Clinical trial NCT03800420
Conditions: Ulcerative Colitis
Keywords: Pellino-1
Sponsor: Bridge Biotherapeutics, Inc.
Start date: 2019-04-22; Completion date: 2020-07-31
Enrollment: 16 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is randomized, placebo-controlled, dose-escalation, multicenter, Phase 2 study to evaluate the efficacy and safety of BBT-401-1S in patients with active ulcerative colitis.

This study consists of three cohorts with 16-week treatment period per cohort that will be conducted sequentially.

Detailed description:

Arms: arm 1: BBT-401-1S, Oral capsule, QD arm 2: Placebo, Oral capsule, QD
Interventions: intervention 1: BBT-401-1S first and then Placebo intervention 2: Placebo first and then BBT-401-1S
Intervention descriptions: intervention 1: Total 16 week treatment period: The subject takes BBT-401-1S, QD for the first 12 weeks, then placebo for the last 4 weeks. intervention 2: Total 16 week treatment period: The subject takes the placebo, QD for the first 8 weeks, then BBT-401-1S for the last 8 weeks.

Protocol documents:
Prot_000.pdf: 
 
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Clinical Study Protocol 
 
 
Protocol Title:  
A Multicenter, Randomized, Double-blind, Placebo-
controlled, Phase 2a Study to Evaluate the Efficacy and Safety 
of BBT-401-1S in Patients with Active Ulcerative Colitis 
 
Short Title: 
Phase 2a Study of BBT401-1S in Active UC 
 
Protocol Number: 
BBT401-UC-US02 
 
Version Number and Date:  V3.1 / Jul 19, 2019 
Drug Product: 
BBT-401-1S 
 
IND No.: 
136188 
 
Study Phase: 
2 
 
Sponsor: 
Bridge Biotherapeutics, Inc. 
C’s Tower #303 
58, Pangyo-ro 255beon-gil, Bundang-gu 
Seongnam-si, Gyeonggi-do, Republic of Korea 
 
 
GCP Statement 
This study is to be performed in full compliance with the protocol, Good Clinical Practices (GCP), and 
applicable regulatory requirements. All required study documentation will be archived as required by 
regulatory authorities. 
 
Confidentiality Statement 
This document is confidential. It contains proprietary information of Bridge Biotherapeutics. Any viewing 
or disclosure of such information that is not authorized in writing by Bridge Biotherapeutics is strictly 
prohibited. Such information may be used solely for the purpose of reviewing or performing this study. 


  
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Table of Contents 
1 
PROTOCOL SUMMARY ................................................................................................... 2 
1.1 
Synopsis ....................................................................................................................................2 
1.2 
Schema ......................................................................................................................................3 
1.3 
Schedule of Assessments ..........................................................................................................6 
2 
INTRODUCTION ................................................................................................................ 7 
2.1 
Background and Study Rationale .............................................................................................7 
2.2 
Risk/Benefit Assessment ..........................................................................................................8 
2.2.1 
Known Potential Risks ........................................................................................................8 
2.2.2 
Known Potential Benefits ....................................................................................................9 
2.2.3 
Assessment of Potential Risks and Benefits ........................................................................9 
3 
OBJECTIVES AND ENDPOINTS .................................................................................... 10 
4 
STUDY DESIGN ............................................................................................................... 11 
4.1 
Overall Design ........................................................................................................................11 
4.2 
Scientific Rationale for Study Design ....................................................................................11 
4.3 
Justification for Dose ..............................................................................................................11 
4.4 
End of Study Definition ..........................................................................................................12 
5 
STUDY POPULATION ..................................................................................................... 13 
5.1 
Inclusion Criteria ....................................................................................................................13 
5.2 
Exclusion Criteria ...................................................................................................................13 
5.3 
Lifestyle Considerations .........................................................................................................14 
5.4 
Screen Failures .......................................................................................................................14 
5.5 
Strategies for Recruitment and Retention ...............................................................................14 
6 
STUDY INTERVENTION ................................................................................................ 15 
6.1 
Study Drug Administration ....................................................................................................15 
6.1.1 
Study Drug Description .....................................................................................................15 
6.1.2 
Dosing and Administration ................................................................................................15 
6.2 
Preparation/Handling/Storage/Accountability ........................................................................16 
6.2.1 
Acquisition and accountability ..........................................................................................16 
6.2.2 
Formulation, Appearance, Packaging, and Labeling .........................................................16 
6.2.3 
Product Storage and Stability ............................................................................................17 
6.3 
Measures to Minimize Bias: Randomization and Blinding ....................................................17 
6.4 
Treatment Compliance ...........................................................................................................17 
6.5 
Concomitant Therapy .............................................................................................................18 
6.6 
Removal of Patients from the Trial or Study Drug ................................................................18 
6.6.1 
Handling of Withdrawals ...................................................................................................19 
6.6.2 
Replacements .....................................................................................................................19 
7 
STUDY ACTIVITIES ........................................................................................................ 20 
7.1 
Screening Visit (Day -28 to -1) ..............................................................................................20 
7.2 
Treatment Period ....................................................................................................................20 
7.2.1 
Visit 2 (Baseline, Week 0/Day 1) ......................................................................................20 
7.2.2 
Visit 3 (Week 4) .................................................................................................................21 
7.2.3 
Visit 4 (Week 8) .................................................................................................................21 
7.2.4 
Visit 5 (Week 12) ...............................................................................................................22 
7.2.5 
Visit 6 (Week 16) ...............................................................................................................22 


  
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7.3 
Safety Follow-Up (SFU) Visit ................................................................................................23 
7.4 
Early Termination (ET) Visit .................................................................................................23 
8 
STUDY PROCEDURES .................................................................................................... 24 
8.1 
Informed Consent and Medical History .................................................................................24 
8.1.1 
Informed Consent ..............................................................................................................24 
8.1.2 
Medical History .................................................................................................................24 
8.2 
Safety Assessments .................................................................................................................24 
8.2.1 
Physical Examination ........................................................................................................24 
8.2.2 
Vital Signs .........................................................................................................................25 
8.2.3 
Electrocardiogram (ECG) ..................................................................................................25 
8.2.4 
Clinical Laboratory Tests ..................................................................................................25 
8.3 
Efficacy Assessments .............................................................................................................27 
8.3.1 
Mayo Score ........................................................................................................................27 
8.3.2 
Endoscopy with Biopsy Procedure ....................................................................................28 
8.3.3 
Ulcerative Colitis Endoscopic Index of Severity (UCEIS) ...............................................28 
8.3.4 
Quality of Life Questionnaire: Short Inflammatory Bowel Disease Questionnaire 
(SIBDQ) 
 ...........................................................................................................................................28 
8.3.5 
Biomarkers .........................................................................................................................28 
8.4 
Pharmacokinetic Assessments ................................................................................................29 
8.4.1 
Plasma Pharmacokinetics ..................................................................................................29 
8.4.2 
Tissue Pharmacokinetics ...................................................................................................29 
8.5 
Adverse Events and Serious Adverse Events Reporting ........................................................29 
8.5.1 
Definition of Adverse Events (AE) ...................................................................................30 
8.5.2 
Definition of Serious Adverse Events (SAE) ....................................................................30 
8.5.3 
Classification of an Adverse Event ....................................................................................32 
8.5.4 
Adverse Event Reporting ...................................................................................................33 
8.5.5 
Reporting Events to Patients ..............................................................................................34 
8.5.6 
Events of Special Interest ..................................................................................................34 
8.5.7 
Reporting of Pregnancy .....................................................................................................34 
9 
STATISTICAL CONSIDERATIONS ............................................................................... 35 
9.1 
General Methodology .............................................................................................................35 
9.2 
Blinding and Randomization ..................................................................................................35 
9.3 
Sample Size and Power ..........................................................................................................35 
9.4 
Population for Analyses ..........................................................................................................35 
9.4.1 
General Approach Procedures for Handling Missing, Unused, and Spurious Data ..........36 
9.4.2 
Demographic and Baseline Descriptive Statistics .............................................................36 
9.4.3 
Subject Disposition ............................................................................................................36 
9.4.4 
Prior and Concomitant Medications ..................................................................................36 
9.4.5 
Protocol Deviations ...........................................................................................................36 
9.5 
Statistical Analyses .................................................................................................................36 
9.5.1 
Analysis of Primary Endpoint ...........................................................................................37 
9.5.2 
Analysis of Secondary Endpoints ......................................................................................37 
9.5.3 
Safety Analyses .................................................................................................................37 
9.5.4 
Planned Interim and Subgroup Analyses ...........................................................................38 
9.5.5 
Tabulation of Individual Participant Data .........................................................................38 
9.5.6 
Pharmacokinetic Analysis .................................................................................................38 


  
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9.5.7 
Pharmacodynamic Analyses ..............................................................................................38 
10 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS ......... 39 
10.1 
Informed Consent Process ......................................................................................................39 
10.2 
Consent/assent and Other Informational Documents Provided to Participants ......................39 
10.3 
Consent Procedures and Documentation ................................................................................39 
10.4 
Study Discontinuation and Closure ........................................................................................39 
10.5 
Confidentiality and Privacy ....................................................................................................40 
10.6 
Future Use of Stored Specimens and Data .............................................................................40 
10.7 
Safety Oversight .....................................................................................................................41 
10.8 
Clinical Monitoring ................................................................................................................41 
10.9 
Quality Assurance and Quality Control ..................................................................................42 
10.10 
Data Handling and Record Keeping .......................................................................................42 
10.11 
Protocol Deviations ................................................................................................................43 
10.12 
Publication and Data Sharing Policy ......................................................................................43 
10.13 
Conflict of Interest Policy .......................................................................................................43 
10.14 
Abbreviations ..........................................................................................................................43 
10.15 
Protocol Amendment History .................................................................................................45 
11 
REFERENCES ................................................................................................................... 48 
Appendix 1. Mayo Score (Modified) ............................................................................................ 50 
Appendix 2. Ulcerative Colitis Endoscopic Index of Severity ..................................................... 52 
Appendix 3. Short Inflammatory Bowel Disease Questionnaire .................................................. 53 
 
 


Phase 2a Study of BBT401-1S in Active UC 
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STATEMENT OF COMPLIANCE 
 
The trial will be carried out in accordance with International Conference on Harmonisation Good 
Clinical Practice (ICH GCP) and the following:  
• United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 
CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812)  
 
Investigators and clinical trial site staff who are responsible for the conduct, management, or 
oversight of clinical trials have completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, ICF(s), recruitment materials, and all participant materials will be submitted to the 
Institutional Review Board (IRB) for review and approval. Approval of both the protocol and the 
consent form must be obtained before any participant is enrolled. Any amendment to the protocol 
will require review and approval by the IRB before the changes are implemented to the study. In 
addition, all changes to the consent form will be IRB-approved; a determination will be made 
regarding whether a new consent needs to be obtained from participants who provided consent, 
using a previously approved consent form. 


Phase 2a Study of BBT401-1S in Active UC 
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1 
PROTOCOL SUMMARY 
 
1.1 
Synopsis  
 
Title: 
A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2a Study to 
Evaluate the Efficacy and Safety of BBT-401-1S in Patients with Active Ulcerative 
Colitis  
Study 
Description: 
This will be a randomized, double-blind, placebo-controlled study of orally 
administered BBT-401-1S to evaluate its efficacy and safety for the treatment of active 
ulcerative colitis (UC)  
Objectives: 
 
Primary Objective:  
§ To assess the efficacy and safety of multiple oral doses of BBT-401-1S in 
patients with active UC 
Secondary Objectives:  
§ To assess the plasma and tissue concentration of multiple oral doses of BBT-
401-1S in patients with active UC 
§ To evaluate the effects of BBT-401-1S on biomarkers 
Endpoints: 
Primary Endpoint: 
§ Change from Baseline in Total Mayo Score at Week 8 
Secondary Endpoints: 
§ Change from Baseline in Partial Mayo Score at Week 8  
§ Change from Baseline in Histologic Assessment of Endoscopic Biopsy at Week 
8 
§ Change from Baseline in Ulcerative Colitis Endoscopic Index of Severity 
(UCEIS) Score at Week 8 
§ Number and Severity of Treatment Emergent Adverse Events (TEAEs) up to 
Week 8  
§ Change from Baseline in Short Inflammatory Bowel Disease Questionnaire 
(SIBDQ) at Week 8 
§ Change from Baseline in Concentration of Biomarkers (C-reactive protein 
[CRP], fecal calprotectin, and fecal lactoferrin) at Week 8 
§ Plasma and Tissue Concentration of BBT-401-1S in Patients with Active UC 
Study 
Population: 
The study plans to enroll up to 48 adult patients with active UC in the United States 
and South Korea.  
 
