Clinical trial NCT05400226
Conditions: Lung Cancer
Sponsor: Vergent Bioscience, Inc.
Start date: 2022-05-24; Completion date: 2023-12-15
Enrollment: 40 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
A Phase 2 open label study to evaluate safety and efficacy of VGT-309 to identify cancer in up to 40 subjects undergoing lung cancer surgery.

Detailed description:
A Phase 2, open-label study to evaluate the safety and efficacy of VGT-309, a tumor-targeted, activatable fluorescent imaging agent, to identify cancer in subjects undergoing lung cancer surgery. A total of 40 subjects will be enrolled to ensure at least 38 evaluable subjects with the option to expand enrollment by protocol amendment if deemed necessary to meet primary and/or secondary objectives.

Following agreement with and signing of the informed consent, subjects will undergo screening measurements for the study. Assessments include the following, unless they have been done within 4 weeks prior to the anticipated dosing:

1. Medical, surgical and medication history.
2. Complete physical exam, including vital signs and weight.
3. Standard pre-operative chemistry, hematology, coagulation and urinalysis clinical laboratory studies.
4. 12-lead ECG.
5. Serum pregnancy test for females of child-bearing potential.

Following clearance of all enrollment criteria, each subject will receive an IV administration of 0.32 mg/kg VGT-309 at 12-36 hours prior to surgery (refer to section VGT-309 Dosing, below). Upon dosing, subjects will be observed for up to 2 hours and asked about possible treatment emergent adverse events.

Subjects will undergo surgical resection as planned and within the time specified following VGT-309 dosing. Measurements of efficacy will be taken during surgery and during the pathological examination of all surgical specimens.

Following surgery, subjects will be monitored for safety during their hospitalization. After discharge from the hospital, and approximately 14 days post-surgery, the subjects will be contacted by telephone to assess their well-being. Between 19 to 39 days post-surgery, subjects will either return to the clinic or participate in a telehealth visit for final safety assessments. If there are no adverse events requiring further follow up, subjects will then be released from the study.

Arms: arm 1: Single arm in an open label study
Interventions: intervention 1: VGT-309
Intervention descriptions: intervention 1: VGT-309 is an tumor-targeted, activatable fluorescent imaging agent which will be used with near infrared imaging during surgery to identify tumor.

Protocol documents:
Prot_000.pdf: 
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TABLE OF CONTENTS 
Study Synopsis ......................................................................................................................... i 
1. 
INTRODUCTION .......................................................................................................... 1 
1.1 
BACKGROUND AND RATIONALE ................................................................................................................. 1 
1.2 
NONCLINICAL IN VITRO AND IN VIVO EXPERIENCE ........................................................................................ 1 
1.2.1 
Genotoxicity ................................................................................................................................. 2 
1.2.2 
Safety Pharmacology ................................................................................................................... 2 
1.2.3 
Local Tolerance ............................................................................................................................. 2 
1.2.4 
Single Dose Toxicity in Sprague-Dawley Rats and Beagle Dogs ................................................... 2 
1.2.5 
VGT-309 NIR imaging of Lung Tumors in Dogs ............................................................................ 2 
1.3 
CLINICAL EXPERIENCE ............................................................................................................................. 3 
2. 
STUDY OBJECTIVE AND ENDPOINTS .................................................................. 3 
2.1 
OBJECTIVES: ......................................................................................................................................... 3 
2.1.1 
Primary Efficacy Objective: ........................................................................................................... 3 
2.1.2 
Secondary Efficacy Objective: ....................................................................................................... 4 
2.1.3 
Safety Objective: ........................................................................................................................... 4 
2.2 
ENDPOINTS: .......................................................................................................................................... 4 
2.2.1 
Primary Efficacy Endpoints: .......................................................................................................... 4 
2.2.2 
Secondary Efficacy Endpoints: ...................................................................................................... 4 
2.2.3 
Exploratory Endpoints: ................................................................................................................. 4 
2.2.4 
Safety Endpoints: .......................................................................................................................... 5 
3. 
STUDY DESIGN ............................................................................................................ 5 
4. 
STUDY DRUG – VGT-309 ........................................................................................... 5 
4.1 
VGT-309 DESCRIPTION .......................................................................................................................... 6 
4.2 
VGT-309 PROPOSED DOSE ..................................................................................................................... 6 
4.3 
VGT-309 PREPARATION ......................................................................................................................... 6 
4.4 
VGT-309 DOSE ADMINISTRATION ............................................................................................................ 6 
4.5 
VGT-309 STORAGE AND ACCOUNTABILITY ................................................................................................. 6 
4.6 
VGT-309 PACKAGING AND LABELING ........................................................................................................ 6 
5. 
SUBJECT POPULATION ............................................................................................ 7 
5.1 
ENROLLMENT ........................................................................................................................................ 7 
5.2 
INCLUSION CRITERIA ............................................................................................................................... 7 
5.3 
EXCLUSION CRITERIA .............................................................................................................................. 8 
5.4 
REPLACEMENT OF SUBJECTS ..................................................................................................................... 8 
6. 
STUDY PROCEDURES ................................................................................................ 8 
6.1 
STUDY VISITS ........................................................................................................................................ 8 
6.1.1 
Informed Consent ......................................................................................................................... 8 
6.1.2 
Screening (Days -60 to -1) ............................................................................................................ 8 
6.1.3 
Day 1: VGT-309 Dosing ................................................................................................................. 9 
6.1.4 
Day 1 or 2: Surgery and Pathology ............................................................................................... 9 
6.1.5 
Day 3: In-hospital follow up ........................................................................................................ 10 
6.1.6 
Day 14 +/- 2 days: Telephone follow up ..................................................................................... 10 
6.1.7 
Days 19 - 39: End of Study Follow up -OR- Early withdrawal ..................................................... 10 
7. 
STOPPING THE STUDY OR EARLY WITHDRAWAL OF SUBJECT ............. 10 
7.1 
INDIVIDUAL SUBJECT WITHDRAWAL ......................................................................................................... 10 
8. 
EFFICACY EVALUATIONS ..................................................................................... 10 
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8.1 
PRIMARY EFFICACY ASSESSMENTS: .......................................................................................................... 11 
8.2 
SECONDARY EFFICACY ASSESSMENTS: ...................................................................................................... 11 
8.3 
INTRA-OPERATIVE EVALUATIONS ............................................................................................................. 11 
8.4 
POST-OPERATIVE EVALUATIONS .............................................................................................................. 11 
9. 
SAFETY EVALUATIONS .......................................................................................... 11 
9.1 
DATA SAFETY COMMITTEE (DSC) ........................................................................................................... 11 
9.1.1 
Constitution of the DSC .............................................................................................................. 11 
9.1.2 
DSC General Rules ...................................................................................................................... 11 
9.2 
ASSESSMENT OF SAFETY ........................................................................................................................ 12 
9.2.1 
Adverse Events ........................................................................................................................... 12 
9.2.2 
Serious Adverse Events (SAEs) .................................................................................................... 14 
9.2.3 
Clinical Laboratory Abnormalities and Other Abnormal Assessments ....................................... 15 
9.2.4 
Pregnancy Reporting .................................................................................................................. 15 
10. STATISTICAL METHODS ....................................................................................... 16 
10.1 
SAMPLE SIZE DETERMINATION ................................................................................................................ 16 
10.2 
POPULATIONS FOR ANALYSIS .................................................................................................................. 16 
10.3 
EFFICACY ANALYSES .............................................................................................................................. 16 
10.3.1 
Primary Efficacy Objective ..................................................................................................... 17 
10.3.2 
Primary Efficacy Endpoints .................................................................................................... 17 
10.3.3 
Secondary Efficacy Objectives ............................................................................................... 17 
10.3.4 
Secondary Efficacy Endpoints ................................................................................................ 17 
 
