Clinical trial NCT04278872
Conditions: Hot Flashes
Sponsor: Sojournix, Inc.
Start date: 2020-11-09; Completion date: 2021-04-07
Enrollment: 13 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study evaluates the efficacy, safety, tolerability, and pharmacokinetics of once daily SJX-653 in postmenopausal women with moderate to severe VMS.

Detailed description:

Arms: arm 1: Participants will receive SJX-653 arm 2: Participants will receive placebo
Interventions: intervention 1: SJX-653 intervention 2: Placebo
Intervention descriptions: intervention 1: administered orally once daily intervention 2: administered orally once daily

Protocol documents:
Prot_000.pdf: 
CONFIDENTIAL 
Page 1 of 12 
 
 
 
CLINICAL STUDY PROTOCOL 
SJX-653-006 
A PHASE 2, PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED CLINICAL STUDY TO ASSESS THE 
EFFICACY, SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF 
SJX-653 IN POSTMENOPAUSAL WOMEN WITH MODERATE TO 
SEVERE VASOMOTOR SYMPTOMS 
 
Investigational Product: 
SJX-653 
Development Phase: 
2 
Date: 
01 July 2020 
Version No.: 
2.0 
Amendment  
1.0 
EudraCT Number: 
2019-002281-12 
Sponsor: 
Sojournix, Inc. 
 
400 Totten Pond Road, Suite 110 
Waltham, MA 02451 USA 
 
This clinical study will be conducted in accordance with the International Council for 
Harmonisation Guideline for Good Clinical Practice (E6). 
 
CONFIDENTIALITY STATEMENT 
This document contains confidential information and is the proprietary property of Sojournix, 
Inc. The protocol is for use by the Principal Investigator and his/her designated representatives 
participating in this investigational study. This document may not be copied or made available 
for review by an unauthorized person or firm without the prior written authorization of 
Sojournix, Inc. 


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1. 
PROTOCOL SYNOPSIS AND SCHEDULE OF ASSESSMENTS 
Name of Investigational Product: SJX-653 
Name of Active Ingredient: 2-Ethylamino-8-fluoro-3-methyl-1-oxo-1,2-dihydroisoquinoline-4-
carboxylic acid ((S)-cyclopropylphenylmethyl) amide 
Protocol Title: A Phase 2, Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical 
Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of SJX-653 in 
Postmenopausal Women with Moderate to Severe Vasomotor Symptoms 
Protocol Number: SJX-653-006 
Development Phase: 2 
Name of Sponsor/Company: Sojournix, Inc. 
Investigator/Study Sites: This study will be conducted at approximately 20 sites in Europe. 
Study Objectives: 
Primary Objective: 
The primary objective of this study is to evaluate the effect of oral 20 mg SJX-653 once daily (QD) for 
4 weeks in postmenopausal women (PMW) with moderate to severe vasomotor symptoms (VMS) on 
VMS frequency after 4 weeks of treatment. 
Secondary Objectives: 
• 
Effect of SJX-653 on measures of VMS severity and frequency by study week 
• 
Safety and tolerability of SJX-653 
• 
Pharmacokinetics (PK) of SJX-653 
Exploratory Objectives:  
• 
Effect of SJX-653 on the following outcomes:  
o Measures of VMS severity and frequency by study day during the first week 
o Daytime and nighttime measures of VMS severity and frequency by study week 
o Sleep and Quality of Life (QoL).  
Methodology: This is a multicenter, prospective, randomized, double-blinded, placebo-controlled, 
parallel-group, Phase 2 study of SJX-653 in PMW with moderate to severe VMS.  
PMW with moderate to severe VMS who sign an informed consent will undergo a Screening process 
for up to 4 weeks including a 14-day Run-in Period. During the Run-in Period, Baseline frequency and 
severity of VMS will be established by recording VMS in a hot flash (HF) electronic diary (eDiary). At 
the end of the Run-in Period, eligibility will be determined. Eligible subjects will be randomized in a 
1:1 ratio to SJX-653 or placebo. 
Subjects will be dosed once daily (QD) with either 20 mg SJX-653 or matching placebo for 4 weeks. 
The Treatment Period will be followed by a 2-week Follow-up Period during which subjects must 
continue to adhere to all protocol restrictions, including prohibited medications and supplements. Data 
on efficacy, tolerability, safety, and PK will be collected.  
Subjects will also complete a QoL assessment (Hot Flash Related Daily Interference Scale [HFRDIS]) 
and a sleep questionnaire (Insomnia Severity Index [ISI]) on Day 1 to establish a baseline and then at 
subsequent visits per the Schedule of Assessments.  
Sampling of blood for PK analyses will occur per the Schedule of Assessments. 


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Safety and tolerability will be assessed by adverse event (AE) collection, physical examination, vital 
signs, 12-lead electrocardiogram (ECG), and safety laboratory tests per the Schedule of Assessments. 
The study design is illustrated in Figure 1, the Schedule of Assessments is presented in Table 1. 
Independent Review: An independent Data Monitoring Committee (DMC) will be established for this 
study. Members of the DMC will be independent of the study Investigators. The DMC will comprise 
relevant medical experts (including a specialist in VMS/women’s health), an independent statistician, 
and additional representatives (to be defined in the DMC Charter). The DMC will review safety data at 
regular intervals according to the DMC Charter. The DMC Charter will establish meeting frequency, 
scope and method of data review, maintenance of blind, and the decision-making process, prior to the 
start of the study. In the event that potential safety issues are identified, the DMC may recommend 
modification of the study design or study termination, which will be communicated to the 
Investigators, Institutional Review Boards/Independent Ethics Committees (IRBs/IECs), and 
regulatory agencies by the Sponsor, in accordance with legal and regulatory requirements. 
Investigational Product: SJX-653 Tablet, 10 mg dose strength. 
Reference Drug (Placebo): Matching placebo tablets containing excipient only. 
Mode of Administration: Oral in the morning with water. 
Frequency of administration: QD 
Number of Subjects (planned): Approximately 66 subjects are planned for randomization in the 
study, assuming a drop-out rate of 12%. Eligible subjects will be randomized in a 1:1 ratio to SJX-653 
or placebo.  
Duration of Subject Participation: Participation will be approximately 10 weeks: up to 4 weeks for 
Screening (including a 14-day Run-in Period), a 4-week Treatment Period, and a 2-week safety 
Follow-up Period.  
Inclusion/Exclusion Criteria: 
Inclusion Criteria 
Subjects must meet the following criteria for inclusion: 
1. Have voluntarily agreed to participate in this study and signed a consent form before Screening 
procedures begin. 
2. Be a postmenopausal female, 40 to 65 years of age (inclusive) at the Screening Visit, defined 
as: 
➢ Spontaneous amenorrhea for at least 12 months, OR 
➢ 6 months of spontaneous amenorrhea with serum FSH level >40 mIU/mL, OR 
➢ 6 weeks past a postsurgical bilateral oophorectomy with or without hysterectomy.  
 
All PMW must have a serum FSH >40 mIU/mL at Screening. 
 
3. Have had VMS for 3 months prior to Screening. 
4. Be compliant with daily HF eDiary completion, as measured by HF eDiary completion on at 
least 12 days during the 14-day Run-in Period. 
5. Have an average of at least 7 moderate to severe VMS per day at Baseline, calculated from 
daily HF eDiary data of at least 12 days during the Run-in Period, with at least 4 of those days 
with 7 or more moderate to severe VMS per day. 