Inclusion Criteria 
1) Provision of signed and dated informed consent form 
2) Stated willingness to comply with all study procedures and availability for the 
duration of the study  
3) Male or female, aged ³18 years 
4) Diagnosed with active UC for at least 3 months prior to screening  
5) Total Mayo score ³5 and Endoscopic sub-score ³1 
6) Stable dosing regimens of oral drugs (if currently administered) as follows:  
5-ASA or sulfasalazine at a stable dose for at least 4 weeks, purine analogues 
(azathioprine, mercaptopurine, thiopurines) or immunosuppressants 
(methotrexate, cyclosporine) at a stable dose for at least 12 weeks, and low-
dose oral corticosteroid (up to 20 mg prednisone/day or equivalent) for at least 
4 weeks prior to the first dose of study treatment. Doses of oral drugs must 


Phase 2a Study of BBT401-1S in Active UC 
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Protocol # BBT401-UC-US02 
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remain stable until the end of study treatment (with possible exception for 
tapering steroid dose after 8 weeks) 
7) For females of reproductive potential: use of highly effective contraception for 
at least 1 month prior to screening and agreement to use such a method during 
study participation and for an additional 3 months after the last dose  
8) For males of reproductive potential: use of condoms or other methods to ensure 
effective contraception with partner during study participation and for an 
additional 3 months after the last dose 
 
Exclusion Criteria 
1) Use of anti-TNF-a biologics, any other biologics, or tofacitinib for treatment of 
UC within 60 days prior to randomization.  
2) Any rectal therapy for treatment of UC or intravenous corticosteroids within 2 
weeks prior to randomization.  
3) Presence of Crohn's disease, indeterminate colitis, ischemic colitis, fulminant 
colitis, ulcerative proctitis, or toxic mega-colon 
4) Previous extensive colonic resection (subtotal or total colectomy) 
5) Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine 
6) Evidence of treatment for Clostridium difficile infection or other pathogenic 
bowel infection within 60 days or for another intestinal pathogen within 30 days 
prior to randomization 
7) Active infection with the HIV or Hepatitis B or C viruses 
8) Clinically significant active extra-intestinal infection (e.g., pneumonia, 
pyelonephritis)  
9) Clinically significant abnormal vital signs, physical examination or 12-lead 
electrocardiogram (ECG) at screening or baseline 
10) Clinically significant abnormal results of liver function tests (ALT/AST, 
bilirubin and alkaline phosphatase) > 2X the upper limit of normal (ULN) at 
screening 
11) Other clinically significant abnormal laboratory results at screening in the 
investigator’s opinion  
12) History of any clinically significant medical condition that, in the investigator's 
opinion, would preclude participation in the study 
13) Pregnancy or lactation 
14) Treatment with another investigational drug or other intervention within 30 
days prior to screening 
Phase: 
Phase 2a 
Description of 
Study 
Intervention: 
BBT-401-1S, the monosodium salt of BBT-401, will be administered as 200-mg 
capsules, once a day (q.d.) for 16 weeks  
 
1.2 
Schema 
 
Summary  
 
This randomized, placebo-controlled, dose-escalation, multicenter, Phase 2 study consists of three 
cohorts with 16-week treatment period per cohort that will be conducted sequentially. The first 
cohort will receive 400 mg of BBT-401-1S (starting dose). Efficacy, safety, and PK data of the 


P h ase 2 a St u d y of B B T 4 0 1 -1 S i n A cti v e U C  
V ersi o n 3. 1
Pr ot o c ol # B B T 4 0 1 -U C -U S 0 2  
J ul y 1 9, 2 0 1 9
C o nfi d e nti al
4
first c o h ort will be use d t o select t he d ose of t he s u bse q ue nt c o h ort. F or t he 1st or 2 n d c o h ort, if 
1 2t h patie nt ( 7 5 %)  c o m pletes Visit 4 ( Wee k 8), u n bli n di n g of 1 2 patie nts will be perf or me d wit hi n 
2 wee ks after Visit 4 ( Wee k 8) a n d t he u n bli n di n g i nf or mati o n will be o nl y pr o vi de d t o t he S p o ns or 
f or t he a nal ysis t o deter mi ne t he d ose of ne xt c o h ort.  
Patie nts will recei ve a dail y oral d ose of B B T - 4 0 1-1 S or place b o f or t he 1 6 wee ks. W hile patie nts 
w h o are assi g ne d t o Acti ve Gr o u p will recei ve B B T - 4 0 1-1 S f or t he first 1 2 wee ks a n d t he n place b o 
f or t he last 4 wee ks, patie nts w h o are assi g ne d t o Place b o Gr o u p will recei ve place b o f or t he first 
8 wee ks a n d t he n B B T- 4 0 1- 1 S f or last 8 wee ks. 
D osi n g C o h orts  
• �A t otal of 1 6 patie nt s i n eac h c o h ort will be ra n d o mize d t o eit her acti ve or place b o gr o u p 
( 1 2 acti ve a n d 4 place b o).  
• �T hree c o h orts will be c o n d ucte d se q ue ntiall y. T he first c o h ort will recei ve 4 0 0 m g of B B T -
4 0 1- 1 S (starti n g d ose). Efficac y, safet y, a n d P K data of t he first c o h ort will be use d t o 
select t he d ose of t he s u bse q ue nt c o h ort. A d ose le vel ma y be re peate d or a d de d base d o n 
res ults of t he pre vi o us c o h ort(s).  
• �T he hi g hest d ose is n ot t o e xcee d 1, 6 0 0 m g dail y.  
St u d y Visits 
• �Visit 1 ( Scree ni n g)  
• �Visit 2 ( Baseli ne): P K a n d baseli ne assess me nts 
• �Visit 3 ( Wee k 4): P K, 4- wee k treat me nt visit  
• �Visit 4 ( Wee k 8): P K, 8- wee k treat me nt visit 
• �Visit 5 ( Wee k 1 2): 1 2- wee k treat me nt visit 
• �Visit 6 ( Wee k 1 6): 1 6- wee k treat me nt visit  
• �Safet y F oll o w- U p ( S F U): 2 wee ks fr o m t he last d ose 


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Efficacy Assessments 
 
• Total Mayo Score (Stool frequency, rectal bleeding, endoscopic findings [flexible 
proctosigmoidoscopy/colonoscopy], physician’s global assessment): Screening and W8 
• Partial Mayo Score: Baseline, W4, W8, W12, and W16 
• Histologic Assessment of Endoscopic Biopsy: Screening and W8  
• Ulcerative Colitis Endoscopic Index of Severity (UCEIS): Screening and W8 
• Short Inflammatory Bowel Disease Questionnaire (SIBDQ): Baseline, W4, W8, W12, and 
W16 
• Serum CRP: Baseline, W4, W8, W12, and W16 
• Fecal calprotectin: Baseline, W4, W8, W12, and W16 
• Fecal lactoferrin: Baseline, W4, W8, W12, and W16 
 
Safety Assessments 
 
• Physical examination: Screening, Baseline, W4, W8, W12, and W16 
• Vital signs: All visits (including SFU) 
• 12-lead ECG: Screening, Baseline, W4, W8, W12, and W16 
• Clinical laboratory testing of serum chemistry/hematology: All visits (including SFU) 
• Recording of AEs: Baseline, W4, W8, W12, W16, and SFU 
 
Pharmacokinetic Assessments 
 
• Concentrations of BBT-401-1S in plasma to assess systemic exposure: Baseline, W4, and 
W8 
• Concentration of BBT-401-1S in tissue to assess exposure: Screening and W8 
 
Statistical Analysis 
 
As this is an initial dose-finding study, it is appropriately based on only a limited number of 
patients in each dose cohort. The number of patients in this study is not based on any statistical 
power calculations; further, no formal inferential statistics analyses are planned. For the 
quantitative endpoints (efficacy, biomarker measure, and some safety data) descriptive statistics 
will be calculated to provide an indication of directional changes in endpoints for each treatment 
group per dose cohort.  
 
Further, to allow for a direct comparison of BBT-401-1S vs placebo for each cohort, descriptive 
statistics will be provided for the difference between the treatment groups at Week 8. For the 
qualitative data, frequency counts and incidence rates will be compiled for each treatment group.  


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1.3 
Schedule of Assessments 
 
 
Screening 
Treatment Period 
SFU 
Visit Number 
V1 
V2 
V3 
V4  
V5  
V6 
ET 
Visit Period Up to W-4 
Baseline 
W4 
W8 
W12 
W16 
N/A 
W2 from LD 
Visit Window 
N/A 
Within 28 
days from V1 ±3 days ±3 days ±3 days ±3 days 
N/A 
+ 7 days from 
LD 
Informed Consent 
X 
 
 
 
 
 
 
 
Demographic Information 
X 
 
 
 
 
 
 
 
Medical/medication History 
X 
X 
 
 
 
 
 
 
Inclusion/exclusion Criteria 
X 
X 
 
 
 
 
 
 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Examination 
X 
Xa 
X 
X 
X 
X 
X 
 
12-lead ECG 
X 
Xa 
X 
X 
X 
X 
X 
 
Clinical Lab Tests and Serum Biomarkerb 
X 
Xa 
X 
X 
X 
X 
X 
X 
Endoscopy (biopsy) 
X 
 
 
X 
 
 
Xc 
 
Randomization 
 
X 
 
 
 
 
 
 
Mayo Score 
X 
X 
X 
X 
X 
X 
X 
 
Ulcerative Colitis Endoscopic Index of 
Severity 
X 
 
 
X 
 
 
Xc 
 
Short Inflammatory Bowel Disease 
Questionnaire 
 
X 
X 
X 
X 
X 
X 
 
Fecal Biomarkerd 
 
X 
X 
X 
X 
X 
X 
 
Plasma Pharmacokineticse 
 
X 
X 
X  
 
 
 
 
Tissue Concentrationf 
X 
 
 
X 
 
 
Xc 
 
Drug Dispensing (with subject diary) 
 
X 
X 
X 
X 
 
 
 
Drug Return and Compliance 
 
 
X 
X 
X 
X 
X 
 
AE and Concomitant Medication 
 
X 
X 
X 
X 
Xg 
Xg 
X 
AE = adverse event; ECG = electrocardiogram; SFU = Safety Follow-Up; V = Visit; W = Week; ET = Early Termination; LD = 
Last Dose 
                                               
 
a 
Waived if the screening visit is conducted within 10 days prior to Visit 2 (Baseline).  
b  Serum chemistry, hematology, coagulation test, HIV and hepatitis screens, serum hCG (women with 
childbearing potential only), and serum CRP (not measured at SFU).  
c 
Only if early termination occurs before Visit 4 (W8).  
d  Fecal calprotectin and fecal lactoferrin. A collection container will be dispensed to patients on the previous visit.  
e  Visit 2 (Baseline) and Visit 3 (W4): pre-dose and 3 and 6 hours post-dose; Visit 4 (W8): pre-dose only. 
f  During the endoscopy (flexible proctosigmoidoscopy/colonoscopy) for biopsy. 
g 
Reviewing any changes in smoking habits of subject during the study period. 


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2 
INTRODUCTION 
 
2.1 
Background and Study Rationale  
 
Ulcerative colitis (UC) is a chronic disorder characterized by inflammation of intestinal mucosa, 
primarily the colon, as well as the rectum in ~95% of cases. Classic symptomatology in the clinical 
presentation of UC is bloody diarrhea accompanied by rectal urgency and tenesmus. Individuals 
with UC may experience periods of active symptoms and of spontaneous or treatment-induced 
remission (Kornbluth et al, 2010). Diagnosis typically occurs in adulthood, although there are 
pediatric and adolescent cases of UC (da Silva et al, 2014).  
 
The prevalence of UC in the United States as of 2009 was estimated to be nearly 600,000 
(Kappelman et al, 2013). Healthcare utilization for UC is substantial; annual direct medical costs 
are reported to exceed US$4 billion. Mortality rates associated with UC range between 11% and 
30% (Jess et al, 2013). Furthermore, individuals with UC suffer reduced quality of life and have 
increased rates of anxiety and depression compared with the general population. (Kornbluth et al, 
2010). 
 
The goals of treatment of UC are to induce and maintain remission of symptoms. Oral 
aminosalicylate (e.g., sulfasalazine) therapy comprises the conventional standard of care (SOC) in 
the 
pharmacological 
treatment 
of 
mild-to-moderate 
active 
UC. 
Corticosteroids, 
immunosuppressants, or antibiotics may also be used to treat symptoms. Patients unable to be 
treated with conventional therapies or those with moderate to severe disease might receive 
biological therapy (i.e., an anti-TNF-a agent) (Kornbluth et al, 2010).  
 
Conventional therapies are broadly limited by safety and tolerability issues, such as thinning of 
the skin, effects on bone contributing to osteoporosis, increased risks of infection, and 
psychological effects with corticosteroid therapy, and headache, nausea, hypersensitivity 
reactions, and potential for nephrotoxicity with sulfasalazine therapy (D'Haens 2016; Curkovic et 
al, 2013). Biologic therapy is known to have immunocompromising effects that increase patient 
risks to other diseases and a range of infections (mycobacterial, fungal, viral) (Andersen and Jess, 
2014). Reported treatment failures further limit the utility of biologic therapies (Gordon et al, 
2015). New therapies with novel mechanisms may help address the unmet needs in treatment of 
UC.  
 
Given the inflammatory pathophysiology of UC and the effects of BBT-401 on inhibiting 
inflammatory processes, there is a pharmacological rationale to evaluate BBT-401 in the treatment 
of UC. A broader view of the inflammatory process is useful context for this description. 
Interleukin-1 receptor (IL-1R) has an important role in amplification of the inflammatory response 
triggered by microbial pathogens. Following IL-1β stimulation, adaptor molecules myeloid 


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differentiation primary response gene 88 (MyD88), interleukin-1 receptor-associated kinase 
(IRAK) 4, IRAK1, and TRAF6 are recruited to IL-1R to form the receptor complex. Toll-like 
receptors (TLRs) and IL-1R have a conserved cytoplasmic Toll–IL-1R domain and share 
downstream signaling complexes that transduce signals from the receptors (Akira et al, 2001; 
Janeway et al, 2002).  
 
Binding of the Pellino-1 protein to the receptor complex triggers activation of NF-kB pro-
inflammatory responses (Jiang et al, 2003). Lee and colleagues identified the sequence of Smad6 
amino acids 422-441 as a sufficient Smad6-derived peptide for alteration of Pellino-1 activity and 
inhibition of pro-inflammatory reaction. Smad6 inhibits lipopolysaccharide (LPS)/IL1b-induced 
formation of the MyD88 and/or receptor-interacting protein 1 (RIP1) that act downstream in the 
signaling pathways involving TLR4 and IL-1b. Pellino-1 was found to be involved in other 
proinflammatory pathways suggesting a more robust inhibitory activity for the Smad-6-Pellino-1 
binding (Choi et al, 2006; Lee et al, 2015). 
 
Based on the idea that Smad6-Pellino-1 binding disrupts Rip1 and MyD88 complex formations in 
the IL-1R-TLR signaling pathway, BBT-401 was derived from Smad6 and developed to modulate 
inflammatory disorders. BBT-401 directly interacts with Pellino-1 protein, competitively binding 
in a dose-dependent manner. 
 
BBT-401-1S is a sodium salt of BBT-401. Nonclinical studies of BBT-401-1S performed to date 
include in vitro and in vivo evaluations in pharmacology, PK, and toxicology studies. BBT-401-
1S was not (or poorly) absorbed following oral administration and drug-drug interaction (DDI) 
potentials were found to be low in the DDI studies. Safety pharmacology data also have been 
generated. Nonclinical toxicology studies showed BBT-401-1S to have a benign safety profile 
with high NOAEL values following oral administration. BBT-401-1S drug product (DP) is 
composed of BBT-401-1S enteric coated drug substance for oral administration. Phase 1 clinical 
trial in healthy subjects showed no systemic exposure and an excellent safety/tolerability profile 
with no serious adverse events (SAEs). Mild diarrhea (usually transient in nature and generally not 
interfering with normal activities) was the most observed AEs in the 1,600 mg single (SAD) and 
multiple ascending doses (MAD) cohorts. Please refer to the current Investigator’s Brochure (IB) 
for additional information.  
 