 
10.4 
SAFETY ANALYSIS ................................................................................................................................. 18 
10.4.1 
Adverse Events ....................................................................................................................... 18 
10.4.2 
Clinical Laboratory Data ........................................................................................................ 18 
10.4.3 
Other Safety Evaluations ....................................................................................................... 18 
11. RECORDING AND COLLECTION OF DATA ...................................................... 18 
11.1 
CASE REPORT FORM ............................................................................................................................. 18 
11.2 
STUDY FILES AND SUBJECT SOURCE DOCUMENTS ....................................................................................... 19 
11.3 
MONITORING ...................................................................................................................................... 19 
11.4 
AUDIT ................................................................................................................................................ 19 
11.5 
RETENTION OF DATA ............................................................................................................................ 19 
12. PUBLICATION POLICY AND SHARING OF DATA ........................................... 20 
ATTACHMENT A: Schedule of Assessments ………………………………………………….. 21 
 
ATTACHMENT B: Summary of Changes ………………………………………………………22 
 
 
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List of Abbreviations: 
 
 
AE 
Adverse Event 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
APTT 
Activated Partial Thromboplastin Time 
AR 
Adverse Reaction 
AST 
Aspartate Aminotransferase 
BP 
Blood Pressure 
BUN 
Blood Urea Nitrogen 
CFR 
Code of Federal Regulations 
CT 
Computed Tomography 
eCRF 
Electronic Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DSC 
Data Safety Committee 
ECG 
Electrocardiogram 
EDC 
Electronic Data Capture  
FDA 
Food and Drug Administration 
GEE 
Generalized Estimating Equation 
GCP 
Good Clinical Practice 
GGT 
Gamma-glutamyl-transferase 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practice 
Hgb 
Hemoglobin 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization  
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat 
IV 
Intravenous 
kg 
kilogram 
L 
Liter 
LDH 
Lactate Dehydrogenase 
LFT 
Liver Function Test 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
mL 
Milliliter 
NIR 
Near-infrared (imaging) 
NOAEL 
No-Observed-Adverse-Effect-Level 
PI 
Principal Investigator 
PK 
Pharmacokinetic 
RBC 
Red Blood Cell 
ROC 
Receiver Operating Characteristic  
SAE 
Serious Adverse Event 
SD 
Sprague-Dawley (rats) 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TC 
Total cholesterol 
TG 
Triglyceride 
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When possible, the assessments should be done in the order listed here to avoid the demands 
of sample collection and ECG prior to the subject passing basic entry criteria requirements.  
1. Review of eligibility requirements – inclusion and exclusion criteria. 
2. Collection of demographic information and medical and surgical history, including review 
of prior and ongoing medications (taken in previous 30 days). 
3. Physical Exam. 
4. Height and weight measurements. 
5. Vital signs measurement (blood pressure, pulse rate, respiratory rate and oral/tympanic 
temperature). 
6. Standard 12-lead ECG (subject should be resting in a supine position for at least 5 minutes 
prior). 
7. Blood sample collection for clinical chemistry, hematology and coagulation. 
8. Urine sample collection for urinalysis. 
9. In women of child-bearing potential, blood sample for serum pregnancy test. 
Upon establishment of eligibility, subjects will be assigned to a dose and scheduled for 
admission to the hospital.  
6.1.3 
Day 1: VGT-309 Dosing 
Subjects will check in to the hospital or infusion center as scheduled. After confirming their 
eligibility by reviewing their medical history and concomitant medications for any changes 
since screening, those subjects still considered eligible will undergo the following: 
1. Targeted Physical Exam (Focus on heart, lungs and any area of change since screening). 
2. Measurement of weight (ONLY if not done within 7 days prior to dosing). 
3. Review of concomitant medications. 
4. Vital signs measurement (blood pressure, pulse rate, respiratory rate and oral/tympanic 
temperature). 
5. Standard 12-lead ECG (subject should be resting in a supine position for at least 5 minutes 
prior) (ONLY if not done within 4 weeks prior to dosing). 
6. In women of child-bearing potential, blood sample for pregnancy test. 
7. Blood sample for chemistry, hematology, coagulation. (ONLY if not done within 4 weeks 
prior to dosing). 
8. Urine sample collection for urinalysis (ONLY if not done within 4 weeks prior to 
admission). 
9. VGT-309 dosing to take place at 12-36 hours prior to induction of general anesthesia. 
(Refer to Section 4: Study Drug – VGT-309, for instruction on dose preparation and dosing 
procedures). 
10. Upon dosing, VGT-309 subjects: 
• Will be observed and queried for possible adverse events. 
• Will have ECGs taken immediately after and 30 minutes after infusion ends. 
• Will have vital signs taken at 30 minutes and 2 hours after infusion ends. 
6.1.4 
Day 1 or 2: Surgery and Pathology 
Following dosing with VGT-309, subjects will undergo planned standard of care surgical 
resection for their lung nodule or mass followed by pathological assessment of the resected 
tumor(s) and/or nodule(s) (Refer to Section 8: Efficacy Evaluations, for details). 
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6.1.5 
Day 3: In-hospital follow up 
The day after surgery (between 24 to 48 hours after surgery), subjects will undergo the 
following: 
1. Targeted Physical Exam (Focus on heart, lungs and any area of change since screening). 
2. Review of concomitant medications. 
3. Vital signs measurement (blood pressure, pulse rate, respiratory rate and oral/tympanic 