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The following definitions for severity are used:  
➢ Mild: Sensation of heat without sweating/damping; if at night, do not wake up but 
later notice damp sheets or clothing. 
➢ Moderate: Sensation of heat with sweating/dampness, but able to continue activity; if 
at night, wake up because hot and/or sweating, but no action is necessary other than 
rearranging the bed sheets. 
➢ Severe: Sensation of heat with sweating causing disruption of current activity; if at 
night, wake up hot and sweating and need to take action (eg, removing layer of 
clothes, open the window, or get out of bed). 
6. Have a body mass index between 18 and 35 kg/m2, inclusive. 
7. Have a clinical breast exam without clinically significant finding at Screening. 
8. For Subjects 50-65 years old, have documentation (written or electronic report) of a 
satisfactory mammogram result at Screening within applicable intervals stated in local breast 
cancer screening guidelines. Subjects 40-49 years old require a mammogram within the same 
intervals.  
9. Have documentation (written or electronic report) of a normal Pap smear (or equivalent 
cervical cytology) in combination with Human Papilloma virus (HPV) testing, or a Pap smear 
of no clinical significance in the opinion of the Investigator, at Screening within applicable 
intervals stated in local cervical cancer prevention guidelines.  
10. Be willing to undergo a transvaginal ultrasound to assess endometrial thickness at Screening 
and at Week 4 (EOT). This is not required for subjects who have had a partial (supracervical) 
or full hysterectomy. 
11. Have an endometrial thickness ≤4 mm by transvaginal ultrasound at Screening 
12. Subjects must be willing to undergo an endometrial biopsy if they have unexplained bleeding 
during the study or an endometrial thickness >4 mm at the EOT Visit. An endometrial biopsy 
is not required for subjects who have had a partial (supracervical) or full hysterectomy. 
Exclusion Criteria 
Subjects are to be excluded from the study if they meet any of the following criteria: 
1. Have clinically significant history or evidence of poorly controlled cardiovascular, respiratory, 
hepatic, renal, gastrointestinal, endocrine, neurological, immunological, or psychiatric 
disorder(s), or have any other medical condition that, in the Investigator’s opinion, would 
make subjects unsuitable for participation in the study. 
2. Have manifest or suspected active COVID-19 infection   
➢ Have tested positive for presence of SARS-CoV-2 based on a RT-PCR or other 
validated test, or 
➢ Have clinical symptoms suggestive of COVID-19 infection, or  
➢ Have to comply with quarantine requirements per local Public Health directive 
3. A history of diagnosis of major depressive disorder in the 3 years prior to Screening, or are on 
antidepressant, anxiolytic or antipsychotic treatment with the following exception:  
➢ Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine 
reuptake inhibitors (SNRIs) treatment for mild depression and/or mild anxiety are 
allowed provided medication is stable and well-tolerated in the 3 months prior to the 
Screening Visit and does not change during study participation. 
➢ SSRIs and SNRIs for treatment of VMS are prohibited (see Exclusion Criterion 26) 


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4. Have a history of suicide ideation or attempt in the past 3 years. 
5. Have a sleep disorder other than insomnia due to VMS (eg, narcolepsy, sleep apnea, restless 
leg syndrome). 
6. Have clinical or biochemical evidence of active hepatitis or other significant hepatic or biliary 
disease (eg, chronic hepatitis, cirrhosis, autoimmune hepatitis, primary biliary cholangitis, 
primary sclerosing cholangitis, nonalcoholic steatohepatitis, nonalcoholic fatty liver disease, or 
hereditary liver disease).  
7. Have any of the following abnormal laboratory values at Screening: 
➢ Alanine aminotransferase (>1.5×upper limit of normal [ULN]),  
➢ Aspartate aminotransferase (>1.5×ULN),  
➢ Gamma glutamyl transpeptidase (>1.5×ULN),  
➢ Total bilirubin (>1.0×ULN) (subjects with Gilbert’s syndrome can be enrolled if other 
LFTs are within stated limits), 
➢ Alkaline phosphatase >1.5×ULN, provided cholestatic or other liver disease is 
excluded, 
➢ Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 (CKD-EPI 2009 
calculation; Levey 2009). 
8. Have tested positive for human immunodeficiency virus antigen or antibodies, hepatitis C 
antibodies, hepatitis B core antibodies or hepatitis B surface antigen (HBsAg), or hepatitis E 
virus RNA (reverse transcriptase polymerase chain reaction) at Screening. 
9. Have any gastrointestinal, liver, kidney or other disorder that would significantly interfere with 
the absorption, distribution, metabolism, or excretion (ADME) of drugs in the opinion of the 
Investigator, including surgery (eg, short bowel syndrome, gastric or intestinal bypass 
surgery). 
10. Have a history of alcohol abuse or a history of substance abuse.  
11. Smoking >10 cigarettes per day. 
12. Regularly working night shifts. 
13. Have a history of hypersensitivity to more than two chemical classes of drugs, or known 
hypersensitivity to SJX-653 or any of its excipients.  
14. Systolic blood pressure ≥140 mmHg and/or diastolic blood pressure as ≥90 mmHg, based on 
the median of a total of 4 to 6 readings, from 2 to 3 readings taken on 2 different occasions.  
15. Have poorly controlled Type II diabetes mellitus as defined by a glycosylated hemoglobin 
(HbA1c) >8.0% despite standard care. Subjects with Type I diabetes and subjects on insulin 
treatment are excluded. 
16. Have a history of or are on treatment for hyperthyroidism or hypothyroidism, or have 
abnormal thyroid tests (T3, T4, thyroid-stimulating hormone) at Screening. Subjects with 
subclinical hypothyroidism, and subjects on stable treatment for hypothyroidism for a least 3 
months prior to Screening with normal thyroid function test results at Screening are allowed.  
17. Have clinically significant abnormal ECG or QT interval prolongation (corrected for heart rate 
using Fridericia formula [QTcF] prolongation >470 ms) at Screening. 
18. Have a history of endometrial hyperplasia or uterine/endometrial cancer. 
19. Have current unexplained uterine bleeding. 
20. Have a history of cancer prior to Screening (other than local, treated basal cell or squamous 
cell carcinoma ). 


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21. Have any significant illness requiring hospitalization or emergency treatment within 4 weeks 
prior to the Screening Visit or during the Screening Period, as determined by the Investigator. 
22. Are pregnant or lactating.  
23. Are taking any drugs considered moderate or strong inducers and/or inhibitors of cytochrome 
P450 3A4 (CYP3A4). 
24. Started statin therapy less than 3 months prior to  Screening, or are not on a stable and well-
tolerated dose in the 3 months prior to Screening. 
25. Have used any of the following hormonal treatments during the timeframes listed prior to the 
start of the Run-in Period:  
➢ Vaginal hormonal products (rings, creams, gels): 7 days  
➢ Transdermal estrogen or estrogen/progestin products: 4 weeks  
➢ Oral estrogen or estrogen/progestin therapy: 8 weeks  
➢ Intrauterine progestin therapy: 8 weeks  
➢ Progestin implants: 3 months  
➢ Estrogen injectable drug therapy: 3 months  
➢ Estrogen pellet therapy: 6 months  
➢ Progestin injectable drug therapy: 6 months  
26. Are taking any nonhormonal medication for treatment of VMS in the 8-week period prior to 
the start of the Run-in Period, including SSRIs, SNRIs, drugs with structural resemblance to 
gamma-aminobutyric acid (including but not limited to gabapentin and pregabalin), or 
clonidine. 
27. Have used herbal supplements or over-the-counter (OTC) medications for treatment of VMS 
8 weeks prior to the start of the Run-in Period. Any other herbal supplements or OTC 
supplements that could interfere with the study objectives require a 28-day wash-out period 
prior to the start of the Run-in Period. 
28. Are taking any antiestrogens, selective estrogen receptor modulators, or aromatase inhibitors. 
29. Are taking any antigonadotropin medication. 
30. Are legally or mentally incapacitated. 
31. Are not a suitable clinical study candidate per Investigator assessment; e.g., perceived 
willingness or ability to comply with protocol and study procedures. 
32. Are currently participating in another drug or device clinical study or have received the last 
dose/device intervention in such a study within 90 days or 5 half-lives (whichever is longer) 
prior to the Screening Visit. 
33. Have previously received SJX-653 in another clinical study. 
34. Are directly involved in the conduct of the study. 
 


