 
completed clinical trial for dry eyes under US IND 119774.  A second group consisting of 24 
subjects received PG101 0.25%.  No drug related serious adverse events were reported.  Adverse 
events with potential relationship to the topical gels in the completed study are approximately 
equal in placebo and treatment groups.  The product demonstrated efficacy in multiple 
symptoms of dry eye disease such as ocular discomfort, dryness, and grittiness in both active 
arms as well as central corneal staining in the 1% active arm.  
 
A study under US IND 123266 for ocular discomfort in glaucoma patients involving 0.5% 
topical gel enrolled approximately 40 subjects with no potential drug related serious adverse 
events reports.  The study has not been unblinded for efficacy analysis. 
 
Since late 2015 Pro-Ocular™ topical gel has been used by a total of 15 chronic ocular GvHD 
patients who had been suffering extreme ocular discomfort, with almost all encountering 
intractable ocular pain despite treatment with all available ocular drugs and devices such as 
BostonSight PROSE (prosthetic replacement of the ocular surface ecosystem). For most patients 
relief in symptoms began with the first application, and greater relief ensued with additional use. 
Symptomatic improvements to various extend were achieved by all patients after several weeks. 
For those wearing scleral lens, daily discomfort during wear and accumulation of debris behind 
the lens was reduced or eliminated. 
 
Topical gels of both concentrations have been prescribed and dispensed through an authorized 
compounding pharmacy to additional patients under care of ophthalmologists. The prescribing 
physicians reported no serious treatment-related adverse events.  
 
The same active ingredient, progesterone USP, occurs naturally in the human body, male and 
female, and can reach levels as high as100-200 ng/mL during late pregnancy.  It is administered 


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at high doses in marketed FDA-approved products orally (200-400 mg/day), vaginally (300-800 
mg/day), intramuscularly (up to 10 mg/day), and topically in marketed supplements (up to 80 
mg/day).  Both progesterone prescription products and marketed supplements are used 
chronically. 
 
Progesterone is also found in foods such as eggs, dairy, yams, beans and dark green leafy 
vegetables. 
 
  c. Rationale behind the proposed research, and potential benefits to patients and/or society 
  A controlled study is necessary to verify findings in isolated patients, and is required for product 
to be approved by the Food and Drug Administration in order that the product can be made 
available to other patients.  Currently available ophthalmic solutions and suspensions, drugs and 
devices have not been effective in alleviating the suffering of the ocular GvHD patients.  Thus 
this is an unmet need that Pro-Ocular™ topical gel can fulfill. 
 
Potential benefits:  Decrease or cessation of adverse ocular symptoms and signs to regain 
quality of life, and prevention of ocular disease progression. 
 
II. 
SPECIFIC AIMS  
 
To evaluate the safety and efficacy of Pro-Ocular™ 1% topical gel administered twice daily for 
70 days in ameliorating symptoms and signs of chronic ocular GvHD. 
 
III. 
SUBJECT SELECTION 
 
The plan is to screen 42 patients in order to achieve a study completion of 33 patients, 2:1 active 
drug:placebo.  Subjects at least 18 years of age with a diagnosis of chronic ocular GvHD and 
fulfilling certain inclusion and exclusion criteria will be eligible.  We anticipate that Dr. Luo, 
Principal Investigator, Ophthalmologist at MEE Longwood will have a sufficient number of 
eligible patients to enable enrollment from one site. 
The inclusion and exclusion criteria are as follows: 
Inclusion Criteria: 
1. Male or female of any race, at least 18 years of age at 
Visit 1 Screening. 
2. Has the diagnosis of chronic ocular GvHD. 
3. Has the NIH Consensus Eye Score of at least 2. 
4. On the GLIA Ocular Surface Disease Symptoms 
Questionnaire at Screening, has ocular discomfort at a 
severity score of moderate or more, and at least one 
other symptom at a severity of moderate or more. 
5. One or more signs from the list of chronic ocular 
GvHD signs below. 
6. Has provided verbal and written informed consent. 


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7. Be able and willing to follow oral and written 
instructions, including participation in all study 
assessments and visits. 
Exclusion Criteria: 
1. Wearing scleral lens within the last month, or those 
who plan to start wearing scleral lens during the 
study. 
2. Anticipate major changes in systemic GvHD 
management during study period. 
3. Comorbidity with other severe or chronic eye 
conditions that in the judgment of the investigator will 
interfere with study assessments, such as but not 
limited to retinal detachment, recent ocular surgery, 
Bell’s palsy, active trigeminal neuritis or neuralgia. 
4. Anticipate change of vision correction or anticipiate 
any ocular procedure during study period. 
5. A woman who is pregnant, nursing an infant, or 
planning a pregnancy. 
6. A woman of childbearing potential who has a positive 
urine pregnancy test at Visit 1, or who does not use an 
adequate method of birth control throughout the study 
period. 
7. Has a known adverse reaction and/or sensitivity to the 
study drug or its components. 
8. Unwilling to cease the use of sunscreen on the 
forehead or eye area. 
9. Intraocular pressure >22 mm Hg at screening visit 
with or without ongoing glaucoma treatment. 
10. Currently enrolled in an investigational drug or device 
study for ocular GvHD. 
 
 
 


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The definition of scoring from the NIH Consensus for ocular GvHD is as follows: 
NIH Consensus:  2014 Diagnosis and Staging Working Group 
 
IV. 
SUBJECT ENROLLMENT 
 
a. Methods of enrollment 
Dr. Luo will review the qualifications of her active chronic ocular GvHD patients to determine 
eligibility, and query the eligible patients via a phone call by Dr. Luo herself as to their interest in 
participation. 
 
b. Procedures for obtaining informed consent  
An informed consent form will be provided for eligible patients to review. Dr. Luo herself will 
obtain the informed consent with each subject. 
 
c. Treatment assignment, and randomization  
Randomized double-masked parallel treatment assignment will be made using a block design at 
the ratio of 2:1, study drug:placebo, 22:11. 
V. 
STUDY PROCEDURES 
 
 
 
The sequence of procedures at each clinic visit is as follows: 
 
Visit 1 (Day -14 to -1) 
Screening 
Ophthalmology assessment 
Informed consent by investigator 
2-digit subject ID number 
GLIA Ocular GvHD symptoms questionnaire 
SANDE symptoms questionnaire 
NIH Ocular GvHD score 
Visual acuity with current correction 
Slit-lamp biomicroscopy 
Undilated fundoscopy exam 
Corneal and conjunctival staining 
Intraocular pressure 
Urine pregnancy testing (as needed) 
Inclusion/Exclusion criteria 


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Screening Pass or Fail by investigator 
Subject assigned 3-digit randomization code 
Review medical records for medical & ocular history  
Review prior and current medications 
Demographics 
BMT (DFCI) physician systemic evaluation 
History 
Physical 
Concomitant medications 
Laboratory tests, standard & endocrine panel 
GvHD assessment 
 
Visit 2 (Day 1) 
Baseline & First Drug Application 
Medical/ocular update 
Medication update 
Facial photo 
1 minute video of face and eyes (+ blink interval) 
TearScan examination 
GLIA Ocular GvHD symptoms questionnaire 
Dispense study drug by investigator 
STUDY DRUG APPLICATION by investigator 
30-90 minutes’ wait from application 
1 minute video of face and eyes (+ blink interval) 
TearScan examination 
Adverse event query 
GLIA Ocular GvHD symptoms questionnaire 
Dispense daily diary and ocular medication log 
 
Visit 3 (Day 14 ± 2), 2 weeks’ treatment 
Medical and medication update 
Diary and ocular medication log collection & compliance 
Drug collection & accountability 
1 minute video of face and eyes (+ blink interval) 
TearScan examination 
Adverse event query 
SANDE symptoms questionnaire 
GLIA Ocular GvHD symptoms questionnaire 
Slit-lamp biomicroscopy 
Corneal and conjunctival staining 
Study drug, daily diary and ocular medication log dispensed 
 
Visit 4 (Day 42 ± 3), 6 weeks’ treatment 
Ophthalmology assessment 
Medical and medication update 
Diary and ocular medication log collection & compliance 


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Drug collection & accountability 
1 minute video of face and eyes (+ blink interval) 
TearScan examination 
Adverse event query 
SANDE symptoms questionnaire 
GLIA Ocular GvHD symptoms questionnaire 
Slit-lamp biomicroscopy 
Corneal and conjunctival staining 
Study drug, daily diary and ocular medication log dispensed 
BMT(DFCI) physician systemic evaluation 
Standard lab tests, GvHD assessment 
 
Visit 5 (Day 70 ± 3), 10 weeks’ treatment 
Ophthalmology assessment 
Visual acuity 
Medical and medication update 
Diary and ocular medication collection & compliance 
Drug collection & accountability 
Urine pregnancy test if applicable 
Facial photo 
1 minute video of face and eyes (+ blink interval) 
TearScan examination 
Adverse event query 
SANDE symptoms questionnaire 
GLIA Ocular GvHD symptoms questionnaire 
Slit-lamp biomicroscopy 
Undilated fundoscopy exam 
Corneal and conjunctival staining 
NIH Ocular GvHD score 
Intraocular pressure 
Urine pregnancy test 
End of study phase 
Reconfirm drug dispensing for Open label Phase  
Dispense diary, ocular medication log and drug to Placebo 
group 
BMT (DFCI) physician systemic evaluation 
Concomitant medications 
Laboratory tests, standard & endocrine panel 
GvHD assessment 
 
Visit 6, 13 weeks for Placebo group only 
Medical and medication update 
Diary and ocular medication log collection & compliance 
Drug collection & accountability 
1 minute video of face and eyes (+ blink interval) 
TearScan examination 
Adverse event query 
SANDE symptoms questionnaire 


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GLIA Ocular GvHD symptoms questionnaire 
Slit-lamp biomicroscopy 
Corneal and conjunctival staining 
 
Visit 7,  16 weeks for Placebo group only  
Facial photo 
Medical and medication update 
Diary and ocular medication log collection & compliance 
Drug collection & accountability 
1 minute video of face and eyes (+ blink interval) 
TearScan examination 
Adverse event query 
SANDE symptoms questionnaire 
GLIA Ocular GvHD symptoms questionnaire 
NIH Ocular GvHD Score1 
Slit-lamp biomicroscopy 
Corneal and conjunctival staining 
Intraocular pressure 
BMT (DFCI) physician systemic evaluation 
Concomitant medications 
Laboratory tests, standard & endocrine panel 
GvHD assessment 
 
Long Term Follow Up for Subjects in Open Label Phase (for 
Eligible & Interested Subjects) Visit 8, 66 weeks ± 6 weeks (15 
months) 
Facial photo 
1 minute video of face and eyes (+ blink interval) 
TearScan examination 
Adverse event query 
SANDE symptoms questionnaire 
GLIA Ocular GvHD symptoms questionnaire 
NIH Ocular GvHD Score 
Slit-lamp biomicroscopy 
Visual Acuity 
Undilated fundoscopy exam 
Corneal and conjunctival staining 
Intraocular pressure 
BMT (DFCI) physician systemic evaluation 
Concomitant medications 
Laboratory tests 
GvHD assessment 
Long Term Follow Up for Subjects in Open Label Phase (for 
Eligible & Interested Subjects)  
Visit 9, 117 ± 6 weeks (27 months) 
Facial photo 
 
1 Added as protocol deviation to original protocol v4. 


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1 minute video of face and eyes (+ blink interval) 
TearScan examination 
Adverse event query 
SANDE symptoms questionnaire 
GLIA Ocular GvHD symptoms questionnaire 
NIH Ocular GvHD Score 
Slit-lamp biomicroscopy 
Visual Acuity 
Undilated fundoscopy exam 
Corneal and conjunctival staining 
Intraocular pressure 
BMT (DFCI) physician systemic evaluation 
Concomitant medications 
Laboratory tests, standard and relevant panel 
GvHD assessment 
 
 
 
 
 
 


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The evaluation criteria are as follows: 
 
 
Efficacy Measures: 
Glia Ocular GvHD Symptoms Questionnaire  
Clinic Daily Diary 
- 
Ocular discomfort 
- 
Dryness 
- 
Grittiness 
- 
Burning 
- 
Stinging 
- 
Foreign body sensation 
- 
Ocular pain 
- 
Conjunctival redness 
- 
Itching 
- 
Photophobia 
- 
Mucus discharge 
- 
Blurred or cloudy vision 
- 
Air flow sensitivity 
- 
Lid redness 
- 
Lid sticking 
Use of eye drops (Restasis®, Xiidra® , artificial tears and/or 
gels, autologous tears , # times administered per wake-time 
hours and sleep-time hours) 
SANDE – Symptom Assessment iN Dry Eye Questionnaire 
National Institutes of Health Eye Score 
Ocular GvHD Signs (physician examination at each visit) 
- 
TearScan examination:  Tear film, lid margins, and 
meibum expression. 
- 
Visual acuity with current correction. 
- 
Slit lamp without staining:  Lids (lid margin erythema, 
edema, ulceration, notches, entropion/ ectropion, 
trichiasis/madarosis, floppy eyelids, hordeolum); 
Conjunctiva (hyperemia, cicatricial changes, 
pseudomembranes, chalasis); Cornea (edema, ulcers, 
filamentous keratitis, thinning, corneal 
neovascularization, scars, conjunctivial epithelium 
invasion, limbal thickening). 
- 
Corneal and conjunctival fluorescein staining 
Non-Ocular GvHD Signs (recorded by patient and physician): 
- 
Systemic assessment by BMT physician such as dry 
mouth 
 
Safety Measures: 
- 
Adverse events 
- 
Visual acuity 
- 
Slit lamp biomicroscopy 
- 
Undilated fundoscopy examination 
- 
Intraocular pressure  
- 
Systemic assessment by BMT physician at Dana Farber 
Cancer Institute 
Laboratory Tests 
Routine and for 
Tests to be run at Visits 1, 4, 5, 7, 8, and 9:  CBC with 
differential, metabolic panel, tacrolimus/sirolimus levels, 


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Assessment of HPA 
(hypothalamic-
pituitary-adrenal axis) 
Function  
Vitamin D Total 25-hydroxy (D2 and D3), T4 (Total and free), 
T3, ACTH, TSH, DHEA-S, estradiol, FSH, LH, progesterone, 
testosterone (total and free). 
 
 
Laboratory tests will be performed at the Dana Farber Cancer Institute (DFCI) and the 
Brigham Research Assay Core, Brigham and Women’s Hospital. As DFCI 
patients study subject will continue to be followed at DFCI by the MD that referred 
them to Mass Eye and Ear. In addition to their standard of care examinations the study 
subjects will undergo additional laboratory testing including: 
 
• 
CBC with differential 
• 
Metabolic panel 
• 
Tacrolimus/sirolimus levels 
• 
Vitamin D Total 25-hydroxy (D2 and D3) 
• 
T4 (Total and free) 
• 
T3 
• 
ACTH 
• 
TSH.   
• 
DHEA-S 
• 
Estradiol 
• 
FSH 
• 
LH 
• 
Progesterone 
• 
Testosterone (total and free). 
 
These DFCI physicians will be co-investigators in the study and will review the laboratory tests 
outcomes to ensure the safety of the subjects. 
 
A selection of the key questionnaires and examination procedures specific to oGvHD are shown 
in the Appendix. 
 
VI. 
BIOSTATISTICAL ANALYSIS 
 
Analysis Populations: 
Intent-to-Treat Population 
The intent-to-treat (ITT) population includes all randomized subjects.  The efficacy analyses will 
be performed on the ITT population with Last Observation Carried Forward (LOCF) method for 
missing values.  The efficacy variables may also be analyzed utilizing the ITT population with 
observed data only (i.e. without LOCF) to assess sensitivity. 
 
Per-Protocol Population 
The per protocol (PP) population excludes subjects with significant protocol deviations and 
excludes any incomplete subject data.  Protocol deviations will be assessed by the clinical team, 
prior to database lock.  Efficacy analyses will be performed on the PP population with observed 
data only. 
 


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Sample Size 
33 subjects. 
 
Efficacy Analyses 
The continuous and ordinal efficacy variables collected at each visit (and time point, where 
relevant) will be summarized with number of observations (n), mean, standard deviation, median, 
minimum and maximum.  Statistical inference testing will be conducted and the results will be 
utilized as additional descriptors of the data.  Two-sample t-tests will be employed for continuous 
variables.  Two-sample t-tests, Wilcoxon rank sum tests and analysis of covariance (ANCOVA) 
models adjusting for baseline will be employed for ordinal variables.  For the ANCOVA models, 
treatment will be compared to the placebo.  Pearson’s chi-square or Fisher’s exact tests (in the 
case of expected counts less than 5) will be employed for qualitative variables.  Where 
appropriate, the change from baseline for each parameter will also be summarized using 
descriptive statistics. 
 