temperature). 
4. Blood sample for chemistry, hematology, coagulation. 
5. Urine sample collection for urinalysis. 
6. Observation for and solicitation of adverse events. 
6.1.6 
Day 14 +/- 2 days: Telephone follow up 
Each subject will be contacted by telephone by a designated member of the study team, to 
inquire as to their general well-being, query for possible adverse events and any changes in 
their use of concomitant medications.  If deemed necessary, a subject may be asked to return 
to the clinic for treatment or assessment of a possible adverse event. 
6.1.7 
Days 19 - 39: End of Study Follow up -OR- Early withdrawal 
This visit may be conducted in clinic or by telehealth visit. During this visit or if the subject 
withdraws from the study early, the following assessments will be done: 
1. Review of concomitant medications for changes since last visit. 
2. Observation for and solicitation of adverse events. 
Following completion of these assessments, subjects will be released from the study. 
Additional follow-up may be necessary if an SAE is reported and has not yet resolved (See 
Section 10.2.2 for details). 
7. STOPPING THE STUDY OR EARLY WITHDRAWAL OF SUBJECT 
This study may be stopped (terminated) by the Sponsor at any time and for any reason. Subjects 
on study at the time the study is stopped will be asked to complete all assessments in the Early 
Termination visit (see Attachment A). 
NOTE: The study may also be stopped or delayed by the DSC as outlined in Section 9.1.2. 
7.1 Individual Subject Withdrawal 
The participation of an individual subject in the study may be terminated in the following 
circumstances: 
1. Withdrawal of informed consent by the subject. 
2. Any occurrence that, in the Investigator’s opinion, makes continued participation 
contrary to the subject’s best interests. 
If an Investigator removes a subject from the study, or if a subject declines further study 
participation, an Early Withdrawal Visit, consisting of the assessments required at the Day 30 
visit, will be completed as soon as possible.  It will be the responsibility of the Investigator to 
ensure that all withdrawn subjects receive appropriate follow-up and medical care if needed. 
8. EFFICACY EVALUATIONS 
Intra-operative and post-operative evaluations will be used to support the efficacy endpoints 
of the study. 
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December 2012.  A copy of this guidance will be provided in the to the site and should be 
referred to if and when the following do not provide sufficient guidance for an investigator to 
make an assessment regarding the occurrence, severity, relationship and expectedness of an 
adverse event (AE). 
Adverse event solicitation and recording will begin immediately following dosing with the 
study product (VGT-309) and will include only on-treatment (treatment-emergent) events. 
Any changes to a subject’s health that occur between the signing of the informed consent and 
dosing will be recorded as updates to the subject’s medical history.  
Subjects will be instructed to report AEs during the study and staff will query subjects 
regarding AEs throughout the study. The Investigator (and/or designee) must document all 
AEs reported from the time of dosing through completion of the End-of-study Visit (Days 22-
36). Any subject who is withdrawn from the study due to an AE shall be followed until the 
event has resolved or stabilized or 30 days after last dose and the Investigator will document 
available follow-up information on the subject’s source documentation and CRF 
9.2.1.1 Definition of an Adverse Event 
The FDA Safety Guidance, referencing 21CFR312.32(a), defines an Adverse Event as follows: 
Adverse event means any untoward medical occurrence associated with the use of a 
drug in humans, whether or not considered drug related.    
An adverse event (also referred to as an adverse experience) can be any unfavorable 
and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a drug and does not imply any judgment about 
causality.  An adverse event can arise with any use of the drug (e.g., off-label use, use 
in combination with another drug) and with any route of administration, formulation, 
or dose, including an overdose.   
Adverse Events are NOT: 
• Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, transfusion).  
The condition that leads to the procedure is the AE. 
• Situations where an untoward medical occurrence has not occurred (e.g., hospitalization 
for elective surgery, social and/or convenience admissions). 
9.2.1.2 Evaluating and Reporting of Adverse Events 
All AEs (i.e., a new event or an exacerbation of a pre-existing condition) that occur after dosing 
with VGT-309 and up to 30 days post-dosing (if the subject is withdrawn due to an AE) or 
during the End-of-Study Visit (Days 22 – 36) must be recorded as an AE or SAE (if applicable), 
on the Adverse Event eCRF.  The Investigator must follow all AEs until the AE resolves, or 
until the Investigator and/or the Medical Monitor determine the event is chronic or clinically 
stable.  If an AE remains unresolved at the conclusion of the study, the Investigator and 
Medical Monitor will make a clinical assessment to determine whether continued follow-up of 
the AE is warranted.  All subjects who have received any exposure to VGT-309 (even if dosing 
is not completed) will be evaluated for AEs. 
The Investigator should attempt to establish a diagnosis of the event based on signs, symptoms 
and/or other clinical information.  In such cases, the diagnosis should be documented as the 
AE and not the individual signs/symptoms. 
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All AEs must be promptly documented on the Adverse Event eCRF and assessed by the 
Investigator.  Details of the event must include the dates of onset and resolution, severity, 
relationship to study drug, seriousness, and whether the event caused the subject to withdraw 
from the study, outcome and timing with regard to administration of the study drug. 
Grade: Each AE will be assigned a “Grade” based on the Common Terminology Criteria for 
Adverse Events (CTCAE). Version 5.0 of the CTCAE will be used for this study. Refer to 