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Study Endpoints 
Primary Endpoint: 
Mean change in average daily frequency of moderate to severe VMS in the intent-to-treat (ITT) 
population from Baseline to Week 4. 
Secondary Endpoints: 
Efficacy 
• 
Mean change and percent change of the following parameters of VMS frequency and severity 
from Baseline by study week through End of Study (EOS): 
o Average daily frequency of moderate to severe VMS. 
o Average daily frequency of all VMS (mild, moderate, and severe).  
o Average daily severity score for moderate to severe VMS. 
o Average daily severity score for all VMS (mild, moderate, and severe). 
o Average daily VMS score for moderate to severe VMS. 
o Average daily VMS score for all VMS (mild, moderate, and severe). 
“Study week” refers to all weeks in the study from Baseline through EOS. 
Safety 
• 
Incidence and severity of AEs and serious AEs for SJX-653. 
• 
Change from Baseline to worst (parameter dependent) and last values in vital sign parameters. 
• 
Change from Baseline in clinical laboratory values. 
• 
Change from Baseline in physical examination and ECG. 
Pharmacokinetics 
• 
Assessment of Ctrough concentration at steady state.  
Exploratory Endpoints:  
• 
Mean change and percent change of parameters of VMS frequency and severity from Baseline by 
study day through Week 1. 
• 
Mean change and percent change of daytime and nighttime VMS frequency and severity from 
Baseline by study week through EOS. 
• 
Change in ISI score from Baseline to Week 4. 
• 
Change in HFRDIS total score from Baseline to Week 2 and 4. 
 
Statistical Methods: A formal statistical analysis plan will be developed and finalized before database 
lock.  
Analysis populations 
• 
ITT – all subjects randomized. 
• 
Per Protocol (PP) – all subjects in the ITT who completed the 4-week assessments with no major 
protocol violations that may impact the interpretation of the primary efficacy endpoint.  
• 
Safety (SAF) – all subjects who received at least 1 dose of study drug (Investigational drug or 
placebo). 
• 
PK – all subjects in the SAF who had at least 1 evaluable PK sample collected. 


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The primary endpoint will be assessed using Mixed effect Model Repeat Measurement (MMRM) with 
Baseline VMS frequency as a covariate. Secondary and exploratory endpoints assessing change in 
continuous endpoints over time will use MMRM for individual time points and trends over time. 
Safety endpoints will be summarized using descriptive statistics.  
Sample size considerations: Sample size requirements were calculated under the following 
assumptions for the primary efficacy endpoint: 
• 
Two sided α=0.05 
• 
Target power=80%. 
• 
Unpaired t-test with two treatment arms (placebo and 20 mg SJX-653). 
• 
Pooled standard deviation = 4.0 based on the change from Baseline to Week 4 for placebo and 20 
mg SJX-653. 
• 
Drop-out rate of 12%. 
• 
Mean improvement in placebo group from an average daily frequency of 10 moderate to severe 
VMS/day to 6.0 moderate to severe VMS/day at Week 4. 
• 
Mean improvement in 20 mg SJX-653 group from an average daily frequency of 10 moderate to 
severe VMS/day to 3.0 moderate to severe VMS/day at Week 4 
Under these assumptions, approximately 29 subjects per group need to complete the study to detect a 
mean 3.0 moderate to severe VMS /day improvement for 20 mg SJX-653 over placebo in the ITT 
Population. Approximately 66 (33+33) eligible subjects will initially be randomized 1:1 (20 mg SJX-
653: placebo) to achieve 58 (29+29) subjects reaching Week 4.  
Adjustment for Multiplicity: No adjustment for multiplicity is planned; Secondary and exploratory 
endpoints, being supportive in nature, will be tested at 2-sided α=0.05 each (nominal testing). 
Inferential analysis associated with secondary and exploratory endpoints will be considered as 
supportive. 
Missing data: There will be no imputation of missing safety endpoints unless specified otherwise. 
Missing efficacy endpoints will be handled using MMRM.  


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Figure 1: 
Study Schema 
 
Abbreviations: D = Day; PMW = postmenopausal women; QD = once daily; VMS = vasomotor symptoms. 
Vertical upwards arrows indicate study Visit days. See Schedule of Assessment for permissible Visit windows.  
Randomization is on Day 1, the Start of dosing. 
 
 


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Table 1: 
Schedule of Assessments  
 
Screening Period 
Treatment Period 
Follow-Up 
 
Screening 
Run-In 
Baseline 
Study Visit 
End of 
Treatment/ 
Early 
Termination1 
End of Study 
Study Day -30 to -15 
-14 to -1 
1 ±2 
7 ±2 
14 ±2 
28±3 
42±3 
Study Week 
-4 to -2 
-2 to -1 
 
1 
2 
4 
6 
Visit Location2 
Clinic 
Phone 
option 
Clinic 
At home 
option 
At home 
option 
Clinic 
At home option 
Events 
 
 
 
 
 
 
 
Informed consent form signed 
X 
 
 
 
 
 
 
Review inclusion/exclusion criteria & medical history 
X 
 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Physical examination3 
X 
 
X 
 
 
X 
 
Randomization 
 
 
X 
 
 
 
 
Height and weight4 
X 
 
X 
 
 
X 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
Adverse event monitoring 
X 
X 
X 
X 
X 
X 
X 
HIV and hepatitis tests 
X 
 
 
 
 
 
 
Pregnancy test (urine) 
X 
 
X 
 
 
X 
 
Drugs of abuse screening5 
X 
 
X 
 
 
X 
X 
Vital signs6 
X 
 
X 
X 
X 
X 
X 
12-lead ECG 
X 
 
X 
 
 
X 
 
Hematology 
X 
 
X 
 
X 
X 
X 
Total serum chemistry7 
X 
 
X 
 
X 
X 
X 
LFTs only 
 
 
 
X 
 
 
 
Urinalysis 
X 
 
X 
 
X 
X 
X 
COVID-19 testing8 
X 
 
X 
 
X 
X 
X 
E2, SHBG, LH, FSH9 
X10 
 
X 
X 
X 
X 
X 
Endometrial biopsy11 
 
 
 
 
 
X 
 
Transvaginal ultrasound12 
X 
 
 
 
X 
 
Mammogram13 
X 
 
 
 
 
 


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Screening Period 
Treatment Period 
Follow-Up 
 
Screening 
Run-In 
Baseline 
Study Visit 
End of 
Treatment/ 
Early 
Termination1 
End of Study 
Study Day -30 to -15 
-14 to -1 
1 ±2 
7 ±2 
14 ±2 
28±3 
42±3 
Study Week 
-4 to -2 
-2 to -1 
 
1 
2 
4 
6 
Visit Location2 
Clinic 
Phone 
option 
Clinic 
At home 
option 
At home 
option 
Clinic 
At home option 
Events 
 
 
 
 
 
 
 
Pap smear and HPV testing14 
X 
 
 
 
 
 
 
Plasma PK collection15 
 
 
 
X 
 
X 
 
Dispensing of medication 
 
 
X 
 
 
 
 
Drug accountability and compliance check 
 
 
 
X 
X 
X 
 
Dosing of medication in clinic16 
 
 
X 
 
 
X 
 
Recording of VMS frequency/severity in daily HF eDiary17 
 
Recording of body temperature in daily eDiary18 
 
 
 
 
HFRDIS 
 
 
X 
 
X 
X 
 
ISI 
 
 
X 
 
 
X 
 
Abbreviations: ALP = alkaline phosphatase; BP = blood pressure; ECG = electrocardiogram; eDiary = electronic diary; EOS = End of Study; EOT = End of Treatment; ET = Early 
Termination; E2 = estradiol; FSH = Follicle Stimulating Hormone; HDL-C = high density lipoprotein – cholesterol; HF = hot flash; HFRDIS = Hot Flash Related Daily 
Interference Scale; HIV = human immunodeficiency virus; INR = international normalized ratio; ISI = Insomnia Severity Index; LDL-C = low density lipoprotein – cholesterol; 
LFT = liver function test; LH = luteinizing hormone; PK = pharmacokinetic; PT = prothrombin time; SHBG = sex hormone binding globulin; VMS = vasomotor symptoms.  
 
