Conditions: Dry Eye Syndrome
Keywords: Dry Eye Dry Eye Syndrome SkQ1 KCS Keratoconjunctivitis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 610
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate whether SkQ1 Ophthalmic Solution is safe and effective compared to Vehicle for the treatment of the signs and symptoms of dry eye syndrome.

Detailed description:
Multi-center, double-masked, randomized, placebo-controlled study comprising 5 visits over the course of approximately 9 weeks. Qualified subjects are randomized 1:1 to receive either SkQ1 Ophthalmic Solution, or Placebo (vehicle of SkQ1 Ophthalmic Solution).

The Primary Endpoints are:

Change from Baseline (Visit 2) to Visit 5 of Ocular Discomfort;

Change from Baseline (Visit 2) to Visit 5 of conjunctival fluorescein staining (sum of temporal and nasal regions)

Arms:
arm 1: Vehicle for SkQ1 Ophthalmic Solution arm 2: SkQ1 Ophthalmic Solution

Interventions: intervention 1: SkQ1 Vehicle Solution intervention 2: SkQ1 Ophthalmic Solution
Intervention descriptions: intervention 1: SkQ1 Ophthalmic Solution Vehicle intervention 2: SkQ1 Ophthalmic Solution

Protocol document:
Prot_SAP_000.pdf: 
SkQ1 ophthalmic solution  
Sponsor: Mitotech, SA 
Clinical Trial Protocol: VISTA-2 / 19-110-0011 
Final V1.0 04Nov2019 
Confidential 
Page 1 of 75 
Clinical Trial Protocol: VISTA-2 / 19-110-0011 
Protocol Title: 
A Phase 3, Multi-Center, Randomized, Double-Masked, 
Placebo-Controlled Clinical Study to Assess the Safety 
and Efficacy of SkQ1 Ophthalmic Solution in the 
Environment and During Challenge in the Controlled 
Adverse Environmental (CAE®) Model for the Treatment 
of Dry Eye Syndrome 
Protocol Number: 
VISTA-2 / 19-110-0011 
Study Phase: 
3 
Product Name: 
SkQ1 Ophthalmic Solution 
IND Number: 
113433 
Indication: 
Dry Eye Syndrome (DES) 
Investigators: 
Multi-Center 
 
Sponsor: 
Mitotech, SA 
42, rue de la Vallée 
L-2661 
Luxembourg 
 
Contract Research 
Organization: 
Ora. Inc. 
300 Brickstone Square, 3rd Floor 
Andover, MA 01810 
 
IRB: 
Alpha IRB 
1001 Avenida Pico 
Suite C, #497 
San Clemente, CA 92673 
 
 
 
Date 
Original Protocol: 
Version 1.0  4 November 2019 
Confidentiality Statement 
This protocol contains confidential, proprietary information of Ora, Inc. and/or Mitotech. 
Further dissemination, distribution or copying of this protocol or its contents is strictly 
prohibited. 
 




SkQ1 ophthalmic solution  
Sponsor: Mitotech, SA 
Clinical Trial Protocol: VISTA-2 / 19-110-0011 
Final V1.0 04Nov2019 
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SYNOPSIS 
Protocol Title: 
A Phase 3, Multi-Center, Randomized, Double-
Masked, Placebo-Controlled Clinical Study to 
Assess the Safety and Efficacy of SkQ1 Ophthalmic 
Solution in the Environment and During Challenge 
in the Controlled Adverse Environmental (CAE®) 
Model for the Treatment of Dry Eye Syndrome 
Protocol Number: 
VISTA-2 / 19-110-0011 
Study Drug: 
1) 1.55 µg/mL SkQ1 ophthalmic solution  
2) Placebo SkQ1 ophthalmic solution (Vehicle of 
SkQ1 ophthalmic solution) 
Study Phase: 
3 
Study Objective: 
The objective of this study is to compare the safety 
and efficacy of SkQ1 ophthalmic solution to placebo 
for the treatment of the signs and symptoms of dry 
eye syndrome. 
 