This is the first clinical trial of BBT-401-1S, designed to assess the safety and efficacy of BBT-
401 administered in patients with active ulcerative colitis.  
 
2.2 
Risk/Benefit Assessment   
 
2.2.1 Known Potential Risks  
 


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Nonclinical toxicology of BBT-401-1S is presented in Section 2.1 and described in the IB.  
 
As there may be unknown and potential risks with administration of BBT-401-1S by virtue of its 
pharmacological action and based on clinical experience with compounds that have inhibitory 
effects on proinflammatory pathways, all patients will be closely monitored for safety and 
tolerability. 
 
2.2.2 Known Potential Benefits  
 
Patients participating in this study who are randomized to receive BBT-401-1S may experience 
therapeutic benefit to symptoms of UC compared with those who receive placebo. Approximately 
three-quarters of the patients enrolled in this study will be randomized to receive BBT-401-1S. 
 
2.2.3 Assessment of Potential Risks and Benefits  
 
Based on the assessment of potential risks and benefits, there is adequate justification for this study 
in the planned population.  
 
There is low risk (or low clinical relevance) of drug DDIs between BBT-401-1S and common 
comedications, including the SOC drugs listed in the inclusion criteria, based on the lack of (or 
low) systemic exposure and benign safety profiles demonstrated in the nonclinical and Phase 1 
clinical studies and on the enteric-coating of BBT-401-1S designed to deliver the API to the colon. 
 
Given the observed safety with no signs of systemic exposure in the Phase 1 trial and the overall 
favorable safety profile seen in the nonclinical toxicology studies, BBT-401-1S is expected to 
demonstrate safety and tolerability with minimal systemic absorption in patients with active UC. 
Accordingly, routine safety monitoring is considered appropriate risk management in this Phase 
2a study. 
 


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3 
OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
 
 
§ To assess the efficacy 
and safety of multiple 
oral doses of BBT-401-
1S in patients with active 
UC 
§ Change from Baseline in Total 
Mayo Score (Stool frequency, 
rectal bleeding, endoscopic 
findings, physician’s global 
assessment) at Week 8 
§ The Mayo Score is a well-
recognized tool for assessing 
efficacy in UC trials and is an 
appropriate primary endpoint for a 
study of this size and nature. 
Secondary 
 
 
§ To assess the plasma and 
tissue concentration of 
multiple oral doses of 
BBT-401-1S in patients 
with active UC 
§ To evaluate the effects of 
BBT-401-1S on 
biomarkers  
§ Change from Baseline in 
Partial Mayo Score at Week 8 
§ Change from Baseline in 
histologic assessment of 
endoscopic biopsy at Week 8 
§ Change from Baseline in 
UCEIS at Week 8 
§ Number and severity of 
TEAEs up to 8 weeks after the 
last dose 
§ Change from Baseline in 
SIBDQ at Week 8  
§ Change from Baseline in 
Concentration of Biomarkers 
(CRP, fecal calprotectin, and 
fecal lactoferrin) at Week 8 
§ Plasma and Tissue 
Concentration of BBT-401-1S  
§ The Mayo Score is an appropriate 
endpoint for assessing efficacy, as 
described above.  
§ Histological assessment of 
endoscopic biopsy is an 
appropriate method for evaluating 
mucosal healing (Carbonnel et al, 
1994). 
§ Measurement of plasma and tissue 
BBT-401-1S concentrations is an 
appropriate method for evaluating 
systemic exposure. 
§ Changes in concentrations of 
biomarkers provide non-
endoscopic assessment of 
inflammation (Canani et al, 2008; 
D'Haens et al, 2012; Lamb et al, 
2011).  


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4 
STUDY DESIGN  
 
4.1 
Overall Design 
 
This randomized, placebo-controlled, dose-escalation, multicenter, Phase 2 study consists of three 
cohorts with 16-week treatment period per cohort that will be conducted sequentially. The first 
cohort will receive 400 mg of BBT-401-1S (starting dose). Efficacy, safety, and PK data of the 
first cohort will be used to select the dose of the subsequent cohort. For the 1st or 2nd cohort, if 
12th patient (75%) completes Visit 4 (Week 8), unblinding of 12 patients will be performed within 
2 weeks after Visit 4 (Week 8) and the unblinding information will be only provided to the Sponsor 
for the analysis to determine the dose of next cohort. A dose level may be repeated or added based 
on results of the previous cohort(s). 
  
Patients will receive a daily oral dose of BBT 401-1S or placebo for the 16 weeks. While patients 
who are assigned to Active Group will receive BBT-401-1S for the first 12 weeks and then placebo 
for the last 4 weeks, patients who are assigned to Placebo Group will receive placebo for the first 
8 weeks and then BBT-401-1S for last 8 weeks.  
 
The primary objective of the study is to evaluate the efficacy and safety of multiple oral doses of 
BBT-401-1S in patients with active UC.  
 
4.2 
Scientific Rationale for Study Design 
 
Given the disease pattern of UC, in which remission from active symptoms may be induced by 
treatment or spontaneously, trials with a placebo control are useful for isolating the treatment effect 
of an investigational treatment. The use of endoscopy is an important tool for evaluating active 
disease. Its inclusion in this study as an endpoint and the assessment of change from baseline also 
may reduce confounding of efficacy results due to placebo effect (Jairath et al, 2016). 
 
4.3 
Justification for Dose 
 
In preclinical studies, oral administration of 300 and 400 mg/kg BBT-401-1S reduced clinical 
colitis scores in mice with DSS-induced colitis. Another preclinical study demonstrated that intra-
colonic administration of as low as 3 mg/kg BBT-401-1S decreased the clinical colitis score in rats 
with DSS-induced colitis. As BBT-401-1S appears to be non-absorbable and is given as the enteric 
formulation, the data following intra-colonic administration in rats was considered more applicable 
for determining the lowest effective dose in humans. Consequently, the pharmacologic human 
equivalent dose of 3 mg/kg BBT-401-1S was calculated as 28.8 mg (FDA, 2005). 
 


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The starting dose planned for the trial is 400 mg daily, which is well below the maximum 
recommended starting dose (830–970 mg with application of safety factor of 10) as determined 
through preclinical study data. The maximum daily dose in this study (1,600 mg/day) is well below 
the human equivalent dose (HED) to the NOAEL (2,700 mg HED in dog, the more sensitive 
species based on oral administration), as determined in 13-week toxicity studies. In Phase 1 clinical 
trial in healthy subjects to assess the safety and tolerability of single (SAD) and multiple ascending 
doses (MAD), BBT-401-1S is not systemically absorbed (all plasma concentration values were 
BLQ, <1 ng/mL) with no SAEs in the SAD up to 1,600 mg per person and in the MAD at doses 
of 400, 800, and 1,600 mg daily per person for 7 consecutive days. Mild diarrhea (usually transient 
in nature and generally not interfering with normal activities) was the most observed AEs in the 
1,600 mg SAD and MAD cohorts. Please refer to the IB Section 6.1 for additional details. 
 
4.4 
End of Study Definition 
 
A participant is considered to have completed the study if he or she has completed all phases of 
the study including the last visit or the last scheduled procedure shown in Section 1.3 Schedule of 
Assessments. 
 
The end of the study is defined as completion of the last visit or procedure shown in the Schedule 
of Assessments in the trial overall. 
 


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5 
STUDY POPULATION 
 
5.1 
Inclusion Criteria 
 
To be eligible to participate in this study, an individual must meet all of the following criteria: 
1) Provision of signed and dated informed consent form (ICF) 
2) Stated willingness to comply with all study procedures and availability for the duration of 
the study  
3) Male or female, aged ³18 years 
4) Diagnosed with active UC for at least 3 months prior to screening  
5) Total Mayo score ³5 and Endoscopic sub-score ³1 
6) Stable dosing regimens of oral drugs (if currently administered) as follows:  
5-ASA or sulfasalazine at a stable dose for at least 4 weeks, purine analogues (azathioprine, 
mercaptopurine, thiopurines) or immunosuppressants (methotrexate, cyclosporine) at a 
stable dose for at least 12 weeks, and low-dose oral corticosteroid (up to 20 mg 
prednisone/day or equivalent) for at least 4 weeks prior to the first dose of study treatment. 
Doses of oral drugs must remain stable until the end of study treatment (with possible 
exception for tapering steroid dose after 8 weeks) 
7) For females of reproductive potential: use of highly effective contraception for at least 1 
month prior to screening and agreement to use such a method during study participation 
and for an additional 3 months after the last dose  
8) For males of reproductive potential: use of condoms or other methods to ensure effective 
contraception with partner during study participation and for an additional 3 months after 
the last dose 
 
5.2 
Exclusion Criteria 
 
Individuals who meet any of the following criteria will be excluded from this study: 
1) Use of anti-TNF-a biologics, any other biologics, or tofacitinib for treatment of UC within 
60 days prior to randomization 
2) Any rectal therapy for treatment of UC or intravenous corticosteroids within 2 weeks prior 
to randomization 
3) Presence of Crohn's disease, indeterminate colitis, ischemic colitis, fulminant colitis, 
ulcerative proctitis, or toxic mega-colon 
4) Previous extensive colonic resection (subtotal or total colectomy) 
5) Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine 
6) Evidence of treatment for Clostridium difficile infection or other pathogenic bowel 
infection within 60 days or for another intestinal pathogen within 30 days prior to 
randomization 
7) Active infection with the HIV or Hepatitis B or C viruses 


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8) Clinically significant active extra-intestinal infection (e.g., pneumonia, pyelonephritis)  
9) Clinically significant abnormal vital signs, physical examination or 12-lead 
electrocardiogram (ECG) at screening or baseline 
10) Clinically significant abnormal results of liver function tests (ALT/AST, bilirubin and 
alkaline phosphatase) > 2X the upper limit of normal (ULN) at screening 
11) Other clinically significant abnormal laboratory results at screening in the investigator’s 
opinion  
12) History of any clinically significant medical condition that, in the investigator's opinion, 
would preclude participation in the study 
13) Pregnancy or lactation 
14) Treatment with another investigational drug or other intervention within 30 days prior to 
screening 
 
5.3 
Lifestyle Considerations 
 
No new non-pharmacological therapies should be started during the study period. In addition, no 
elective surgery should be scheduled during the study period. Patients should avoid smoking 
cessation during the study and should maintain existing habits, such as exercise levels and dietary 
habits throughout the study. Contraceptive measures for both males and females of childbearing 
potential should be documented in the source documents.  
 
5.4 
Screen Failures 
 
Screen failures are defined as participants who consent to participate in the clinical trial but are 
not subsequently randomized in the study. A minimal set of screen failure information is required 
to ensure transparent reporting of screen failure participants, to meet the Consolidated Standards 
of Reporting Trials (CONSORT) publishing requirements and to respond to queries from 
regulatory authorities. Minimal screening failure information includes demography, screen failure 
details, eligibility criteria, and any SAE. 
 
5.5 
Strategies for Recruitment and Retention 
 
The study plans to enroll up to 48 adult patients (aged ≥18 years) with active UC in the United 
States and South Korea.  
 


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6 
STUDY INTERVENTION 
 
6.1 
Study Drug Administration 
 
6.1.1 Study Drug Description 
 
BBT-401-1S is the monosodium salt of BBT-401, an N-terminal lipidated 4aa peptide that targets 
Pellino E3 ubiquitin protein ligase 1 (Pellino-1) which leads to suppression of NF-kB–mediated 
inflammatory signals (Choi et al, 2006; Jiang et al, 2003; Lee et al, 2015).  
 
6.1.2 Dosing and Administration 
 
BBT-401-1S or placebo will be administered orally in capsule form. Study medication will be self-
administered by the subject. Patients should be advised not to crush, break, chew, or dissolve the 
capsules. On days with scheduled study visits, patients should not take their dose of study 
medication at home in order to complete pre-dose study procedures including PK and safety lab. 
Patients will be instructed to fast for up to eight hours before their scheduled study visits.  
 
Dosing will be determined for 3 cohorts conducted sequentially, starting with the first cohort that 
will receive BBT-401-1S 400 mg once daily.  
 
Patients will receive a daily oral dose of BBT-401-1S or placebo for the 16 weeks. While patients 
who are assigned to Active Group will receive BBT-401-1S for the first 12 weeks and then placebo 
for the last 4 weeks, patients who are assigned to Placebo Group will receive placebo for the first 
8 weeks and then BBT-401-1S for last 8 weeks.  
 
Efficacy, safety, and PK data of the first cohort will be used to select the dose of the subsequent 
cohort. After 75% of patients of the current dose level cohort complete Visit 4 (Week 8), sponsor 
will review all pertinent data and decide dose level of next cohort. Dose level can be increased 
within 2-fold of previous dose level. A dose level may be repeated or added based on results of 
the previous cohort(s). The highest dose is not to exceed 1,600 mg daily.  
 
Based on nonclinical toxicology studies, the safety margin of BBT-401-1S in humans is expected 
to be high. BBT-401-1S showed no noteworthy findings of drug related AEs at SAD up to 1,600 
mg per person and at MAD 400, 800, and 1,600 mg daily per person in the Phase 1 clinical trial in 
healthy subjects. However, in the absence of an adequate clinical safety database in active UC 
patients, every investigator should be aware that BBT-401-1S has the potential to cause certain 
adverse effects by virtue of its pharmacological action and based on clinical experience with 
compounds of similar pharmacological effect. Please refer to the current IB for additional 
information regarding expected and anticipated adverse reactions. Please refer to Sections 6.6 of 
this protocol for additional information regarding reasons for discontinuation of study intervention 
and participant discontinuation/withdrawal from the study. 


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6.2 
Preparation/Handling/Storage/Accountability 
 
6.2.1 Acquisition and accountability 
 
The investigator will maintain accurate records of the receipt of all study medications. In addition, 
accurate records will be kept regarding when and how much study medication is dispensed and 
used by each patient in the study. Reasons for deviation from the expected dispensing regimen 
must also be recorded. Study medication will be reconciled by the site. The investigator agrees to 
provide sufficient access to study medication as required for the reconciliation process to be 
completed in a timely fashion. 
 
6.2.2 Formulation, Appearance, Packaging, and Labeling 
 
The oral drug product, BBT-401-1S capsules for use in the clinic will be administered as a delayed-
release (DR) capsule containing 200 mg of BBT-401-1S, the monosodium salt of an N-terminal 
lipidated tetrapeptide. The formulation has been manufactured so as to selectively fuse particles of 
an Eudragit®, pH-dependent enteric polymer, with adjacent particles of drug substance and HPMC 
to form a loose matrix powder. This powder is then blended with magnesium stearate and filled 
into white, opaque HPMC capsules to provide the labelled active strength.  
 