The individual symptoms collected in the diary will be analyzed including all data across the 70-
day treatment period, testing for a treatment effect using a generalized linear model that accounts 
for repeated measures with an unstructured correlation structure, including terms for diary day 
and the treatment-by-day interaction. 
 
VII. 
RISKS AND DISCOMFORTS  
 
Based on the clinical use of the drug within and outside of controlled studies, there are no 
known risks.  The amount of the active progesterone is several hundred-fold lower than the 
current injectable, topical, and oral forms.  Skin penetration studies by Sponsor using the Franz 
cell has shown that less than 5% of progesterone passes through the top layer of the skin 
(stratum corneum). 
 
Use of other ocular medications can continue, concurrent with use of Pro-ocular. 
   
VIII. POTENTIAL BENEFITS 
 
a. Potential benefits to participating individuals 
 
The potential benefits to participating individuals are reduction or elimination of ocular 
discomfort, especially the extreme pain experienced by many ocular GvHD patients, and ocular 
tissue damage repair, potentially preventing progression to when surgical procedures may be 
required. 
 
Another potential benefit is the reduction of use of artificial tears and other eye drops that only 
provide temporary relief. 
 
There is potential improvement of the overall quality of life, and enabling the return to normal 
daily living, sleep, work, and other activities. 
 
b. Potential benefits to society  
 
The study is expected to prove that the study drug fulfills an unmet need for ocular GvHD 
treatment. 


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IX. 
MONITORING AND QUALITY ASSURANCE 
a. Independent monitoring of source data 
The sponsor intends to provide independent monitoring to ensure all data are collected, and 
entered into a database accurately. 
 
b. Safety monitoring  
A Safety Management Plan is provided to clinical management personnel.  A 24-hour telephone 
physician safety monitor line will be provided for the subjects to call. 
 
c. Outcomes monitoring 
Data will be analyzed by a third-party statistical group. 
 
d. Adverse event reporting guidelines 
All adverse events will be collected, whether potentially related or unrelated to study drug use. 
The adverse events will be categorized according to the latest version of MedDRA (Medical 
Dictionary for Regulatory Activities) using Common Terminology Criteria (CTCAE).  The 
Safety Management Plan provides guidance for what is considered a serious adverse event, the 
forms to be completed in such cases, and when a serious adverse event needs to be reported to 
the FDA.  
 


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X. 
REFERENCES 
Ocular Findings in Chronic GvHD 
Reference 
Ocular Changes Chronic GvHD 
Amparo F et al.  
Corneal fluorescein staining and ocular symptoms but not 
Schirmer test are useful as indicators of response to 
treatment in chronic ocular GVHD.  Ocul Surf. 2018 May 
12. pii: S1542-0124(18)30040-5. 
Corneal fluorescein staining and symptoms better 
indicators than Schirmer scores 
Anderson NG, Regillo C 
Ocular manifestations of graft versus host disease.  Curr 
Opin Ophthalmol. 2004 Dec;15(6):503-7. 
“Ocular findings include keratoconjunctivitis sicca, 
pseudomembranous conjunctivitis, corneal ulceration and 
perforation, and microvascular retinopathy.” 
Berchicci L et al. 
Ocular chronic graft-versus-host disease after allogeneic 
hematopoietic stem cell transplantation in an Italian 
referral center. Ocul Surf. 2018 Jul;16(3):314-321. 
More than 50% developed chronic ocular GVHD after 
allogeneic HSCT.  Meibomian gland dysfunction, 
conjunctival hyperemia, and conjunctival fibrosis were 
major findings. 
Blecha C et al. 
Verification of the new grading scale for ocular chronic 
graft-versus-host disease developed by the German-
Austrian-Swiss consensus conference on chronic GVHD.  
Ann Hematol. 2016 Feb;95(3):493-9. 
“85% of patients suffered from functional impairment 
due to ocular cGVHD.” 
Ocular tissue involved: 
Lacrimal glad dysfunction 100% 
Lids 89% 
Conjunctiva 96% 
Cornea 76% 
Blecha C et al. 
Retinal Involvement in a Patient with Cerebral 
Manifestation of Chronic Graft-Versus-Host-Disease.  
Oncol Res Treat. 2015;38(10):532-4. 
“2 years later, she complained of right-sided blurred 
vision and floaters; both eyes showed whitish 
circumscribed retinal infiltrations, cellular infiltration of 
the vitreous and mild bilateral optic disc edema. 
Oncological and neurological work-up ruled out infectious 
diseases and other GvHD manifestations. Symptoms and 
signs resolved under continued systemic IS, leaving 
pigmented retinal scars.” 
Busin M, Giannaccare G, Sapigni L, Testoni N, Leon P, 
Versura P, Campos E.  Conjunctival and Limbal 
Transplantation From the Same Living-Related Bone 
Marrow Donor to Patients With Severe Ocular Graft-vs-
Host Disease.  JAMA Ophthalmol. 2017 Oct 
1;135(10):1123-1125. 
“To date, no treatment has proven to be effective for 
severe ocular graft-vs-host disease (GVHD) after allogenic 
hematopoietic stem cell transplantation that leads to 
conjunctivalization and keratinization of the cornea 
through damage of conjunctival goblet cells and limbal 
epithelial stem cells (LESCs). We report the outcomes of 
chimerism induced by transplantation from the same 
living-related bone marrow donor of conjunctiva and 
LESCs in 4 eyes of 2 patients with severe ocular GVHD.” 
Claes K, Kestelyn P 
Ocular manifestations of graft versus host disease 
following bone marrow transplantation. Bull Soc Belge 
Ophtalmol. 2000;(277):21-6. 
“The ocular manifestations of Graft Versus Host Disease 
(GVHD) include keratoconjunctivitis sicca, cicatricial 
lagophthalmos, sterile conjunctivitis, corneal epithelial 
defects, corneal ulceration and melting.” 


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Reference 
Ocular Changes Chronic GvHD 
Curtis LM et al. 
Predictive models for ocular chronic graft-versus-host 
disease diagnosis and disease activity in transplant clinical 
practice.  Haematologica. 2015 Sep;100(9):1228-36. 
Significant findings in ocular cGvHD patients: 
Visual acuity deficits and vision difficulty 
Corneal staining 
Meibomian glands plugged 
Lid margin swelling 
Lid margin erythema 
Lid margin tear film debris 
Conjunctival injection [hyperemia → pseudomembranous 
conjunctivitis] 
Conjuntival chemosis [swelling] 
Dry eye 
(Schirmer test and tear film breakup time not as valuable  
as indicators.) 
Dierich-Ntoukas T 
[Clinical Signs of Ocular Graft-versus-Host Disease].  Klin 
Monbl Augenheilkd. 2015 May;232(5):647-51. 
“It is not only associated with reduced quality of life 
because of dry eye symptoms but can also impair visual 
acuity and lead to blindness due to corneal complications.  
Patients with ocular GvHD are often resistant to therapy 
because of the severe dry eye disease and persistent 
inflammatory activity.” 
Eberwein P et al 
[Patient-Centred Care of Ocular Graft-vs-Host Disease in 
Germany].  Klin Monbl Augenheilkd. 2015 
May;232(5):664-8. 
“Ocular GvHD is a severe complication following allogenic 
blood stem cell transplantation leading to massive 
reduction in quality of life and ocular pathologies 
including corneal perforation.” 
Gama I et al. 
Chronic Ocular Graft vs Host Disease as a Serious 
Complication of Allogeneic Hematopoietic Stem Cell 
Transplantation: Case Report.  Transplant Proc. 2015 
May;47(4):1059-62. 
“Bilateral corneal ulcers and ocular perforation, although 
not frequent, can occur in most extreme cases.” 
Giannaccare G et al. 
Ocular surface analysis in hematological patients before 
and after allogeneic hematopoietic stem cell 
transplantation: implication for daily clinical practice.  Eye 
(Lond). 2017 Oct;31(10):1417-1426. 
50 patients or 53% were diagnosed as dry eye sufferers 
prior to HSCT.  The incidence increased 77% or 72 
patients post HSCT. 
Significant changes post HSCT:  OSDI, TFBUT, MGD score, 
conjunctival injection; not so much Schirmer’s. 
Karwacka E et all 
Pemphigoid-like ocular lesions in patients with graft-
versus-host disease following allogeneic bone marrow 
transplantation.  Transplant Proc. 2006 Jan-
Feb;38(1):292-4. 
Pemphigoid-like ocular lesions in addition to keratitis 
sicca were seen in patients with graft-versus-host disease. 
Kim S et al. 
Changes of meibomian glands in the early stage of post 
hematopoietic stem cell transplantation.  Exp Eye Res. 
2017 Oct;163:85-90. 
“A significant increase was seen in the upper eyelid post-
HSCT meiboscore at 2 months and 3 months, and in the 
total eyelid meiboscore at 3 months. 
Kim SK 2006 
Update on ocular graft versus host disease. 
Curr Opin Ophthalmol. 2006 Aug;17(4):344-8. 
“Ocular graft versus host disease is a common sequela of 
allogeneic hematopoietic transplantation affecting up to 
80% of chronic graft versus host disease patients. Clinical 
features of ocular graft versus host disease encompass all 
parts of the eye, from the lid to the choroids, although 
ocular graft versus host disease is most commonly viewed 
as a disease of the ocular surface, with the conjunctiva 
and lacrimal gland most commonly affected.” 


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Reference 
Ocular Changes Chronic GvHD 
Kusne Y et al 
Conjunctival subepithelial fibrosis and meibomian gland 
atrophy in ocular graft-versus-host disease. Ocul Surf. 
2017 Oct;15(4):784-788. 
“Clinical CSEF [conjunctival subepithelial fibrosis) may be 
an important sign of GVHD impact on the ocular surface 
and may be relevant in oGVHD severity assessment.” 
Lin X, Cavanagh HD 
Ocular manifestations of graft-versus-host disease: 10 
years' experience.  Clin Ophthalmol. 2015 Jul 3;9:1209-13. 
“The most common presentations were 
keratoconjunctivitis sicca, cataract, blepharitis, ocular 
hypertension, and filamentary keratitis.  Visual acuity at 
presentation was 20/49; at the worst point in the disease 
was 20/115; and at most recent visit was 20/63.”…”…they 
are prone to serious ocular complications such as corneal 
perforation and endophthalmitis.” 
Nassar A et al. 
Ocular manifestations of graft-versus-host disease.  Saudi 
J Ophthalmol. 2013 Jul;27(3):215-22. 
“Eyelid changes may occur in GVHD leading to 
scleroderma-like changes. Patients may develop poliosis, 
madarosis, vitiligo, lagophthalmos, and entropion. The 
cornea may show filamentary keratitis, superficial 
punctate keratitis, corneal ulcers, and peripheral corneal 
melting which may lead to perforation in severe cases. 
Scleritis may also occur which can be anterior or 
posterior. Keratoconjunctivis sicca appears to be the most 
common presentation of GVHD. The lacrimal glands may 
be involved with mononuclear cell infiltration of both the 
major and accessory lacrimal glands and decrease in tear 
production. Severe dry eye syndrome in patients with 
GVHD may develop conjunctival scarring, keratinization, 
and cicatrization of the conjunctiva.” 
Ogawa Y et al. 
Dry eye as a major complication associated with chronic 
graft-versus-host disease after hematopoietic stem cell 
transplantation.  Cornea. 2003 Oct;22(7 Suppl):S19-27. 
Ocular complications were listed for “chronic phase” 
Dry eye 
Meibomian gland dysfunction 
Retinal hemorrhage 
Aseptic conjunctivitis 
Lagophthalmos [inability to close eyelids completely] 
Corneal thinning 
Corneal melting 
Nasolacrimal obstruction 
Calcerous corneal degeneration 
Iritis 
Optic disc edema 
Cotton wool spots [fluffy white patches on retina] 
Cataract 
Ogawa, Y. Sjögren's Syndrome, Non-Sjögren's Syndrome, 
and Graft-Versus-Host Disease Related Dry Eye. Invest. 
Ophthalmol. Vis. Sci. 2018;59(14):DES71-DES79. 
“In most cases [of chronic ocular GvHD] severe dry eye 
progresses rapidly after the onset of symptoms and can 
lead to blindness. Despite improvements in the therapy 
for acute GVHD, specific therapies remain a substantial 
problem with little progress…Glaucoma, cataract, 
infection, and corneal perforation should be prevented as 
side effects that occur after topical or systemic 
corticosteroid administration for preventing or treating 
GVHD…The 2014 NIH diagnostic criteria stated ocular 
cGVHD as a new onset of dry eye in the post-transplant 
patient. Additional symptoms may include photophobia, 
periorbital hyperpigmentation, or blepharitis. 


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Reference 
Ocular Changes Chronic GvHD 
Examination by ophthalmologists is necessary for 
diagnostic confirmation of keratoconjunctivitis sicca, 
cicatricial conjunctivitis, or punctate keratopathy. 
Schirmer’s test was removed from the 2014 NIH 
diagnostic criteria.” 
Qiu Y et al. 
Manifestation of clinical categories of ocular graft-versus-
host disease.  J Ophthalmol. 2018 Aug 8;2018:6430953. 
Acute ocular GVHD predicts chronic ocular GVHD, is 
typified by acute conjunctivitis, increased mucus eye 
secretions, red eye, and lacrimation.  Chronic ocular 
GVHD signs beyond severe eye include corneal lesions 
such as filamentary keratitis, corneal ulcer, and corneal 
vascularization, pseudomembrane formation, corneal 
epithelium loss. 
Saboo US et al. 
Vision-Related Quality of Life in Patients with Ocular 
Graft-versus-Host Disease.  Ophthalmology. 2015 
Aug;122(8):1669-74. 
“Compared with healthy subjects, patients with ocular 
GVHD reported reduced scores on all NEI-VFQ-25 
subscales (each P < 0.001) with the exception of color 
vision (P = 0.11).”… “Patients with ocular GVHD 
experience measurable impairment of vision-related 
QOL.” 
Shikari H et al. 
Onset of ocular graft-versus-host disease symptoms after 
allogeneic hematopoietic stem cell transplantation.  
Cornea. 2015 Mar;34(3):243-7. 
Schirmer score can be “unreliable”.  Proposed reliance on 
incorporation of ophthalmological examination in BMT 
patients. 
Shikari H et al. 
Ocular graft-versus-host disease: a review.  Surv 
Ophthalmol. 2013 May-Jun;58(3):233-51. 
Offers grading in acute and chronic GVHD. 
 
“Cicatricial conjunctival changes (Table 1) and superior 
limbic keratoconjunctivitis are commonly seen in chronic 
ocular GVHD. There is associated palpebral and fornicial 
conjunctival symblepharon with consequent lid scarring 
and disturbed lid anatomy (ectropion, entropion, 
meibomian gland atrophy, and punctal stenosis)… 
Secondary epithelial changes such as punctate 
keratopathy develop with the formation of corneal 
filaments and painful erosions with resultant secondary 
infections, non-healing ulcerations, and corneal 
perforations.” 
“KCS has been observed in 69--77% of patients with 
chronic systemic GVHD and is an early sign of systemic 
involvement in extensive chronic GVHD.” 
Siebelmann S et al. 
“Potential complications include visual loss, pain and 
damage to the ocular structures with, e. g. corneal 


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Reference 
Ocular Changes Chronic GvHD 
[Non-Invasive Diagnosis of Ocular Graft-versus-Host 
Disease].  Klin Monbl Augenheilkd. 2015 May;232(5):652-
7. 
ulcerations….. Available tests are mostly evaluated for 
usage in dry eye diagnosis but are, however, mostly 
unspecific for diagnosing ocular GvHD reliably.” 
Sun YC et al. 
Impact of Ocular Chronic Graft-versus-Host Disease on 
Quality of Life.  Biol Blood Marrow Transplant. 2015 
Sep;21(9):1687-91. 
“Of the 284 chronic GVHD patients, 116 (41%) had ocular 
GVHD within 3 months of chronic GVHD diagnosis ("early 
ocular GVHD"). Late ocular GVHD (new onset > 3 months 
after chronic GVHD diagnosis) occurred in 64 patients. 
Overall cumulative incidence at 2 years was 57%.” 
Tung CI  
Graft versus host disease: what should the oculoplastic 
surgeon know?  Curr Opin Ophthalmol. 2017 Sep; 
28(5):499-504. 
 