Overall Study Design 
 
Structure: 
Multi-center, double-masked, randomized, placebo-
controlled study 
Duration: 
An individual subject’s participation is estimated to 
be approximately 9 weeks (63 days) 
Controls: 
Placebo SkQ1 ophthalmic solution (Vehicle of SkQ1 
ophthalmic solution) 
Dosage/Dose Regimen: 
Subjects eligible to be randomized will receive one 
of the following treatments to be administered 
bilaterally as 1-2 drops 
 for 56 days (from Visit 
2 to Visit 5): 
1) 1.55 µg/mL SkQ1 ophthalmic solution 
2) Placebo SkQ1 ophthalmic solution (Vehicle) 
During a 7-day study run-in period (beginning at the 
end of Visit 1 for the purpose of subject selection) 
prior to randomization, all subjects will receive 1-2 
drops of Placebo SkQ1 ophthalmic solution 
(Vehicle) bilaterally 
   
Summary of Visit Schedule: 
5 visits over the course of approximately 9 weeks 
• Visit 1 = Day -7 -2/+1 days,  Screening 
• Visit 2 = Day 1, Baseline,  Screening 
Confirmation, Randomization and Initiation of 
Double-Masked Treatment 
• Visit 3 = Day 29 ± 2 days 
• Visit 4 = Day 43 ± 2 days 






















SkQ1 ophthalmic solution  
Sponsor: Mitotech, SA 
Clinical Trial Protocol: VISTA-2 / 19-110-0011 
Final V1.0 04Nov2019 
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TABLE OF CONTENTS 
SYNOPSIS ......................................................................................................................................3 
TABLE OF CONTENTS ............................................................................................................14 
LIST OF ABBREVIATIONS .....................................................................................................17 
1 
INTRODUCTION ..............................................................................................................18 
2 
STUDY OBJECTIVES ......................................................................................................20 
3 
CLINICAL HYPOTHESES ..............................................................................................20 
4 
OVERALL STUDY DESIGN ............................................................................................20 
5 
STUDY POPULATION .....................................................................................................21 
5.1 
Number of Subjects (approximate) ........................................................................ 21 
5.2 
Study Population Characteristics .......................................................................... 21 
5.3 
Inclusion Criteria .................................................................................................... 21 
5.4 
Exclusion Criteria .................................................................................................... 22 
5.5 
Withdrawal Criteria (if applicable) ....................................................................... 23 
6 
STUDY PARAMETERS ....................................................................................................24 
6.1 
Efficacy Measures .................................................................................................... 24 
6.1.1 
Primary Efficacy Measures .......................................................................... 24 
6.1.2 
Key Secondary Efficacy Measures .............................................................. 24 
6.1.3 
Criteria for Effectiveness ............................................................................. 24 
6.2 
Safety Measures ....................................................................................................... 24 
7 
STUDY MATERIALS ........................................................................................................25 
7.1 
Study Drug(s) ........................................................................................................... 25 
7.1.1 
Run-In .......................................................................................................... 25 
7.1.2 
Study Drug(s)/ Formulation(s) ..................................................................... 25 
7.1.3 
Study Drug Packaging Configuration .......................................................... 25 
7.1.4 
Study Drug Storage and Accountability ...................................................... 25 
7.1.5 
Instructions for Dispensation, Use, and Administration .............................. 26 
7.2 
Other Study Supplies .............................................................................................. 26 
8 
STUDY METHODS AND PROCEDURES .....................................................................26 
8.1 
Subject Entry Procedures ....................................................................................... 26 
8.1.1 
Overview ...................................................................................................... 26 
8.1.2 
Informed Consent......................................................................................... 26 
8.1.3 
Washout Intervals ........................................................................................ 27 
8.1.4 
Procedures for Final Study Entry ................................................................. 27 
8.1.5 
Methods for Assignment to Treatment Groups: .......................................... 27 
8.2 
Concurrent Therapies ............................................................................................. 28 
8.2.1 
Prohibited Medications/Treatments ............................................................. 28 
8.2.2 
Escape Medications ..................................................................................... 28 
8.2.3 
Special Diet or Activities ............................................................................. 28 