Footnotes are on the following page. 
 
 


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1 
Participants who discontinue study treatment and/or the study prior to the scheduled EOT Visit on Day 28 should attend an Early Termination Visit. The 
procedures at this Early Termination Visit will be the same as those specified for EOT. 
2 
The Run-In visit may be conducted by phone. During Treatment and Follow-up Period, Day 7, 14, and/or Day 42 (EOS) visits may be conducted either in-
clinic or at home.  
3 
Clinical breast examination will be performed only at Screening. Gynecological examination to be performed at Screening and Day 28 (EOT). 
4 
Height will be measured at Screening only.  
5 
Drugs of abuse panel (see Appendix 4). 
6 
Vital signs (supine BP and heart rate, and aural body temperature); vital signs should be taken after the subject has been resting for at least 5 minutes.  BP 
assessment for eligibility must be based on the median of a total of 4 to 6 readings, based on 2-3 readings from two different occasions.  
7 
Total Cholesterol, HDL-C, LDL-C, triglycerides, and fasted glucose will only be collected at Screening and Day 28 (EOT). PT/INR will only be collected 
at Screening. 
8 
Testing for presence of virus (SARS-CoV-2) at Screening, Baseline (Day 1), Days 14, 28 (EOT), and 42 (EOS). COVID-19 antibody testing only at 
Screening, EOT, and EOS. 
9 
At the discretion of the Sponsor, other analyses including but not limited to hormone assessments may be performed. 
10 
FSH level to confirm eligibility. All postmenopausal women must have a serum FSH >40 mIU/mL at Screening.  
11 
Endometrial biopsy to be performed only if endometrial thickness is >4 mm as measured by transvaginal ultrasound at Day 28 (EOT). Subjects with uterine 
bleeding during the study must also undergo an endometrial biopsy.   
12 
Transvaginal ultrasound not required for women who have had a partial (supracervical) or full hysterectomy. 
13 
For mammograms, the Screening Period can be extended by 2 weeks 
14 
Pap smear or equivalent cervical cytology, and HPV screening will be processed at the central laboratory. 
15 
PK sampling to occur prior to dosing on Day 28 (EOT), and on Day 7 if possible. 
16 
Medication will be dosed in the clinic on Days 1 (Baseline) and 28 (EOT).  
17 
Subjects are expected to complete the daily HF eDiary every day from Screening through Day 42 (EOS). 
18 
Subjects are expected to record daily body temperature in eDiary from Day 1(Baseline) through Day 28 (EOT).  
 
 

SAP_001.pdf: 
 
 
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Statistical Analysis Plan 
SJX-653-006 
02APR2021 
TMP-SOP-0202-001-03_SAP Template 
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CONFIDENTIAL 
SJX-653-006_SAP_TEXT_v1 
Statistical Analysis Plan 
Sojournix, Inc. 
SJX-653-006 
A Phase 2, Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Study to 
Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of SJX-653 in Postmenopausal 
Women with Moderate to Severe Vasomotor Symptoms 
Protocol Version 2.0 and 2.1: 01 JUL 2020 (Amendment 1.0) 
EudraCT Number: 2019-002281-12 
Sponsor:  
 
Sojournix, Inc. 
400 Totten Pond Road, Suite 110 
Waltham, MA 02451 USA 
Prepared by:  
Nancy Fitzgerald 
Synteract 
5909 Sea Otter Place, Suite 100 
Carlsbad, CA 92010 
 
 
Version 
Date 
1 
02 APR 2021
 
 


 
 
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Statistical Analysis Plan 
SJX-653-006 
02APR2021 
TMP-SOP-0202-001-03_SAP Template 
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CONFIDENTIAL 
SJX-653-006_SAP_TEXT_v1 
Approval 
Upon review of this document, including the table, listing, and figure shells, the undersigned 
approves the statistical analysis plan. The analysis methods and data presentation are acceptable. 
Signature 
Date 
 
 
_______________________________________________ 
Nancy Fitzgerald, MS, MBA 
Biostatistics Director 
Synteract 
 
 
_______________ 
 
 
_______________________________________________ 
Ruth Thieroff-Ekerdt, MD  
Chief Medical Officer   
Sojournix, Inc. 
 
 
_______________ 


 
 
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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ....................................................................................................... 4 
1. 
INTRODUCTION .................................................................................................................. 7 
2. 
STUDY DOCUMENTS ......................................................................................................... 7 
3. 
STUDY OBJECTIVES .......................................................................................................... 7 
3.1 PRIMARY OBJECTIVE .......................................................................................................... 7 
3.2 SECONDARY OBJECTIVES ................................................................................................... 7
3.3 EXPLORATORY OBJECTIVES ............................................................................................... 7 
4. 
STUDY DESIGN AND PLAN .............................................................................................. 8 
5. 
DETERMINATION OF SAMPLE SIZE ............................................................................ 9 
6. 
GENERAL ANALYSIS CONSIDERATIONS ................................................................... 9 
7. 
NOTATION OF TREATMENT GROUPS AND VISITS ............................................... 10 
8. 
ANALYSIS SETS ................................................................................................................. 11 
9. 
STUDY POPULATION....................................................................................................... 11 
9.1 
SUBJECT DISPOSITION .................................................................................................. 11 
9.2 
PROTOCOL DEVIATIONS .............................................................................................. 12 
9.3 
DEMOGRAPHIC AND BASELINE CHARACTERISTICS ..................................................... 12
9.4 
PRIOR AND CONCOMITANT MEDICATIONS .................................................................. 12 
10. EFFICACY ANALYSES ..................................................................................................... 12 
10.1 HANDLING OF DROPOUTS OR MISSING DATA ............................................................. 12 
10.1.1 Missing Safety Data ........................................................................................ 12 
10.2 INTERIM ANALYSIS AND DATA MONITORING ............................................................. 13 
10.3 MULTICENTER STUDIES ............................................................................................... 13
11. METHODS OF EFFICACY ANALYSIS .......................................................................... 13 
12. PHARMACOKINETIC ANALYSES ................................................................................ 13 
13. SAFETY ANALYSES .......................................................................................................... 14 
13.1 EXTENT OF EXPOSURE ................................................................................................. 14 
13.2 ADVERSE EVENTS ........................................................................................................ 14 
13.3 CLINICAL LABORATORY EVALUATION ....................................................................... 15 
13.4 ELECTROCARDIOGRAM ................................................................................................ 15 
13.5 VITAL SIGNS ................................................................................................................ 15 
13.6 PHYSICAL EXAMINATION ............................................................................................ 15 
14. CHANGES TO PROTOCOL-SPECIFIED ANALYSES ................................................ 15 
15. REFERENCES ..................................................................................................................... 16 
16. APPENDICES ...................................................................................................................... 17 
APPENDIX A: PRESENTATION OF DATA AND PROGRAMMING SPECIFICATIONS17 
APPENDIX B: SAS PROGRAMMING QC REQUIREMENTS ........................................... 19 
APPENDIX C: LIST OF TABLES, LISTINGS, AND FIGURES .......................................... 23 