“Ocular GVHD occurs as a common immune-mediated 
complication of hematopoietic stem cell transplantation 
that presents as a Stevens-Johnson-like syndrome in the 
acute phase or a Sjögren-like syndrome in the chronic 
phase.  Cicatricial conjunctivitis may be underreported in 
ocular GVHD. The spectrum of oculoplastic 
manifestations includes GVHD of the skin, cicatricial 
entropion, nasolacrimal duct obstruction, and lacrimal 
gland dysfunction. Surgical treatment is indicated for 
patients with significant corneal complications from 
entropion. Surgical approach to repair of nasolacrimal 
duct obstruction is presented in this review, including 
modified approaches for treating patients at risk for 
keratitis sicca.” 
Westeneng AC et al 
Ocular graft-versus-host disease after allogeneic stem cell 
transplantation.  Cornea. 2010 Jul;29(7):758-63. 
“Over time, ocular GvHD developed in 54% of patients 
and consisted mainly of dry eyes and conjunctivitis, which 
increased in severity during follow-up; blepharitis and 
uveitis were less often encountered….eye symptoms 
affecting activities of daily living were reported in 24 of 54 
patients (44%) and 16 of 54 patients (30%) experienced 
temporary loss of visual acuity of more than 2 Snellen 
lines, only 1 developed permanent unilateral loss 
(counting fingers) because of ischemic vasculopathy.” 
 
 
 
 


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APPENDICES 
 
 
 
 
 
 
 


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SCHEDULE OF VISITS AND ASSESSMENTS 
Visits 1-7 
 
2 Added as protocol deviation to original protocol v4. 
Blue = Conducted at DFCI 
 
Study Treatment Phase 
Placebo Cross-over Phase 
Black = Conducted at MEEI 
Visit 1 
(Screening) 
Visit 2 Baseline &  
First Drug Application 
Visit 3  
Visit 4 
Visit 5   
Visit 6 
Visit 7   
 
Day -14 to -1 
Day 1 
Day 1 
Day 14±2 
Day 42±3 
Day 70±3 
3 weeks 
6 weeks 
Procedure 
 
Pre-Dose 
30-60 min  
Post-Dose 
 
 
 
 
 
2-digit screening number 
X 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
Visual acuity (current correction) 
X 
 
 
 
 
X 
 
 
NIH Ocular GvHD Score 
X 
 
 
 
 
X 
 
X2 
Facial photo 
 
X 
 
 
 
X 
 
X 
Slit lamp biomicroscopy 
X 
 
 
X 
X 
X 
X 
X 
Undilated fundoscopy exam 
X 
 
 
 
 
X 
 
 
Corneal and conjunctival staining 
X 
 
 
X 
X 
X 
X 
X 
Intraocular pressure 
X 
 
 
 
 
X 
 
X 
Inclusion/Exclusion criteria 
X 
 
 
 
 
 
 
 
Medical/Ophthalmology history and updates 
X 
X 
 
X 
X 
X 
X 
X 
Prior and concomitant medication query 
X 
X 
 
X 
X 
X 
X 
X 
Concomitant medications (BMT) 
X 
 
 
 
X 
X 
 
X 
Medical history & physical (BMT) 
X 
 
 
 
 
 
 
 
Demographic data 
X 
 
 
 
 
 
 
 
Video of face & eyes (1 minute) 
 
X 
X 
X 
X 
X 
X 
X 
TearScan examination 
 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy test 
X 
 
 
 
 
X 
 
 
Modified SANDE questionnaire 
X 
 
 
X 
X 
X 
X 
X 
GLIA Ocular Surface Disease Symptoms 
Questionnaire 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse event query 
 
 
X 
X 
X 
X 
X 
X 
Screen Pass/Fail 
X 
 
 
 
 
 
 
 
3-digit random number 
X 
 
 
 
 
 
 
 
BMT systemic evaluation & GvHD assessment 
X 
 
 
 
X 
X 
 
X 
Standard GvHD, CBC, and metabolic labs 
X 
 
 
 
X 
X 
 
X 
Endocrine panel  
X 
 
 
 
X 
X 
 
X 
Daily diary and ocular medication log collected 
 
 
 
X 
X 
X 
X 
X 
Study drug collected/ accountability 
 
 
 
X 
X 
X 
X 
X 
Study drug application 
(in-clinic)  
 
X 
 
 
 
 
 
 
Study drug dispensed 
 
X 
 
X 
X 
X 
X 
 
Daily diary & ocular medication log dispensed  
 
 
X 
X 
X 
X 
X 
 


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SCHEDULE OF VISITS AND ASSESSMENTS 
Visits 8-9 Long Term Open Label 
 
 
 
 
 
 
 
 
Blue = Conducted at DFCI 
Visit 8 
Visit 9 
Black = Conducted at MEEI 
66 ± 6 weeks  
(15 months) 
117 ± 6 weeks  
(27 months) 
Procedure 
 
 
Informed consent for long term open phase 
X 
X 
Visual acuity (current correction) 
X 
X 
NIH Ocular GvHD Score 
X 
X 
Facial photo 
X 
X 
Slit lamp biomicroscopy 
X 
X 
Undilated fundoscopy exam 
X 
X 
Corneal and conjunctival staining 
X 
X 
Intraocular pressure 
X 
X 
Ophthalmology updates 
X 
X 
Concomitant medications (BMT) 
X 
X 
Video of face & eyes (1 minute) 
X 
X 
TearScan examination 
X 
X 
Urine pregnancy test 
X 
X 
Modified SANDE questionnaire 
X 
X 
GLIA Ocular Surface Disease Symptoms Questionnaire 
X 
X 
Adverse event query 
X 
X 
BMT systemic evaluation & GvHD assessment 
X 
X 
Standard GvHD, CBC, and metabolic labs 
X 
X 
Endocrine panel  
X 
X 


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Sponsor: GLIA LLC 
 
CONFIDENTIAL 
Page 29 of 43 
 
 
 
Initials: ______ Subject #:_______ Date: __________  Examiner: ________________ 
 
Symptom Assessment iN Dry Eye (SANDE) Questionnaire 
 
PLEASE COMPLETE THE FOLLOWING QUESTIONS REGARDING THE FREQUENCY AND SEVERITY 
OF YOUR DRY EYE SYMPTOMS. 
 
1. Frequency of symptoms: 
 
Please place an ‘X’ on the line to indicate how often, on average, your eyes feel dry and/or 
irritated: 
 
 
Left 
Rarely ________________________________________________ All the time 
 
 
 
Right Rarely ________________________________________________ All the time 
 
 
2. Severity of symptoms: 
 
Please place an ‘X’ on the line to indicate how severe, on average, you feel your symptoms of 
dryness and/or irritation: 
 
 
Left 
Very Mild ________________________________________________ Very Severe 
 
 
 
Right Very Mild ________________________________________________ Very Severe 
 
 


OCULAR GvHD PROTOCOL oGvHD, v5.1 
3/17/2020 
Pro-Ocular 1% Topical Gel 
 
Sponsor: GLIA LLC 
 
CONFIDENTIAL 
Page 30 of 43 
 
 
 
 
GLIA™ OCULAR SURFACE DISEASE SYMPTOMS QUESTIONNAIRE - CLINIC RECORD
Initials: _____   Subject #: ___________ Date: _____________  Examiner: __________________
Grade by placing X on the line from 'None' to 'Most severe'
None ____________________ Most
OD
OS
OD
OS
Ocular discomfort
None ____________________ Most
None ____________________ Most
None ____________________ Most
None ____________________ Most
Dryness
None ____________________ Most
None ____________________ Most
None ____________________ Most
None ____________________ Most
Grittiness
None ____________________ Most
None ____________________ Most
None ____________________ Most
None ____________________ Most
Burning
None ____________________ Most
None ____________________ Most
None ____________________ Most
None ____________________ Most
Stinging
None ____________________ Most
None ____________________ Most
None ____________________ Most
None ____________________ Most
Foreign body sensation
None ____________________ Most
None ____________________ Most
None ____________________ Most
None ____________________ Most
Ocular pain
None ____________________ Most
None ____________________ Most
None ____________________ Most
None ____________________ Most
Conjunctival redness
None ____________________ Most
None ____________________ Most
None ____________________ Most
None ____________________ Most
Additional notes below: (Details and other ocular symptoms)
Baseline          Time: ______________
Post-application 30-90 min   Time: _______________


OCULAR GvHD PROTOCOL oGvHD, v5.1 
3/17/2020 
Pro-Ocular 1% Topical Gel 
 
Sponsor: GLIA LLC 
 
CONFIDENTIAL 
Page 31 of 43 
 
 
 
GLIA™ OCULAR SURFACE DISEASE SYMPTOMS QUESTIONNAIRE - CLINIC RECORD
Initials: _____   Subject #: ___________ Date: _____________  Examiner: __________________
Grade by placing X on the line from 'None' to 'Most severe'
None ____________________ Most
OD
OS
OD
OS
Itching
None ____________________ Most
None ____________________ Most
None ____________________ Most
None ____________________ Most
Mucus discharge
None ____________________ Most
None ____________________ Most
None ____________________ Most
None ____________________ Most
Photophobia
None ____________________ Most
None ____________________ Most
None ____________________ Most
None ____________________ Most
Blurred or cloudy vision
None ____________________ Most
None ____________________ Most
None ____________________ Most
None ____________________ Most
Airflow sensitivity
None ____________________ Most
None ____________________ Most
None ____________________ Most
None ____________________ Most
Lid redness
None ____________________ Most
None ____________________ Most
None ____________________ Most
None ____________________ Most
Lid sticking
None ____________________ Most
None ____________________ Most
None ____________________ Most
None ____________________ Most
Additional notes below: (Details and other ocular symptoms)
Baseline          Time: ______________
Post-application 30-90 min   Time: _______________


OCULAR GvHD PROTOCOL oGvHD, v5.1 
3/17/2020 
Pro-Ocular 1% Topical Gel 
 
Sponsor: GLIA LLC 
 
CONFIDENTIAL 
Page 32 of 43 
 
 
Ocular GvHD Evaluations & Scoring in clinic 
Evaluation 
Method 
Scoring 
Pre-fluorescein stain 
 
 
Visual acuity  
Eye chart, OD and OS 
See below 
Slit lamp: 
Lids:  Lid margin erythema, 
edema, ulceration, notches, 
entropion/ ectropion, 
trichiasis/madarosis, floppy 
eyelids, hordeolum;  
Conjunctiva: Hyperemia, 
cicatricial changes, 
pseudomembranes, chalasis; 
Cornea: Edema, ulcers, 
filamentous keratitis, thinning, 
corneal neovascularization, 
scars, conjunctivial epithelium 
invasion, limbal thickening; 
Anterior chamber: Cells, flare; 
Lens opacity 
Visual or slit lamp 
 
     __________________________________ 
     None                                      Most severe 
 
     __________________________________ 
     None                                      Most severe 
Tear film evaluation + lid 
margin 
TearScan 
0,1, 2, 3 
After fluorescein stain 
 
 
Fluorescein staining 
Slit lamp 
     __________________________________ 
     None                                      Most severe  
     __________________________________ 
     None                                      Most severe 
 
Intraocular pressure 
Applanation tonemetry 
Reading in mm Hg 
 
NIH Ocular GvHD Score 
 
 
 
 
 


OCULAR GvHD PROTOCOL oGvHD, v5.1 
3/17/2020 
Pro-Ocular 1% Topical Gel 
 
Sponsor: GLIA LLC 
 
CONFIDENTIAL 
Page 33 of 43 
 
 
Tearscan™ Examinations 
The TearScan enables non-invasive viewing of the lipid film on the surface of the eye that does not 
require the use of fluorescein staining.  It provides a white light source that encircles the eye, to allow 
illumination of the ocular surface.  A video camera inserted in the center of the ring of light, and 
connected to a computer, allows viewing and video recording of the tear film 
 During the examination, a one-minute video that includes 3 natural blinks should be recorded. 
The grading will be from 0 to 3: 
 
0 = no discernible tear film 
 
1 = thin tear film 
 
2 = moderate tear film 
 
3 = copious tear film 
 
 
Initials: ______ Subject #:_______ Date: __________  Examiner: ________________ 
 
 
OD (right eye) Score: ______________ 
 
OS (left eye) Score: ________________ 
 
Red eye lid:  Yes______ 
No_________ 
 
 
Visual Acuity 
Distance and near Snellen acuity in current glasses if wearing, (or no glasses if not wearing), then 
pinhole.  
OD (right eye) ______________ 
 
OS (left eye) ________________ 
 
 


OCULAR GvHD PROTOCOL oGvHD, v5.1 
3/17/2020 
Pro-Ocular 1% Topical Gel 
 
Sponsor: GLIA LLC 
 
CONFIDENTIAL 
Page 34 of 43 
 
 
SLIT LAMP BIOMICROSCOPY WITHOUT STAINING – OCULAR GvHD 
 
Initials: ______ Subject #:_______ Date: __________  Examiner: ________________ 
Indicate a Grade by placing X on the line for all POSITIVE FINDINGS: 
If finding present, Check NCS or CS  (NCS = Non Clinically Significant 
CS  = Clinically Significant) 
Lids 
□ No positive findings 
 
OD 
 
OS 
Erythema 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Edema 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Lid margin ulceration 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Lid margin notches 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Entropion/Ectropion 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Trichiasis/Madarosis 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Floppy eyelids 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Hordeolum (stye) 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Other pathology, specify: 
  
□CS   □NCS;   
□CS  □NCS;   
□CS  □NCS 
Conjunctiva 
□ No positive findings 
OD 
 
OS 
Hyperemia 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Cicatricial changes 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Pseudomembranes 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Chalasis 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Other pathology, specify: 
  
□CS   □NCS;   
□CS  □NCS;   
□CS  □NCS 
Cornea 
□ No positive findings 
OD 
OS 
Edema 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Corneal ulcers 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Filamentous keratitis 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 


OCULAR GvHD PROTOCOL oGvHD, v5.1 
3/17/2020 
Pro-Ocular 1% Topical Gel 
 
Sponsor: GLIA LLC 
 
CONFIDENTIAL 
Page 35 of 43 
 
 
Indicate a Grade by placing X on the line for all POSITIVE FINDINGS: 
If finding present, Check NCS or CS  (NCS = Non Clinically Significant 
CS  = Clinically Significant) 
Corneal thinning 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Corneal 
neovascularization 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Scars 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Conjunctival epithelium 
invasion 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Limbal thickening 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Other pathology, specify: 
  
□CS   □NCS;   
□CS  □NCS;   
□CS  □NCS 
Anterior Chamber 
□ No positive findings 
 
OD 
 
OS 
Cells 
    __________________________________ 
    None                                      Most severe □CS  □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Flare 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
Other pathology, specify: 
  
□CS   □NCS;   
□CS  □NCS;   
□CS  □NCS 
Lens Status 
OD 
OS 
□Phakic 
□Pseudophakic 
□Aphakic 
□Phakic 
□Pseudophakic 
□Aphakic 
Lens Opacity 
(Phakic Eye ONLY) 
□ No positive findings 
OD 
OS 
□0□+1□+2 □+3 
□CS   □NCS □0□+1□+2 □+3 
□CS   □NCS 
Comments: 
 
 
 
 
 


OCULAR GvHD PROTOCOL oGvHD, v5.1 
3/17/2020 
Pro-Ocular 1% Topical Gel 
 
Sponsor: GLIA LLC 
 
CONFIDENTIAL 
Page 36 of 43 
 
 
FLUORESCEIN STAINING 
Initials: ______ Subject #:_______ Date: __________  Examiner: ________________ 
 
Sodium Fluorescein strips (thin tipped, DET™ strips preferred) should be moistened with one or two drops of 
sterile irrigating or saline solution.   Apply moistened tip to conjunctiva or fornix.  The subject should blink 
several times after application and wait for 2 minutes before examination. 
 