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Clinical Trial Protocol: VISTA-2 / 19-110-0011 
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8.3 
Examination Procedures ......................................................................................... 28 
8.3.1 
Procedures to be Performed at Each Study Visit with Regard to 
Study Objective(s) ..................................................................................................... 28 
8.4 
Schedule of Visits, Measurements and Dosing ..................................................... 34 
8.4.1 
Scheduled Visits........................................................................................... 34 
8.4.2 
Unscheduled Visits ...................................................................................... 35 
8.5 
Compliance with Protocol ....................................................................................... 35 
8.6 
Subject Disposition .................................................................................................. 35 
8.6.1 
Completed Subjects ..................................................................................... 35 
8.6.2 
Discontinued Subjects .................................................................................. 35 
8.7 
Study Termination .................................................................................................. 36 
8.8 
Study Duration ........................................................................................................ 36 
8.9 
Monitoring and Quality Assurance ....................................................................... 36 
9 
ADVERSE EVENTS ..........................................................................................................36 
9.1 
Adverse Event .......................................................................................................... 36 
9.1.1 
Severity ........................................................................................................ 37 
9.1.2 
Relationship to Investigational Product ....................................................... 37 
9.1.3 
Expectedness ................................................................................................ 38 
9.2 
Serious Adverse Events ........................................................................................... 38 
9.3 
Procedures for Reporting Adverse Events ............................................................ 39 
9.3.1 
Reporting a Suspected Unexpected Adverse Reaction ................................ 39 
9.3.2 
Reporting a Serious Adverse Event ............................................................. 40 
9.4 
Procedures for Unmasking of Study Drug ............................................................ 40 
9.5 
Type and Duration of the Follow-up of Subjects after Adverse Events ............. 41 
10 
STATISTICAL HYPOTHESES AND METHODS OF ANALYSES ...........................41 
10.1 Analysis Populations ............................................................................................... 41 
10.2 Statistical Hypotheses .............................................................................................. 42 
10.3 Sample Size .............................................................................................................. 43 
10.4 Statistical Analysis ................................................................................................... 44 
10.4.1 General Considerations ................................................................................ 44 
10.4.2 Unit of Analysis ........................................................................................... 44 
10.4.3 Missing Data ................................................................................................ 44 
10.4.4 Multiplicity Adjustments ............................................................................. 45 
10.4.5 Primary Efficacy Analyses .......................................................................... 46 
10.4.6 Key Secondary Efficacy Variables .............................................................. 47 
10.4.7 Exploratory Efficacy Analyses .................................................................... 47 
10.4.8 Safety Variables ........................................................................................... 47 
10.4.9 Interim Analyses .......................................................................................... 48 


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Sponsor: Mitotech, SA 
Clinical Trial Protocol: VISTA-2 / 19-110-0011 
Final V1.0 04Nov2019 
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11 
COMPLIANCE WITH GOOD CLINICAL PRACTICES, ETHICAL 
CONSIDERATIONS, AND ADMINISTRATIVE ISSUES ...........................................48 
11.1 Protection of Human Subjects................................................................................ 48 
11.1.1 Subject Informed Consent............................................................................ 48 
11.1.2 Institutional Review Board (IRB) Approval ................................................ 48 
11.2 Ethical Conduct of the Study ................................................................................. 48 
11.3 Subject Confidentiality ........................................................................................... 49 
11.4 Documentation ......................................................................................................... 49 
11.4.1 Retention of Documentation ........................................................................ 49 
11.5 Labeling, Packaging, Storage, Accountability, and Return or Disposal of 
Study Drug ............................................................................................................... 50 
11.5.1 Labeling/Packaging...................................................................................... 50 
11.5.2 Storage of Study Drug ................................................................................. 50 
11.5.3 Accountability of Study Drug ...................................................................... 50 
11.5.4 Return or Disposal of Study Drug ............................................................... 50 
11.6 Recording of Data on Source Documents and electronic Case Reports 
Forms (eCRFs)......................................................................................................... 50 
11.7 Publications .............................................................................................................. 51 
12 
REFERENCES....................................................................................................................52 
13 
APPENDICES .....................................................................................................................53 
Appendix 1:  Schedule of Visits and Measurements .................................................................53 
Appendix 2:  Examination Procedures, Tests, Equipment, and Techniques .........................55 
Appendix 5:  Investigator’s Signature .......................................................................................75 
 