Section 9.1.2 for stopping rules based on the assigned Grade of AE. 
Severity: Severity should be graded and recorded as follows: 
• Mild: Awareness of event but easily tolerated. 
• Moderate: Discomfort enough to cause interference with usual activity. 
• Severe: Inability to carry out usual activity, incapacitating, requires medical intervention. 
Relationship: The relationship of the Adverse Event to the study drug will be determined by 
the Principal Investigator, and assessed using the following definitions: 
• Related:  There is a distinct temporal relationship between the event onset and 
administration of the study drug.  There is a known reaction to agent or chemical group 
or predicted by known pharmacology.  The event cannot be explained by subject’s 
clinical state or other factors. 
• Unrelated:  Evidence exists that the AE has an etiology other than the study drug (e.g., 
pre-existing condition, underlying disease, intercurrent illness, or concomitant 
medication). 
These criteria, in addition to good clinical judgment, should be used as a guide for determining 
the causal assessment.  If it is felt that the event is not related to study drug therapy, then an 
alternative explanation should be provided. 
9.2.2 
Serious Adverse Events (SAEs) 
All SAEs as defined below and that occur after the first dose of VGT-309 and up to 30 days 
post-dose must be reported to Vergent as soon as the site becomes aware of them.  Any SAEs 
occurring more than 30 days after last study drug administration and considered at least 
possibly drug-related must also be reported. 
An SAE is an AE from this study that results in any of the following outcomes:  
• Death.  
• Life-threatening situation (subject is at immediate risk of death). 
• Inpatient hospitalization or prolongation of existing hospitalization. 
• Persistent or significant disability/incapacity. 
Congenital anomaly/birth defect in the offspring of a subject who received study drug.  
(Refer to Section 9.2.4 for reporting of pregnancy) 
NOTE: Important medical events that may not result in death, be immediately life-threatening, 
or require hospitalization, may be considered an SAE when, based upon appropriate medical 
judgment, they may jeopardize the subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition.  
A life-threatening AE is defined as any adverse experience that places the subject in the view 
of the Investigator, at immediate risk of death from the event as it occurred.  This does not 
include an event that might have led to death, if it had occurred with greater severity. 
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 “Inpatient hospitalization” means the subject has been formally admitted to a hospital for 
medical reasons, for any length of time.  Presentation and care within an emergency department 
does not necessarily constitute an SAE.  Complications that occur during hospitalization are 
AEs.  If a complication prolongs hospitalization, it is an SAE. 
All deaths, regardless of cause, must be reported for subjects on study (within 28 days of last 
study drug dose).  The SAE term should reflect the event that leads to the death with “death” 
recorded as the outcome 
9.2.2.1 SAE Reporting Requirements to Vergent  
The procedure for reporting SAEs, regardless of causal relationship, is as follows: 
• Within 24 hours of the Investigator’s knowledge of an SAE, the site must notify Vergent 
by phone call to their site monitor, medical monitor or other Vergent representative. They 
should also immediately complete the AE eCRF and select “Serious”. 
• This initial reporting of an SAE should contain as much information as is available to the 
Investigator.  Submission of the SAE via the EDC should not be delayed in order to collect 
additional information to complete the form.  
• Follow-up SAE reports may be generated in cases in which additional information becomes 
available.  Hospital records, autopsy reports, and other documents may become available 
and scanned copies can be provided to Vergent when applicable.  The follow-up SAE 
report should describe whether the event has resolved or continues, if and how it was 
treated, whether the blind was broken or not, and whether the subject continued or 
withdrew from study participation. 
• Vergent will distribute completed SAE forms, which may be used to notify the IRB/EC 
when applicable, via a secure internet-based document depository. 
The Investigator must take all therapeutic measures necessary for resolution of the SAE.  Any 
medications necessary for treatment of the SAE must be recorded onto the concomitant 
medication section of the subject’s eCRF.  However, treatment medication should only be 
recorded in the narrative description section of the SAE form. 
9.2.3 
Clinical Laboratory Abnormalities and Other Abnormal Assessments 
Laboratory abnormalities are usually not recorded as AEs unless considered to be clinically 
significant by the site clinician.  An abnormal laboratory result will be considered an AE if it 
induces clinical signs or symptoms, if the abnormality is of a degree that requires active 
management (e.g., discontinuation of the study drug, dose modification) or when the event is 
requiring treatment or other therapeutic intervention (e.g., iron supplements, blood transfusion, 
etc.). 
The Investigator will evaluate the relationship of any significantly abnormal result to protocol 
treatment and clinical condition, if possible.  All clinically significant abnormal laboratory 
results will be followed until they return to normal or become stabilized. 
9.2.4 
Pregnancy Reporting 
Any pregnancy that occurs between dosing through Day 30, should be verified and recorded.  
Subjects will sign a separate consent form allowing the Study Site and Sponsor to follow up 
with them through 6 weeks post-delivery or termination of the pregnancy. 
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This study will be descriptive in nature, however, additional post-hoc statistical tests may be 
performed and will be further described in the SAP. 
10.3.1 
Primary Efficacy Objective  
Identification of the proportion of subjects with at least one Clinically Significant Event 
(CSE) as defined by: 
 