The BBT-401-1S placebo capsules are intended to mimic the appearance of the active drug 
product, BBT-401-1S capsules, 200 mg. The content of the BBT-401-1S placebo capsules is a 
blend mixture of the same quantity of excipients as present in the drug product with the active 
ingredient replaced by microcrystalline cellulose. BBT-401-1S placebo capsules are filled to the 
same nominal weight as the drug product and are used as per the clinic dosing regimen.  
 
BBT-401-1S 200 mg or placebo capsules will be provided in HDPE bottles of 32 capsules, sealed 
with a child-resistant closure. Each bottle of the test products (BBT-401-1S Capsules, 200 mg or 
Placebo) will be labeled with the following sample labeling: 
 
Protocol Number: BBT401-UC-US02                                                                                   IP Code: BBTXXXX 
BBT-401-1S Capsules (200 mg or Placebo)                                                                           Quantity: 32 capsules 
Lot: L334-01055BOT32/L334-01055ABOT32/L334-01056BOT32                                             Mfg Date: Sept-2018 
For oral administration as directed in the study protocol. 
Store between 59-86°F (15-30°C) and ≤ 60% RH. Protect from exposure to high humidity. Protect from light. Keep 
out of reach of children. 
Caution: New Drug – Limited by United States law to investigational use. 
Manufactured by Corealis Pharma Inc., Laval (QC), Canada, H7V 4A6 
Sponsor: Bridge Biotherapeutics Inc. 
US Representative: KCRN Research, 20251 Century Blvd. #325, Germantown, MD 20874, Phone: 301-540-2600 
 


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6.2.3 Product Storage and Stability 
 
BBT-401-1S capsules will be stored at controlled room temperature (limited excursions permitted 
between 59°F and 86°F, 15-30 °C) and £ 60% RH. Protect from exposure to high humidity. The 
bottle should be tightly sealed after use. 
 
6.3 
Measures to Minimize Bias: Randomization and Blinding 
 
A total of 16 subjects in each of the 3 dosing cohorts will be randomized to either active or placebo 
group in a 3:1 ratio (12 active and 4 placebo) using the electronic data capture (EDC) system.  
 
The randomization code will be generated by a unblinded statistician who is not involved with the 
study. The Sponsor,  investigators, patients, and CRO and other relevant personnel involved with 
the conduct of the study, with the exception of clinical supply staff and the unblinded statistician, 
will be blinded to the identity of study medication. 
 
For the 1st or 2nd cohort, if the 12th patient (75%) completes Visit 4 (Week 8), the CRO data 
management (DM) team confirm all clinical data of the 12 patients have no issue and then obtain 
the written consent from the Sponsor to breaking the code. Per the request of the CRO DM team, 
the randomization codes of the 12 patients will be opened via the unblinded statistician and notified 
to the Sponsor for the analysis to determine the next dose. After confirming all clinical data of 
remaining 4 patients for the 1st or 2nd cohort, the randomization codes will be subsequently 
opened to the sponsor through the same procedures stated above.  
 
After the last patient of last cohort completes the SFU, the CRO DM team confirm the whole 
clinical database has no issue and then request the database lock to the Sponsor. Per the Sponsor’s 
approval on the database lock, the randomization code of all patients will be opened via the 
unblinded statistician and notified to the CRO for the statistical analysis.  
 
Breaking of the randomization code without Company’s permission is expressly forbidden except 
in the event of a medical emergency where the identity of the study medication must be known in 
order to properly treat the patient. In the event of a medical emergency, it is requested that the 
investigator make every effort to contact the study monitor or designee prior to breaking the code.  
 
If the blind is broken due to the medical emergency, the subject must be early terminated; a written 
explanation must be prepared immediately. 
 
6.4 
Treatment Compliance 
 


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Treatment compliance with the study drugs will be documented by drug dispensing procedures, 
including a subject diary, on Visits 2–5 and by drug return and compliance assessments conducted 
on Visits 3–6 and/or Early Termination visit. 
 
The investigator will manage the treatment compliance to be maintained between 80% and 120%. 
If the subject’s drug compliance is deviated from the allowed treatment compliance at a scheduled 
visit, the investigator should explain the importance of drug compliance to the subject and re-
instruct the dosing methods to the patient for appropriate administration of next doses. 
 
6.5 
Concomitant Therapy 
 
Concomitant therapy with the following oral drugs is allowed during the study, provided that the 
dosing regimen has been stable for the specified durations as assessed at screening:  
• 5-ASA or sulfasalazine at a stable dose for at least 4 weeks prior to the first dose of study 
treatment 
• Purine analogues (azathioprine, mercaptopurine, thiopurines) or immunosuppressants 
(methotrexate, cyclosporine) at a stable dose for at least 12 weeks prior to the first dose of 
study treatment 
• Low-dose oral corticosteroid (up to 20 mg prednisone/day or equivalent) at a stable dose 
for at least 4 weeks prior to the first dose of study treatment   
 
Doses of oral drugs must remain stable until the end of study treatment (with a possible exception 
for tapering the steroid dose after 8 weeks).  
 
Concomitant therapy with anti-TNF-a biologics, any other biologics, or tofacitinib for treatment 
of UC within 60 days prior to randomization is not allowed, and individuals receiving such therapy 
will not be permitted to enroll in the study. Given the effects of anti-TNF-a biologics, other 
biologics, and tofacitinib on the inflammatory process, there is reasonable potential for interactions 
and/or confounding effects on the study endpoints. 
 
Concomitant therapy with intravenous corticosteroids or any rectal administration therapy for 
treatment of UC within 2 weeks prior to randomization is not allowed, and individuals receiving 
such therapy will not be permitted to enroll in the study. 
 
Assessments of concomitant therapy will be conducted at Visits 3–7. 
 
6.6 
Removal of Patients from the Trial or Study Drug  
 
The study may be terminated early if, in the opinion of the Sponsor, investigator, or IRB upon 
review of key safety data, an unacceptable risk to the safety and welfare of patients is posed by the 
continuation of the study. 


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Patients will be free to withdraw from the study at any time if so desired. A patient may be 
withdrawn from the study for any of the following reasons (including but not limited to): 
• Withdrawal of consent - Any patient may withdraw his/her consent from the study at any 
time. The investigator should make a reasonable attempt to document the specific reason 
why consent was withdrawn. 
• Deviation/noncompliance with the protocol or study drug 
• AE 
• Lost to follow-up 
 
6.6.1 Handling of Withdrawals 
 
Although a patient is not obliged to give his/her reason for withdrawing prematurely, the 
investigator will make a reasonable effort to obtain the reason while fully respecting the patient’s 
rights. If there is a medical reason for withdrawal, the patient will remain under the supervision of 
the study physician until in satisfactory health. Reasonable efforts will be made to contact a patient 
who fails to attend any follow-up appointments, in order to ensure that he/she is in satisfactory 
health. 
 
If a patient is prematurely withdrawn or discontinues from this study, every attempt will be made 
to follow the early termination (ET) visit procedures described in Section 7.4. 
 
6.6.2 Replacements 
 
Patients who terminate early from the study will not be replaced. 
 


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7 
STUDY ACTIVITIES 
 
7.1 
Screening Visit (Day -28 to -1) 
 
Patient’s eligibility for the study will be evaluated during this period based on medical history, 
physical examination, including flexible proctosigmoidoscopy or colonoscopy where indicated, 
laboratory values and additional tests.  
 
Patients will be screened within 28 days prior to baseline and administration of study medication 
to confirm that they meet the entrance criteria for the study. The study investigator or appropriate 
delegate at the site will discuss with each patient the nature of the study, its requirements, risks 
and benefits. Written informed consent must be obtained prior to performing any protocol-specific 
procedures, including washout of prohibited medications.  
 
In addition to obtaining informed consent, the following procedures will be performed:  
• 
Collection of demographic information 
• 
Completion of medical history (including prior medication, history of alcohol and drug use, 
smoking status and weekly alcohol consumption) 
• 
Vital signs (including temperature) 
• 
Physical examination (including weight and height) 
• 
12-lead ECG 
• 
Mayo score (stool frequency, rectal bleeding, endoscopic findings [flexible 
proctosigmoidoscopy/colonoscopy], physician’s global assessment) 
• 
Review of inclusion/exclusion criteria 
• 
Blood sampling for clinical lab tests (serum chemistry, hematology, pregnancy, and CRP)  
• 
Endoscopy which must be evaluated by a central reader to confirm the endoscopic sub-
score for the eligibility.  
• 
Biopsy sampling for histologic assessment and tissue concentration during the endoscopy. 
• 
UCEIS 
• 
Distribution of a fecal sample collection container for V2 (baseline) sample 
 
7.2 
Treatment Period  
 
7.2.1 Visit 2 (Baseline, Week 0/Day 1) 
 
Visit 2 will occur within 28 days after Visit 1. In this visit, the eligibility of patients will be 
confirmed and eligible patients will be randomized to either active or placebo group for 16-week 
treatments. The following procedures will be performed during Visit 2:  
• 
Confirmation of fecal samples  
• 
Confirmation of medical history  
• 
Vital signs (including temperature) 


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• 
Physical examination (including weight), which is waived if the screening visit is 
conducted within 10 days prior to Visit 2  
• 
12-lead ECG, which is waived if the screening visit is conducted within 10 days prior to 
Visit 2 
• 
Confirmation of inclusion/exclusion criteria 
• 
Randomization  
• 
Mayo score (stool frequency, rectal bleeding, physician’s global assessment) 
• 
SIBDQ 
• 
Blood sampling for clinical lab tests (serum chemistry, hematology, pregnancy, and CRP), 
which is waived if the screening visit is conducted within 10 days prior to Visit 2 
• 
Blood sampling for pharmacokinetics: pre-dose, 3 and 6 hours post-dose  
• 
Administration of study drug  
• 
Record of AEs and concomitant medications 
• 
Distribution of a fecal sample collection container for V3 (Week 4) sample 
• 
Distribution of study drugs and subject diary 
 
7.2.2 Visit 3 (Week 4) 
 
Visit 3 will occur at 4 weeks (± 3 days) from the first dosing date. During this visit, the following 
assessments/procedures will be performed: 
• 
SIBDQ 
• 
Mayo score (stool frequency, rectal bleeding, physician’s global assessment) 
• 
Record of AEs and concomitant medications 
• 
Confirmation of fecal samples  
• 
Review of returned study drugs and subject diary 
• 
Vital signs (including temperature) 
• 
Physical examination (including weight) 
• 
12-lead ECG 
• 
Blood sampling for clinical lab tests (serum chemistry, hematology, pregnancy, and CRP)  
• 
Blood sampling for pharmacokinetics: pre-dose, 3 and 6 hours post-dose  
• 
Administration of study drug  
• 
Distribution of a fecal sample collection containers for V4 (Week 8) sample 
• 
Distribution of study drugs and subject diary 
 
7.2.3 Visit 4 (Week 8) 
 
Visit 4 will occur at 8 weeks (± 3 days) from the first dosing date. During this visit, the following 
assessments/procedures will be performed: 
• 
SIBDQ 
• 
Mayo score (stool frequency, rectal bleeding, endoscopic findings [flexible 
proctosigmoidoscopy/colonoscopy], physician’s global assessment) 


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• 
UCEIS 
• 
Record of AEs and concomitant medications 
• 
Confirmation of fecal samples  
• 
Review of returned study drugs and subject diary 
• 
Vital signs (including temperature) 
• 
Physical examination (including weight) 
• 
12-lead ECG 
• 
Blood sampling for clinical lab tests (serum chemistry, hematology, pregnancy, and CRP)  
• 
Blood sampling for pharmacokinetics: pre-dose 
• 
Endoscopy which can be performed within 3 days before this visit if it is not feasible at the 
same date of Visit 4 
• 
Biopsy sampling for histologic assessment and tissue concentration during the endoscopy. 
• 
Distribution of a fecal sample collection containers for V5 (Week 12) sample 
• 
Distribution of study drugs and subject diary 
 
7.2.4 Visit 5 (Week 12) 
 
Visit 5 will occur at 12 weeks (± 3 days) from the first dosing date. During this visit, the following 
assessments/procedures will be performed: 
• 
SIBDQ 
• 
Mayo score (stool frequency, rectal bleeding, physician’s global assessment) 
• 
Record of AEs and concomitant medications 
• 
Confirmation of fecal samples  
• 
Review of returned study drugs and subject diary 
• 
Vital signs (including temperature) 
• 
Physical examination (including weight) 
• 
12-lead ECG 
• 
Blood sampling for clinical lab tests (serum chemistry, hematology, pregnancy, and CRP) 
• 
Distribution of a fecal sample collection container for Visit 6 (Week 16) sample  
• 
Distribution of study drugs and subject diary 
 
7.2.5 Visit 6 (Week 16) 
 
Visit 6 will occur at 16 weeks (± 3 days) from the first dosing date. During this visit, the following 
assessments/procedures will be performed: 
• 
SIBDQ 
• 
Mayo score (stool frequency, rectal bleeding, physician’s global assessment) 
• 
Record of AEs and concomitant medications 
• 
Review of any changes in smoking habits of subject during the study period 
• 
Confirmation of fecal samples  
• 
Review of returned study drugs and subject diary 


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• 
Vital signs (including temperature) 
• 
Physical examination (including weight) 
• 
12-lead ECG 
• 
Blood sampling for clinical lab tests (serum chemistry, hematology, pregnancy, and CRP) 
• 
Scheduling of the SFU visit at 2 weeks (+ 7 days) from the last dosing 
 
7.3 
Safety Follow-Up (SFU) Visit 
 
SFU visit will occur at 2 weeks (+7 days) from the date of last dose. During this visit, the following 
assessments/procedures should be performed: 
• 
Record of AEs and concomitant medications 
• 
Vital signs (including temperature) 
• 
Blood sampling for clinical lab tests (serum chemistry, hematology, and pregnancy)  
 
7.4 
Early Termination (ET) Visit 
 
If a patient will drop-out the study before the last treatment visit, the clinical site will try to 
schedule an ET visit. During this visit, the following assessments/procedures should be performed: 
• 
SIBDQ 
• 
Mayo score (stool frequency, rectal bleeding, endoscopic findings [flexible 
proctosigmoidoscopy/colonoscopy] - if applicable, physician’s global assessment) 
• 
Record of AEs and concomitant medications 
• 
Review of any changes in smoking habits of subject during the study period 
• 
Confirmation of fecal samples, if applicable  
• 
Review of returned study drugs and subject diary 
• 
Vital signs (including temperature) 
• 
Physical examination (including weight) 
• 
12-lead ECG 
• 
Blood sampling for clinical lab tests (serum chemistry, hematology, pregnancy, and CRP) 
• 
Endoscopy (biopsy), only if this ET occurs before Visit 4 (Week 8), which can be 
performed within 3 days before or after this visit if it is not feasible at the same date of ET 
Visit (if applicable) 
• 
UCEIS (if the endoscopy is performed) 
• 
Scheduling of SFU visit at 2 weeks (+ 7 days) from the last dosing unless this ET visit 
occurs after 2 weeks from the last dosing.  
 