 












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Sponsor: Mitotech, SA 
Clinical Trial Protocol: VISTA-2 / 19-110-0011 
Final V1.0 04Nov2019 
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5.4 Exclusion Criteria 
Subjects must not: 
a. Have been exposed to SkQ1 ophthalmic solution; 
b. Have any clinically significant slit lamp findings at Visit 1 that may 
include active blepharitis, meibomian gland dysfunction (MGD), lid 
margin inflammation or active ocular allergies that require therapeutic 
treatment, and/or in the opinion of the investigator may interfere with 
study parameters; 
c. Be diagnosed with an ongoing ocular infection (bacterial, viral, or 
fungal), or active ocular inflammation (e.g. follicular conjunctivitis) at 
Visit 1; 
d. Have worn contact lenses within 7 days of Visit 1 or anticipate using 
contact lenses during the study; 
e. Have used any eye drops within 2 hours of Visit 1; 
f. Have previously had laser-assisted in situ keratomileusis (LASIK) 
surgery within the last 12 months; 
g. Have used Restasis®, Xiidra® or CEQUATM within 60 days of Visit 1; 
h. Have had any ocular and/or lid surgeries within 6 months of Visit 1 or 
any planned over the study period; 
i. Be using or anticipate using temporary punctal plugs during the study 
that have not been stable within 30 days of Visit 1; 
j. Be currently taking any topical ophthalmic prescription (including 
medications for glaucoma) or over-the-counter (OTC) solutions, 
artificial tears, gels or scrubs, and cannot discontinue these 
medications for the duration of the trial (excluding medications 
allowed for the conduct of the study); 
k. Have corrected visual acuity greater than or equal to logMAR+0.7 as 
assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS) 
scale in both eyes at Visit 1; 
l. Have an uncontrolled systemic disease; 
m. Be a woman who is pregnant, nursing or planning a pregnancy; 
n. Be unwilling to submit a urine pregnancy test at Visit 1 and Visit 5 (or 
early termination visit) if of childbearing potential. Non-childbearing 
potential is defined as a woman who is permanently sterilized (e.g. has 




























SkQ1 ophthalmic solution  
Sponsor: Mitotech, SA 
Clinical Trial Protocol: VISTA-2 / 19-110-0011 
Final V1.0 04Nov2019 
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• administrative reasons (e.g., inability to continue due to scheduling 
changes); 
• lost to follow up; 
• sponsor termination of study; 
• subject choice (e.g. withdrawal of consent); and 
• other 
Note: In addition, any subject may be discontinued for any sound medical 
reason at the discretion of the investigator. 
Notification of a subject discontinuation and the reason for discontinuation 
will be made to Ora and/or study sponsor and will be clearly documented 
on the eCRF. 
8.7 Study Termination 
The study may be stopped at any time by the investigator, the sponsor, and/or Ora with 
appropriate notification. 
8.8 Study Duration 
An individual subject’s participation will involve 5 visits over approximately a 9-week 
period (63 days). 
8.9 Monitoring and Quality Assurance 
During the course of the study a monitor, or designee, will make routine site visits to 
review protocol compliance, assess study drug accountability and storage conditions, 
subject safety, and ensure the study is being conducted according to the pertinent 
regulatory requirements.  The review of the subjects’ medical records will be performed 
in a manner that adequately maintains subject confidentiality.  Further details of the study 
monitoring will be outlined in a monitoring plan. 
Regulatory authorities of domestic and foreign agencies, Ora, Inc. quality assurance, the 
sponsor and/or its designees may carry out on-site inspections and/or audits, which may 
include source data checks.  Therefore direct access to the original source data will be 
required for inspections and/or audits.  All inspections and audits will be carried out 
giving consideration to data protection as well as subject confidentiality to the extent that 
local, state, and federal laws apply. 
9 ADVERSE EVENTS 
9.1 Adverse Event 
An adverse event is defined as any untoward medical occurrence associated with the use 
of a drug in humans, whether or not the event is considered IP-related.  An adverse event 
can therefore be any unfavorable and unintended sign (e.g., an abnormal laboratory 
finding), symptom, or disease occurring after the subject started dosing with the IP, 