 
 
 
 
 
10.3.2 
Primary Efficacy Endpoints 
The proportion of subjects with at least one Clinically Significant Event (CSE) as defined by: 
 
 
 
 
 
10.3.3 
Secondary Efficacy Objectives 
• 
To evaluate the sensitivity, specificity, positive predictive value (PPV) and negative 
predictive value (NPV) of VGT-309 to detect cancer utilizing near-infrared (NIR) 
fluorescence and histopathology results. 
10.3.4 
Secondary Efficacy Endpoints 
1. Sensitivity
 
 
2. Specificity
 
 
3. Positive predictive value (PPV) 
 
 
4. Negative predictive value (NPV) 
 
 
* TP = true positive (fluorescent lesion that is cancer), FP = false positive (fluorescent lesion 
that is not cancer), TN = true negative (non-fluorescent lesion that is not cancer), FN =false 
negative (non-fluorescent lesion that is cancer). 
 
 
 
 
 
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10.4 Safety Analysis 
Unless otherwise specified, safety analyses will be conducted in the safety population. Safety 
will be evaluated by assessment of clinical laboratory tests, PE, ECG and vital sign 
measurements at various time points during the study, and by the documentation of AEs.  
10.4.1 
Adverse Events 
Adverse events will be summarized by the Medical Dictionary for Regulatory Activities 
(MedDRA) system organ class and preferred term. Events will be summarized on the basis of 
the date of onset for the event. A treatment-emergent adverse event (TEAE) is defined as any 
adverse event that begins on or after the date of administration of VGT-309. 
An overall summary of TEAEs will be provided. The following summaries (number and 
percentage of subjects) of TEAEs (by System Organ Class and Preferred Term) will be 
provided: 
• TEAEs. 
• Treatment-related TEAEs. 
• TEAEs leading to study drug discontinuation. 
• Serious TEAEs. 
• Treatment-related Serious TEAEs. 
No statistical testing will be performed.  All AEs collected during the study will be presented 
in a listing. Additionally, a listing will be provided for any AEs leading to death. 
10.4.2 
Clinical Laboratory Data 
Summaries of clinical laboratory results and change from baseline will be performed using 
descriptive statistics by scheduled visit. No statistical testing will be performed. 
10.4.3 
Other Safety Evaluations 
Individual data for physical examination findings, prior and concomitant medications and 
medical history will be provided. Twelve-lead ECGs and vital signs measurements will be 
listed by subject and summarized by incidence of events/abnormalities or descriptive statistics 
as appropriate. No statistical testing will be performed. 
11. RECORDING AND COLLECTION OF DATA 
11.1 Case Report Form 
The Investigator or designee will record all data collected by an Electronic Data Capture 
system (EDC) containing the electronic Case Report Form (eCRF) provided for that purpose.  
The site will be suitably trained on the use of the EDC and eCRF and appropriate site personnel 
will be provided electronic signatures. 
All site entries will be made in a secured web site and the Principal Investigator will review 
the record for completeness.  Upon completion of the review, the PI will sign electronically in 
the signature page of the eCRF.  
The Investigator or designee will make necessary eCRF corrections.  The investigator must 
authorize the corrections to the entered data on eCRF. 
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Specific instructions on use of the EDC system and guidelines for data entry and correction 
will be provided to the sites in the study manual. 
11.2 Study Files and Subject Source Documents 
Subject confidentiality is strictly held in trust by the participating investigators, research staff, 
Vergent and their designees.  This confidentiality is extended to cover testing of biological 
samples in addition to the clinical information relating to subjects.  Authorized representatives 
of Vergent may inspect all documents and records required to be maintained by the 
Investigator, including but not limited to, medical records (office, clinic or hospital) and 
pharmacy records for the subjects in this study.  Any data, specimens, forms, reports, and other 
records that leave the site will be identified only by a subject identification number to maintain 
confidentiality. 
The Investigator must maintain adequate and accurate records to enable the conduct of the 
study to be fully documented and the study data to be subsequently verified.  These documents 
include Investigators’ Study Files and original subject clinical source documents generated at 
the study site.  The term “original” means the first recording of the data. 
The Investigator will ensure the site master files are maintained, including the study protocol 
and its amendments, IRB and regulatory approvals with associated correspondence, informed 
consents, study drug records, staff curriculum vitae, all correspondence, and other appropriate 
documents. 
Subject clinical source documents may include, but are not limited to, subject hospital/clinic 
records, physicians’ and nurses’ notes, appointment books, laboratory reports, ECGs, 
radiographs, and consultant letters.  The Investigator must assure that all original source 
documents are available to support monitoring activities. 
11.3 Monitoring 
During the study each site will be visited at regular intervals by a Vergent clinical research 
monitor.  Monitoring visits will be conducted according to the applicable ICH and GCP 
guidelines to ensure protocol adherence, quality of data, drug accountability, compliance with 
regulatory requirements and continued adequacy of the investigational site and its facilities.  
The Investigator will cooperate in the monitoring process by ensuring the availability of the 
eCRFs, source documents and other necessary documents at the time of the monitoring visits 
and by prompt attention to any matters brought to his/her attention by the monitor. 
11.4 Audit 
ICH guidelines for GCP require independent inspection of clinical program activities.  Such 
inspections may be performed at any time - before, during and/or after the study.  The 
Investigator and study staff are responsible for maintaining the site master file containing all 
study-related regulatory documentation as outlined by Vergent that will be suitable for 
inspection at any time by Vergent, its designees, and/or regulatory agencies.  The Investigator 
understands and agrees to give access to the necessary documentation and files. 
11.5 Retention of Data 
All records connected with this clinical study will be retained for at least two years following 
the date of an approved marketing application [21 CFR 312.62(c)]; or at least three years from 
the formal discontinuation of VGT-309 development; or seven years from the end of the study, 
whichever is longer.  All local laws regarding retention of records must also be followed.  The 
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CONFIDENTIAL 
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27OCT2023 
STATISTICAL ANALYSIS PLAN 
Study Title: 
A Phase 2, Open-label Study to Evaluate the Safety and 
Efficacy of VGT-309, a Tumor-Targeted, Activatable 
Fluorescent Imaging Agent, to Identify Cancer in 
Subjects Undergoing Lung Cancer Surgery 
Name of Test Drug: 
VGT-309 
Study Number: 
VGT-309-2-2021USA 
Protocol Version: 
Amendment 4 
Protocol Date: 
20 May 2022 
Analysis Type: 
Final 
Analysis Plan Version: 
1.0 
Analysis Plan Date: 
27 October 2023 
Analysis Plan Author: 
NCT05400226


 
 
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Page 2 of 25 
27OCT2023 
AUTHOR(S): 
 
 
 
 
______________________ 
 
 
________________________________ 
 
 
____________ 
 
 
 
Signature 
Date 
 
 
SPONSOR APPROVAL: 
 
 
 
 
 
 
 
______________________ 
 
 
________________________________ 
 
 
____________ 
 
 
 
Signature 
Date 
 
 
 
 
 
 
 
______________________ 
 
 
_________________________________ 
 
 
____________ 
 
 
 
Signature 
Date 
 
 
 
 
 
