Treatment Safety and Efficacy Using Pro-ocular™ 1% for Chronic Ocular Graft-versus-host Disease (GvHD) Following Allogeneic Hematopoietic Stem Cell Transplantation.
Phase: PHASE2
Conditions: Chronic Ocular Graft-versus-host Disease
Sponsor: Glia, LLC

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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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 
 
 

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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 
 
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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 
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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 
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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