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8 
STUDY PROCEDURES  
 
8.1 
Informed Consent and Medical History  
 
8.1.1 Informed Consent 
 
The investigator will obtain informed consent and complete an ICF for each patient screened for 
this study. All patients will be informed in writing of the nature of the protocol and investigational 
therapy, their possible hazards, and their right to withdraw at any time, and will sign an ICF 
indicating their consent to participate prior to the initiation of study procedures. The patient’s 
medical record should contain written documentation indicating that informed consent was 
obtained. The ICF must be reviewed and approved by the investigator’s designated IRB and by 
the Sponsor. The ICF should include all the elements as outlined in Section 4.8.10 of the ICH 
guideline for GCP (E6). 
 
8.1.2 Medical History  
 
At screening, a complete medical history including a full history of UC will be collected by patient 
interview. Concomitant medications, recent blood donations, illnesses, and participation in other 
investigational drug studies will also be recorded. 
 
Prior therapies related to UC and a detailed history of UC, including date of diagnosis, disease 
severity, hospitalizations, and extraintestinal manifestations will be collected during screening.  
 
8.2 
Safety Assessments  
 
• Physical examination: Screening, Baseline, W4, W8, W12, and W16 
• Vital signs: All visits (including SFU) 
• 12-lead ECG: Screening, Baseline, W4, W8, W12, and W16 
• Clinical laboratory testing of serum chemistry/hematology: All visits (including SFU) 
• Recording of AEs: W4, W8, W12, W16, and SFU 
 
8.2.1 Physical Examination  
 
Complete physical examination including weight, general appearance, examination of skin, 
HEENT (head, ears, eyes, nose, throat), lungs (auscultation), heart (auscultation for presence of 
murmurs, gallops, rubs, peripheral edema), abdomen (palpation and auscultation), neurology 
(mental status, station, gait, reflexes, motor and sensory function, coordination), and lymph nodes 
will be performed.  
 


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Any clinically significant changes from the baseline examination should be recorded as AEs.  
 
8.2.2 Vital Signs  
 
Vital signs will be recorded throughout the study as per the Schedule of Assessments. Blood 
pressure (BP) will be measured in the patient’s dominant arm and recorded to the nearest mmHg. 
The same arm will be used throughout the study. All BP in this study will be measured with the 
patient in the sitting position after resting for at least 5 minutes. The use of automated devices for 
measuring BP and pulse rate are acceptable, although, when done manually, pulse rate will be 
measured in the brachial/radial artery for at least 30 seconds. On visits when a blood sample is 
collected, the BP and pulse rate should be obtained prior to blood sample collection.  
 
Temperature will be recorded as either oral, axillary or tympanic temperature, with the same 
method used throughout the study. 
 
8.2.3 Electrocardiogram (ECG)   
 
Twelve (12)-lead ECGs will be obtained on all patients as per Schedule of Assessments. All 
scheduled ECGs should be performed after the patient has rested quietly for at least 10 minutes in 
a supine position.  
 
ECG measurement collected at the Screening visit will serve as the patient’s baseline value if 
conducted within 10 days prior to baseline. To ensure patient safety, a qualified individual at the 
investigator site will make comparisons to the baseline measurement.  
 
If the QTc measurement at a time post-dose is > 45 msec increase from the baseline; or an absolute 
QTc value is ≥ 500 msec for any scheduled ECG, a single ECG will be repeated at least hourly 
until QTc values from successive ECGs fall below the threshold value that triggered the repeat 
measurement.  
 
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead placement 
as a factor of the ECG abnormality. It is important that leads are placed in the same positions each 
time in order to achieve precise ECG recordings. If a machine-read QTc value is prolonged, as 
defined above, repeat measurements may not be necessary if a qualified physician’s interpretation 
determines that the QTc values are in the acceptable range. 
 
8.2.4 Clinical Laboratory Tests   
 
All details regarding clinical laboratory sample collection, preparation, and shipment are included 
in the laboratory manual provided by the CRO. In the event of abnormal clinical laboratory values, 


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the physician will make a judgment as to whether or not the abnormality is clinically significant 
and/or is deemed an AE. 
 
8.2.4.1 Laboratory Parameters 
 
Clinical safety laboratory tests will be conducted as outlined in the Schedule of Assessments, and 
should be completed pre-dose. Laboratory tests will include the following: 
 
Serum Chemistry 
 
Albumin  
Alkaline phosphatase  
Alanine aminotransferase (ALT; SGPT) 
Amylase 
Aspartate aminotransferase (AST; SGOT) 
Bicarbonate 
Blood urea nitrogen   
Calcium  
Chloride  
Creatinine 
Creatine kinase and MB subtype (if elevated) 
(% and total MB) 
Gamma-glutamyl transferase  
Glucose 
Lactate dehydrogenase  
Lipase 
Magnesium 
Phosphate 
Potassium   
Sodium  
Total bilirubin  
Total cholesterol  
Total protein 
Triglycerides 
Hematology  
 
Hematocrit  
Hemoglobin  
Mean corpuscular hemoglobin  
Mean corpuscular volume  
Platelet count 
Red blood cell count  
White blood cell count with differential (% 
and absolute counts) 
 
Coagulation 
 
Prothrombin time  
Activated partial thromboplastin time  
International Normalized Ratio  
 
Additional Tests 
 
Serum hCG (women with childbearing 
potential only) 
Serum FSH (women only) 
HIV test  
HBsAg  
Anti-HCV 
VZV IgG  
 
8.2.4.2 Additional Tests 
 
• Serum hCG will be performed at every visit for women with childbearing only.  
• Serum FSH test can be performed to confirm postmenopausal status at screening only. 
• Human immunodeficiency virus (HIV), hepatitis B (HBsAg), hepatitis C virus (RIBA 2 or 
3), and VZV IgG antibody will be performed at screening only. 


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8.2.4.3 Sample Collection, Storage, and Shipping 
 
Blood samples for hematology, coagulation parameters, serum chemistry, HIV and hepatitis 
screens, serum hCG (women with childbearing potential only), and serum CRP will be collected 
according to the laboratory manual provided by the CRO and according to the Schedule of 
Assessments and descriptions of visits. 
 
8.2.4.4 Blood Volume 
 
The total blood volume to be collected for clinical laboratory tests during the study is less than 150 
mL. 
 
8.3 
Efficacy Assessments  
 
• Total Mayo Score (Stool frequency, rectal bleeding, endoscopic findings [flexible 
proctosigmoidoscopy/colonoscopy], physician’s global assessment): Screening and W8  
• Partial Mayo Score: Baseline, W4, W8, W12, and W16 
• Histologic Assessment of Endoscopic Biopsy: Screening and W8  
• UCEIS score: Screening and W8 
• SIBDQ: Baseline, W4, W8, W12, and W16 
• Serum CRP: Baseline, W4, W8, W12, and W16 
• Fecal calprotectin: Baseline, W4, W8, W12, and W16 
• Fecal lactoferrin: Baseline, W4, W8, W12, and W16 
 
8.3.1 Mayo Score 
 
The Total Mayo score is an instrument designed to measure disease activity of ulcerative colitis, 
with scores ranging from 0 to 12 points. The Total Mayo score consists of 4 subscores, each graded 
from 0 to 3 with higher scores indicating more severe disease (Mayo scoring system is listed in 
Appendix 1). For the endoscopic subscore, the Modified Mayo Endoscopic Score will be used to 
exclude any friability from Grade 1 per the FDA guidance. 
• Stool frequency (0-3)  
• Rectal bleeding (0-3)  
• Findings of endoscopy (0-3)  
• Physician global assessment (PGA) (0-3)  
 
The Partial Mayo score consists of 3 subscores (stool frequency, rectal bleeding, and PGA). The 
subscores of stool frequency and rectal bleeding will be answered by a patient and the subscore of 
PGA will be assessed by an investigator.    


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8.3.2 Endoscopy with Biopsy Procedure 
 
All details regarding endoscopic examination, standardized performing procedures, video 
recordings,  assessment, biopsy sampling procedures, storage, and shipping will be provided in the 
laboratory manual by the CRO. 
 
Endoscopy examination (flexible proctosigmoidoscopy/colonoscopy) will be required at screening 
in order to establish the Mayo endoscopic subscore and confirm patient eligibility for the study at 
baseline. Mayo endoscopic subscores will be assessed by both local and central reader. If the single 
central reader and local reader assessment results do not match, another central reader will score 
for adjudication.  
 
Any patient who has not had a colonoscopy performed within 10 years since the onset of symptoms 
will be required to undergo a colonoscopy for screening surveillance. Therefore, in such cases, a 
colonoscopy will be required at screening (a flexible proctosigmoidoscopy will not be an option). 
 
An appropriately trained endoscopist should perform the flexible proctosigmoidoscopy/ 
colonoscopy. Where possible the same endoscopist should perform the endoscopy for both 
screening and Week 8 visits. If this is not possible, it should be clearly documented who performed 
each endoscopy procedure.  
 
8.3.3 Ulcerative Colitis Endoscopic Index of Severity (UCEIS) 
 
The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) is the first validated index for the 
assessment of overall endoscopic activity (Appendix 2). The final model incorporates the vascular 
pattern, the presence of bleeding and the presence of ulcerations with accurate definitions and 3 or 
4 levels of severity as measurable parameters, which explain almost 90% of variations in 
determining overall activity. 
 
8.3.4 Quality of Life Questionnaire: Short Inflammatory Bowel Disease Questionnaire (SIBDQ) 
 
The SIBDQ is a health-related quality of life (HRQoL) tool measuring physical, social, and 
emotional status. Scores range between 10 and 70, reflecting poor to good HRQoL. The SIBDQ 
has been predominantly used in trials for Crohn's disease, and further validation of the SIBDQ is 
desirable in UC patients. A sample of the SIBDQ is provided in Appendix 3. 
 
8.3.5 Biomarkers  
 
The following biomarkers will be analyzed to support the efficacy assessments: 


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• Serum C-reactive protein (CRP)  
• Fecal calprotectin 
• Fecal lactoferrin 
 
Instructions for storage and shipment of biomarker samples will be provided by the CRO. 
 
8.4 
Pharmacokinetic Assessments 
 
8.4.1 Plasma Pharmacokinetics 
 
For all patients, blood samples (approximately 4 mL) for analysis of BBT-401-1S 
pharmacokinetics will be collected in blood collection tubes containing K2EDTA as anticoagulant 
at the following scheduled time points: 
• Visit 2 (Baseline) and Visit 3 (W4): pre-dose and 3 hour (± 15 minutes) and 6 hour (- 30 
to + 150 minutes) post-dose.  
• Visit 4 (W8): pre-dose only  
 
Blood tubes will be gently inverted several times to ensure mixing and placed on wet ice. Plasma 
will be obtained within 2 hours of blood collection by centrifugation approximately at 3200 g and 
at 4 °C for 10 minutes. Plasma will be transferred into two labeled plasma collection tubes each 
containing approximately 0.8 mL and stored in freezing conditions (-20 °C or below) until 
shipment to an analytical lab. Blood sampling, centrifuge time, storage condition, and storage time 
will be documented.  
 
Instructions for sample shipment will be provided in a separate document by the Sponsor. Plasma 
sample analysis will be performed using a validated bioanalytical method. 
 
8.4.2 Tissue Concentration 
 
For all patients, biopsy samples for analysis of BBT-401-1S concentration will be collected in 
tissue collection tubes during the endoscopy following Visit 1 (Screening) and prior to Visit 4 
(W8).  
 
The collection tubes will be stored in freezing conditions (-20 °C or below) until shipment to an 
analytical lab. Tissue sampling, storage condition, and storage time will be documented.  
 
Instructions for sample shipment will be provided in a separate document by the Sponsor. Tissue 
sample analysis will be performed using a non-validated bioanalytical method. 
 
8.5 
Adverse Events and Serious Adverse Events Reporting 


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8.5.1 Definition of Adverse Events (AE)  
 
An adverse event (AE) is any untoward medical occurrence in a patient administered a 
pharmaceutical product, which does not necessarily have a causal relationship with the treatment. 
An AE can be any unfavorable and unintended sign (e.g., including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of the study drug, whether or not 
it is considered to be study drug related. This includes any newly occurring event or previous 
condition that has increased in severity or frequency since the administration of study drug. 
 
Note that progression of the ulcerative colitis investigated in this protocol, including secondary 
events that are subsumed under a unifying diagnosis of disease progression, will NOT be 
considered an AE unless the investigator judges the progression to be related to treatment with 
study drug. 
 
An AE includes, but is not limited to, the following: 
• Any clinically significant worsening of a pre-existing condition 
• An AE occurring from overdose (i.e., a dose higher than that indicated in the protocol) of 
a study drug, whether accidental or intentional 
• An AE occurring from abuse (e.g., use for nonclinical reasons) of a study drug 
• An AE that has been associated with the discontinuation of the use of a study drug 
• Any treatment-emergent abnormal laboratory result that is clinically significant, i.e., 
meeting 1 or more of the following conditions, should be recorded as a single diagnosis on 
the AE page in the eCRF: 
- Accompanied by clinical symptoms 
- Leading to a change in study medication (e.g., dose modification, interruption or 
permanent discontinuation) 
- Requiring a change in concomitant therapy (e.g., addition of, interruption of, 
discontinuation of, or any other change in a concomitant medication, therapy or 
treatment) 
 
8.5.2 Definition of Serious Adverse Events (SAE)  
 
A serious adverse event (SAE) is any AE, occurring at any dose and regardless of causality that: 
• Results in death 
• Is life-threatening “Life-threatening” means that the patient was at immediate risk of death 
from the reaction as it occurred, i.e., it does not include a reaction that hypothetically might 
have caused death had it occurred in a more severe form. 
• Requires inpatient hospitalization or prolongation of existing hospitalization (see 
clarification in the paragraph below on planned hospitalizations) 


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• Results in persistent or significant disability/incapacity “Disability” is defined as a 
substantial disruption of a person’s ability to conduct normal life functions. 
• Is a congenital anomaly/birth defect 
• Is an important medical event 
An “important medical event” is an event that may not result in death, be life-threatening, 
or require hospitalization but may be considered an SAE when, based upon appropriate 
medical judgment, it may jeopardize the patient and may require medical or surgical 
intervention to prevent 1 of the outcomes listed in the definitions for SAEs. Examples of 
such medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse. 
 