CONFIDENTIAL AND PROPRIETARY INFORMATION 
 


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LIST OF ABBREVIATIONS ................................................................................................................................ 4 
1. 
INTRODUCTION ......................................................................................................................................... 6 
2. 
STUDY OBJECTIVES .................................................................................................................................. 6 
2.1. 
Primary Objective ............................................................................................................................. 6 
2.2. 
Secondary Objectives ........................................................................................................................ 6 
2.3. 
Safety Objective ................................................................................................................................ 6 
3. 
STUDY DESIGN .......................................................................................................................................... 7 
4. 
DETERMINATION OF SAMPLE SIZE ...................................................................................................... 7 
5. 
TYPE OF PLANNED ANALYSIS ............................................................................................................... 8 
6. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES ....................................................................... 8 
6.1. 
Data Presentation and Summarization .............................................................................................. 8 
6.2. 
Missing or incomplete dates.............................................................................................................. 8 
6.3. 
Analysis Sets ..................................................................................................................................... 9 
6.3.1. 
Enrolled Population ......................................................................................................... 9 
6.3.2. 
Safety Population ............................................................................................................ 9 
6.3.3. 
Efficacy Population ......................................................................................................... 9 
7. 
STUDY POPULATION .............................................................................................................................. 10 
7.1. 
Subject Disposition ......................................................................................................................... 10 
7.1.1. 
Subject Enrollment and Disposition .............................................................................. 10 
7.1.2. 
Exposure to Study Drug ................................................................................................ 10 
7.2. 
Protocol Deviations ......................................................................................................................... 10 
7.3. 
Inclusion/Exclusion Criteria............................................................................................................ 11 
7.4. 
Demographics and Baseline Characteristics ................................................................................... 11 
7.5. 
Medical History .............................................................................................................................. 11 
7.6. 
Prior and Concomitant Medications ................................................................................................ 11 
8. 
EFFICACY ANALYSES ............................................................................................................................ 11 
8.1. 
Definition of the Primary Efficacy Endpoint .................................................................................. 11 
8.2. 
Statistical Hypothesis for the Primary Efficacy Endpoint ............................................................... 12 
8.3. 
Analysis of the Primary Efficacy Endpoint ..................................................................................... 12 
8.4. 
Secondary Efficacy Endpoints ........................................................................................................ 12 
8.4.1. 
Definition of Secondary Efficacy Endpoints ................................................................. 12 
8.4.2. 
Analysis Methods for Secondary Efficacy Endpoints ................................................... 13 
8.5. 
 ....................................................................................................... 13 
9. 
SAFETY ANALYSES................................................................................................................................. 13 
9.1. 
Adverse Events and Deaths ............................................................................................................. 13 
9.1.1. 
Adverse Event Dictionary ............................................................................................. 14 
9.1.2. 
Adverse Event Severity ................................................................................................. 14 
9.1.3. 
Relationship of Adverse Events to Study Drug ............................................................. 14 
9.1.4. 
Serious Adverse Events ................................................................................................. 15 
9.1.5. 
Summaries of Adverse Events and Deaths .................................................................... 15 
9.2. 
Clinical Laboratory Evaluation ....................................................................................................... 16 
9.2.1. 
Summaries of Numeric Laboratory Results .................................................................. 16 
9.2.2. 
Shifts Relative to the Normal Range ............................................................................. 16 
9.3. 
Vital Signs ....................................................................................................................................... 16 
9.4. 
Physical Examination ...................................................................................................................... 17 
9.5. 
Electrocardiogram ........................................................................................................................... 17 


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9.6. 
Other Safety Measures .................................................................................................................... 17 
10. REFERENCES ............................................................................................................................................ 18 
11. SOFTWARE ................................................................................................................................................ 19 
12. SAP REVISION .......................................................................................................................................... 20 
13. APPENDICES ............................................................................................................................................. 21 
 
Appendix 1. 
Table of Contents for Statistical Tables, Figures, and Listings ..................................... 21 
 


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LIST OF ABBREVIATIONS 
 
AE 
Adverse Event 
AR 
Adverse Reaction 
AUC 
Area under the curve 
BMI 
Body mass index 
BPM 
Beats per minute 
CDER 
Center for Drug Evaluation and Research 
CHMP 
Committee for Medicinal Products for Human Use 
CPMP 
Committee for Proprietary Medicinal Products 
CRF 
Case report form 
CRO 
Contract research organization 
CSE 
Clinically Significant Event 
CSR 
Clinical study report 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DMC 
Data monitoring committee 
ECG 
Electrocardiogram 
FN 
False Negative 
FP 
False Positive 
FR 
Federal Register 
GEE 
Generalized Estimating Equation 
HLT 
High level term 
ICH 
International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
ITT 
Intent to treat 
IVRS/IWRS 
Interactive voice/web response system 
LLT 
Lower level term 
MedDRA 
Medical dictionary for regulatory activities 
NIR 
Near-Infrared 
NPV 
Negative Predictive Value 
PPV 
Positive Predictive Value 
PT 
Preferred term 
ROC 
Receiver Operating Characteristic 
SAP 
Statistical analysis plan 
SOC 
System organ class 
TFLs 
Tables, figures, and listings 
TN 
True Negative 
TP 
True Positive 
WHO 
World Health Organization 


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1. 
INTRODUCTION 
This statistical analysis plan (SAP) describes the statistical analysis methods and data 
presentations to be used in tables, figures, and listings (TFLs) to be implemented during the 
analyses of data collected within the scope of Protocol VGT-309-2-2021USA [A Phase 2, 
Open-label Study to Evaluate the Safety and Efficacy of VGT-309, a Tumor-Targeted, 
Activatable Fluorescent Imaging Agent, to Identify Cancer in Subjects Undergoing Lung 
Cancer Surgery] sponsored by Vergent Bioscience, Inc. This SAP will be finalized before 
database lock. Any deviations from this plan after SAP finalization will be documented in the 
clinical study report (CSR). 
2. 
STUDY OBJECTIVES 
2.1. Primary Objective 
The primary efficacy objective of this study is the identification of the proportion of subjects 
with at least one Clinically Significant Event (CSE) as defined by: 
 
 
 
 
 
 
 
 
 
2.2. Secondary Objectives 
The secondary objective of this study is to evaluate the sensitivity, specificity, positive 
predictive value (PPV), and negative predictive value (NPV) of VGT-309 to detect cancer 
utilizing NIR fluorescence and histopathology results. 
2.3. Safety Objective 
The safety objective of this study is to determine the safety and tolerability of VGT-309 
when used as a fluorescent imaging agent in subjects with suspected or proven lung cancer. 
 