Indicate a Grade by placing X on the line for all POSITIVE FINDINGS: 
If finding present, Check NCS or CS  (NCS = Non Clinically Significant 
CS  = Clinically Significant) 
Cornea ( C) 
□ No positive findings 
 
OD 
 
OS 
Inferior 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe 
□CS   □NCS 
Superior 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe 
□CS   □NCS 
Central 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe 
□CS   □NCS 
Other pathology, specify: 
  
□CS   □NCS;   
□CS  □NCS;   
□CS  □NCS 
Conjunctiva 
□ No positive findings 
 
OD 
 
OS 
Inferior  
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe 
□CS   □NCS 
Superior 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe 
□CS   □NCS 
Temporal 
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe 
□CS   □NCS 
Nasal  
    __________________________________ 
    None                                      Most severe □CS   □NCS 
    __________________________________ 
    None                                      Most severe 
□CS   □NCS 
Other pathology, specify: 
  
□CS   □NCS;   
□CS  □NCS;   
□CS  □NCS 
 
 
 
 
 
 
        
             
 
 
 
 
Superior 
Superior 
Inferior 
Inferior
Central
Central
Nasal 
Temporal 
Temporal 
Nasal 
Superior 
Superior 
Inferior 
Inferior 


OCULAR GvHD PROTOCOL oGvHD, v5.1 
3/17/2020 
Pro-Ocular 1% Topical Gel 
 
Sponsor: GLIA LLC 
 
CONFIDENTIAL 
Page 37 of 43 
 
 
 
UNDILATED FUNDOSCOPY – OCULAR GvHD 
(To be performed only at Screening and Last Visit) 
 
 
Initials: ______ Subject #:_______ Date: __________  Examiner: ________________ 
 
Check Normal or Abnormal 
(If Abnormal, check CS or 
NCS)* 
OD 
OS 
Normal 
Abnormal 
Abnormal 
comments 
Normal 
Abnormal 
Abnormal 
comments 
NCS 
CS 
NCS 
CS 
Vitreous 
□ 
□ 
□ 
□ 
□ 
□ 
Optic nerve  
□ 
□ 
□ 
□ 
□ 
□ 
Macula 
□ 
□ 
□ 
□ 
□ 
□ 
Vessels 
□ 
□ 
□ 
□ 
□ 
□ 
Cup to disc ratio  
 
 
 
 
 
 
URINE PREGNANCY TEST FOR WOMEN OF CHILDBEARING AGE 
 
Urine Test Strip:   HCG One Step Pregnancy Test or similar. 
 
Urine Collection:   A nurse will dispense a urine collection cup for urine collection. 
 
Test Procedure:   Follow directions, but usually the test strip is dipped into the urine for 3 
seconds, and laid flat for reading within 5 minutes. 
 
 
Initials: ______ Subject #:_______ Date: __________  Examiner: ________________ 
 
 


OCULAR GvHD PROTOCOL oGvHD, v5.1 
3/17/2020 
Pro-Ocular 1% Topical Gel 
 
Sponsor: GLIA LLC 
 
CONFIDENTIAL 
Page 38 of 43 
 
 
CBC and DIFFERENTIAL 
Normal Range 
WBC 
3.81 - 8.94 K/uL 
RBC 
4.35 - 5.61 M/uL 
HGB 
12.5 - 16.3 g/dL 
HCT 
37.1 - 49.5 % 
PLT 
152 - 440 K/uL 
MCV 
79.0 - 97.0 fL 
MCH 
26.2 - 32.0 pg 
MCHC 
33.3 - 35.7 g/dL 
RDW 
12.1 - 16.0 % 
MPV 
7.0 - 10.8 fl 
NRBC 
0.00 /100 WBCs 
ABSOLUTE NRBC 
K/uL 
NEUTS 
46.5 - 82.4 % 
EOSINOPHIL 
0.1 - 6.0 % 
BASOPHIL 
0.1 - 1.1 % 
LYMPHS 
8.5 - 32.7 % 
MONOS 
5.4 - 14.2 % 
ABSOLUTE NEUTS 
2.23 - 6.11 K/uL 
ABSOLUTE EOS 
0.00 - 0.52 K/uL 
ABSOLUTE BASO 
0.00 - 0.11 K/uL 
ABSOLUTE LYMPHS 
0.21 - 2.74 K/uL 
ABSOLUTE MONOS 
0.2 - 0.87 K/uL 
 
COMPREHENSIVE METABOLIC PANEL 
Normal Range 
SODIUM 
135 - 145 mmol/L 
POTASSIUM 
3.5 - 5.0 mmol/L 
CHLORIDE 
98 - 108 mmol/L 
CO2 
23 - 32 mmol/L 
BUN 
9 - 25 mg/dL 
CREATININE 
0.7 - 1.3 mg/dL 
GLUCOSE 
70 - 100 mg/dL 
ALBUMIN 
3.7 - 5.4 g/dL 
TOTAL PROTEIN 
6.0 - 8.0 g/dL 
CALCIUM 
8.8 - 10.5 mg/dL 
ALKALINE PHOSPHATASE 
36 - 118 U/L 
TOTAL BILIRUBIN 
0.2 - 1.2 mg/dL 
AST 
9 - 30 U/L 
ALT 
7 - 52 U/L 
GLOBULIN 
2.3 - 4.2 g/dL 
EGFR 
>59 mL/min/1.73m2 
ANION GAP 
5 - 17 mmol/L 
 
 
 


OCULAR GvHD PROTOCOL oGvHD, v5.1 
3/17/2020 
Pro-Ocular 1% Topical Gel 
 
Sponsor: GLIA LLC 
 
CONFIDENTIAL 
Page 39 of 43 
 
 
OTHER STANDARD GvHD 
Normal Range 
TACROLIMUS 
3.0 - 15.0 ng/mL 
VITAMIN D Total, 25-OH (D2 and D3) 
Sunquest Lab, OHDT 
20-80 ng/mL 
 
T4 (thyroxine), Total, Serum 
11 -19 years: 5.9-13.2 µg/dL  
Adult (> or =20 years): 4.5-11.7 µg/dL 
T4 (thyroxine), Free, Serum 
11-19 years: 1.0-1.6 ng/dL 
Adult (> or =20 years): 0.9-1.7 ng/dL 
T3 (triodothyronine), Total, Serum 
11-19 years: 91-218 ng/dL 
Adult (> or =20 years): 80-200 ng/dL 
ACTH (adrenocorticotropic hormone), Plasma 
7.2-63 pg/mL (a.m. draws) 
TSH (thyroid stimulating hormone), Serum 
0.27 - 4.20   µIU/mL 
 
ENDOCRINE PANEL 
Normal Range 
DHEA-S (dehydroepiandrosterone sulfate), 
Serum 
18-30 years: 105-728 µg/dL  
31-40 years: 57-522 µg/dL 
41-50 years: 34-395 µg/dL 
51-60 years: 20-299 µg/dL 
61-70 years: 12-227 µg/dL 
> or =71 years: 6.6-162 µg/dL 
ESTRADIOL, Serum 
Follicular Phase 27-156 pg/mL 
Mid Cycle Peak 48-314 pg/mL 
Luteal Phase 33-298 pg/mL 
Postmenopausal <50 pg/mL 
FSH (follicle stimulating hormone), Serum 
Male 1.6-8.0 mIU/mL 
Female 
Follicular Phase 2.5-10.2 mIU/mL 
Mid-Cycle Peak 3.1-17.7 mIU/mL 
Luteal Phase 1.5- 9.1 mIU/mL 
Postmenopausal 23.0-116.3 mIU/mL 
LH (luteinizing hormone), Serum 
Male 
18-59 Years 1.5-9.3 mIU/mL 
≥60 Years 1.6-15.2 mIU/mL 
Female 
Follicular Phase 1.9-12.5 mIU/mL 
Mid-Cycle Peak 8.7-76.3 mIU/mL 
Luteal Phase 0.5-16.9 mIU/mL 
Postmenopausal 10.0-54.7 mIU/mL 
PTH (Parathyroid Hormone), Serum 
15-65 pg/mL 
PROGESTERONE, Serum 
MALES > or =18 year: <0.20 ng/mL 
FEMALES > or =18 years: 
-Follicular phase: < or =0.89 ng/mL 
-Ovulation: < or =12 ng/mL 
-Luteal phase: 1.8-24 ng/mL 
-Post-menopausal: < or =0.20 ng/mL 
-Pregnancy 
- 1st trimester: 11-44 ng/mL 
- 2nd trimester: 25-83 ng/mL 


OCULAR GvHD PROTOCOL oGvHD, v5.1 
3/17/2020 
Pro-Ocular 1% Topical Gel 
 
Sponsor: GLIA LLC 
 
CONFIDENTIAL 
Page 40 of 43 
 
 
ENDOCRINE PANEL 
Normal Range 
- 3rd trimester: 58-214 ng/mL 
TESTOSTERONE, Total and Free, Serum 
Mayo Clinic test code TGRP 
TESTOSTERONE, FREE 
Males (adult): 
20-<25 years: 5.25-20.7 ng/dL 
25-<30 years: 5.05-19.8 ng/dL 
30-<35 years: 4.85-19.0 ng/dL 
35-<40 years: 4.65-18.1 ng/dL 
40-<45 years: 4.46-17.1 ng/dL 
45-<50 years: 4.26-16.4 ng/dL 
50-<55 years: 4.06-15.6 ng/dL 
55-<60 years: 3.87-14.7 ng/dL 
60-<65 years: 3.67-13.9 ng/dL 
65-<70 years: 3.47-13.0 ng/dL 
70-<75 years: 3.28-12.2 ng/dL 
75-<80 years: 3.08-11.3 ng/dL 
80-<85 years: 2.88-10.5 ng/dL 
85-<90 years: 2.69-9.61 ng/dL 
90-<95 years: 2.49-8.76 ng/dL 
95-100+ years: 2.29-7.91 ng/dL 
Females (adult): 
20-<25 years: 0.06-1.08 ng/dL 
25-<30 years: 0.06-1.06 ng/dL 
30-<35 years: 0.06-1.03 ng/dL 
35-<40 years: 0.06-1.00 ng/dL 
40-<45 years: 0.06-0.98 ng/dL 
45-<50 years: 0.06-0.95 ng/dL 
50-<55 years: 0.06-0.92 ng/dL 
55-<60 years: 0.06-0.90 ng/dL 
60-<65 years: 0.06-0.87 ng/dL 
65-<70 years: 0.06-0.84 ng/dL 
70-<75 years: 0.06-0.82 ng/dL 
75-<80 years: 0.06-0.79 ng/dL 
80-<85 years: 0.06-0.76 ng/dL 
85-<90 years: 0.06-0.73 ng/dL 
90-<95 years: 0.06-0.71 ng/dL 
95-100+ years: 0.06-0.68 ng/dL 
TESTOSTERONE, TOTAL 
Males 
17-18 years: 300-1,200 ng/dL 
> or =19 years: 240-950 ng/dL 
Females 
17-18 years: 20-75 ng/dL 
> or =19 years: 8-60 ng/dL 


OCULAR GvHD PROTOCOL oGvHD, v5.1 
3/17/2020 
Pro-Ocular 1% Topical Gel 
 
Sponsor: GLIA LLC 
 
CONFIDENTIAL 
Page 41 of 43 
 
 
Initials: ______ Subject #:_______  
 
Home Record of Actual Ocular Medication and Artificial Tear Use 
(Record date and number of times used per day and night) 
 GV-1 
Ocular Med 1 
Ocular Med 2 
Artificial 
Tears & Gels 
Artificial 
Tears & Gels 
Ocular Med 4 
Ocular Med 5 
Ocular Med 6 
  
 
 
Use only when 
necessary 
 
 
 
 
Name of 
medication  
 
 
 
 
 
 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


OCULAR GvHD PROTOCOL oGvHD, v5.1 
3/17/2020 
Pro-Ocular 1% Topical Gel 
 
Sponsor: GLIA LLC 
 
CONFIDENTIAL 
Page 42 of 43 
 
 
 
 
GLIA OCULAR SURFACE DISEASE SYMPTOMS QUESTIONNAIRE - DIARY
DATE: ________________DAY OF WEEK: ____________
Initials: _____   Subject #: ___________   Reviewed by / date: _____________________   
Grade by placing X on the line from 'None' to 'Most severe'
None ____________________ Most
OD
OS
Ocular discomfort
None ____________________ Most
None ____________________ Most
Dryness
None ____________________ Most
None ____________________ Most
Grittiness
None ____________________ Most
None ____________________ Most
Burning
None ____________________ Most
None ____________________ Most
Stinging
None ____________________ Most
None ____________________ Most
Foreign body sensation
None ____________________ Most
None ____________________ Most
Ocular pain
None ____________________ Most
None ____________________ Most
Conjunctival redness
None ____________________ Most
None ____________________ Most
Itching
None ____________________ Most
None ____________________ Most
Mucus discharge
None ____________________ Most
None ____________________ Most
Photophobia
None ____________________ Most
None ____________________ Most
Blurred or cloudy vision
None ____________________ Most
None ____________________ Most
Airflow sensitivity
None ____________________ Most
None ____________________ Most
Lid redness
None ____________________ Most
None ____________________ Most
Lid sticking
None ____________________ Most
None ____________________ Most
Additional notes below: (Details and other ocular symptoms)
Baseline          Time: ______________


OCULAR GvHD PROTOCOL oGvHD, v5.1 
3/17/2020 
Pro-Ocular 1% Topical Gel 
 
Sponsor: GLIA LLC 
 
CONFIDENTIAL 
Page 43 of 43 
 
 
Initials: ______ Subject #:_______  
ADVERSE EVENT LOG 
 
Visit 
Number 
Report date 
(mm/dd/yyyy) 
Adverse event 
Relationship 
to study 
drug(1, 2, or 3) 
Adverse event 
onset date 
(mm/dd/yyyy) 
Adverse event 
end date 
(mm/dd/yyyy) 
Severity 
(1, 2,or 3) 
Action taken 
with study 
drug(1-, 2, 3, 
or 4) 
Specify, if 
action taken 
with study 
drug=”4. Other” 
Outcome 
(1, 2,or 3) 
Serious 
adverse 
event 
(Yes/No) 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
  
  
  
  
  
  
  
  
Enter numerical responses for following Questionnaire categories 
Relationship to study drug: 
Severity: 
Action taken with study drug: 
Outcome: 
 
1. None 
1. Mild 
1. None 
1. Resolved 
 
2. Possibly related 
2. Moderate 
2. Permanently Discontinued* 
2. Ongoing 
 
3. Probably related 
3. Severe 
3. Temporarily Discontinued 
3. Lost to follow-up 
 
 
 
4. Other(specify) 
 
 
* Complete study discontinuation form 
 

SAP_001.pdf: 
ClinicalTrials.gov ID NCT03990051 
 
 
Treatment Safety and Efficacy of Pro-ocular™ 1% for Chronic 
Ocular Graft Following Allogeneic HSCT 
 
 
Sponsor:  Glia, LLC 
 
 
Statistical Analytical Plan 
September 18, 2019 


STATISTICAL ANALYSIS PLAN 
Treatment safety and efficacy using Pro-ocular™ 1% for chronic ocular 
graft-versus-host disease (GvHD) following allogeneic hematopoietic 
stem cell transplantation. 
Sponsor:  
Glia, LLC 
Protocol Number: 
oGvHD-1 
Author:  
Sara Ziebell 
Associate Biostatistician 
Statistics & Data Corporation 
Date:  
18Sep2019 
Version: 
1.0 


18 Sep 2019
18 Sep 2019


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Table of Contents 
1. 
Introduction............................................................................................................................... 6 
2. 
Study Objectives ...................................................................................................................... 6 
2.1 Study Variables ........................................................................................................................ 6 
2.2 Efficacy Variables ..................................................................................................................... 6 
2.3 Safety Variables ....................................................................................................................... 7 
2.4 Other Variables ........................................................................................................................ 7 
2.5 Statistical Hypotheses .............................................................................................................. 7 
3. 
Study Design and Procedures ................................................................................................. 8 
3.1 General Study Design .............................................................................................................. 8 
3.2 Schedule of Visits and Assessments ....................................................................................... 9 
4. 
Study Treatments ................................................................................................................... 10 
4.1 Method of Assigning Subjects to Treatment Groups ............................................................. 10 
4.2 Masking and Unmasking ........................................................................................................ 11 
5. 
Sample Size and Power Considerations ................................................................................ 11 
6. 
Data Preparation .................................................................................................................... 11 
7. 
Analysis Populations .............................................................................................................. 12 
7.1 Modified Intent-to-Treat .......................................................................................................... 12 
7.2 Per Protocol............................................................................................................................ 12 
7.3 Safety ..................................................................................................................................... 12 
8. 
General Statistical Considerations ......................................................................................... 12 
8.1 Unit of Analysis....................................................................................................................... 12 
8.2 Missing or Inconclusive Data Handling .................................................................................. 13 
8.3 Definition of Baseline ............................................................................................................. 13 
8.4 Data Analysis Conventions .................................................................................................... 13 
8.5 Adjustments for Multiplicity ..................................................................................................... 14 
8.6 Visual Analog Scale Standardization ..................................................................................... 14 
9. 
Disposition of Subjects ........................................................................................................... 14 
10. 
Demographic Variables and Iris Color ................................................................................... 15 
11. 
Medical History and Concomitant Medications or Devices .................................................... 15 
11.1 Medical History ....................................................................................................................... 15 
11.2 Prior and Concomitant Medications or Devices ..................................................................... 15 
12. 
Treatment Exposure ............................................................................................................... 16 
13. 
Efficacy Analyses ................................................................................................................... 17 
13.1 GLIA Ocular Surface Disease Symptoms Questionnaire, Clinic & Daily Diary ..................... 17 
13.1.1 
ANALYSIS OF GLIA OCULAR SURFACE DISEASE SYMPTOMS QUESTIONNAIRE COLLECTED IN 
CLINIC 
18 