Clarification should be made between the terms “serious” and “severe” because they are not 
synonymous. The term “severe” is often used to describe the intensity (severity) of a specific event 
(as in mild, moderate, or severe myocardial infarction); however, the event itself may be of 
relatively minor medical significance (such as a severe headache). This is NOT the same as a 
“serious” adverse event (SAE), which is based on patient/event outcome or action criteria 
described above. An SAE is usually an event that poses a threat to a patient’s life or ability to 
function. In contrast, an AE assessed as “severe” is not automatically considered “serious” in 
nature (i.e., an SAE). For example, persistent nausea of several hours duration may be considered 
severe nausea but not an SAE. On the other hand, a stroke resulting in only a minor degree of 
disability may be considered mild, but would be defined as an SAE based on the above noted 
criteria. Seriousness (not severity) serves as a guide for defining regulatory reporting obligations. 
 
Other Reportable Information: certain information, although not considered an SAE, must be 
recorded, reported, and followed up as indicated for an SAE. This includes: 
• A case involving a pregnancy exposure to a test article, unless the product is indicated for 
use during pregnancy e.g., prenatal vitamins. Information about use in pregnancy 
encompasses the entire course of pregnancy and delivery and perinatal and neonatal 
outcomes, even if there were no abnormal findings. If a pregnancy is confirmed, test article 
must be discontinued immediately in female patients. All reports of pregnancy must be 
followed for information about the course of the pregnancy and delivery, as well as the 
condition of the newborn. When the newborn is healthy, additional follow-up is not needed. 
Pregnancies occurring up to 3 months after completion of the study treatment must also be 
reported to the investigator. 
• Overdose (e.g., a dose higher than that indicated in the protocol) with or without an AE. 
• Abuse (e.g., use for nonclinical reasons) with or without an AE 
• Inadvertent or accidental exposure with or without an AE 
• Device malfunction with or without an AE 
 


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8.5.3 Classification of an Adverse Event 
 
8.5.3.1 Severity of Event 
 
The severity of AEs should be graded as follows: 
• Mild – Usually transient in nature and generally not interfering with normal activities 
• Moderate – Sufficiently discomforting to interfere with normal activities 
• Severe – Inability to perform normal daily activities 
 
Medically significant AEs considered related to the study drug by the investigator or Sponsor will 
be followed until resolved or considered stable. 
 
It will be left to the investigator’s clinical judgment to determine whether an AE is related and of 
sufficient severity to require the patient’s removal from treatment or from the study. A patient may 
also voluntarily withdraw from treatment due to what he or she perceives as an intolerable AE. If 
either of these situations arises, the patient should be strongly encouraged to undergo an end-of-
study assessment and be under medical supervision until symptoms cease or the condition becomes 
stable. 
 
8.5.3.2 Relationship to Study Intervention 
 
The following AE attributes must be assigned by the investigator:  AE diagnosis or syndrome(s) 
(if known, signs or symptoms if not known); event description (with detail appropriate to the 
event); dates of onset and resolution; severity; assessment of relatedness to study drug and action 
taken. The investigator may be asked to provide follow-up information, discharge summaries, and 
extracts from medical records or eCRFs. 
 
Relatedness to study drug administration will be determined by the investigator responding to the 
question, ‘Is there a reasonable possibility that the AE is associated with the study drug?’ 
Relatedness to study drug administration will be graded as “related”, “probably,” “possibly,” or 
“not related,” as follows: 
• Not Related  
- Another cause of the event is most plausible, or 
- Clinically plausible temporal sequence is inconsistent with the onset of the event 
and the study treatment administration, or 
- A causal relationship is considered biologically implausible. 
• Possibly Related 
- An event that follows a reasonable temporal sequence from administration of the 
study treatment or a known or expected response pattern to the suspected drug, but 
that could readily have been produced by a number of other factors. 


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• Probably Related 
- An event that follows a reasonable temporal sequence from administration of the 
study treatment, and 
- There is a biologically plausible mechanism for study treatment causing or 
contributing to the AE, and  
- The event could not be reasonably explained by the known characteristics of the 
patient’s clinical state.  
• Related 
- An event that occurs in a plausible time relationship to drug administration, and 
which cannot be explained by concurrent disease or other drugs or chemicals. 
- The response to withdrawal of the drug (dechallenge) should be clinically plausible. 
The event must be definitive pharmacologically or phenomenologically, using a 
satisfactory rechallenge procedure if necessary. 
 
In addition, the relationship may be confirmed by improvement on stopping the study treatment 
and reappearance of the event on repeated exposure. 
 
8.5.3.3 Expectedness  
 
The Sponsor will be responsible for determining whether an AE is expected or unexpected. An AE 
will be considered unexpected if the nature, severity, or frequency of the event is not consistent 
with the risk information previously described for the study intervention. 
 
8.5.4 Adverse Event Reporting  
 
All AEs and SAEs will be collected and recorded from the time of the patient receives the first 
dose of study drug until the end-of-study visit for all subjects with informed consent. The 
Investigator will assess all AEs and SAEs and record the following information where appropriate 
on the CRF: 
• Event description 
• Date of onset 
• Date of resolution or stabilization 
• Assessment of severity 
• Relationship to study drug 
• Action taken with study medication 
 
The Investigator should employ best medical judgment in determining how to manage AEs and 
SAEs. Any questions regarding AE or SAE management should be directed to the Medical 
Monitor.  
 


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The Sponsor will be responsible for notifying the FDA of any unexpected fatal or life-threatening 
suspected adverse reaction as soon as possible, but in no case later than 7 calendar days after the 
Sponsor's initial receipt of the information. In addition, the Sponsor must notify the FDA and all 
participating investigators in an IND safety report of potential serious risks, from clinical trials or 
any other source, as soon as possible, but in no case later than 15 calendar days after the Sponsor 
determines that the information qualifies for reporting. 
 
8.5.5 Reporting Events to Patients  
 
Not applicable. 
 
8.5.6 Events of Special Interest  
 
Not applicable. 
 
8.5.7 Reporting of Pregnancy  
 
Serum pregnancy testing will be conducted for all female patients with child-bearing potential at 
screening and all treatment visits. If a female patient becomes pregnant during clinical study, the 
investigator should prepare and submit an initial pregnancy report to the Sponsor within 24 hours 
of becoming aware of the pregnancy. The investigator should follow up and document all 
progresses and results of pregnancy, even if the patient withdraws consent or terminate the clinical 
study. In addition, the investigator should prepare and submit the pregnancy outcome report within 
24 hours of becoming aware of all results of pregnancy.  
 
Pregnancy itself is not considered as an AE if the pregnancy is not related to the investigational 
product.  
 
All SAEs that occur during pregnancy will be recorded in an SAE report and the reporting will be 
performed according to the SAE reporting procedures.  
 
 


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9 
STATISTICAL CONSIDERATIONS  
 
The statistical analysis of the data obtained from this study will be the responsibility of the CRO. 
Details of the statistical analyses will be included in a separate statistical analysis plan (SAP) which 
will be finalized before the first individual unblinding. If, after the study has been unblinded, 
changes are made to the pre-specified statistical analysis plan, the changes will be listed along with 
an explanation as to why they occurred in the Clinical Study Report. 
 
9.1 
General Methodology  
 
No formal inferential statistical analyses are planned. Rather, for the quantitative endpoints 
(efficacy, biomarker measure, and some safety data) descriptive statistics will be calculated to 
provide an indication of directional changes in endpoints for each treatment group. For the 
qualitative data, frequency counts and incidence rates will be compiled for each treatment group. 
 
Summary of tabulations will be presented by treatment group displaying the number of 
observations, mean, standard deviation, median, minimum, and maximum for continuous 
variables, and the number and percent per category for categorical data. 
 
9.2 
Blinding and Randomization  
 
The study is double blind, with patients randomized to either the active or placebo group. The 
randomization will be conducted to produce a 3:1 ratio of active to placebo—each cohort will 
include 12 active and 4 placebo patients. 
 
9.3 
Sample Size and Power 
 
As this is an initial dose-escalation study, it is appropriately based on only a limited number of 
patients in each dose cohort. The size of the study is not based on any statistical power calculations 
and no formal sample size calculations have been done. Based on experience from previous studies 
and the use of a sequential dose-escalation design for this study, a total of 48 patients (16 patients 
per dose cohort) is considered appropriate for the study. 
 
9.4 
Population for Analyses 
 
The analyses of the efficacy endpoints will be based on a modified Intent-to-Treat (mITT) 
population. The mITT population consists of all randomized patients who receive at least 1 dose 
of study medication. Note that, for the analysis of an individual endpoint, it must have a baseline 
measurement and at least one post-randomization measurement. Therefore, the patients included 
in an analysis can vary with endpoints since some patients may have the needed data for inclusion 
in the mITT analysis for some endpoints but not for others. For the efficacy analyses, patients are 


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counted in the treatment group to which they were randomized, regardless of the treatment 
received during the course of the trial. 
 
The analysis of the safety endpoints will be based on a Safety population which will include all 
randomized patients who received at least 1 dose of study medication. Patients are counted in the 
treatment group based on the treatment they receive. 
 
PK population consists of all randomized patients who receive at least 1 dose of the study 
medication and have plasma and tissue concentration data. 
 
9.4.1 General Approach Procedures for Handling Missing, Unused, and Spurious Data 
 
All available efficacy and safety data will be included in the data listings and tabulations. No 
imputation of values for missing data will be performed. 
 
9.4.2 Demographic and Baseline Descriptive Statistics  
 
The baseline value is defined as the last value obtained on or before the date and time of the first 
study drug dose. 
 
9.4.3 Subject Disposition 
 
Subject disposition will be summarized for subjects who complete the study or discontinue early. 
The overall summary will comprise the number and percentage of subjects for each analysis 
population, as well as the number and percentage of subjects who completed the study parts and 
treatment, and discontinued early with reasons for discontinuation. 
 
9.4.4 Prior and Concomitant Medications 
 
Medications administered prior to and concomitantly with study drug will be tabulated and 
listed.  
 
9.4.5 Protocol Deviations 
 
A list of subjects with protocol deviations will be compiled based on entry criteria deviations as 
well as deviations from study conduct and assessments.  
 
9.5 
Statistical Analyses 
 
No formal inferential statistics are planned for this study. Descriptive statistics will be calculated 
to summarize the changes from baseline in the primary and secondary endpoints. Frequency counts 
will be compiled for qualitative safety analysis.  


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• Primary Endpoint(s):   
- Change from Baseline in Total Mayo Score at Week 8 
• Secondary Endpoint(s): 
- Change from Baseline in Partial Mayo Score at Week 8  
- Change from Baseline in Histologic Assessment of Endoscopic Biopsy at Week 8 
- Change from Baseline in UCEIS Score at Week 8 
- Number and Severity of treatment-emergent AE (TEAEs) up to Week 8  
- Change from Baseline in SIBDQ at Week 8 
- Change from Baseline in Concentration of Biomarkers (serum CRP, fecal calprotectin, 
and fecal lactoferrin) at Week 8 
- Plasma and Tissue Concentration of BBT-401-1S in Patients with Active UC 
 
9.5.1 Analysis of Primary Endpoint 
 
The primary objective is to determine the efficacy of BBT-401-1S in patients with active 
Ulcerative Colitis. Response to treatment will be evaluated using the change from baseline in Total 
Mayo score at week 8 based on the mITT population. The baseline value is defined as the last 
value obtained on or before the date and time of the first study drug dose. Descriptive statistics 
will be presented including mean, standard deviation (SD), median, max, and min by treatment 
and cohort group (and overall cohort) at each timepoint. However, to allow for a direct comparison 
of BBT-401-1S vs placebo for each cohort, descriptive statistics will be provided for the difference 
in the change from baseline between the treatment groups during the double-blind portion of the 
study. 
 
9.5.2 Analysis of Secondary Endpoints 
 
The secondary efficacy analyses will be based on the mITT population. Analysis on the TEAEs 
and other safety endpoints is discussed under the Safety Analysis section below.  
 
For each efficacy endpoint, descriptive statistics will be presented by treatment and cohort group 
(and overall cohort) at each timepoint, including mean, SD, median, max, and min as there is no 
formal inferential statistical analysis is planned. 
 
9.5.3 Safety Analyses 
 
All analyses based on safety data (AEs, laboratory data, ECGs, vital signs, and physical exam data) 
will be based on the Safety population.  
 
AE terms recorded on the eCRFs will be mapped to preferred terms using the Medical Dictionary 
for Regulatory Activities (MedDRA®) version 17.0 or later. AEs included in summary tables will 
be restricted to treatment-emergent AEs (TEAEs). A TEAE is defined as an AE that occurs (or 
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number and percentage of patients who experienced the event, according to the system organ class 
and preferred term. Additional summaries will also be provided by severity and relationship to 
study drug. Listings of deaths, SAEs and AEs leading to early termination of study drug or 
premature withdrawal from study will also be provided.  
 
Descriptive statistics will be provided for laboratory results by scheduled time of evaluation and 
by treatment group, as well as for change from baseline. Laboratory variables will be evaluated 
using mean change in value from baseline to scheduled time points. The baseline value of a 
variable is defined as the last value obtained on or before the date and time of the first study drug 
dose. Individual laboratory test results that are outside the normal range for that test will be flagged 
as high (H) or low (L), as appropriate, in the listings.  
 
ECGs, vital sign measurements and weight will be summarized by change from baseline to 
scheduled time points using descriptive statistics. 
 
9.5.4 Planned Interim and Subgroup Analyses  
 
Not applicable. 
 
9.5.5 Tabulation of Individual Participant Data 
 
All available efficacy and safety data will be included in the data listings and tabulations. 
 
9.5.6 Pharmacokinetic Analysis 
 
Not applicable. 
 