 
 
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LIST OF ABBREVIATIONS 
Abbreviation 
Full Notations 
ADL 
activities of daily living 
ADME 
absorption, distribution, metabolism and excretion 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase  
AST 
aspartate aminotransferase 
AUC 
area under the concentration-time curve 
AUC(0-24)
area under the concentration-time curve from time 0 to 24 hours
BMI 
body mass index 
BP 
blood pressure 
Cmax 
maximum plasma concentration 
CSR 
Clinical study report 
Ctrough 
trough concentration 
CYP 
cytochrome P450 
CYP3A4 
cytochrome P450 3A4
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
eCRF 
electronic case report form
EDC 
electronic data capture 
eDiary 
electronic diary
eGFR 
estimated glomerular filtration rate 
eITT 
exploratory intent-to-treat 
EOS 
End of Study 
EOT 
End of Treatment 
ePRO 
electronic subject reported outcomes 
ET 
Early Termination 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GGT 
gamma glutamyl transferase 
GnRH 
gonadotropin-releasing hormone 
HbA1c 
glycosylated hemoglobin 
HBsAg 
hepatitis B surface antigen 
HF 
hot flash 
HFRDIS 
Hot Flash Related Daily Interference Scale 
HT 
hormone therapy 
IB
Investigator Brochure
ICF 
informed consent form 
ICH 
International Council for Harmonisation 


 
 
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IEC 
Independent Ethics Committee 
INR 
international normalized ratio  
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
ISI 
Insomnia Severity Index 
ITT 
intent-to-treat
KNDy 
kisspeptin, neurokinin B, and dynorphin 
LFT 
Liver function test 
LH 
luteinizing hormone 
MEDRA 
Medical Dictionary for Regulatory Activities 
MENQOL 
Menopause-Specific Quality of Life 
MMRM 
Mixed effect Model Repeat Measurement 
MS-VMS 
moderate to severe vasomotor symptoms 
NK3R 
neurokinin-3 receptor 
NKB 
neurokinin B
OOR 
out of range 
OTC 
over the counter
PD 
pharmacodynamic(s) 
PGI-C 
Subject’s Global Impression of Change 
PK
pharmacokinetic(s)
PMW 
postmenopausal women 
PSQI 
Pittsburgh Sleep Quality Index 
QD 
once daily 
QoL 
Quality of Life
QTcF 
QT interval corrected by Fridericia formula 
RT-PCR 
Reverse transcription polymerase chain reaction 
SAE 
serious adverse event 
SAF 
safety population 
SAP 
statistical analysis plan 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SD 
standard deviation 
SSRI 
selective serotonin reuptake inhibitor 
SNRI 
serotonin and norepinephrine reuptake inhibitor 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
t1/2 
terminal half-life 
TEAE 
treatment-emergent adverse event 
TLF 
tables, listings, figures
Tmax 
time to peak plasma concentration 
TSH 
thyroid-stimulating hormone 
ULN 
upper limit of normal 


 
 
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VMS 
vasomotor symptoms 


 
 
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1. INTRODUCTION 
This document outlines the statistical methods to be implemented during the analyses of data 
collected within the scope of Sojournix, Inc. protocol SJX-653-006 [A Phase 2, Prospective, 
Randomized, Double-Blind, Placebo-Controlled Clinical Study to Assess the Efficacy, Safety, 
Tolerability, and Pharmacokinetics of SJX-653 in Postmenopausal Women with Moderate to 
Severe Vasomotor Symptoms]. The purpose of this plan is to provide specific guidelines from 
which the statistical analyses will proceed. Any deviations from this plan will be documented in 
the clinical study report (CSR). 
2. STUDY DOCUMENTS 
The following study documents are used for the preparation of the SAP: 
• Protocol version 2.0 and 2.1, 01JUL2020 
• Annotated electronic eSource forms: Capture, 24MAR2021;  
• Data management plan version 2.0, 18FEB2021 
3. STUDY OBJECTIVES 
3.1 Primary Objective 
The primary objective of the study is to evaluate the effect of oral 20 mg SJX-653 once daily 
(QD) for 4 weeks in postmenopausal women (PMW) with moderate to severe vasomotor 
symptoms (VMS) on VMS frequency after 4 weeks of treatment. 
3.2 Secondary Objectives 
Secondary objectives include: 
• Effect of SJX-653 on measures of VMS severity and frequency by study week 
• Safety and tolerability of SJX-653 
• Pharmacokinetics (PK) of SJX-653 
3.3 Exploratory Objectives 
Exploratory objectives include: 
• Measures of VMS severity and frequency by study day during the first week 
• Daytime and nighttime measures of VMS severity and frequency by study week 
• Sleep and Quality of Life (QOL)  
 
 


 
 
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4. STUDY DESIGN AND PLAN 
This is a multicenter, prospective, randomized, double-blind, placebo-controlled, parallel-group, 
Phase 2 study of SJX-653 in PMW with moderate to severe VMS. It will be conducted at 
approximately 20 sites in Europe. 
PMW with moderate to severe VMS who sign an informed consent will undergo a Screening 
process for up to 4 weeks including a 14-day Run-in Period. During the Run-in Period (Day -14 
to Day -1), subjects will record the frequency and severity of daytime VMS in the hot flash (HF) 
eDiary for a period of 14 days.  These data will determine each subject’s Baseline VMS 
frequency per the Schedule of Assessments in the protocol. Subjects will be trained in the use of 
the HF eDiary and will be required to complete the HF eDiary on at least 12 days during the 14-
day Run-in Period to be eligible for the study. At the end of the Run-in Period, eligibility will be 
determined by the investigator.  
Eligible subjects will be randomized in a 1:1 ratio to the following treatment groups: 
• 20 mg SJX-653 (Treatment Group) 
• Matching placebo (Placebo Group) 
Subjects will receive their randomized study medication QD for 4 weeks. The Treatment Period 
will be followed by a 2-week Follow-up Period during which subjects must continue to adhere to 
all protocol restrictions, including prohibited medications and supplements. Data on efficacy, 
tolerability, safety, PK, and PD will be collected according to the Schedule of Assessments in the 
protocol. Monitoring of severe acute respiratory syndrome – coronavirus 2010 (SARS-CoV-2) 
by a validated reverse transcription-polymerase chain reaction (RT-PCR) method will also be 
conducted prior to and during the study through EOS visit. 
Frequency and severity of daytime VMS will be recorded by subjects in the HF eDiary during the 
day; VMS occurring during the night can be entered into the HF eDiary either during the night or 
the following morning.  
Subjects will complete QoL assessment Hot Flash Related Daily Interference Scale (HFRDIS) 
on Baseline, Day 14 and at Day 28/End of Treatment (EOT) and Insomnia Severity Index (ISI) 
at Baseline and (EOT) visits.  
PK sampling will occur prior to dosing on Day 28/EOT, and on Day 7, also prior to dosing if 
possible. 
Safety and tolerability will be assessed by adverse event (AE) collection, physical examination, 
vital signs, 12-lead ECG, and safety laboratory parameters per the Schedule of Assessments 
included as Table 1 in the protocol. 