SkQ1 ophthalmic solution  
Sponsor: Mitotech, SA 
Clinical Trial Protocol: VISTA-2 / 19-110-0011 
Final V1.0 04Nov2019 
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without any judgment about causality.  Any pre-existing medical condition that worsens 
after administration of the IP will also be considered a new adverse event.   
If there is a worsening of a medical condition that was present prior to the administration 
of the IP, this should also be considered a new adverse event and reported.  Any medical 
condition present prior to the administration of the IP that remains unchanged or 
improved should not be recorded as a treatment emergent adverse event at subsequent 
visits unless it worsens during treatment. 
Investigational Product (IP) includes the investigational drug under evaluation and 
placebo, or any other medications required by the protocol given during any stage of the 
study. 
Documentation regarding the adverse event should be made as to the nature, date of 
onset, end date, severity, relationship to IP, action(s) taken, seriousness, and outcome of 
any sign or symptom observed by the physician or reported by the patient upon indirect 
questioning.  
9.1.1 Severity 
Severity of an adverse event is defined as a qualitative assessment of the 
degree of intensity of an adverse event as determined by the investigator 
or reported to him/her by the patient/subject.  The assessment of severity 
is made irrespective of relationship to IP or seriousness of the event and 
should be evaluated according to the following scale: 
• Mild: Event is noticeable to the subject, but is easily tolerated and 
does not interfere with the subject’s daily activities. 
• Moderate: Event is bothersome, possibly requiring additional 
therapy, and may interfere with the subject’s daily activities. 
• Severe: Event is intolerable, necessitates additional therapy or 
alteration of therapy, and interferes with the subject’s daily 
activities. 
9.1.2 Relationship to Investigational Product 
The relationship of each adverse event to the Investigational Product (IP) 
should be determined by the investigator using these explanations: 
• Definite: When there are good reason and sufficient documentation 
to demonstrate a direct causal relationship between investigational 
product and AE; 
• Probable: When there are good reasons and sufficient 
documentation to assume a causal relationship in the sense of 
plausible, conceivable, likely but not necessarily highly probable. 
• Possible: When there is sufficient information to accept the 
possibility of a causal relationship in the sense of not impossible 
and not unlikely, although the connection is uncertain or doubtful, 
for example, due to missing data or insufficient evidence. 
None: When there is sufficient information to accept a lack of a 
causal relationship, in the sense of impossible and improbable. 


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Clinical Trial Protocol: VISTA-2 / 19-110-0011 
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• Unclassified: When the causal relationship is not assessable for 
whatever reason due to insufficient evidence, conflicting data or 
poor documentation. 
Suspected adverse reaction means any adverse event for which there is a 
reasonable possibility that the IP caused the adverse event.  “Reasonable 
possibility” means there is evidence to suggest a causal relationship 
between the IP and the adverse event.  Types of evidence that would 
suggest a causal relationship between the IP and the adverse event include: 
a single occurrence of an event that is uncommon and known to be 
strongly associated with drug exposure (e.g., angioedema, hepatic injury, 
Stevens-Johnson Syndrome); one or more occurrences of an event that is 
not commonly associated with drug exposure, but is otherwise uncommon 
in the population exposed to the drug (e.g., tendon rupture); an aggregate 
analysis of specific events observed in a clinical trial (such as known 
consequences of the underlying disease or condition under investigation or 
other events that commonly occur in the study population independent of 
drug therapy) that indicates those events occur more frequently in the drug 
treatment group than in a concurrent or historical control group. 
9.1.3 Expectedness 
The expectedness of an adverse event should be determined based upon 
existing safety information about the IP using these explanations: 
• Unexpected: An adverse event that is not listed in the 
Investigator’s brochure or is not listed at the specificity or severity 
that has been observed. 
• Expected: An adverse event that is listed in the Investigator’s 
brochure at the specificity and severity that has been observed. 
• Not Applicable: Any adverse event that is unrelated to the IP. 
Adverse events that are mentioned in the Investigator’s brochure as 
occurring with a class of drugs or as anticipated from the pharmacological 
properties of the drug, but are not specifically mentioned as occurring with 
the particular drug under investigation are to be considered unexpected. 
The investigator should initially classify the expectedness of an adverse 
event, but the final classification is subject to the Medical Monitor’s 
determination. 
9.2 Serious Adverse Events 
An adverse event is considered serious if, in the view of either the investigator or 
sponsor, it results in any of the following outcomes: 
• Death; 
• A life-threatening adverse event; 