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5. 
TYPE OF PLANNED ANALYSIS 
This analysis plan outlines planned analysis procedures for the Final Analysis, as described 
below. Data outliers and other raw data issues are planned to be identified and logged on a 
rolling basis throughout the study, with appropriate resolution decided upon and documented 
prior to the planned analyses outlined below. The Final Analysis will take place after the 
study is completed and the database has been locked. All tables, figures, and listings 
described in this SAP are planned to be included in the final analysis. 
6. 
GENERAL CONSIDERATIONS FOR DATA ANALYSES 
6.1. Data Presentation and Summarization 
The statistical analyses will be reported using summary tables, listings, and figures (TLFs). 
The International Conference on Harmonisation (ICH) numbering convention will be used 
for all TLFs. Continuous variables will be summarized with means, standard deviations, 
medians, minimums, and maximums. Other summaries (e.g., quartiles, 5%, 95% intervals, 
CV or %CV) may be used as appropriate. Categorical variables will be summarized by 
counts and by percentage of patients in corresponding categories. Summaries will generally 
be presented by treatment cohort and for all participants overall. P-values will be presented 
for hypothesis testing, with a value of 0.05 being the threshold of significance under which 
the null hypothesis can be rejected. 
All analyses and tabulations will be performed using SAS® Version 9.4 or higher. Tables, 
listings, and figures will be provided in PDF format. 
6.2. Missing or incomplete dates 
The most conservative approach will be systematically considered. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Stop Dates 
• 
 
  
 
 
  
 
 
 
 
 
6.3. Analysis Sets 
Analysis sets define the participants to be included in an analysis. Analysis sets and their 
definitions are provided in this section. The analysis set will be identified and included as a 
subtitle of each table and listing.  
Inclusion in the analysis set will be determined prior to database lock. A summary of the 
number and percent of participants in each analysis set will be provided. A by-participant 
listing of each analysis set will also be provided.  
6.3.1. 
Enrolled Population 
This population consists of all subjects who are enrolled in the study (signed informed 
consent). 
6.3.2. 
Safety Population 
This population consists of all subjects who have enrolled in the study and received any 
amount of VGT-309. 
6.3.3. 
Efficacy Population 
This population consists of all subjects who have received any amount of VGT-309 and have 
surgery with NIR imaging. 


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7. 
STUDY POPULATION 
In general, subjects who signed informed consent and were enrolled for the study will be 
used for data summaries and listings for subject disposition. Safety population will be used 
for safety summaries and listings, while Efficacy Population will be used for all efficacy 
analyses, unless otherwise specified. 
7.1. Subject Disposition 
7.1.1. 
Subject Enrollment and Disposition 
A summary of subject disposition will be provided and will present the number of subjects 
enrolled, and the number and percent of subjects:  
• Included in the Safety analysis set; 
• Included in the Efficacy analysis set;  
• Completing the study (includes the study treatment period and any post-treatment follow-
up period); and  
• Not completing the study, (with summary of reasons for not completing the study). 
 
  
 
  
 
7.1.2. 
Exposure to Study Drug 
Extent of exposure to study drug will be summarized for the safety population. 
 
 
 
  
 
7.2. Protocol Deviations 
All protocol violations and deviations will be summarized by classification category 
(major/minor) and listed.  
 


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7.3. Inclusion/Exclusion Criteria 
Subjects who did not meet inclusion/exclusion criteria will be listed for all screened subjects, 
along with the criterion number and description not met. 
7.4. Demographics and Baseline Characteristics 
Subject demographic data (e.g., age, sex, race, and ethnicity) and baseline characteristics 
(e.g., body weight, height, BMI) will be summarized using descriptive statistics (sample size, 
mean, standard deviation, median, Q1, Q3, minimum and maximum) for continuous data and 
by the number and percent of subjects for categorical data. The summaries of demographic 
data and baseline characteristics will be provided for the safety analysis set. 
7.5. Medical History 
Medical history will be summarized by Medical Dictionary for Regulatory Activities 
(MedDRA) system organ class (SOC) and preferred term (PT) (version 25.0).  Participants 
will only be counted once at each level of summation.  Summaries will be sorted by 
decreasing total incidence by SOC (overall) and then by PT (within each SOC); for SOCs or 
PTs (within SOC) with the same frequency, sorting will be performed alphabetically.  By-
participant listings of this information will also be provided along with onset and resolution 
dates and grades (collected in the CRF if the condition is ongoing).  
7.6. Prior and Concomitant Medications 
Concomitant medications are defined as medications that started on or after the treatment 
start date or were ongoing at the date of treatment start. Prior medications are defined as 
medications that started and stopped prior to the date of treatment start.  
Medications will be coded using the World Health Organization (WHO) Drug Dictionary B3 
Global (updated March 2022) and Anatomical Therapeutic Chemical (ATC) Level 4 drug 
classes and preferred drug names (PN) will be attached to the clinical database.  The number 
and percentage of subjects with at least one instance of medication use will be summarized 
by ATC class and PN (within ATC class) ordered by decreasing total incidence of ATC and 
PN (within ATC); ties in frequency will be broken alphabetically.  Patients will only be 
counted once at each level of summation.  By-participant listings will also be provided. 
8. 
EFFICACY ANALYSES  
8.1. Definition of the Primary Efficacy Endpoint 
The proportion of subjects with at least one Clinically Significant Event (CSE) as defined by: 
A. 
 
 
 
 




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• Positive predictive value (PPV): 
 
 
• Negative predictive value (NPV): 
 
 
 
 
 
8.4.2. 
Analysis Methods for Secondary Efficacy Endpoints 
 
 
 
 
 
 
  
 
 
 
 
 
 
9. 
SAFETY ANALYSES 
9.1. Adverse Events and Deaths 
Adverse events will be summarized by the Medical Dictionary for Regulatory Activities 
(MedDRA) system organ class and preferred term. Events will be summarized on the basis of 
the date of onset for the event. Only treatment-emergent adverse events (TEAEs), defined as 
any adverse event that begins on or after the date of administration of VGT-309, will be 
collected and analyzed in this study. For purposes of this document, AEs refers to TEAEs. 
An overall summary of TEAEs will be provided. The following summaries (number and 
percentage of subjects) of TEAEs (by System Organ Class and Preferred Term) will be 
provided: 
• TEAEs 
• Treatment-related TEAEs 
• TEAEs leading to study drug discontinuation 
• Serious TEAEs 
• Treatment-related Serious TEAEs 
 


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All AEs collected during the study will be presented in a listing. Additionally, a listing will 
be provided for any AEs leading to death. 
 