 
 
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5. DETERMINATION OF SAMPLE SIZE 
Sample size requirements were calculated under the following assumptions for the primary 
efficacy endpoint: 
• One-sided α=0.025  
• Two sided α=0.05 
• Target power=80%. 
• Unpaired t-test with two treatment arms (placebo and 20 mg SJX-653). 
• Pooled standard deviation = 4.0 based on the change from Baseline to Week 4/ET for 
placebo and 20 mg SJX-653  
• Drop-out rate of 12%. 
• Mean improvement in placebo group from an average daily frequency of 10 moderate 
to severe VMS/day to 6.0 moderate to severe VMS/day at Week 4.  
• Mean improvement in 20 mg SJX-653 group from an average daily frequency of 10 
moderate to severe VMS/day to 3.0 moderate to severe VMS/day at Week 4 
Under these assumptions, approximately 29 subjects per group need to complete the study to 
detect a mean 3.0 moderate to severe VMS /day improvement for 20 mg SJX-653 over placebo 
in the ITT Population. Approximately 66 (33+33) eligible subjects will initially be randomized 
1:1 (20 mg SJX-653: placebo) to achieve 58 (29+29) subjects reaching Week 4. 
6. GENERAL ANALYSIS CONSIDERATIONS 
The statistical analyses will be reported using summary tables, listings, and figures (TLFs). The 
International Council for 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., 95% confidence intervals) may be used as appropriate 
and will be mentioned in the respective sections.  
Categorical variables will be summarized by counts and by percentage of subjects in 
corresponding categories. Percentages for missing values are omitted and do not account for the 
percent calculation of other categories. Percentages are routinely based on the total category 
count excluding the missing category if not otherwise mentioned. Percentages showing a rate 
relative to the total number of subjects in this group are given in special tables (e.g., adverse 
event [AE] tables). Footnotes will specify the percent basis in those cases. 
All summary tables will be presented by treatment group and will also include a total column.  


 
 
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Individual subject data obtained from the eSource forms and external vendors (e.g., central 
clinical laboratory) will be presented in data listings as identified in Sections 9 and 13. 
The analyses described in this plan are considered a priori, in that they have been defined prior to 
breaking the blind.  
Any analyses performed subsequent to breaking the blind will be considered post hoc and 
exploratory. Post hoc analyses will be labeled as such on the output and identified in the CSR. 
All analyses and tabulations will be performed using SAS software Version 9.4 or higher 
unless otherwise noted. Tables and listings will be presented in RTF format. Upon completion, 
all SAS programs will be validated by an independent programmer. In addition, all program 
output will undergo a senior level statistical review. The validation process will be used to 
confirm that statistically valid methods have been implemented and that all data manipulations 
and calculations are accurate. Checks will be made to ensure accuracy, consistency with this 
plan, consistency within tables, and consistency between tables and corresponding data listings. 
Upon completion of validation and quality review procedures, all documentation will be 
collected and filed by the project statistician or designee.  
7. NOTATION OF TREATMENT GROUPS AND VISITS 
Notation of treatment groups 
The following notation of treatment groups will be used throughout the report: 
Full notation (as used in the study protocol) 
Notation as used throughout all 
tables, listings and figures 
20 mg SJX-653  
Placebo 
20 mg SJX-653 
Placebo 
 
 


 
 
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Visit terminology 
Week 
Day 
Visit 
Notation as used 
throughout all 
tables, listings 
and figures 
Week -4 
through -1 
Day -30  to -1 
V1 (Screening) 
Screening/Run-In
Week 1 
Day 1 
V2 (Baseline) 
Baseline 
Week 1 
Day 2 to 7 
V3 
Day 7 
Week 2 
Day 8 to 14 
V4 
Day 14 
Week 4 
Day 15 to 28 
V5 
Day 28 / EOT 
Week 6 
Day 29 to 42 
V6 
Day 42 / EOS 
Days are measured from date of randomization. Study days corresponding to measurements are 
calculated as: 
 Assessment date – date of randomization + 1, if assessment date is on or after the 
date of randomization. 
 Assessment date – date of randomization, if measurement date is before the date of 
randomization. 
8. ANALYSIS SETS
The study was terminated early (see Section 14), and therefore only a safety population is 
defined. The following population will be used for safety summaries: 
• Safety population will include all subjects who receive at least one dose of study drug 
(Investigational drug or placebo). Treatment assignment will be based on treatment 
randomization. 
9. STUDY POPULATION 
9.1
Subject Disposition
Subject disposition information will be summarized for all subjects by treatment group. 
Summaries will include: the number of subjects screened under protocol Version 2.0 and 2.1, the 
number of enrolled (randomized) subjects, the number of subjects in the safety population, the 
number of subjects discontinuing the study, and the primary reason for discontinuation.  


 
 
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9.2
Protocol Deviations 
Protocol deviations will be evaluated as per the clinical database and additionally as tracked by 
operational study team members.  
Protocol deviations due to COVID-19 will be summarized by treatment group. Missed 
assessments due to COVID-19 will be reported in a data listing. 
9.3
Demographic and Baseline Characteristics 
Demographic and baseline characteristics will be summarized descriptively for the safety 
population. Demographic characteristics will include age, ethnicity, and race. Age will be 
calculated in years relative to the informed consent date. Baseline characteristics will include 
height, weight, and body mass index (BMI). 
9.4 Prior and Concomitant Medications 
Prior and concomitant medication verbatim terms in the eSource forms will be mapped to 
Anatomical/Therapeutic/Chemical (ATC) class and preferred names using the WHODrug global 
dictionary (Version Sep, 2020). 
Prior medications are those medications that started before the initial dose of study drug. 
Concomitant medications are those medications that started after the initial dose of study drug or 
medications that started before the initial dose of study drug and continued during the treatment 
period. If no classification to prior and/ or concomitant can be done, the medication will be 
considered as both prior and concomitant. Concomitant medications will be listed. 
SARS-CoV2 test results and antibodies will be listed. 
10. EFFICACY ANALYSES 
Not applicable. See Section 14.  
10.1 Handling of Dropouts or Missing Data 
10.1.1 Missing Safety Data 
When tabulating AE data, partial dates will be imputed as follows.  
• If the day of the month is missing, the onset day will be set to the first day of the 
month unless it is the same month and year as study treatment. In this case, to 
conservatively report the event as treatment-emergent, the onset date will be assumed 
to be the first date of treatment.  


 
 
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•
If the onset day and month are both missing, the day and month will be assumed to be 
January 1, unless the event occurred in the same year as the study treatment. In this 
case, the event onset will be coded to the first date of treatment in order to 
conservatively report the event as treatment-emergent. A missing onset date will be 
coded as the first day of treatment.  
• Listings will present all data as reported (i.e., without imputations). 
10.2 Interim Analysis and Data Monitoring 
An independent Data Monitoring Committee (DMC) will be established for this study. Members 
of the DMC will be independent of the study Investigators and the sponsor. The DMC will 
comprise of relevant medical experts in the following disciplines: women’s health specialist with 
experience in management of and clinical research in vasomotor symptoms, clinical drug 
development in women’s health, hepatology. The DMC will also include an independent 
statistician who will have access to the clinical database and the randomization code. The DMC 
will review safety data at regular intervals according to the DMC Charter. The DMC Charter will 
establish meeting frequency, scope and method of data review, maintenance of blind, and the 
decision-making process, prior to the start of the study. In the event that potential safety issues 
are identified, the DMC may recommend modification of the study design or study termination, 
which will be communicated to the Investigators, Institutional Review Boards/Independent 
Ethics Committees (IRBs/IECs), and regulatory agencies by the Sponsor, in accordance with 
legal and regulatory requirements. The DMC Charter is finalized in synSOJd_DMC 
Charter_V2_16JUL2020_Final.doc.pdf. 
There are no planned interim efficacy analyses for this study. 
10.3 Multicenter Studies 
This is multicenter study, with approximately 20 centers participating in the study. 
Approximately 66 subjects will be randomized, leading to approximately 3 subjects per center. 
This expected low number of subjects at some centers does not allow center to be included as a 
covariate in the statistical model.  
11. METHODS OF EFFICACY ANALYSIS 
Not applicable. See Section 14. 
12. PHARMACOKINETIC ANALYSES 
PK sampling will occur prior to dosing on Day 28 (EOT), and on Day 7, also prior to dosing if 
possible. Trough plasma concentrations of SJX-653 and its 2 metabolites M2 and M3 in steady 
state will be reported by the PK laboratory. PK data will not be summarized or tabulated.  