9.5.7 Pharmacodynamic Analyses 
 
No formal statistical analysis of PD endpoints (i.e. biomarkers) will be performed. PD data from 
each assay will be listed, and possible relationships between clinical response and PD variables 
will be explored. Any biological activity will be described. The exploratory analyses will 1) assess 
ulcerative colitis biomarkers and cell growth and 2) correlate clinical outcomes with response and 
ulcerative colitis parameters.  
 


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10 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS  
 
10.1 
Informed Consent Process 
 
In obtaining and documenting informed consent, the investigator must comply with applicable 
regulatory requirements (e.g., 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56) and should adhere 
to ICH GCP. Prior to the beginning of the trial, the investigator should have the IRB’s written 
approval for the protocol and the written ICF(s) and any other written information to be provided 
to the participants.  
 
10.2 
Consent/assent and Other Informational Documents Provided to Participants 
 
The IRB-approved ICF describing in detail the study intervention, study procedures, potential 
benefits and risks is to be given to the participant, and written documentation of informed consent 
is required prior to administering the study intervention.  
 
The ICF contains a statement that consent is freely given, that the patient is aware of the risks of 
entering the study, and that the patient is free to withdraw from the study at any time. Informed 
consent must be given by the patient and/or legal representative after the receipt of detailed 
information on the study. 
 
10.3 
Consent Procedures and Documentation 
 
The Investigator is responsible for ensuring that informed consent is obtained from each patient or 
legal representative and that the ICF is completed (i.e., signed and dated) prior to the performance 
of any protocol procedures and prior to the administration of study drug.  
 
Patients will be asked to read and review the IRB-approved ICF. The investigator will explain the 
study purpose, procedures, and potential risks, as well as the patient's rights as a research 
participant, in clear terms suited to the patient's comprehension. It should be noted that the quality 
of the patient's medical care will not be adversely affected if he or she declines to participate in the 
study. 
 
Patients will have the opportunity to carefully review the written consent form and ask questions 
prior to signing. The patient should have the opportunity to discuss the study with their family or 
surrogates or think about it prior to agreeing to participate.  
 
Patients must be informed that participation is voluntary and that they may withdraw from the 
study at any time. A copy of the ICF will be given to the participants for their records.  
 
10.4 
Study Discontinuation and Closure 
 


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This study may be temporarily suspended or prematurely terminated by the Sponsor if there is 
sufficient reasonable cause. Written notification documenting the reason for study suspension or 
termination by the Sponsor or PI will be provided to investigators or the Sponsor, respectively, 
study participants, the IRB, and regulatory authorities. Study participants will be contacted, as 
applicable, and be informed of any changes to the study visit schedule. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to participants 
• Demonstration of efficacy that would warrant stopping    
• Insufficient compliance to protocol requirements 
• Data that are not sufficiently complete and/or evaluable 
• Determination that the primary endpoint has been met 
• Determination of futility 
 
The study may resume once concerns are addressed to the satisfaction of the Sponsor, IRB and/or 
regulatory authorities. 
 
10.5 
Confidentiality and Privacy  
 
Patient confidentiality and privacy is held by the participating investigators, their staff, and the 
Sponsor. Therefore, the study protocol, documentation, data, and all other information generated 
will be held in strict confidence. The study monitor and other authorized representatives of the 
Sponsor, IRB, or regulatory agencies may inspect all documents and records required to be 
maintained by the investigator. The clinical study site will permit access to such records. 
 
No information concerning the study or the data will be released to patients, any insurance 
company, employer, family member, general physician, or other unauthorized third party unless 
required by law or with prior written approval of the Sponsor. In exceptional circumstances, certain 
individuals might see both the medical data and personal identifiers of a patient. For example, in 
the case of a medical emergency, or Sponsor or representative physician or an investigator might 
become aware of a patient’s identity and have access to his or her medical data.  
 
Patient contact information will be securely stored at each clinical site for internal use during the 
study. At the end of the study, all records will continue to be kept in a secure location for as long 
a period as dictated by the reviewing IRB, Institutional policies, or Sponsor requirements. Patient 
research data will not include the patient's contact or identifying information but will be labeled 
with a unique study identification number. The study data entry and study management systems 
used by clinical sites and by research staff will be secured and password protected. At the end of 
the study, all study databases will be de-identified and archived.  
 
10.6 
Future Use of Stored Specimens and Data  
 


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The US FDA regulations (21 CFR §312.62[d]) and the ICH Guideline for GCP require that records 
and documents pertaining to the conduct of this study and the distribution of study drug, including 
eCRFs, consent forms, laboratory test results, and medication inventory records, must be retained 
by the investigator for 2 years after the last marketing application approval in an ICH region or 
after at least 2 years have elapsed since formal discontinuation of clinical development of the 
investigational drug. Patient identification codes (patient names and corresponding study numbers) 
will be retained for this same period of time. The Sponsor will notify the Principal Investigator of 
these events. These documents may be transferred to another responsible party, acceptable to the 
Sponsor, who agrees to abide by the retention policies. Permission to transmit data to another 
responsible party will be included in the ICF. Written notification of transfer must be submitted to 
the Sponsor. The investigator must contact the Sponsor prior to disposing of any study records.  
 
As part of understanding the PK of the study drug, plasma samples may be used for metabolite 
identification and profiling evaluation. As part of understanding the efficacy and safety of the 
study drug, biopsy samples may be used for gene expression and profiling evaluation. Residual 
plasma and biopsy samples may be stored up to 2 years. If the residual samples are used, the results 
will be reported to the regulatory agencies.  
 
10.7 
Safety Oversight 
 
The study will be monitored by the Safety Monitoring Committee (SMC) comprised of the 
Principal Investigator for each site, the Medical Monitor, and Sponsor representative(s) or 
designee. During the study period, all SAEs or safety issues will be sent to the SMC on a continual 
basis. The SMC will be responsible for reviewing all SAEs or safety issues and making the 
decision of proceeding to a new dose level after completing each cohort based on the relevant 
safety data. If at any point a safety concern arises, an ad hoc meeting of the SMC can be performed.  
 
Further information describing a scope of work and procedures for the SMC will be provided in 
the SMC Charter. 
 
10.8 
Clinical Monitoring 
 
The Sponsor has engaged the services of a CRO, to perform all monitoring functions within this 
clinical study. CRO monitors will work in accordance with CRO SOPs and have the same rights 
and responsibilities as monitors from the Sponsor organization. Monitors will establish and 
maintain regular contact between the Investigator and the Sponsor. 
 
Monitors will evaluate the competence of each study center, informing the Sponsor about any 
problems relating to facilities, technical equipment or medical staff. During the study, monitors 
will check that written informed consent has been obtained from all patients correctly and that data 
are recorded correctly and completely. Monitors are also entitled to compare entries in eCRFs with 
corresponding source data and to inform the Investigator of any errors or omissions. Monitors will 


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also control adherence to the protocol at the study center. They will arrange for the supply of 
investigational product and ensure appropriate storage conditions are maintained. 
 
Monitoring visits will be conducted according to all applicable regulatory requirements and 
standards. Regular monitoring visits will be made to each center while patients are enrolled in the 
study. The monitor will make written reports to the Sponsor on each occasion contact with the 
Investigator is made, regardless of whether it is by phone or in person. 
 
During monitoring visits, entries in the eCRFs will be compared with the original source 
documents (source data verification). For the following items, this check will be 100%:  
• Patient identification number. 
• Patient consent obtained. 
• Patient eligibility criteria (inclusion and exclusion criteria). 
• Efficacy variables. 
• Medical record of AE. 
 
10.9 
Quality Assurance and Quality Control 
 
Each clinical site will perform internal quality management of study conduct, data and biological 
specimen collection, documentation and completion. An individualized quality management plan 
will be developed to describe a site’s quality management. 
 
Quality control (QC) procedures will be implemented beginning with the data entry system and at 
each stage of data handling. Any missing data or data anomalies will be communicated to the 
site(s) for clarification/resolution.  
 
The Sponsor is responsible for implementing and maintaining quality assurance and QC systems 
with written Standard Operating Procedures (SOPs). In accordance with the written SOPs, 
monitors will verify that the clinical trial is conducted, data are generated, and biological 
specimens are collected, recorded, and reported in compliance with the protocol, ICH GCP, and 
applicable regulatory requirements (e.g., Good Laboratory Practices (GLP), Good Manufacturing 
Practices (GMP)). The Sponsor and monitor will determine the frequency of monitoring visits. 
 
In addition, during the study the Sponsor may conduct audits separately from routine monitoring. 
The investigational site will provide direct access to all trial-related sites, source data/documents 
including medical history and concomitant medication documentation, and reports for both routine 
monitoring and auditing by the Sponsor, and inspection by local and regulatory authorities. 
 
10.10 Data Handling and Record Keeping 
 
The US FDA regulations (21 CFR §312.62[c]) and the ICH Guideline for GCP (see Section 4.9 of 
the guideline) require that records and documents pertaining to the conduct of this study and the 


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distribution of study drug, including eCRFs, consent forms, laboratory test results, and medication 
inventory records, must be retained by the Investigator for 15 years after the last marketing 
application approval in an ICH region or after at least 15 years have elapsed since formal 
discontinuation of clinical development of the investigational drug. Patient identification codes 
(patient names and corresponding study numbers) will be retained for this same period of time. 
The Sponsor will notify the Principal Investigator of these events. These documents may be 
transferred to another responsible party, acceptable to Sponsor, who agrees to abide by the 
retention policies. Written notification of transfer must be submitted to Sponsor. The Investigator 
must contact the Sponsor prior to disposing of any study records. 
 
10.11 Protocol Deviations  
 
A protocol deviation is any noncompliance with the clinical trial protocol. The noncompliance 
may be on the part of the patient, the investigator, or the study site/CRO staff. Corrective actions 
in response to deviations are to be developed by the site and implemented promptly.  
 
It is the responsibility of the site investigator to use continuous vigilance to timely identify and 
report deviations. All deviations must be addressed in study source documents and reported to the 
monitor and/or Sponsor. Protocol deviations must be sent to the reviewing IRB per their policies. 
The site investigator is responsible for knowing and adhering to the reviewing IRB requirements.  
 
For minor protocol deviations deemed to have no influence on the interpretation of study results, 
the level and reason of deviation or delay will be accurately described and comprehensively 
considered by the Investigator, Sponsor, monitor or statistician when preparing the study report.  
 
10.12 Publication and Data Sharing Policy 
 
The data generated by this study are the proprietary information of the Sponsor. The Sponsor will 
make the results of the study publicly available, which may include publication in a peer-reviewed 
journal. The publication policy with respect to the investigator and clinical site will be set forth in 
the Clinical Trial Agreement. This trial will be registered at ClinicalTrials.gov, and data from this 
trial will be submitted to ClinicalTrials.gov.  
 
10.13 Conflict of Interest Policy 
 
Actual or perceived conflict of interest of persons who have a role in the design, conduct, analysis, 
publication, or any aspect of this trial will be disclosed and managed.  
 
10.14 Abbreviations 
 
AE 
Adverse Event 
ALT 
Alanine Transaminase 


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API 
Active Pharmaceutical Ingredient 
ASA 
5-aminosalicylic acid 
AST 
Aspartate Transaminase 
CFR 
Code of Federal Regulations 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
CRP 
C-Reactive Protein 
DDI 
Drug-drug Interaction 
DP 
Drug Product 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
HBsAg 
Hepatitis B Surface Antigen 
HED 
Human Equivalent Dose 
HIV 
Human Immunodeficiency Virus 
HRQoL 
Health-related Quality of Life 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation  
IND 
Investigational New Drug Application 
ICF 
Informed Consent Form 
IL-1R 
Interleukin-1 Receptor 
IRAK 
Interleukin-1 Receptor-associated Kinase 
IRB 
Institutional Review Board 
ITT 
Intent-To-Treat 
LPS 
Lipopolysaccharide 
MAD 
Multiple Ascending Dose 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intent-To-Treat 
MyD88 
Myeloid Differentiation Primary Response Gene 88 
NOAEL 
No-observed-adverse-effect Level 
PD 
Pharmacodynamics 
PGA 
Physician Global Assessment 
PI 
Principal Investigator 
PK 
Pharmacokinetics 
QC 
Quality Control 
RIP1 
Receptor-interacting Protein 1 
SAD 
Single Ascending Dose 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SFU 
Safety Follow-Up 
SIBDQ 
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SMC 
Safety Monitoring Committee 
SOC 
Standard of Care 
SOP 
Standard Operating Procedure 
TEAE 
Treatment-Emergent Adverse Event 
TNF 
Tumor Necrosis Factor 
TLR 
Toll-like Receptor 
UC 
Ulcerative Colitis 
UCEIS 
Ulcerative Colitis Endoscopic Index of Severity 
ULN 
Upper Limit of Normal 
 
10.15 Protocol Amendment History 
 
Version 
Date 
Description of Change  
Brief Rationale 
V1.1 
Dec 24, 2018 • Updated the 2nd paragraph of Section 10.6 like the 
following: 
As part of understanding the PK of the study drug, plasma 
samples may be used for metabolite identification and 
profiling evaluation. As part of understanding the efficacy 
and safety of the study drug, biopsy samples may be used 
for gene expression and profiling evaluation. Residual 
plasma and biopsy samples may be stored up to 2 years. If 
the residual samples are used, the results will be reported 
to the regulatory agencies.  
Clarification 
request from the 
IRB 
• Updated a term of ‘dosing diary’ to ‘subject diary’. 
• Clarified the conditions of repeat ECG on Section 8.2.3 like 
the following: 
If the QTc measurement at a time post-dose is > 45 msec 
increase from the baseline; or an absolute QTc value is ≥ 
500 msec for any scheduled ECG 
Updated for the 
clarifications 
 
• Removed PK sampling procedures from an early 
termination (ET) visit. 
• Distributed a subject diary at screening. 
• Added a procedure to review any changes in smoking habits 
of subject during the study period at Visit 6 (Week 16) or 
ET visit.   
Updated 
the 
study design 
V2.0 
Jan 20, 2019 • Using the Modified Mayo Endoscopic Score for the Mayo 
Endoscopic Subscores in Section 8.3.1 and Appendix 1 like 
the following (new text in bold; deleted text in 
strikethrough):  
 
8.3.1 Mayo Score 
The Total Mayo score is an instrument designed to measure 
disease activity of ulcerative colitis, with scores ranging 
Updated per the 
FDA guidance  


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from 0 to 12 points. The Total Mayo score consists of 4 
subscores, each graded from 0 to 3 with higher scores 
indicating more severe disease (Mayo scoring system is 
listed in Appendix 1). For the endoscopic subscore, the 
Modified Mayo Endoscopic Score will be used to 
exclude any friability from Grade 1 per the FDA 
guidance. 
  