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13.1.2 
Analysis of GLIA Ocular Surface Disease Symptoms Questionnaire Collected in Daily Diary
 
19 
13.2 Modified SANDE – Symptom Assessment iN Dry Eye Questionnaire .................................. 19 
13.2.1 
Analysis of SANDE Questionnaire ............................................................................. 20 
13.3 Daily use of eye drops ............................................................................................................ 20 
13.4 National Institutes of Health (NIH) Eye Score ........................................................................ 21 
13.5 Chronic ocular GvHD Signs ................................................................................................... 21 
13.5.1 
TearScan Examination ............................................................................................... 22 
13.5.2 
Visual Acuity ............................................................................................................... 22 
13.5.3 
Slit Lamp without Staining .......................................................................................... 23 
13.5.4 
Corneal and Conjunctival Fluorescein Staining ......................................................... 24 
13.5.5 
Facial Presentation and Blinks per Minute ................................................................. 25 
14. 
Safety Analyses ..................................................................................................................... 25 
14.1 Adverse Events ...................................................................................................................... 25 
14.2 Visual Acuity ........................................................................................................................... 26 
14.3 Slit-Lamp Biomicroscopy Examination ................................................................................... 26 
14.4 Undilated Fundoscopy Examination ...................................................................................... 27 
14.5 Intraocular Pressure (IOP) ..................................................................................................... 27 
14.6 Clinical Laboratory Data ......................................................................................................... 27 
15. 
Interim Analyses ..................................................................................................................... 31 
16. 
Changes from Protocol-Stated Analyses ............................................................................... 31 
17. 
References ............................................................................................................................. 31 
18. 
Revision History ..................................................................................................................... 31 
19. 
Tables, Listings and Figures .................................................................................................. 31 
 
 
 


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List of Abbreviations 
AE 
Adverse Event 
ADL 
Activities of Daily Life 
ANOVA 
Analysis of Variance 
ATC 
Anatomical Therapeutic Chemical 
BCVA 
Best-corrected Visual Acuity 
BMT 
Bone marrow transplant 
CBC 
Complete Blood Count 
CI 
Confidence Interval 
CRF 
Case Report Form 
CS 
Clinically Significant 
CSR 
Clinical Study Report 
DFCI 
Dana-Farber Cancer Institute 
GvHD 
Graft-versus-host disease 
ICH 
International Conference on Harmonisation 
IOP 
Intraocular Pressure 
ITT 
Intent-to-Treat 
KCS 
Keratoconjunctivitis Sicca 
LOCF 
Last Observation Carried Forward 
logMAR 
Logarithm of the Minimum Angle of Resolution 
LS 
Least Squares 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCS 
Not Clinically Significant 
NIH 
National Institutes of Health 
PDF 
Portable document format 
PP 
Per Protocol 
PT 
Preferred Term 
RTF 
Rich Text Format 
SAE 
Serious Adverse Event 
SANDE 
Symptom Assessment iN Dry Eye 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SDC 
Statistics & Data Corporation 
SOC 
System Organ Class 
TEAE 
Treatment-Emergent Adverse Event 
VA 
Visual Acuity 
VAS 
Visual Analog Scale 
VCMA 
Video Capture Manual Analysis 
WHO DDE 
World Health Organization Drug Dictionary Enhanced 
 
 


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1. Introduction 
The purpose of this statistical analysis plan (SAP) is to describe the planned analyses and reporting for 
protocol oGvHD-1, version 4.0 dated 07APR2019. 
This SAP is being written with due consideration of the recommendations outlined in the most recent 
International Conference on Harmonisation (ICH) E9 Guideline entitled Guidance for Industry: Statistical 
Principles for Clinical Trials and the most recent ICH E3 Guideline, entitled Guidance for Industry: Structure 
and Content of Clinical Study Reports. 
This SAP describes the data that will be analyzed and the subject characteristics, efficacy, and safety 
assessments that will be evaluated. This SAP provides details of the specific statistical methods that will 
be used. The statistical analysis methods presented in this document will supersede the statistical analysis 
methods described in the clinical protocol. If additional analyses are required to supplement the planned 
analyses described in this SAP, they may be completed and will be identified in the clinical study report. 
The planned analyses include:  
1. The Primary analysis of the Study Treatment Phase will occur after all subjects have completed or 
discontinued through Visit 5. 
2. The final/secondary analysis of the Cross-over Phase will occur after all subjects who enter the Cross-
over Phase have completed or discontinued through Visit 7.  
This SAP will be finalized and signed prior to the database lock for the primary analysis. 
2. Study Objectives 
The primary objective of this study is to evaluate the safety and efficacy of Pro-ocular™ 1% topical gel 
administered twice daily for 70 days in ameliorating symptoms and signs of chronic ocular graft-versus-host 
disease (GvHD).  
2.1 
Study Variables 
2.2 
Efficacy Variables 
The key efficacy variables include the following: 
• 
GLIA Ocular Surface Disease Questionnaire taken at the clinic 
• 
Modified Symptom Assessment iN Dry Eye Questionnaire (SANDE) taken at the clinic 
Additional efficacy variables include the following: 
• 
Chronic Ocular GvHD Signs including the following: 
o 
TearScan Examination 
o 
Visual acuity with current correction 
o 
Slit lamp biomicroscopy without staining:  


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 
Lid Edema, Lid Erythema, Lid Margin Ulceration and Conjunctival Hyperemia are of 
interest however all ocular regions will be analyzed similarly 
o 
Corneal and conjunctival fluorescein staining 
o 
Facial Presentation and Blinks per Minute 
• 
Daily diary GLIA Ocular Surface Disease Questionnaire 
• 
Daily use of eye drops 
• 
National Institutes of Health (NIH) Eye Score  
 
2.3 
Safety Variables 
The safety variables include the following: 
• 
Incidence and severity of Adverse events (AE) 
• 
Visual acuity 
• 
Slit lamp biomicroscopy 
• 
Undilated fundoscopy examination 
• 
Intraocular pressure (IOP) 
• 
Systemic assessment by bone marrow transplant (BMT) physician at Dana- Farber Cancer 
Institute (DFCI) 
2.4 
Other Variables 
Other variables include laboratory tests for: 
• 
Complete Blood Count (CBC) with differential 
• 
Metabolic panel 
• 
Other Standard GvHD 
• 
Endocrine panel for the assessment of hypothalamic-pituitary-adrenal axis (HPA) function and for 
Progesterone to detect whether applied drug product is detected in the blood 
2.5 
Statistical Hypotheses 
The null and alternative hypotheses, based on the primary variables, are as follows: 
H01: There is no difference between Pro-ocular™ 1% topical gel and placebo in the change from baseline 
in ocular symptom scores based on the GLIA Ocular Surface Disease Questionnaire when comparing the 
worse eye for each symptom. 
Ha1: The change from baseline in ocular symptom scores based on the GLIA Ocular Surface Disease 
Questionnaire is larger with Pro-ocular™ 1% topical gel than with placebo when comparing the worse eye 
for each symptom. 


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H02: There is no difference between Pro-ocular™ 1% topical gel and placebo in the change from baseline 
in ocular symptom scores based on the modified SANDE Questionnaire when comparing the worse eye for 
each symptom. 
Ha2: The change from baseline in ocular symptom scores based on the modified SANDE Questionnaire is 
larger with Pro-ocular™ 1% topical gel than with placebo when comparing the worse eye for each symptom. 
3. Study Design and Procedures 
3.1 
General Study Design 
This is a Phase 2 randomized, single-center, parallel, double-masked, placebo-controlled study assessing 
the safety and efficacy and the of Pro-ocular™ 1% topical gel administered twice daily for 70 days in 
ameliorating symptoms and signs of chronic ocular GvHD. 
Thirty-three subjects will be enrolled and randomly assigned in a 2:1 ratio to one of two treatments arms: 
• 
Pro-ocular™ 1% topical gel (22 subjects) 
• 
Placebo (11 subjects) 
After a Screening visit to assess eligibility, subjects will enter a double-masked 70-day Study Treatment 
Phase (Visit 2 – Visit 5). Upon completion of the double-masked phase, subjects who were originally 
randomized to Placebo will cross-over into an open-label Placebo Cross-over Phase and will receive 
Pro-ocular 1% topical gel for twice-daily administration over 6 weeks (Visit 5 – Visit 7). 
Analyses will be conducted separately for the Study Treatment Phase and the Placebo Cross-over Phase. 
The analysis of the Study Treatment Phase is the Primary analysis, and the analysis of the Placebo Cross-
over Phase is secondary. 
Study visits will be referred to in all tables and listings as the expected study day corresponding to the visit 
to enable reviewers to understand the assessment timing without referring to the protocol visit schedule. 
Listings, tables and figures will include visits and study days in the following format: Visit 1 (Day -14), Visit 
2 (Day 1), Pre-Dose,  Visit 2 (Day 1), Post-Dose, Visit 3 (Day 14), Visit 4 (Day 42), Visit 5 (Day 70), Visit 6 
(Week 3) and Visit 7 (Week 6). 
Table 1 shows the scheduled study visits, their planned study day, and the acceptable visit window for each 
study visit. 
Table 1. Study Visit Windows 
Study Phase 
Scheduled 
Visit 
Planned Study Day 
Visit Window 
Study Treatment Phase 
(Double-masked) 
Visit 1 
Screening/ Day -14 
Day -14 to -1 
Visit 2 
Baseline/ Day 1, Pre-Dose 
N/A 
Visit 2 
Day 1, Post Dose 
N/A 


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Study Phase 
Scheduled 
Visit 
Planned Study Day 
Visit Window 
Visit 3 
Week 2/ Day 14 
± 2 Day 
Visit 4 
Week 6/ Day 42 
± 3 Day 
Visit 5 
Week 10/ Day 70 
± 3 Day 
Placebo Cross-over Phase for 
Subjects on Placebo (Open Label) 
Visit 6 
Week 13 or Week 3 after 
active treatment / Day 91 
N/A 
Visit 7 
Week 16 or Week 6 after 
active treatment/ Day 112 
N/A 
3.2 
Schedule of Visits and Assessments 
The schedule of visits and assessments is provided in Table 2. 
Table 2. Schedule of Visits and Assessments 
Blue = Conducted at DFCI 
Study Treatment Phase 
Placebo Cross-over Phase 
Black = Conducted at MEEI 
Visit 1 
(Screening) 
Visit 2 Baseline & 
First Drug Application 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Day -14 to -1 
Day 1 
Day 1 
Day 14±2 
Day 42±3 
Day 70±3 
3 weeks 
6 weeks 
Procedure 
Pre-Dose 
30-60 min 
Post-Dose 
2-digit screening number 
X 
Informed consent 
X 
Visual acuity (current correction) 
X 
X 
NIH Eye Score 
X 
X 
X 
Facial photo 
X 
X 
X 
Slit Lamp Biomicroscopy 
X 
X 
X 
X 
X 
X 
Undilated Fundoscopy Exam 
X 
X 
Corneal and Conjunctival Staining 
X 
X 
X 
X 
X 
X 
Intraocular Pressure 
X 
X 
X 
Inclusion/Exclusion Criteria 
X 
Medical/Ophthalmology history and updates 
X 
X 
X 
X 
X 
X 
X 
Prior and concomitant medication query 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications (BMT) 
X 
X 
X 
X 
Medical History & Physical (BMT) 
X 
Demographic data 
X 
Video of face & eyes (1 minute) 
X 
X 
X 
X 
X 
X 
X 
TearScan Examination 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy test 
X 
X 
Modified SANDE Questionnaire 
X 
X 
X 
X 
X 
X 
GLIA Ocular Surface Disease Symptoms 
Questionnaire 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Event Query 
X 
X 
X 
X 
X 
X 


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Blue = Conducted at DFCI 
Study Treatment Phase 
Placebo Cross-over Phase 
Black = Conducted at MEEI 
Visit 1 
(Screening) 
Visit 2 Baseline & 
First Drug Application 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Day -14 to -1 
Day 1 
Day 1 
Day 14±2 
Day 42±3 
Day 70±3 
3 weeks 
6 weeks 
Screen Pass/Fail 
X 
3-digit random number 
X 
BMT systemic evaluation & GvHD assessment 
X 
X 
X 
X 
Standard GvHD, CBC, and metabolic labs 
X 
X 
X 
X 
Endocrine panel 
X 
X 
X 
X 
Daily diary collected 
X 
X 
X 
X 
X 
Study drug collected/ accountability 
X 
X 
X 
X 
X 
Study drug application 
(in-clinic) 
X 
Study Drug Dispensed 
X 
X 
X 
X 
X 
Daily Diary Dispensed 
X 
X 
X 
X 
X 
Abbreviations: CBC = Complete Blood Count, DFCI = Dana-Farber Cancer Institute, GvHD = graft-versus-host disease, MEEI = Massachusetts Eye and Ear Infirmary. 
 
4. Study Treatments 
The study treatment is approximately 0.07g Pro-ocular™ 1% topical gel applied and massaged into the 
forehead skin twice daily, morning and before bedtime. 
All tables, listings, and figures will refer to the treatments as Pro-ocular and Placebo. 
4.1 
Method of Assigning Subjects to Treatment Groups 
At Visit 1 (Screening), subjects who provide verbal and written informed consent will be assigned a 2-digit 
Screening number (beginning with 01). Subjects who meet all eligibility criteria will be randomized in a 2:1 
assignment ratio to either Pro-ocular™ 1% topical gel or Placebo.  
An independent statistician who is not otherwise involved in the trial will generate the complete 
randomization schedule. The statistician will scramble a list of 3-digit numbers from 201 to 290 using a 
random number generation scheme so that the random number assignment will not be sequential. The 
statistician will devise a randomization scheme to provide a 2:1 ratio in a block design of active 
drug:placebo. The 3-digit randomization number will be assigned in the sequence provided by the 
randomization statistician. If a randomized subject is discontinued from the study for any reason, their 
randomization number will not be reassigned. 
A unique 5-digit subject ID will be used to identify subjects in all datasets and listings for this study.  
This unique 5-digit subject ID consists of the 2-digit Screening number plus the unique 3-digit randomization 
number. If a subject withdraws during screening or fails screening, then 000 or 999 will be used in lieu of 
the randomization number. 


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4.2 
Masking and Unmasking 
During the Study Treatment Phase of the study (Visit 1 – Visit 5), the subject, Investigator, and study staff 
will be masked. 
For each randomization number, the Sponsor will label each of a set of 11 study drug pouches prominently 
with the 3-digit randomization code followed by container number. 
e.g. 
Pouch #1, #2, and #3 will be labeled xxx-1, xxx-2 and xxx-3 for dispensing at Visit 2 Day 1 Baseline. 
Pouch #4, 5, 6, and 7 will be labeled xxx-4, -5, -6, and -7 for dispensing at Visit 3 Day 14. 
Pouch #8, 9, 10, and 11 will be labeled xxx-8, -9,-10 and -11 for dispensing at Visit 4 Day 42 
Open label pouches will be supplied for Visit 5 (3 pouches active), and Visit 6 (3 pouches). 
Note: Rarely a tube may fail to pump due to airlock. Therefore an extra tube is provided each time to ensure 
there will be sufficient product. (Each tube dispenses approximately 24 doses.) 
The Sponsor is responsible for emergency unmasking as needed.  
For each subject, after the completion of all Visit 5 assessments, the Investigator will unmask the individual 
subject to determine eligibility for the Placebo Cross-over Phase. If the subject was originally randomized 
to Placebo, then the subject will enter the Placebo Cross-over Phase. If the subject was originally 
randomized to Pro-ocular™ 1% topical gel, then the subject’s participation in the study will be complete. 
5. Sample Size and Power Considerations 
This study will randomize 33 subjects (22 to Pro-ocular™ 1% topical gel, and 11 to Placebo).  
6. Data Preparation 
All study data will be recorded on an Excel file prepared by Glia. The file contains multiple worksheets. 
Diary data will be collected from subjects at the protocol specified visits and entered by Ora  staff into the 
Excel file as well. Glia and the Ora data entry specialists will review data to ensure accuracy and 
cleanliness. 
The data will be transferred to SDC and then converted into SAS datasets. After data are converted to SAS, 
limited electronic edit checks and data review will be performed to ensure data is analyzable.  
This study will be locked in 2 phases. The first lock will occur after completion of the Study Treatment 
Phase, including all data up to Visit 5. This will constitute the Primary database lock. The second database 
lock will occur after completion of the Placebo Cross-over Phase, including all data up to Visit 7. This will 
constitute the Final database lock. 
When all prerequisites for database lock have been met, including availability of all masked external data, 
the database will be locked. Following database lock, approval will be obtained from the Sponsor to unmask 


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the study. Once the study has been unmasked, unmasked data will be sent to SDC. Any changes to the 
database after data have been locked can only be made with the approval of the Sponsor in consultation 
with SDC.  
The primary analysis will be carried out after the following have occurred: 
• 
Primary Database lock has occurred, including receipt of all final versions of external vendor data, 
with written authorization provided by appropriate SDC and Sponsor personnel. 
• 
Protocol deviations have been identified and status defined (major/minor deviations). 
• 
Analysis populations have been determined. 
• 
Randomized treatment codes have been unmasked. 
The final analysis will be carried out after the following have occurred: 
• 
Final Database lock has occurred, including receipt of all final versions of external vendor data, 
with written authorization provided by appropriate SDC and Sponsor personnel. 
7. Analysis Populations 
7.1 
Modified Intent-to-Treat 
The modified intent-to-treat (ITT) population includes all randomized subjects who received at least 1 
application of the study drug. Subjects will be analyzed as randomized. 
7.2 
Per Protocol 
The per protocol (PP) population excludes subjects from the ITT population with significant protocol 
deviations and any subjects with more than 10% missing data in the Glia Ocular Surface Disease 
Questionnaire. Protocol deviations will be assessed for inclusion by the clinical team, prior to database lock. 
The subjects will be analyzed as randomized. If  both treatments groups in the PP population retain ≥ 85% 
of the subjects from the corresponding treatment group in the ITT population, all analyses using the PP 
population will not be conducted. 
7.3 
Safety 
All subjects who received at least 1 application of the study drug will be included in the Safety population. 
Subjects will be analyzed as treated. 
8. General Statistical Considerations 
8.1 
Unit of Analysis 
The unit of analysis in this study will be the worse eye at baseline for each ocular sign and symptom efficacy 
measurement. The other eye will be referred to as the fellow eye. Both eyes will be summarized separately 
unless stated otherwise. The term, eye type, will refer to worse eye and fellow eye.  Additionally all eyes 
under active treatment will be compared to all eyes under placebo. (Combined eye.) 