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Clinical Trial Protocol: VISTA-2 / 19-110-0011 
Final V1.0 04Nov2019 
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Note:  An adverse event is considered “life-threatening” if, in the view of 
either the investigator or sponsor, its occurrence places the patient or subject 
at immediate risk of death.  It does not include an adverse event that, had it 
occurred in a more severe form, might have caused death. 
• Inpatient hospitalization or prolongation of existing hospitalization; 
Note:  The term “inpatient hospitalization” refers to any inpatient admission 
(even if less than 24 hours).  For chronic or long-term inpatients, inpatient 
admission includes transfer within the hospital to an acute/intensive care 
inpatient unit.  Inpatient hospitalization does not include:  emergency room 
visits; outpatient/same-day/ambulatory procedures; observation/short stay 
units; rehabilitation facilities; hospice facilities; nursing homes; or clinical 
research/phase 1 units. 
Note:  The term “prolongation of existing hospitalization” refers to any 
extension of an inpatient hospitalization beyond the stay anticipated or 
required for the reason for the initial admission as determined by the 
investigator or treating physician. 
• A persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions; 
Note:  A serious adverse event specifically related to visual threat would be 
interpreted as any potential impairment or damage to the subject’s eyes (e.g., 
hemorrhage, retinal detachment, central corneal ulcer or damage to the optic 
nerve). 
• A congenital anomaly/birth defect. 
Important medical events that may not result in death, are life-threatening, or 
require hospitalization may be considered serious when, based upon appropriate 
medical judgment, they may jeopardize the patient or subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this 
definition. 
9.3 Procedures for Reporting Adverse Events 
All adverse events and their outcomes must be reported to Ora, the study sponsor, and the 
IRB as required by the IRB, federal, state, or local regulations and governing health 
authorities and recorded on the appropriate eCRF.  
9.3.1 Reporting a Suspected Unexpected Adverse Reaction 
All adverse events that are ‘suspected’ and ‘unexpected’ are to be reported 
to Ora, the study sponsor and the IRB as required by the IRB, federal, 
state, or local regulations and governing health authorities. 


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Clinical Trial Protocol: VISTA-2 / 19-110-0011 
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9.3.2 Reporting a Serious Adverse Event 
To ensure subject safety, all serious adverse events, regardless of 
relationship to the study drug, must be immediately reported.  All 
information relevant to the serious adverse event must be recorded on the 
appropriate eCRF.  The investigator is obligated to pursue and obtain 
information requested by Ora and/or the sponsor in addition to that 
information reported on the eCRF.  All subjects experiencing a serious 
adverse event must be followed up and the outcome reported. 
In the event of a serious adverse event, the investigator must notify Ora 
and the sponsor immediately (within 24 hours); obtain and maintain in 
his/her files all pertinent medical records, information, and medical 
judgments from colleagues who assisted in the treatment and follow-up of 
the subject; provide Ora and the study sponsor with a complete case 
history, which includes a statement as to whether the event was or was not 
suspected to be related to the use of the study drug; and inform the IRB of 
the adverse event within their guidelines for reporting serious adverse 
events.  
Serious adverse events should be reported within one day to the contacts 
listed below:  
                                   
 
                                    
 
                            
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9.4 Procedures for Unmasking of Study Drug 
All subjects, investigators, and study personnel involved with the conduct of the study 
will be masked with regard to treatment assignments. When medically necessary, the 
investigator may need to determine what treatment arm has been assigned to a subject.  
When possible (i.e., in non-emergent situations), Ora and/or the study sponsor should be 
notified, when possible, before unmasking study drug as described in the following 
paragraph. 
