 
 
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13. SAFETY ANALYSES 
All safety analyses will be based on the safety population defined as all randomized subjects who 
took at least one dose of study drug, will be descriptive only, and will be presented by treatment 
group. No inferential testing will be performed. Missing safety data will not be imputed.  
13.1 Extent of Exposure 
Study drug exposure based on expected exposure will be summarized by treatment group. 
Expected exposure will be derived as follows: 
• Subjects who complete the Day 28/EOT visit: (64 tablets dispensed – number tablets 
returned – number tablets lost) / (2*28) 
• Subjects who prematurely discontinue prior to Day 28/EOT: (64 tablets dispensed – 
number tablets returned – number tablets lost) / 2*(12FEB2021 – date of first dose + 1) 
Note: 12FEB2021 is the date of sponsor notification of sites of study termination for safety 
reasons.
13.2 Adverse Events 
All AE summaries will be restricted to treatment-emergent AEs (TEAEs), which are defined as 
those AEs that occurred after dosing and those existing AEs that worsened after start of dosing. 
If it cannot be determined whether the AE is treatment-emergent due to a partial onset date, then 
it will be counted as such. Verbatim terms in the eSource forms will be mapped to preferred 
terms and system organ classes using the Medical Dictionary for Regulatory Activities 
(MedDRA) (version 23.0).  
Each AE summary will be displayed by treatment group. Summaries that are displayed by 
system organ class and preferred terms will be ordered by descending subject count in the total 
column by system organ class and preferred term. Summaries of the following types will be 
presented: 
• Overall summary of TEAEs. 
• Subject incidence of TEAEs and total number of unique TEAEs by MedDRA system 
organ class and preferred term. 
• Subject incidence of TEAEs of special interest and total number of unique TEAEs by 
MedDRA system organ class and preferred term.  
• Subject incidence of treatment-related TEAEs and total number of unique TEAEs by 
MedDRA system organ class and preferred term.  
• Subject incidence of serious TEAEs and total number of unique serious TEAEs by 
MedDRA system organ class and preferred term. 


 
 
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•
Subject incidence of TEAEs leading to study discontinuation and total number of unique 
TEAEs leading to study discontinuation by MedDRA system organ class and preferred 
term.   
13.3 Clinical Laboratory Evaluation 
Laboratory samples will be analyzed by a central laboratory. The central laboratory will provide 
normal reference ranges for the laboratory results and a flag for all abnormal values.  
Laboratory safety parameters for hematology, serum chemistry, and urinalysis will be 
summarized descriptively at baseline and at each post-baseline time point (Day 14, 28/EOT, and 
Day 42/EOS) and will include change from baseline. Baseline is defined as the last non-missing 
value prior to first dose of study drug.  
Laboratory safety parameters for liver function tests (LFTs) will be summarized descriptively at 
baseline and at each post-baseline time point (Day 7, Day 14, 28/EOT, and Day 42/EOS) and 
will include frequency count and percent for each test category. Potential Hy’s Law cases will be 
identified using the common criteria of 2x upper limit normal (ULN) total bilirubin concurrent 
with 3x ULN aspartate aminotransferase (AST) or alanine aminotransferase (ALT) (whichever is 
higher) when aspartate aminotransferase (ALP) is < 2x ULN. 
Categorical parameters for urinalysis laboratory results will not be summarized but will be 
presented in a data listing. 
13.4 Electrocardiogram 
Descriptive statistics at baseline and end of treatment (Day 28) as well as changes from baseline 
will be summarized for each electrocardiogram (ECG) parameter. Baseline is defined as the last 
non-missing value prior to first dose of study drug. 
13.5 Vital Signs 
Vital signs will be summarized using descriptive statistics at baseline and at each post-baseline 
time point (Day 7, 14, 28/EOT, 42/EOS) and will include change from baseline. Baseline is 
defined as the last non-missing value prior to first dose of study drug. 
13.6 Physical Examination 
Physical examination results will be listed. 
14. CHANGES TO PROTOCOL-SPECIFIED ANALYSES 
Based on the DMC meeting on Thursday Feb 11th and a subsequent internal company meeting, 
Sojournix terminated the SJX-653-006 study early. At the time of termination, sites were 


 
 
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informed to stop screening and withdraw all subjects from the study. Subjects on treatment were 
notified to stop dosing immediately.  
Due to limited number of randomized subjects, select safety data will be summarized as outlined 
in Section 13. Efficacy data will not be summarized or tabulated. 
15. REFERENCES 
None. 


 
 
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16. APPENDICES 
APPENDIX A: PRESENTATION OF DATA AND PROGRAMMING SPECIFICATIONS 
General  
• Specialized text styles, such as bold, italics, borders, shading, superscripted and 
subscripted text will not be used in tables, figures, and data listings unless they add 
significant value to the table, figure, or data listing. 
• Only standard keyboard characters are to be used in tables and data listings. 
• Special characters, such as non-printable control characters, printer-specific, or font-
specific characters, will not be used on a table, figure, or data listing. 
• Hexadecimal character representations are allowed (e.g., µ, a, ß). 
• All footnotes will be left justified and at the bottom of a page. Footnotes should be used 
sparingly and must add value to the table, figure, or data listing. 
Tables 
• Means and medians will be presented to one more decimal place than the raw data. 
Standard deviations will be presented to two more decimal places than the raw data. 
Minimums and maximums will be reported with the same number of decimal places as 
the raw data.  
• Percentages will be presented with two decimal places. 
• For frequency counts of categorical variables, categories whose counts are zero will be 
displayed for the sake of completeness. For example, if none of the subjects discontinue 
due to “lost to follow-up,” this reason will be included in the table with a count of 0. 
Categories with zero counts will not have zero percentages displayed. 
• Percentiles (e.g., 25%, 75%) should be presented to one decimal place more than the 
raw/derived data. 
• The first footnote will be “Source: xxx”, where xxx indicates the source listing number(s) 
and/or source datatset(s) (e.g., ADaM).   
Listings 
• If not otherwise specified, all data listings will be sorted by treatment, center, subject 
number, visit, and date/time as appropriate.   
• All date values will be presented in a SAS date (e.g., 29AUG2001) format.  
• All observed time values will be presented using a 24-hour clock HH:MM:SS format 
(e.g., 01:35:45 or 11:26). Seconds will only be reported if they were measured as part of 
the study. 
 
 


 
 
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Standard Calculations 
Variables requiring calculation will be derived using the following formulas: 
• Days – A duration expressed in days between one date (date1) and another later date (date2) 
is calculated using the formulas noted below: 
duration in days = date2 – date1 + 1 
• Months – A duration expressed in months is calculated using the INTCK function of SAS as 
follows:  
duration in months=intck('month','date1'd,date2'd, 'continuous');. 
• Years – A duration expressed in years between one date (date1) and another later date 
(date2) is calculated as follows:  
duration in years = intck(‘year,'date1'd,date2'd, 'continuous');. 
• Change from baseline – Change from baseline will be calculated as: 
Change = post baseline value – baseline value 
• Percent change from baseline – Change from baseline will be calculated as: 
Percent change from baseline = post baseline value – baseline value / baseline value  
x 100 
 
 


 
 
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APPENDIX B: SAS PROGRAMMING QC REQUIREMENTS  
Programmer / Validator Review 
1. Program Review 
1.1.
Program name follows standard naming conventions and is consistent with other 
study program names. 
1.2.
Program header uses standard template with all relevant information completed.  
1.3.
Program flow is logical (i.e., header → initialization code → macro variable 
definitions → format definitions → main body). 
1.4. Programmer comments are included throughout program to describe purpose of 
individual sections or macros and provide understanding of specific code, if necessary. 
All comments are clear and up-to-date. 
1.5. Hard coding, if any, is implemented correctly and documented in program header 
with: date, reason, and reference to sponsor approval. A comment is also inserted at the 
location of the hard coding. 
1.6. SAP Derivation rules, if any, are followed.  Significant deviations from mock table or 
SAP text are documented in the SAS Program Header. 
1.7.
Permanent intermediate datasets utilized as source data have either been fully 
validated elsewhere or are fully validated within the scope of this QC.  
1.8. Program runs properly and output dataset is generated as intended. 
 