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The eye will be the unit for analysis for safety summaries and both eyes will be summarized as Right Eye 
(OD) and Left Eye (OS) separately.  
Non-ocular AEs, non-ocular medical history, non-ocular concomitant medications, Facial Presentation and 
Blinks per Minute and NIH eye score will be presented at the subject level.  
8.2 
Missing or Inconclusive Data Handling 
There will be not imputation for missing data. 
8.3 
Definition of Baseline 
For the Study Treatment Phase, baseline is defined as the last measurement prior to the first dose of study 
medication. 
For the Cross-over Phase, baseline is defined as the last measurement prior to the first dose of Pro-ocular™ 
1% topical gel, which is expected to start on the day after Visit 5. 
8.4 
Data Analysis Conventions 
The Primary analysis will be performed by Statistics & Data Corporation (SDC) after the Study Treatment 
Phase is completed and the database has been locked and released for unmasking. An additional analysis 
will be completed once the Cross-over Phase is completed and the database for that portion is locked. 
Statistical programming and analyses will be performed using SAS® version 9.4 or higher. Output will be 
provided in rich text format (RTF) for tables, Excel format for tables and listings, and portable document 
format (PDF) for figures using landscape orientation for any PDF or RTF. All study data will be listed by 
subject, treatment, and visit (as applicable) based on all randomized subjects unless otherwise specified. 
Summaries for continuous and ordinal variables will include the number of observations (n), arithmetic 
mean, standard deviation (SD), median, minimum, and maximum. Minima and maxima will be reported with 
the same precision as the raw values; means and medians will be presented to one additional decimal 
place than reported in the raw values. Standard deviations will be presented to two additional decimal 
places than reported in the raw values. Summaries for discrete variables will include counts and 
percentages. All percentages will be rounded to one decimal place (ie, XX.X%). Differences between active 
treatment group and placebo will be calculated as active minus placebo and change from baseline will be 
calculated as follow-up visit minus baseline.  
All statistical tests will be two-sided with a significance level of 0.05 (α = 0.05) unless otherwise specified. 
Confidence intervals (CI) for differences between treatment groups will be two-sided at 95% confidence 
intervals. All p-values will be rounded to 4 decimal places; p-values less than 0.0001 will be presented as 
“<0.0001”; p-values greater than 0.9999 will be presented as “>0.9999.” 


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Unless otherwise specified, summaries will be presented by treatment group and, where appropriate, visit. 
Listings will be sorted by treatment group, subject number, visit/time point, and parameter as applicable. 
8.5 
Adjustments for Multiplicity 
The Benjamini-Hochberg procedure will be used to adjust for multiplicity for the primary analysis of the key 
efficacy variables.  
The Benjamini-Hochberg procedure is as follows: 
1) Sort the original p-values from smallest to largest 
2) Assign ranks to the original p-values smallest to largest 
3) Calculate the p-values’ adjusted Benjamini-Hochberg critical value as follows: 
 
Adjusted critical p-value = (rank of original p-value/ number of tests i.e. largest rank)*false 
discovery rate, or α = 0.05. 
4) Compare the original p-values to adjusted critical p-values; find the largest original p-value that 
is ≤ 0.05;  
5) Reject the null for any original p-values that is the largest original p-value in 4) or smaller than 
the p-value in 4). 
8.6 
Visual Analog Scale Standardization 
The Visual Analog Scale (VAS) forms used in this study may have varied in length, ie, the Case Report 
Form (CRF) scale length may have varied by subject or visit. To ensure consistency across subjects and 
visits, all VAS scores are standardized to account for these differences. The VAS standardized score will 
be derived by converting the measure length to a maximum score of VASmax with one decimal place as 
follows: 
Score = Measured Result (mm)* VASmax /CRF Scale Length (mm) 
The maximum score for each VAS is discussed in the analysis section. 
9. Disposition of Subjects 
The number of subjects screened, along with the number and percentage of screen failure subjects, will be 
summarized for all screened subjects. 
The number and percentage of subjects included in each analysis population will be summarized by 
treatment group and overall for all randomized subjects.  
A listing of subjects excluded from the PP population and the reason(s) for exclusion will be provided. 
Reasons will include screen failure, major protocol violation, and >10% missing data on the Glia 
Questionnaire. 


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The number and percentage of subjects who enter, complete, and discontinue the Study Treatment Phase, 
and the Cross-over Phase will be summarized by treatment group and overall for the ITT population. A 
listing of discontinued subjects including the date and phase discontinued and the reason for 
discontinuation will be provided. 
A subject listing will be provided for all protocol deviations. The listing will include the date of the deviation, 
the deviation category, the deviation description, and the classification of whether the deviation was judged 
to be major or minor in a blinded review. 
In addition, subject listings will be provided that include informed consent date, randomized treatment and 
actual treatment. 
10. Demographic Variables and Iris Color 
The demographic variables collected in this study include age, sex, race, ethnicity, and iris color. Subjects 
who record more than one race will be grouped into a single category denoted as multi-racial. Demographic 
variables will be summarized for the ITT population. 
Age will be reported in years and calculated using the following formula: 
Age = (Informed Consent Date – Date of Birth) / 365.25, truncated as an integer 
Age will be summarized, overall and by treatment, using continuous descriptive statistics. Age will also be 
categorized as follows: < 65 years and ≥ 65 years. Age will be reported in years. 
The number and percentage of subjects will be presented, overall and by treatment, for age category, sex, 
race, ethnicity, and iris color.  
A subject listing that includes all demographic variables will be provided. 
11. Medical History and Concomitant Medications or Devices 
11.1 
Medical History 
Ocular and Non-Ocular medical history will be coded using version 22.0. 
Ocular and Non-ocular medical history will be summarized using discrete summary statistics and presented 
by treatment group at the subject level by System Organ Class (SOC) and Preferred Term (PT) using the 
Safety population. If a subject reports the same PT multiple times within the same SOC, then that PT will 
only be reported once within that SOC. As with the PT, if a subject reports multiple conditions within the 
same SOC, that SOC will only be reported once.  
Listings of medical history will be generated separately for ocular and non-ocular data. 
11.2 
Prior and Concomitant Medications or Devices 
Concomitant medications will be coded using WHO ATC/DDD Index 2019, searchable version of the 
complete Anatomical Therapeutic Chemical (ATC) index with defined daily doses (DDDs) and summarized 


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to the therapeutic drug class (Anatomical Therapeutic Chemical [ATC] 4 classification) and preferred name. 
If the ATC 4 classification is not provided, then the next lowest classification that is provided in the coding 
dictionary will be used. The preferred name will be defined as the active ingredient; if the active ingredient 
is not provided or includes more than two ingredients (eg, multivitamins), then the drug name will be 
summarized as the preferred name. Any uncoded terms will be summarized under the ATC classification 
and preferred name of “Uncoded.” 
Concomitant medications are defined as those medications listed as having been taken 1) prior to initiation 
of study drug administration and continuing for any period of time following the first administration of study 
drug or 2) at any time following the first administration of study drug. 
Concomitant medications will be summarized using the Safety population. Medications will be tabulated for 
each treatment group using frequencies and percentages. Subjects may have more than one medication 
per ATC text. At each level of subject summarization, a subject will be counted once if he/she reports one 
or more medications. Percentages will be based on the number of subjects in each treatment group. Listings 
of concomitant medications will be generated. 
Prior medications are defined as those medications or devices with start and end dates before the first dose 
of study drug. Prior medications or devices will be listed only. 
12. Treatment Exposure and Compliance 
The duration of treatment exposure by study phase will be calculated in days. 
Duration of treatment exposure during the Study Treatment Phase: 
Duration (days) = Date of last dose in Study Treatment Phase minus date of first dose in Study Treatment 
Phase + 1. 
Note that the last dose in the Study Treatment Phase is expected to be the morning of Visit 5. 
Duration of treatment exposure during the Placebo Crossover Phase: 
Duration (days) = last dose date in Placebo Crossover Phase - first dose date in Placebo Cross-over Phase 
+ 1. 
Compliance during the Study Treatment Phase: 
Compliance = (total count of time entries for drug application in Study Treatment Phase) x 100 / (treatment 
durationin for the Study Treatment Phase x 2 applications per day)  
Compliance during the Placebo Crossover Phase: 
Compliance = (total count of time entries for drug application in Placebo Crossover Phase) x 100 / 
(treatment durationin for the Placebo Crossover Phase x 2 applications per day)  
 


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Note that the first dose in the Placebo Crossover Phase is expected to be the day following Visit 5. 
Duration of treatment exposure for each subject exposed to study drug will be summarized with continuous 
descriptive statistics for each treatment group and study phase using the Safety population. A subject listing 
of treatment exposure will also be produced. 
13. Efficacy Analyses 
The efficacy measures in this study are described below. All analyses will be conducted separately for the 
Study Treatment Phase and the Placebo Cross-over Phase. Where applicable a worse eye at baseline will 
be determined for each individual sign or symptom. Analyses will include the worse eye and fellow eye 
separately.  
13.1 
GLIA Ocular Surface Disease Symptoms Questionnaire, Clinic & Daily Diary 
The GLIA Ocular Surface Disease Symptoms Questionnaire will be collected in the clinic at every visit (both 
pre-dose and post-dose at Visit 2) and will be collected via subject daily diary. 
A VAS ranging from None to Most Severe will be used to assess subject’s symptom severity, by eye, for 
the following: 
• 
Ocular discomfort 
• 
Dryness 
• 
Grittiness 
• 
Burning 
• 
Stinging 
• 
Foreign body sensation 
• 
Ocular pain 
• 
Conjunctival redness 
• 
Itching  
• 
Mucus discharge 
• 
Photophobia 
• 
Blurred or cloudy vision 
• 
Air flow sensitivity 
• 
Lid redness 
• 
Lid sticking 
Subjects will be asked to rate each symptom by placing a vertical mark on the horizontal line to indicate the 
level of severity. The result (in mm) will be measured from the left endpoint (None) to the slash marked by 
subject on the line.  
For each symptom, a score is derived by converting the measure length to a maximum score of 10 with 
one decimal place as follows: 


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13.1.1 ANALYSIS OF GLIA OCULAR SURFACE DISEASE SYMPTOMS QUESTIONNAIRE COLLECTED IN CLINIC 
The primary analysis (Study Treatment Phase): 
For each symptom, an analysis of covariance (ANCOVA) will be used to compare change from baseline 
between Pro-ocular and placebo with adjustments for baseline symptom score (BASELINE), treatment 
group (TRT), visit (VISIT), and treatment x visit interaction (TRT*VISIT) as the explanatory variable. The 
least squares (LS) means, LS mean differences, SEs, two-sided 95% CIs for the difference in LS means, 
and two-sided p-values (unadjusted and Benjamini-Hochberg adjusted p-values) will be reported for the 
treatment effect at each visit and all visits combined. Model effects will also be displayed. 
SAS pseudo-code for this model follows: 
 
PROC MIXED data=indata order=internal; 
                          By EYETYPE; 
 
 
class TRT VISIT; 
 
 
model CFB = TRT  BASELINE VISIT TRT*VISIT; 
 
 
LSMEANS TRT VISIT TRT*VISIT / CL PDIFF; 
 
run; 
The ITT population will be used as the primary population using LOCF for imputation. 
Sensitivity analyses will include the ITT population and PP population using observed cases. 
Additional analyses: 
For each symptom, an analysis of covariance (ANCOVA) will be used to compare change from baseline 
between Pro-ocular and placebo with adjustments for baseline symptom score (BASELINE), treatment 
group (TRT), visit (VISIT), eye type (EYETYPE) and treatment x visit interaction (TRT*VISIT) as the 
explanatory variable. The least squares (LS) means, LS mean differences, SEs, two-sided 95% CIs for the 
difference in LS means, and two-sided p-values (unadjusted only) will be reported for the treatment effect 
at each visit and all visits combined. The model effect will also be displayed. 
 
PROC MIXED data=indata order=internal; 
                          class TRT VISIT; 
 
 
model CFB = TRT EYETYPE  BASELINE VISIT TRT*VISIT; 
 
 
LSMEANS TRT VISIT EYETYPE  TRT*VISIT / CL PDIFF; 
 
run; 
The ITT population using only observed cases will be used for this analysis. Both ANCOVA analyses will 
be truncated at Visit 5 and any data presented after Visit 5 will be summarized with continuous descripted 
statistics. Continuous descriptive statistics will be used to summarize each symptom score by eye type, 
visit, and treatment group. Change from baseline will also be summarized. Two sample t-tests will be used 
to compare Pro-ocular to placebo for the visit score and for the change from baseline.  