9.1.1. 
Adverse Event Dictionary 
Clinical and laboratory adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA version 25.0). System Organ Class (SOC), High Level 
Group Term (HLGT), High Level Term (HLT), Preferred Term (PT), and Lower-Level Term 
(LLT) will be attached to the clinical database. 
9.1.2. 
Adverse Event Severity 
Each AE will be assigned a “Grade” based on the Common Terminology Criteria for 
Adverse Events (CTCAE). Version 5.0 of the CTCAE will be used for this study. The 
severity grade of events for which the investigator did not record severity will be categorized 
as “missing” for tabular summaries and data listings and will be considered the least severe 
for the purposes of sorting for data presentation. 
9.1.3. 
Relationship of Adverse Events to Study Drug 
The relationship of the Adverse Event to the study drug will be determined by the Principal 
Investigator, and assessed using the following definitions: 
• Related: There is a distinct temporal relationship between the event onset and 
administration of the study drug. There is a known reaction to agent or chemical 
group or predicted by known pharmacology. The event cannot be explained by 
subject’s clinical state or other factors. 
• Unrelated: Evidence exists that the AE has an etiology other than the study drug 
(e.g., pre-existing condition, underlying disease, intercurrent illness, or concomitant 
medication). 
Events for which the investigator did not record relationship to study drug will be considered 
related to study drug. Data listings will show relationship as missing. 


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9.1.4. 
Serious Adverse Events 
An SAE is an AE from this study that results in any of the following outcomes: 
• Death 
• Life-threatening situation (subject is at immediate risk of death). 
• Inpatient hospitalization or prolongation of existing hospitalization. 
• Persistent or significant disability/incapacity. 
• Congenital anomaly/birth defect in the offspring of a subject who received study 
drug. 
Important medical events that may not result in death, be immediately life-threatening, or 
require hospitalization, may be considered an SAE when, based upon appropriate medical 
judgment, they may jeopardize the subject and may require medical or surgical intervention 
to prevent one of the outcomes listed in this definition. 
 
9.1.5. 
Summaries of Adverse Events and Deaths 
Summaries (number and percent of subjects) of adverse events (by SOC, and PT) will be 
provided using the safety analysis set as follows: 
• All treatment-emergent adverse events, 
• All treatment-emergent treatment-related adverse events, 
• All treatment-emergent treatment-related serious adverse events,  
• All treatment-emergent adverse events that caused permanent discontinuation from study 
drug, 
• Deaths 
A brief overall summary of TEAEs will show the number and percentage of subjects who 
had at least one of each of the above categories.  
Multiple events will be counted once only per subject in each summary. For data 
presentation, SOC will be ordered alphabetically, with PT sorted by decreasing total 
frequency. For summaries by severity grade, the most severe event will be selected. In 
addition to the presentation by SOC, each summary will also be presented by preferred term 
only, ordered by decreasing frequency.  
In addition to the summaries, data listings will be provided for the following: 


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• All treatment-related adverse events 
• Serious adverse events 
• Deaths 
• Adverse events leading to discontinuation of study drug  
9.2. Clinical Laboratory Evaluation 
Laboratory parameters (including clinical chemistry, hematology, urinalysis, coagulation) 
will be summarized using descriptive statistics at baseline and at each protocol-specified visit 
time points. Unscheduled visits will be listed. Changes from baseline will also be 
summarized.  
All laboratory parameters and pregnancy test results will be provided in listings. 
9.2.1. 
Summaries of Numeric Laboratory Results 
Descriptive statistics (sample size, mean, standard deviation, median, Q1, Q3, minimum and 
maximum) of  
 
  
 
 
 
 
 
9.2.2. 
Shifts Relative to the Normal Range 
The following summaries (number and percentage of subjects) relative to the respective 
laboratory test normal ranges will be provided by treatment group: 
• Shift from baseline value (low, normal, or high) to post-baseline value (low, normal, or 
high) at each post-baseline analysis window.   
9.3. Vital Signs 
Vital signs will be summarized using descriptive statistics at baseline and at each protocol-
specified visit time point. Unscheduled visits will be listed. Changes from baseline will also 
be summarized.  
All vital signs data will be provided in listings. 


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9.4. Physical Examination 
Physical Examination results will be listed.  
9.5. Electrocardiogram 
All ECG results will be listed. Overall interpretation and percent change for each parameter 
from baseline will be summarized by time point.  
 
 
 
 
 
 
 
 
 
 
9.6. Other Safety Measures 
The following safety measures collected will also be provided in listings: 
• Pregnancy test results 
 
 
 


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10. 
REFERENCES 
U.S. Department of Health and Human Services, Food and Drug Administration, Center for 
Drug Evaluation and Research (CDER). Guideline for Industry: E3 Structure and Content of 
Clinical Study Reports Federal Register. July 17, 1996 (61 FR 37320). 
U.S. Department of Health and Human Services, Food and Drug Administration, Center for 
Drug Evaluation and Research (CDER). Guidance for Industry: E9 Statistical Principles for 
Clinical Trials. Federal Register. September 16, 1998 (63 FR 49583). 
U.S Department of Health and Human Services, Food and Drug Administration, Center for 
Drug Evaluation and Research (CDER). Guidance for Industry: E14 Clinical Evaluation of 
QT/QTc Interval Prolongation and Pro-arrhythmic Potential for Non-Antiarrhythmic Drugs. 
Federal Register, October 19, 2005 
Karjalainen J, Viitasalo M, Manttari M, Manninen V. 1994. Relation between QT intervals 
and heart rates from 40 to 120 beats/min in rest electrocardiograms of men and a simple 
method to adjust QT interval values. J Am Coll Cardiol 23:1547-1553. 
Ying GS, Maguire MG, Glynn RJ, Rosner B. Calculating Sensitivity, Specificity, and 
Predictive Values for Correlated Eye Data. Invest Ophthalmol Vis Sci. 2020 Sep 
1;61(11):29. doi: 10.1167/iovs.61.11.29. PMID: 32936302; PMCID: PMC7500131. 


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11. 
SOFTWARE 
SAS Software Version 9.4. SAS Institute Inc., Cary, NC, USA. 
 
 


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12. 
SAP REVISION 
Revision Date 
(dd month, yyyy) 
Section 
Summary of Revision 
Reason for Revision 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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13. 
APPENDICES 
Appendix 1. 
Table of Contents for Statistical Tables, Figures, and Listings 
The following TFL numbering is completed according to ICH guidelines. The ICH heading 
number and description are in bold. Minor changes from this planned index do not need to be 
amended in the SAP. Formal organization of tabulations may be changed during 
programming if appropriate, e.g., tables for the different variables may be combined into a 
single table, or tables with more than one variable may be split into several tables. 
List of Tables 
ICH 
Heading 
Table 
Number 
Table Description 
Analysis Population 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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