2. SAS Log Review 
2.1. Scan of entire log confirming that each data step and procedure completed properly.  
2.2. Critical messages such as: errors, warnings, merge notes, or uninitialized variables are 
not found in log. Unavoidable critical messages are verified to not adversely affect the 
output and the reasons why they are unavoidable are documented. 
2.3. Other messages such as “PUT” or “INFO” messages (e.g., overwritten variables 
following merge) are handled appropriately, if they are found in log. 
 
3. Output Review 
3.1. Output file name follows standard naming conventions and is consistent with other 
study output file names. 
3.2. Titles and footnotes are verified against mock table (if available). Discrepancies, 
including footnotes added for clarification, are noted and verified.  
3.3. Column/row header text is verified against mock table and/or CRF.  
3.4. Format and sorting order are correct relative to mock table and/or CRF.  
3.5. Pages breaks are as intended throughout the document. 
3.6. Significant digits are appropriate for summary results (e.g., mean is one more digit 
than collected on the CRF, etc.). 


 
 
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3.7.
Analysis population totals are verified as correct based on SAP definitions and are 
consistent with other tables using the same population(s). 
3.8.
Inappropriate data: checked for outliers, invalid numbers, missing results, etc. 


 
 
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1. Verification of Data  
1.1. Analysis datasets (ADaM or ADaM-Like) 
1.1.1. Programmer 
- 
Each Analysis dataset is opened and data are reviewed for consistency 
with the protocol, SAP, and/or CRF (no additional QC programming is 
necessary). 
1.1.2. Validator 
- 
Validation is performed against the protocol, SAP, and/or eSource.  A 
spot-check of source data against the output dataset is performed on at 
least 2 subjects. Each eSource section/form should be populated at least 
once for the spot-check. If a section/ form is repeated (e.g., at several 
visits) one repeat per subject has to be spot-checked. 
1.2. Tables 
1.2.1. Program Review 
• Verify that the appropriate datasets, variables, analysis populations, 
parameters/tests, and visits/timepoints are used. 
• Verify that all keyword and positional parameters of the standardized macro call 
are accurate and are implemented as intended. 
1.2.2. Output Review 
• All expected data (parameters/tests, visits/timepoints, treatments, totals, etc.) are 
included on the output. 
• Units and the range of values are confirmed to be consistent. 
• Percentages are based on the correct denominator and confirmed to not exceed 
100%. 
• Counts within subgroups or subsets of data are checked for internal consistency 
(e.g., subset counts do not exceed overall counts). 
1.3. Listings 
• Listing content is as expected (e.g., listing includes all enrolled subjects, all 
expected visits, etc.) 
• Variables directly from source dataset are spot-checked for accuracy and 
completeness. 
• Derived or calculated variables are compared to corresponding source data and 
manual calculation for at least 2 subjects are done. 
 
 


 
 
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2. Documentation 
2.1.
The Programmer and Validator must document completion of QC (e.g., date of QC and 
method used) in TMP-SOP-0205-002 Program Status Document. 
2.2. Validator findings and/or comments may be tracked in the Program Status Document 
along with a description of how the finding was resolved and resolution date. 
2.3. The following must be retained electronically within the study folder by the Validator 
as supporting documentation:  
• 
If a spot-check of subject data is performed, output that clearly identifies the 
subjects and CRF forms/sections that are checked 
 
 


 
 
 
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APPENDIX C: LIST OF TABLES, LISTINGS, AND FIGURES 
The following proposal for section 14 and 16.2 is completed according to ICH E3 guidelines. The ICH heading numbers and 
description are in bold. Minor changes from this planned index do not need to be amended in the SAP.   
 
TABLES, FIGURES AND LISTINGS  
Index of Section 14  
Table 
Number 
 
Table Title 
 
Analysis Set 
14 
Tables and Figures Referred to but not Included in the Text 
 
14.1 
Demographic Data 
 
14.1.1
Subject Disposition
14.1.2 
Summary of Demographic and Baseline Characteristics 
Safety Population 
14.1.3 
Summary of Protocol Deviations Due to COVID-19 
Safety Population 
14.3 
Safety Data 
 
14.3.1 
Displays of Adverse Events 
 
14.3.1.1 
Overall Summary of Treatment-Emergent Adverse Events 
Safety Population 
14.3.1.2 
Treatment-emergent Adverse Events by System Organ Class and Preferred Term in Descending 
Frequency 
Safety Population 
14.3.1.3 
Treatment-emergent Adverse Events of Special Interest by System Organ Class and Preferred Term in 
Descending Frequency 
Safety Population 
14.3.1.4 
Treatment-emergent Treatment-related Adverse Events by System Organ Class and Preferred Term in 
Descending Frequency  
Safety Population 
14.3.1.5 
Serious Adverse Event by System Organ Class and Preferred Term 
Safety Population 
14.3.1.6 
Treatment-emergent Adverse Event Leading to Study Discontinuation by System Organ Class and 
Preferred Term 
Safety Population 
14.3.5 
Extent of Exposure 
 
14.3.5 
Summary of Study Drug Exposure 
Safety Population 
14.3.6 
Other Safety Data 
 
14.3.6.1 
Observed Values and Change from Baseline in Clinical Laboratory Parameters, Hematology 
Safety Population 


 
 
 
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Table
Number 
Table Title 
Analysis Set 
14.3.6.2 
Observed Values and Change from Baseline in Clinical Laboratory Parameters, Chemistry 
Safety Population 
14.3.6.3
Observed Values and Change from Baseline in Clinical Laboratory Parameters, Urinalysis 
Safety Population
14.3.6.4 
Observed Value and Change from Baseline in Clinical Laboratory, Liver Function Tests 
Safety Population 
14.3.6.5 
Liver Function Abnormalities 
Safety Population 
14.3.7 
Observed Values and Change from Baseline in ECG Tests 
Safety Population 
14.3.8 
Observed Values and Change from Baseline in Vital Signs 
Safety Population 


 
 
 
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Index of Section 16.2 
ICH Listing 
Number 
 
Listing Title 
16.2 
Subject Data Listings 
16.2.1 
Discontinued Subjects 
16.2.1 
Subject Disposition 
16.2.4 
Demographic Data 
16.2.4.1 
Demographic Characteristics 
16.2.4.2 
Concomitant Medications 
16.2.5 
Visits 
16.2.5 
Missed Assessments Due to COVID-19 
16.2.7 
Adverse Events Listings 
16.2.7 
Adverse Events 
16.2.8 
Listing of Individual Laboratory Measurements by Subject, When Required by Regulatory Authorities 
16.2.8.1 
Central Laboratory Test - Hematology 
16.2.8.2 
Central Laboratory Test - Chemistry
16.2.8.3 
Central Laboratory Test - Urinalysis 
16.2.8.4 
Clinical Laboratory, Coagulation and Liver Serology 
16.2.9 
Other Data 
16.2.9.1 
ECG  
16.2.9.2 
Vital Signs 
16.2.9.3 
Physical Examinations 
16.2.9.4 
SARS-CoV2 Test