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During the Study Treatment Phase, the changes from baseline will be relative to the Study Treatment Phase 
baseline. During the Placebo Cross-over Phase, the changes from baseline will be relative to the Placebo 
Cross-over Phase baseline. 
Analyses will be performed on the ITT population using observed cases.  
All Symptom scores will be presented in a subject listing. 
13.1.2 Analysis of GLIA Ocular Surface Disease Symptoms Questionnaire Collected in Daily Diary 
The individual symptoms collected in the diary will be analyzed including all data across the 70-day 
treatment period, testing for a treatment effect using a generalized linear model that accounts for repeated 
measures, with an unstructured correlation structure, including terms for diary day. The LS means, LS mean 
differences, SEs, two-sided 95% CIs for the difference in LS means, and two-sided p-values will be 
reported. Model effects will be presented. 
SAS pseudo-code for this model follows: 
 
PROC MIXED data=indata order=internal; 
 
 
class TRT; 
 
 
model SYMPTOM = TRT  DAY; 
 
 
repeated / subject=SUBJ type=UN ; 
random DAY;  
LSMEANS TRT / CL PDIFF; 
 
run; 
The LS mean (and SE) daily scores will be displayed graphically by treatment group across the 70 days. 
The mixed effects model analyses will be truncated at Visit 5 and any data presented after Visit 5 will be 
summarized with continuous descripted statistics. 
Individual subject plots will also be presented displaying the subject score by day.  
Analyses will be performed on the ITT population using observed cases only. 
All Symptom scores collected via diary will be presented in a subject listing. 
13.2 
Modified SANDE – Symptom Assessment iN Dry Eye Questionnaire 
The Modified SANDE – Symptom Assessment iN Dry Eye Questionnaire will be collected at Visit 1 and 
Visits 3 – 7. 
A VAS will be used to assess subject’s symptoms, by eye, for the following: 
• 
Frequency of Symptoms 
• 
Severity of Symptoms 


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First, the subject will be asked to place a vertical line to indicate how often, on average, their eyes feel dry 
and/or irritated. For frequency, the VAS ranges from Rarely to All the Time. 
Second, the subject will be asked to place a vertical line to indicate how severe, on average, they feel their 
symptoms of dryness and/or irritation are. For severity, the VAS ranges from Very Mild to Very Severe. 
The result (in mm) will be measured from the left endpoint to the slash marked by subject on the line.  
For each symptom, a score is derived by converting the measure length to a maximum score of 100 with 
one decimal place as follows: 
Score = Measured Result (mm)*100/CRF Scale Length (mm) 
The total SANDE score is calculated by multiplying the frequency of symptoms score with the severity of 
symptoms score and obtaining the square root. 
Subjects whose values are all 0 for a given symptom for all visits will not be included in the analysis for that 
symptom 
13.2.1 Analysis of SANDE Questionnaire 
The primary and additional analyses for the modify SANDE Questionnaire will be the same as the Glia 
Ocular Surface Disease Symptoms Questionnaire. Both ANCOVA analyses will be truncated at Visit 5 and 
any data presented after Visit 5 will be summarized with continuous descripted statistics. 
13.3 
Daily use of eye drops 
The daily use of eye drops (e.g. Restasis®, Xiidra®, artificial tears and/or gels, autologous tears) will be 
collected via subject diary. For each eye, subjects will record the time drops were used, the type of drops 
used, as well as the number of times drops are administered per wake-time hours and per sleep-time hours. 
For each subject and each eye, the average daily use of artificial tears for each week will be calculated as 
follows: 
           Weeks are defined relative to the first day of dosing. For example,  
                              Week 1 Day 1 = first day of dosing;  
                              Week 1 Day 2 = first day of dosing + 1; 
                               Etc. 
                              Week 1 Day 7 = first day of dosing + 7; 
                              Week 2 Day 1 = first day of dosing + 8; 
                              Etc. 
The sum of the number of times a subject used artificial tears in a given day will be calculated. The average 
daily frequency for a given week will be the average of the daily sums for all days associated within the 
same week. 
The average daily use of artificial gels will be calculated the same as for artificial tears. 


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Average daily use of artificial tears and gels will be summarized using continuous descriptive statistics by 
week and treatment group for each eye separately. Two sample t-tests will be used to compare Pro-ocular 
to placebo.  Artificial tears and gel usage will be summarized and analyzed separately. 
Analyses will be performed on the ITT population using observed data only. 
All daily use of eye drops (Restasis®, Xiidra®, artificial tears and/or gels, autologous tears) will be presented 
in a subject listing. 
13.4 
National Institutes of Health (NIH) Eye Score 
NIH Eye Score will be collected at Visits 1, 5, and 7. 
The score ranges from 0 to 3 as follows: 
• 
Score 0: No symptoms 
• 
Score 1: Mild dry eye symptoms not affecting Activities of Daily Life (ADL) (requirement of 
lubricant eye drops <= 3 x per day) 
• 
Score 2: Moderate dry eye symptoms partially affecting ADL (requiring lubricant eye drops > 3 x 
per day or punctal plugs), WITHOUT new vision impairment due to keratoconjunctivitis sicca 
(KCS) 
• 
Score 3: Severe dry eye symptoms significantly affecting ADL (special eyewear to relieve pain) 
OR unable to work because of ocular symptoms OR loss of vision due to KCS 
Continuous descriptive statistics will be used to summarize the eye scores by visit and treatment group. 
Change from baseline will also be summarized. 
Wilcoxon Rank Sum tests will be used to compare Pro-ocular to placebo for the visit score and for the 
change from baseline. Wilcoxon Rank Sum Tests will be truncated to visit 5 and  any data after visit 5 will 
be summarized with counts and percentages.  
During the Study Treatment Phase, the changes from baseline will be relative to the Study Treatment 
Phase baseline. During the Placebo Cross-over Phase, the changes from baseline will be relative to the 
Placebo Cross-over Phase baseline. 
Analyses will be performed on the ITT population using observed data only. 
All NIH Eye Scores will be presented in a subject listing. 
13.5 
Chronic ocular GvHD Signs  
The evaluations included as part of the Chronic ocular GvHD Signs are described below. 


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13.5.1 TearScan Examination  
TearScan examinations will be conducted at Visits 2 – 7 (both pre-dose and post-dose at Visit 2). The 
TearScan will examine the tear film and lid margin as well as meibum expression. 
Tear film will be assessed by eye using a VAS with anchors No Tear Film 0, Tear Film Visible 1, Reliable 
Tear Film 2, and Copious Tear Film 3. 
Red eyelids will be assessed by Yes or No. 
Meibomian gland expression will be assessed by eye using a VAS with anchors None, Few, and Many. 
For each VAS, the Investigator will mark a vertical slash on the VAS to indicate the level of severity. 
The result (in mm) will be measured from the left endpoint to the slash marked by the Investigator on the 
line.  
A score is derived by converting the measure length to a maximum score of 3 with one decimal place as 
follows: 
 
Score = Measured Result (mm)*3/CRF Scale Length (mm) 
 
Continuous descriptive statistics will be used to summarize the results by eye type, visit and treatment 
group. Change from baseline will also be summarized. 
Two sample t-tests will be used to compare Pro-ocular to placebo for the visit score and for the change 
from baseline.  
During the Study Treatment Phase, the changes from baseline will be relative to the Study Treatment Phase 
baseline. During the Placebo Cross-over Phase, the changes from baseline will be relative to the Placebo 
Cross-over Phase baseline. 
The number and percentage of subjects with red eye will be presented by eye type, treatment, and visit. 
Analyses will be performed on the ITT population using observed data only. 
All TearScan results will be presented in a subject listing. 
13.5.2 Visual Acuity  
Visual acuity in each eye will be measured at Visits 1 and 5 using a Snellen chart, then pinhole test, both 
distance visual acuity and near visual acuity. Visual acuity is based on the current corrected vision, with 
correction if wearing glasses, or without correction if not wearing glasses. Snellen scores will be 
transformed into logMAR scores as follows: 
Snellen Base score – 0.02*(number of correct letters from next smaller line) or 
Snellen Base score + 0.02*(number of correct letters from previous larger line) 
where the Snellen Base score is the logMAR equivalent score defined below in Table 3. 


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Table 3. Snellen Base Scores and LogMAR Conversions 
Snellen Base Score 
LogMAR Score 
20/200 
1.00 
20/160 
0.90 
20/125 
0.80 
20/100 
0.70 
20/80 
0.60 
20/63 
0.50 
20/50 
0.40 
20/40 
0.30 
20/32 
0.20 
20/25 
0.10 
20/20 
0.00 
20/16 
-0.10 
20/12.5 
-0.20 
20/10 
-0.30 
The observed and change from baseline visual acuity will be summarized for each eye (worse eye 
and fellow eye) using continuous descriptive statistics by visit for each treatment group and for all 
actively treated subjects. A subject listing of visual acuity will also be produced. 
13.5.3 Slit Lamp without Staining  
Slit lamp biomicroscopy examinations without staining will be performed at Visit 1 and Visits 3 – 7. The 
exam will assess the following components, by eye: 
• 
Lids (erythema, edema, lid margin ulceration, lid margin notches, entropion/ ectropion, 
trichiasis/madarosis, floppy eyelids, hordeolum (stye))  
• 
Conjunctiva (hyperemia, cicatricial changes, pseudomembranes, chalasis) 
• 
Cornea (edema, corneal ulcers, filamentous keratitis, corneal thinning, corneal 
neovascularization, scars, conjunctival epithelium invasion, limbal thickening) 
• 
Anterior Chamber (cells, flare) 
• 
Lens (status, opacity) 
A VAS ranging from None to Most will be used to score each component except for Lens.  
The Investigator will mark a vertical slash on the VAS to indicate the level of severity. 
The result (in mm), will be measured from left endpoint to the slash marked by the Investigator on the line.  
For each component, a score is derived by converting the measure length to a maximum score of 10 with 
one decimal place as follows: 
 
Score = Measured Result (mm)*10/CRF Scale Length (mm) 
The Investigator will classify any abnormal results as Abnormal Clinically Significant (CS), or Abnormal Not 
Clinically Significant (NCS), including any other pathologies noted by the Investigator. 


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The Lens status will be classified as Phakic, Pseudophakic or Aphakic. For Phakic lens, the Lens Opacity 
will be scored as 0, +1, +2, or +3. 
All continuous slit-lamp measures will be analysed the same as Glia Ocular Surface Disease Symptoms 
Questionnaire and the modified SANDE Questionnaire with the following exceptions. Only the ITT 
populations using observed cases will be performed and no adjustments for multiplicity will be applied. 
The abnormal findings will be summarized using counts and percentages for each treatment group at each 
visit for each eye. Percentages will be based on the number of subjects in each treatment group with 
responses. Shift tables will also be provided comparing each follow-up visit to baseline.  
During the Study Treatment Phase, the changes (or shifts) from baseline will be relative to the Study 
Treatment Phase baseline. During the Placebo Cross-over Phase, the changes (or shifts) from baseline 
will be relative to the Placebo Cross-over Phase baseline. 
Analyses will be performed on the ITT population using observed data only. 
All slit lamp results will be presented in a subject listing. 
13.5.4 Corneal and Conjunctival Fluorescein Staining 
Corneal and conjunctival examinations with fluorescein staining will be performed at Visit 1 and Visits 3 – 7. 
The exam will assess the following components, by eye: 
• 
Cornea (inferior, superior, central) 
• 
Conjunctiva (inferior, superior, temporal, nasal) 
A VAS ranging from None to Most will be used to score each component.  
The Investigator will mark a vertical slash on the VAS to indicate the level of severity. 
The result (in mm) will be measured from left endpoint to the slash marked by the Investigator on the line.  
For each component, a score is derived by converting the measure length to a maximum score of 10 with 
one decimal place as follows: 
 
Score = Measured Result (mm)*10/CRF Scale Length (mm) 
The Investigator will classify any abnormal results as Normal, Abnormal CS, or Abnormal NCS, including 
any other pathologies noted by the Investigator. 
The corneal sum score will be the sum of scores from the inferior, superior, and central regions. The 
conjunctival sum score will be the sum of scores from the inferior, superior, temporal, and nasal regions.  
Continuous descriptive statistics will be used to summarize each score by visit and treatment group. 
Change from baseline will also be summarized.  
Two sample t-tests will be used to compare Pro-ocular to placebo for the visit score and for the change 
from baseline.  


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The abnormal findings will be summarized using counts and percentages for each treatment group at each 
visit for each eye. Percentages will be based on the number of subjects in each treatment group with 
responses. Shift tables will also be provided comparing each follow-up visit to baseline.  
During the Study Treatment Phase, the changes (or shifts) from baseline will be relative to the Study 
Treatment Phase baseline. During the Placebo Cross-over Phase, the changes (or shifts) from baseline 
will be relative to the Placebo Cross-over Phase baseline. 
Analyses will be performed on the ITT population using observed data only. 
All fluorescein staining results will be presented in a subject listing. 
13.5.5 Facial Presentation and Blinks per Minute 
The blinks per minute will be measured with Video Capture Manual Analysis (VCMA) at Visits 2 – 7 (both 
pre-dose and post-dose at Visit 2). A 1-minute video will be captured for each subject while subjects are 
under normal conditions. The Investigator will count the number of times the subject has complete or 
incomplete blinks within a 1 minute ± 5 second interval. 
The facial presentation score at the start of the session will also be captured (0 = eyes closed, 1 = eyes 
partially open, 2 = eyes fully open). 
Continuous descriptive statistics will be used to summarize the number of blinks by visit and treatment 
group. Change from baseline will also be summarized.  
Two sample t-tests will be used to compare Pro-ocular to placebo for the visit score and for the change 
from baseline.  
Analyses will be performed on the ITT population using observed data only. 
All facial presentation and blinks per minute results will be presented in a subject listing. 
14. Safety Analyses 
All safety analyses will be conducted using the Safety population using observed data only. All analyses 
will be conducted separately for the Study Treatment Phase and the Placebo Cross-over Phase. 
14.1 
Adverse Events 
All adverse events will be collected, whether potentially related or unrelated to study drug use. Study drug 
includes the investigational drug under evaluation and placebo given during any stage of the study. 
Treatment-emergent adverse events (TEAE) are defined as any event that occurs on or after the day that 
randomized study treatment is initiated. Adverse events recorded in the CRF which began prior to treatment 
will not be included in the summary tables but will be included in the AE data listings. 
The severity of each AE will be evaluated as Mild, Moderate or Severe. 


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The relationship of each AE to the study drug will be determined by the Investigator as None, Possibly 
Related, or Probably Related. 
Action taken with study drug will be classified as None, Permanently Discontinued, Temporarily 
Discontinued, or Other. 
An overall summary will be presented that includes the number of events and the number and percentage 
of subjects who experienced at least one TEAE, by treatment group. This summary will also include 
breakdowns of TEAEs further categorized as ocular or non-ocular, treatment-related TEAEs, serious AEs 
(SAE), and TEAEs leading to early treatment discontinuation. 
Additional summaries of TEAEs will be provided showing the number and percentage of subjects who 
experienced at least one TEAE by treatment group and over all subjects. Non-ocular TEAEs will be 
summarized using discrete summary statistics and presented by treatment group at the subject and event 
level by SOC and PT. Ocular TEAEs will be similarly summarized at the subject level. If a subject reports 
the same PT multiple times within the same SOC, that PT will only be reported once within that SOC. As 
with the PT, if a subject reports multiple conditions within the same SOC, that SOC will only be reported 
once. In the summary, SOCs will be listed in ascending alphabetical order; PTs will be listed in order of 
descending frequency for all subjects within each SOC.  
Separate summaries will be provided for the following categories of AEs:  
• 
Overall AE Summary 
• 
TEAEs  
• 
TEAEs by Relationship to Study Medication 
• 
Treatment Emergent SAEs 
All AEs will be presented in a subject listing. 
14.2 
Visual Acuity  
Visual acuity is discussed in section 13.5.2 for the efficacy analysis. For safety, continuous descriptive 
statistics will be used to summarize visual acuity by eye and treatment group. Change from baseline will 
also be summarized. The Safety table will be produced with an additional categorical summary of subjects 
with logMAR change from baseline ≥0.20 logMAR and both eyes, Right Eye (OD) and Left Eye (OS) will 
be the unit of analysis.  
14.3 
Slit-Lamp Biomicroscopy Examination 
Slit lamp biomicroscopy examination is discussed in section 13.5.3 for the efficacy analysis. For safety, 
descriptive statistics will be used to summarize slit-lamp biomicroscopy by eye and treatment group in the 
Safety population. Right Eye (OD) and Left Eye (OS) will be the unit of analysis. . 


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14.4 
Undilated Fundoscopy Examination 
Undilated Fundoscopy examinations will be performed at Visits 1 and 5. The exam will assess the following 
components, by eye:  
• 
Vitreous Humour 
• 
Optic nerve 
• 
Macula 
• 
Cup to disc ratio (vertical) 
The Investigator will classify the results as Normal, Abnormal CS, or Abnormal NCS. 
The results will be summarized using counts and percentages for each treatment group at each visit for 
each eye. Percentages will be based on the number of subjects in each treatment group with responses. 
Shift tables will also be provided comparing the follow-up visit to baseline.  
All undilated fundoscopy will be presented in a subject listing. 
14.5 
Intraocular Pressure (IOP) 
Intraocular Pressure (IOP) will be assessed by applanation tonometry in each eye at Visits 1, 5, and 7. 
Results will be taken from a single measurement and will be recorded in mmHg. 
Continuous descriptive statistics will be used to summarize the IOP by visit, eye and treatment group. 
Change from baseline will also be summarized.  
During the Study Treatment Phase, the changes from baseline will be relative to the Study Treatment Phase 
baseline. During the Placebo Cross-over Phase, the changes from baseline will be relative to the Placebo 
Cross-over Phase baseline. 
All IOP results will be presented in a subject listing. 
14.6 
Clinical Laboratory Data 
Blood samples for clinical laboratory parameters will be collected at Visits 1, 4, 5, and 7.  
Clinical laboratory data includes Complete Blood Count (CBC) with differential, metabolic panel, standard 
GvHD panel, and an endocrine panel (at Visits 1, 5, and 7 only). 
The quantitative variables will be summarized by treatment group with continuous descriptive statistics. The 
qualitative variables (counts and percentages) will be summarized by treatment group at each visit and time 
point (where appropriate). Change from baseline will also be summarized by treatment group.  
The specific parameters and normal ranges are shown below. 
All laboratory results will be presented in a subject listing. 
 