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Clinical Trial Protocol: VISTA-2 / 19-110-0011 
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Other safety endpoints will be summarized by treatment group and visit 
using descriptive statistics.  Changes or shifts from baseline will also be 
summarized where appropriate. 
10.4.9  Interim Analyses 
There will be no interim analyses. 
11 COMPLIANCE WITH GOOD CLINICAL PRACTICES, 
ETHICAL CONSIDERATIONS, AND ADMINISTRATIVE 
ISSUES 
This study will be conducted in compliance with the protocol, Good Clinical Practices 
(GCPs), including the International Conference on Harmonization (ICH) Guidelines, and 
in general, consistent with the Declaration of Helsinki.  In addition, all applicable local, 
state, and federal requirements relevant to the use of study drugs in the countries involved 
will be adhered to. 
11.1 Protection of Human Subjects 
11.1.1 Subject Informed Consent 
Informed consent/assent must take place before any study specific 
procedures are initiated.  Signed and dated written informed consent must 
be obtained from each subject prior to enrollment into the study.   
All informed consent forms must be approved for use by the sponsor and 
receive approval/favorable opinion from an IRB prior to their use.  If the 
consent form requires revision (e.g., due to a protocol amendment or 
significant new safety information), it is the investigator’s responsibility to 
ensure that the amended informed consent is reviewed and approved by 
Ora prior to submission to the governing IRB and that it is read, signed 
and dated by all subjects subsequently enrolled in the study as well as 
those currently enrolled in the study. 
11.1.2 Institutional Review Board (IRB) Approval 
This study is to be conducted in accordance with Institutional Review 
Board regulations (U.S. 21 CFR Part 56.103).  The investigator must 
obtain appropriate IRB approval before initiating the study and re-
approval at least annually. 
Only an IRB approved version of the informed consent form will be used. 
11.2 Ethical Conduct of the Study 
This study will be conducted in accordance with the ethical principles that originated 
with the Declaration of Helsinki. 


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11.3 Subject Confidentiality 
All personal study subject data collected and processed for the purposes of this study 
should be maintained by the investigator and his/her staff with adequate precautions as to 
ensure that the confidentiality of the data in accordance with local, state, and federal laws 
and regulations. 
Monitors, auditors and other authorized representatives of Ora, the sponsor, the IRB 
approving this study, the FDA, the DHHS, other domestic government agencies, and 
other foreign regulatory agencies will be granted direct access to the study subject’s 
original medical and study records for verification of the data and/or clinical trial 
procedures. Access to this information will be permitted to the aforementioned 
individuals to the extent permitted by law. 
A report of the results of this study may be published or sent to the appropriate health 
authorities in any country in which the study drug may ultimately be marketed, but the 
subject’s identity will not be disclosed in these documents. 
11.4 Documentation 
Source documents may include a subject’s medical records, hospital charts, clinic charts, 
the investigator’s study subject files, as well as the results of diagnostic tests such as X-
rays, laboratory tests, and EKGs.  The investigator’s copy of the eCRF serves as the 
investigator’s record of a subject’s study-related data. 
11.4.1 Retention of Documentation 
All study-related source documents, correspondence, patient records, 
consent forms, record of the distribution and use of all study drug and 
copies of case report forms should be maintained on file for at least two 
years after the last approval of a marketing application in an ICH region 
and until there are no pending or contemplated marketing applications in 
an ICH region; or until at least two years have elapsed since the formal 
discontinuation of clinical development of the study drug. These 
documents will be retained for a longer period if required by the 
applicable regulatory requirements or by an agreement with the sponsor.  
It is the responsibility of the sponsor to inform the investigator/institution 
as to when these documents no longer need to be retained. 
If the responsible investigator retires, relocates, or for other reasons 
withdraws from the responsibility of keeping study records, custody must 
be transferred to a person who will accept the responsibility.  The sponsor 
must be notified in writing of the name and address of the new custodian. 




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entry should make clear who made the correction and when, by adding to the correction 
his/her initials as well as the date of the correction. 
11.7 Publications 
Authorship and manuscript composition will reflect cooperation among all parties 
involved in the study.  Authorship will be established before writing the manuscript.  Ora 
and the study sponsor will have the final decision regarding the manuscript and 
publication. 
 
 


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12 REFERENCES 
1. 
Bakeeva LE, Barskov IV, Egorov MV, et al. Mitochondria-targeted 
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