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Table 3. Complete Blood Count and Differential Parameters and Normal Ranges 
Complete Blood Count Panel Parameter 
Normal Range* 
WBC 
3.81 - 8.94 K/uL 
RBC 
4.35 - 5.61 M/uL 
HGB 
12.5 - 16.3 g/dL 
HCT 
37.1 - 49.5 % 
PLT 
152 - 440 K/uL 
MCV 
79.0 - 97.0 fL 
MCH 
26.2 - 32.0 pg 
MCHC 
33.3 - 35.7 g/dL 
RDW 
12.1 - 16.0 % 
MPV 
7.0 - 10.8 fl 
NRBC 
0.00 /100 WBCs 
ABSOLUTE NRBC 
K/uL 
NEUTS 
46.5 - 82.4 % 
EOSINOPHIL 
0.1 - 6.0 % 
BASOPHIL 
0.1 - 1.1 % 
LYMPHS 
8.5 - 32.7 % 
MONOS 
5.4 - 14.2 % 
ABSOLUTE NEUTS 
2.23 - 6.11 K/uL 
ABSOLUTE EOS 
0.00 - 0.52 K/uL 
ABSOLUTE BASO 
0.00 - 0.11 K/uL 
ABSOLUTE LYMPHS 
0.21 - 2.74 K/uL 
ABSOLUTE MONOS 
0.2 - 0.87 K/uL 
*Reference ranges may change at the time of analysis. Any changes to the reference ranges used in the final tables will be 
approved by the client and will be documented in the clinical summary report. 
 
Table 4. Comprehensive Metabolic Panel Parameters and Normal Ranges 
Comprehensive Metabolic Panel Parameter 
Normal Range* 
SODIUM 
135 - 145 mmol/L 
POTASSIUM 
3.5 - 5.0 mmol/L 
CHLORIDE 
98 - 108 mmol/L 
CO2 
23 - 32 mmol/L 
BUN 
9 - 25 mg/dL 
CREATININE 
0.7 - 1.3 mg/dL 
GLUCOSE 
70 - 100 mg/dL 
ALBUMIN 
3.7 - 5.4 g/dL 
TOTAL PROTEIN 
6.0 - 8.0 g/dL 
CALCIUM 
8.8 - 10.5 mg/dL 
ALKALINE PHOSPHATASE 
36 - 118 U/L 
TOTAL BILIRUBIN 
0.2 - 1.2 mg/dL 
AST 
9 - 30 U/L 
ALT 
7 - 52 U/L 
GLOBULIN 
2.3 - 4.2 g/dL 
EGFR 
>59 mL/min/1.73m2 
ANION GAP 
5 - 17 mmol/L 


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*Reference ranges may change at the time of analysis. Any changes to the reference ranges used in the final tables will be 
approved by the client and will be documented in the clinical summary report. 
 
Table 5. Standard GvHD Panel Parameters and Normal Ranges 
Standard GvHD Panel Parameter 
Normal Range* 
TACROLIMUS 
3.0 - 15.0 ng/mL 
SIROLIMUS 
3.0 – 12.0 ng/mL 
VITAMIN D Total, 25-OH (D2 and D3) 
Sunquest Lab, OHDT 
20-80 ng/mL 
T4 (thyroxine), Total, Serum 
11 -19 years: 5.9-13.2 µg/dL 
Adult (> or =20 years): 4.5-11.7 µg/dL 
T4 (thyroxine), Free, Serum 
11-19 years: 1.0-1.6 ng/dL 
Adult (> or =20 years): 0.9-1.7 ng/dL 
T3 (triodothyronine), Total, Serum 
11-19 years: 91-218 ng/dL 
Adult (> or =20 years): 80-200 ng/dL 
ACTH (adrenocorticotropic hormone), Plasma 
7.2-63 pg/mL (a.m. draws) 
TSH (thyroid stimulating hormone), Serum 
0.27 - 4.20 µIU/mL 
*Reference ranges may change at the time of analysis. Any changes to the reference ranges used in the final tables will be 
approved by the client and will be documented in the clinical summary report. 
 
Table 6. Endocrine Panel Parameters and Normal Ranges 
Endocrine Panel Parameter  
Normal Range* 
DHEA-S (dehydroepiandrosterone sulfate), 
Serum 
18-30 years: 105-728 µg/dL 
31-40 years: 57-522 µg/dL 
41-50 years: 34-395 µg/dL 
51-60 years: 20-299 µg/dL 
61-70 years: 12-227 µg/dL 
> or =71 years: 6.6-162 µg/dL 
ESTRADIOL, Serum 
Follicular Phase 27-156 pg/mL 
Mid Cycle Peak 48-314 pg/mL 
Luteal Phase 33-298 pg/mL 
Postmenopausal <50 pg/mL 
FSH (follicle stimulating hormone), Serum 
Male 1.6-8.0 mIU/mL 
Female 
Follicular Phase 2.5-10.2 mIU/mL 
Mid-Cycle Peak 3.1-17.7 mIU/mL 
Luteal Phase 1.5- 9.1 mIU/mL 
Postmenopausal 23.0-116.3 mIU/mL 
LH (luteinizing hormone), Serum 
Male 
18-59 Years 1.5-9.3 mIU/mL 
≥60 Years 1.6-15.2 mIU/mL 
Female 
Follicular Phase 1.9-12.5 mIU/mL 
Mid-Cycle Peak 8.7-76.3 mIU/mL 
Luteal Phase 0.5-16.9 mIU/mL 
Postmenopausal 10.0-54.7 mIU/mL 
PTH (Parathyroid Hormone), Serum 
15-65 pg/mL 


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Endocrine Panel Parameter  
Normal Range* 
PROGESTERONE, Serum 
MALES > or =18 year: <0.20 ng/mL 
FEMALES > or =18 years: 
-Follicular phase: < or =0.89 ng/mL 
-Ovulation: < or =12 ng/mL 
 
-Luteal phase: 1.8-24 ng/mL 
-Post-menopausal: < or =0.20 
ng/mL 
-Pregnancy 
- 1st trimester: 11-44 ng/mL 
- 2nd trimester: 25-83 ng/mL 
- 3rd trimester: 58-214 ng/mL 
TESTOSTERONE, Total and Free, Serum Mayo 
Clinic test code TGRP 
TESTOSTERONE, FREE 
Males (adult): 
20-<25 years: 5.25-20.7 ng/dL 
25-<30 years: 5.05-19.8 ng/dL 
30-<35 years: 4.85-19.0 ng/dL 
35-<40 years: 4.65-18.1 ng/dL 
40-<45 years: 4.46-17.1 ng/dL 
45-<50 years: 4.26-16.4 ng/dL 
50-<55 years: 4.06-15.6 ng/dL 
55-<60 years: 3.87-14.7 ng/dL 
60-<65 years: 3.67-13.9 ng/dL 
65-<70 years: 3.47-13.0 ng/dL 
70-<75 years: 3.28-12.2 ng/dL 
75-<80 years: 3.08-11.3 ng/dL 
80-<85 years: 2.88-10.5 ng/dL 
85-<90 years: 2.69-9.61 ng/dL 
90-<95 years: 2.49-8.76 ng/dL 
95-100+ years: 2.29-7.91 ng/dL 
Females (adult): 
20-<25 years: 0.06-1.08 ng/dL 
25-<30 years: 0.06-1.06 ng/dL 
30-<35 years: 0.06-1.03 ng/dL 
35-<40 years: 0.06-1.00 ng/dL 
40-<45 years: 0.06-0.98 ng/dL 
45-<50 years: 0.06-0.95 ng/dL 
50-<55 years: 0.06-0.92 ng/dL 
55-<60 years: 0.06-0.90 ng/dL 
60-<65 years: 0.06-0.87 ng/dL 
65-<70 years: 0.06-0.84 ng/dL 
70-<75 years: 0.06-0.82 ng/dL 
75-<80 years: 0.06-0.79 ng/dL 
80-<85 years: 0.06-0.76 ng/dL 
85-<90 years: 0.06-0.73 ng/dL 
90-<95 years: 0.06-0.71 ng/dL 
95-100+ years: 0.06-0.68 ng/dL 
TESTOSTERONE, TOTAL 
Males 
17-18 years: 300-1,200 ng/dL 
> or =19 years: 240-950 ng/dL 
Females 


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Endocrine Panel Parameter  
Normal Range* 
17-18 years: 20-75 ng/dL 
> or =19 years: 8-60 ng/dL 
*Reference ranges may change at the time of analysis. Any changes to the reference ranges used in the final tables will be 
approved by the client and will be documented in the clinical summary report. 
 
15. Interim Analyses 
No interim analyses are planned for this study. 
16. Changes from Protocol-Stated Analyses 
The protocol and SAP call for LOCF imputation and for sensitivity analyses in the Per Protocol population 
for the key efficacy endpoints. Given there is only 1 early discontinuation and no expected major protocol 
deviations, the LOCF imputation and Per Protocol population have been removed due to the expected 
similarity with the ITT Population using only observed data. The protocol calls for t-tests and ANCOVA 
analyses for ordinal data, It has been decided that the Wilcoxon Rank Sum Test will be sufficient and the t-
test and ANCOVA will not be done. 
All crossover data collected will be summarized with continuous descriptive statistics or with counts and 
percentages as appropriate. 
Interblink interval may appear in the protocol however all instances of interblink interval have been changed 
to Facial Presentation and Blinks per Minute 
Per the Sponsor an additional ANCOVA model including eye type has been added for the key efficacy 
variables.  
Additional exploratory analyses may be requested after final analyses and may be detailed in the clinical 
study report. 
17. References 
None. 
18. Revision History 
Documentation of revision to the SAP will commence after approval of the final version 1.0. 
19. Tables, Listings and Figures 
 
 
Tables 
Title 
Population 
Table 14.1.1 
Subject Disposition 
All Enrolled Subjects 
Table 14.1.2 
Demographic and Iris Color  
ITT Population 


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Table 14.1.3.1 
Ocular Medical History  
ITT Population 
Table 14.1.3.2 
Non-Ocular Medical History  
ITT Population 
Table 14.1.4.1 
Ocular Concomitant Medications Intent-to-Treat Population 
ITT Population 
Table 14.1.4.2 
Non-Ocular Concomitant Medications Intent-to-Treat Population 
ITT Population 
Table 14.1.5 
Study Drug Exposure in Days 
Safety Population 
Table 14.2.1.1 
GLIA Ocular Surface Disease Symptoms Questionnaire, in Clinic by Eye 
ITT Population 
Table 14.2.1.2 
GLIA Ocular Surface Disease Symptoms Questionnaire, in Clinic with 
Combined Eyes 
ITT Population 
Table 14.2.2.1 
GLIA Ocular Surface Disease Symptoms Questionnaire, Daily Diary by 
Eye 
ITT Population 
Table 14.2.2.2 
GLIA Ocular Surface Disease Symptoms Questionnaire, Daily Diary with 
Combined Eyes 
ITT Population 
Table 14.2.3.2 
Modified SANDE - Symptom Assessment iN Dry Eye (SANDE) 
Questionnaire by Eye 
ITT Population 
Table 14.2.3.3 
Modified SANDE - Symptom Assessment iN Dry Eye (SANDE) 
Questionnaire with Combined Eyes 
ITT Population 
Table 14.2.4.1.1 
Slit Lamp Biomicroscopy Without Staining by Eye 
ITT Population 
Table 14.2.4.1.2 
Slit Lamp Biomicroscopy Without Staining with Combined Eye 
ITT Population 
Table 14.2.4.1.3 
Slit Lamp Biomicroscopy Without Staining – Shift Table  
ITT Population 
Table 14.2.4.2.1 
Corneal and Conjunctival Fluorescein Staining Examination by Eye 
ITT Population 
Table 14.2.4.2.2 
Corneal and Conjunctival Fluorescein Staining Examination with 
Combined Eye 
ITT Population 
Table 14.2.5 
National Institute of Health (NIH) Eye Score  
ITT Population 
Table 14.2.6 
Daily Use of Eye Drops 
ITT Population 
Table 14.2.7 
TearScan Examination  
ITT Population 
Table 14.2.8 
Visual Acuity in LogMAR Units  
ITT Population 
Table 14.2.9 
Facial Presentation and Blinks per Minute 
ITT Population 
Table 14.3.1.1 
Overall Summary of All Treatment-Emergent Adverse Events (TEAEs)  
Safety Population 
Table 14.3.1.2 
Treatment-Emergent Adverse Events (TEAE) by System Organ Class 
(SOC) and Preferred Term (PT)  
Safety Population 
Table 14.3.1.3 
Treatment-Emergent Adverse Events (TEAEs) by System Organ Class, 
Preferred Term, and Relationship to Study Drug  
Safety Population 
Table 14.3.1.4 
Serious Treatment-Emergent Adverse Events (TEAEs) (Including Death) 
by System Organ Class (SOC) and Preferred Term (PT)  
Safety Population 
Table 14.3.4.1 
Laboratory Results - Complete Blood Count Shifts from Baseline 
Safety Population 
Table 14.3.4.2 
Laboratory Results - Metabolic Panel Shifts from Baseline 
Safety Population 
Table 14.3.4.3 
Laboratory Results - Standard GvHD Panel  
Safety Population 
Table 14.3.4.4 
Laboratory Results - Endocrine Panel  
Safety Population 
Table 14.3.5.1 
Visual Acuity in LogMAR Units  
Safety Population 
Table 14.3.5.2 
Slit Lamp Biomicroscopy Without Staining  
Safety Population 
Table 14.3.5.3 
Slit Lamp Biomicroscopy Without Staining – Shift Table  
Safety Population 
Table 14.3.5.4 
Undilated Fundoscopy Findings  
Safety Population 
Table 14.3.5.4 
Undilated Fundoscopy Findings – Shift Table  
Safety Population 
Listings 
Title 
Population 
Listing 16.1.7 
Randomization Schedule  
All Subjects 
Listing 16.2.1 
Subject Disposition and Informed Consent  
All Subjects 
Listing 16.2.2 
Protocol Deviations  
All Subjects 


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Listing 16.2.3.1 
Demographics  
All Subjects 
Listing 16.2.3.2 
Ocular Medical History  
All Subjects 
Listing 16.2.3.3 
Non-Ocular Medical History  
All Subjects 
Listing 16.2.3.4 
Prior and Concomitant Medication or Device History  
All Subjects 
Listing 16.2.4.1 
Study Medication Accountability Log  
All Subjects 
Listing 16.2.4.2 
Ocular Medication Log & Eye Drop Usage  
All Subjects 
Listing 16.2.5.1 
Glia Ocular Surface Disease Symptoms Questionnaire, In Clinic  
All Subjects 
Listing 16.2.5.2 
Glia Ocular Surface Disease Symptoms Questionnaire, Daily Diary  
All Subjects 
Listing 16.2.5.3 
Modified Symptom Assessment iN Dry Eye (SANDE) Questionnaire  
All Subjects 
Listing 16.2.5.4 
National Institutes of Health (NIH) Ocular Graft-versus-Host Disease 
(GvHD) Score  
All Subjects 
Listing 16.2.5.5 
TearScan Examination  
All Subjects 
Listing 16.2.5.6 
Corneal and Conjunctival Fluorescein Staining Examination All Subject 
All Subjects 
Listing 16.2.5.7 
Facial Presentation and Blinks per Minute by Video Camera All Subject 
All Subjects 
Listing 16.2.6 
All Adverse Events  
All Subjects 
Listing 16.2.7.1 
Visual Acuity  
All Subjects 
Listing 16.2.7.2 
Slit Lamp Biomicroscopy (SLB) Without Staining All Subject 
All Subjects 
Listing 16.2.7.3 
Intraocular Pressure (IOP)  
All Subjects 
Listing 16.2.7.4 
Undilated Fundoscopy Examination All Subject 
All Subjects 
Listing 16.2.8.1 
Pregnancy Test Results  
All Subjects 
Listing 16.2.8.2 
Laboratory Results - Complete Blood Count  
All Subjects 
Listing 16.2.8.3 
Laboratory Results - Metabolic Panel  
All Subjects 
Listing 16.2.8.4 
Laboratory Results - GvHD Panel  
All Subjects 
Listing 16.2.8.5 
Laboratory Results - Endocrine Panel  
All Subjects 
Figures 
Title 
Population 
Figure 14.2.1.1 
GLIA Ocular Surface Disease Symptoms Questionnaire, in Clinic in the 
Worse Eye by Symptom 
ITT Population 
Figure 14.2.1.2 
GLIA Ocular Surface Disease Symptoms Questionnaire, Daily Diary in 
the Worse Eye by Symptom 
ITT Population 
Figure 14.2.2.1 
Modified SANDE - Symptom Assessment iN Dry Eye (SANDE) 
Questionnaire in the Worse Eye by Symptom 
ITT Population