‘Findings of Endoscopy’ of Appendix 1  
Findings of Endoscopy  
 
 
0 = Normal or inactive disease 
1 = Mild disease (erythema, decreased vascular pattern, 
mild friability) 
2 = Moderate disease (marked erythema, absent vascular 
pattern, friability, erosions) 
3 = Severe disease (spontaneous bleeding, ulceration) 
• Updated the section of ‘Bleeding’ of Appendix 1 like the 
following (new text in bold; deleted text in strikethrough):  
Bleeding 
0 = None 
(No visible bloodNormal vascular 
pattern with arborisation of capillaries 
clearly defined, or with blurring or 
patchy loss of capillary margins) 
1 = Mucosal 
(Some spots or streaks of coagulated 
blood on the surface of the 
mucosa ahead of the scope that can be 
washed awayPatchy obliteration of 
vascular pattern) 
2 = Luminal 
mild 
(Some free liquid blood in the 
lumenComplete obliteration of vascular 
pattern) 
3 = Luminal 
moderate 
or severe 
(Frank blood in the lumen ahead of 
endoscope or visible oozing from 
mucosa after washing intraluminal 
blood, or visible oozing from a 
hemorrhagic mucosa) 
Updated the 
definition of 
bleeding 
V3.0 
Apr 10, 2019 • Added tissue sampling and analysis for the tissue 
concentration of BBT-401-1S into the study design and 
procedures 
Updated the 
study design 
• Added clinical sites located in South Korea.  
Updated the 
study region 
• Updated the concomitant medications in Sections 5.1, 5.2, 
and 6.5 
Updated for the 
clarification 
• Removed misleading sentence for the subject 
compensation in Section 5.5 
Updated for the 
clarification 


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• Added the allowed treatment compliance range as 80 to 
120% in Section 6.4 
Updated for the 
clarification 
• Removed an unnecessary procedure from Section 7.2.5 
Updated for the 
correction 
• Updated the definitions of causality in Section 8.5.3.2 
Updated for the 
clarification 
• Updated the sponsor address 
Updated the 
sponsor 
information 
V3.1 
Jul 19, 2019 • Removed a screening diary from screening procedures. 
Updated for the 
correction 
• Moved UCEIS procedure from V2 Baseline to V1 
Screening.  
Updated for the 
clarification 
• Indicated the endoscopy means flexible 
proctosigmoidoscopy/colonoscopy for this study (Section 
1.3) 
Updated for the 
clarification 
• Added ‘Early Termination Visit’ to visits when the 
treatment compliance is performed (Section 6.4) 
Updated for the 
correction 
• Updated concomitant therapies in Section 6.5 
Updated for the 
clarification 
• Clarified who will answer or assess sub-scores of Partial 
Mayo Score (Section 8.3.1). 
Updated for the 
clarification 
• Deleted the central reading of UCEIS from Section 8.3.2. 
Updated for the 
correction 
• Updated the scoring sheets of Mayo Score with actual 
scoring sheets to be used for the study (Appendix 1).  
Updated for the 
correction  
 
 


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11 
REFERENCES  
 
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Carbonnel, F., A. Lavergne, M. Lemann, A. Bitoun, P. Valleur, P. Hautefeuille, A. Galian, R. 
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Choi, K. C., Y. S. Lee, S. Lim, H. K. Choi, C. H. Lee, E. K. Lee, S. Hong, et al. "Smad6 Negatively 
Regulates Interleukin 1-Receptor-Toll-Like Receptor Signaling through Direct Interaction with 
the Adaptor Pellino-1." Nat Immunol 7, no. 10 (Oct 2006): 1057-65. 
 
Curkovic, I., M. Egbring, and G. A. Kullak-Ublick. "Risks of Inflammatory Bowel Disease 
Treatment with Glucocorticosteroids and Aminosalicylates." Dig Dis 31, no. 3-4 (2013): 368-73. 
D'Haens, G. "Systematic Review: Second-Generation Vs. Conventional Corticosteroids for 
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da Silva, B. C., A. C. Lyra, R. Rocha, and G. O. Santana. "Epidemiology, Demographic 
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Gordon, J. P., P. C. McEwan, A. Maguire, D. M. Sugrue, and J. Puelles. "Characterizing Unmet 
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Jairath, V., G. Zou, C. E. Parker, J. K. Macdonald, M. H. Mosli, R. Khanna, L. M. Shackelton, et 
al. "Systematic Review and Meta-Analysis: Placebo Rates in Induction and Maintenance Trials of 
Ulcerative Colitis." J Crohns Colitis 10, no. 5 (May 2016): 607-18. 
 
Jess, T., M. Frisch, and J. Simonsen. "Trends in Overall and Cause-Specific Mortality among 
Patients with Inflammatory Bowel Disease from 1982 to 2010." Clin Gastroenterol Hepatol 11, 
no. 1 (Jan 2013): 43-8. 
 


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Kappelman, M. D., K. R. Moore, J. K. Allen, and S. F. Cook. "Recent Trends in the Prevalence of 
Crohn's Disease and Ulcerative Colitis in a Commercially Insured Us Population." Dig Dis Sci 58, 
no. 2 (Feb 2013): 519-25. 
 
Kornbluth, A., and D. B. Sachar. "Ulcerative Colitis Practice Guidelines in Adults: American 
College of Gastroenterology, Practice Parameters Committee." Am J Gastroenterol 105, no. 3 (Mar 
2010): 501-23; quiz 24. 
 
Lamb, C. A., and J. C. Mansfield. "Measurement of Faecal Calprotectin and Lactoferrin in 
Inflammatory Bowel Disease." Frontline Gastroenterol 2, no. 1 (Jan 2011): 13-18. 
 
Lee, Y. S., J. S. Park, S. M. Jung, S. D. Kim, J. H. Kim, J. Y. Lee, K. C. Jung, et al. "Inhibition of 
Lethal Inflammatory Responses through the Targeting of Membrane-Associated Toll-Like 
Receptor 4 Signaling Complexes with a Smad6-Derived Peptide." EMBO Mol Med 7, no. 5 (May 
2015): 577-92. 
 
 


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Appendix 1. Mayo Score (Modified) 
 
< Partial Mayo Score > 
 
 


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< Mayo Endoscopic Score > 
 
 


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Appendix 2. Ulcerative Colitis Endoscopic Index of Severity  
  
Patient ID ____________ Initials ________ 
         Visit No ________ Date _____________________ 
 
 
Vascular Pattern 
 
 
 
 
 
 
Score: __________________ 
 
0 = Normal 
(Normal vascular pattern with arborisation of capillaries clearly 
defined, or with blurring or patchy loss of capillary margins) 
1 = Patchy obliteration 
(Patchy obliteration of vascular pattern) 
2 = Obliterated 
(Complete obliteration of vascular pattern) 
 
Bleeding 
 
 
 
 
 
 
 
Score: __________________ 
 
0 = None 
(No visible blood) 
1 = Mucosal 
(Some spots or streaks of coagulated blood on the surface of the 
mucosa ahead of the scope that can be washed away) 
2 = Luminal mild 
(Some free liquid blood in the lumen) 
3 = Luminal moderate 
or severe 
(Frank blood in the lumen ahead of endoscope or visible oozing 
from mucosa after washing intraluminal blood, or visible oozing 
from a hemorrhagic mucosa) 
 
Erosions and Ulcers  
 
 
  
 
 
Score: __________________ 
 
0 = None 
(Normal mucosa, no visible erosions or ulcers) 
1 = Erosions 
(Tiny [≤ 5mm] defects in the mucosa, of a white or yellow color 
with a flat edge) 
2 = Superficial ulcer 
(Larger [> 5mm] defects in the mucosa, which are discrete fibrin-
covered ulcers when compared with erosions, but remain 
superficial) 
3 = Deep ulcer 
(Deeper excavated defects in the mucosa, with a slightly raised 
edge) 
 
 
 
Investigator  _______________________________________   Date ________________________ 
 


Phase 2a Study of BBT401-1S in Active UC 
Version 3.1 
Protocol # BBT401-UC-US02 
July 19, 2019 
Confidential 
 
53 
Appendix 3. Short Inflammatory Bowel Disease Questionnaire  
 
Patient ID ____________ Initials ________ 
         Visit No ________ Date _____________________ 
 
This questionnaire is designed to find out how you have been feeling during the last 2 weeks. You will be 
asked about symptoms you have been having as a result of your inflammatory bowel disease, the way you 
have been feeling in general, and how your mood has been. Please check the box of your choice below each 
question. 
 
1. How often has the feeling of fatigue or being 
tired and worn out been a problem for you 
during the past 2 weeks? 
 All of the time  
 Most of the time  
 A good bit of the time  
 Some of the time  
 A little of the time  
 Hardly any of the time  
 None of the time 
 
2. How often during the last 2 weeks have you 
delayed or canceled a social engagement 
because of your bowel problem? 
 All of the time  
 Most of the time  
 A good bit of the time  
 Some of the time  
 A little of the time  
 Hardly any of the time  
 None of the time 
 
3. As a result of your bowel problems, how 
much difficulty did you experience doing 
leisure or sports activities during the past 2 
weeks? 
 A great deal of difficulty; activities made 
impossible 
 A lot of difficulty 
 A fair bit of difficulty 
 Some difficulty 
 A little difficulty 
 Hardly any difficulty 
 No difficulty; the bowel problem did not 
limit sports or leisure activities 
 
4. How often during the past 2 weeks have you 
been troubled by pain in the abdomen?  
 All of the time  
 Most of the time  
 A good bit of the time  
 Some of the time  
 A little of the time  
 Hardly any of the time  
 None of the time 
 
5. How often during the past 2 weeks have you 
felt depressed or discouraged? 
 All of the time  
 Most of the time  
 A good bit of the time  
 Some of the time  
 A little of the time  
 Hardly any of the time  
 None of the time 
 
6. Overall, in the past 2 weeks, how much of a 
problem have you had with passing large 
amounts of gas?  
 A major problem 
 A big problem 
 A significant problem 
 Some problem 
 A little trouble 
 Hardly any trouble 
 No trouble 
 
7. Overall, in the past 2 weeks, how much of a 
problem have you had maintaining or getting 
to the weight you would like to be?  
 A major problem 
 A big problem 
 A significant problem 
 Some problem 
 A little trouble 


Phase 2a Study of BBT401-1S in Active UC 
Version 3.1 
Protocol # BBT401-UC-US02 
July 19, 2019 
Confidential 
 
54 
 Hardly any trouble 
 No trouble 
 
8. How often during the past 2 weeks have you 
felt relaxed and free of tension?  
 All of the time  
 Most of the time  
 A good bit of the time  
 Some of the time  
 A little of the time  
 Hardly any of the time  
 None of the time 
 
9. How much of the time during the past 2 
weeks have you been troubled by a feeling of 
having to go to the bathroom even though 
your bowels were empty?  
 All of the time  
 Most of the time  
 A good bit of the time  
 Some of the time  
 A little of the time  
 Hardly any of the time  
 None of the time 
 
10. How often during the past 2 weeks have you 
felt angry as a result of your bowel problem? 
 All of the time  
 Most of the time  
 A good bit of the time  
 Some of the time  
 A little of the time  
 Hardly any of the time  
 None of the time 
 
 
Study Coordinator  _______________________________________   Date ________________________ 

SAP_001.pdf: 
                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
1 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
 
 
St ati sti c al  A n al y si s  Pl a n  
 
 
 
St u d y  Titl e:   A  R a n d o mi z e d,  D o u bl e -bli n d,  Pl a c e b o -
c o ntr oll e d,  P h a s e  2 a  St u d y t o  E v al u at e t h e 
Effi c a c y  a n d  S af et y  of  B B T -4 0 1 -1 S i n  P ati e nt s 
wit h  A cti v e  Ul c er ati v e  C oliti s  
   
S p o n s or:   Bri d g e  Bi ot h er a p e uti c s, I n c.  
 
C’ s  T o w er  # 3 0 3  
5 8,  P a n g y o -r o  2 5 5  b e o n-gil,  B u n d a n g -g u   
 S e o n g n a m -si,  G y e o n g gi -d o,  R e p u bli c  of  K or e a  
   
U S  R e pr e s e nt ati v e:   K C R N  R e s e ar c h , L L C . 
 2 0 2 5 1  C e nt ur y  B o ul e v ar d  S uit e  3 2 5  
G er m a nt o w n,  M D  2 0 8 7 4  
   
Pr ot o c ol  N u m b er:   B B T 4 0 1 -U C -U S 0 2  
Pr oj e ct  C o d e :  B B T 4 0 1 P 2 A  
   
V er si o n :  2 .1  F i n al 
D at e :  2 2  J u l 2 0 2 0  
 
 
 
 
 
 


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
1 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
 
 
St ati sti c al  A n al y si s  Pl a n  
 
 
 
St u d y  Titl e:   A  R a n d o mi z e d,  D o u bl e -bli n d,  Pl a c e b o -
c o ntr oll e d,  P h a s e  2 a  St u d y t o  E v al u at e t h e 
Effi c a c y  a n d  S af et y  of  B B T -4 0 1 -1 S i n  P ati e nt s 
wit h  A cti v e  Ul c er ati v e  C oliti s  
   
S p o n s or:   Bri d g e  Bi ot h er a p e uti c s, I n c.  
 
C’ s  T o w er  # 3 0 3  
5 8,  P a n g y o -r o  2 5 5  b e o n-gil,  B u n d a n g -g u   
 S e o n g n a m -si,  G y e o n g gi -d o,  R e p u bli c  of  K or e a  
 
U S  R e pr e s e nt ati v e:   K C R N  R e s e ar c h , L L C . 
 2 0 2 5 1  C e nt ur y  B o ul e v ar d  S uit e  3 2 5  
G er m a nt o w n,  M D  2 0 8 7 4  
   
Pr ot o c ol  N u m b er:   B B T 4 0 1 -U C -U S 0 2  
Pr oj e ct  C o d e :  B B T 4 0 1 P 2 A  
   
V er si o n :  2 .1  F i n al 
D at e :  2 2  J u l 2 0 2 0  
 
 
 
 
 
 


3 1 J ul 2 0 2 0
3 1 J ul 2 0 2 0


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
3 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
T A B L E  O F  C O N T E N T S  
 
Gl o s s ar y  a n d  A b br e vi ati o n s  .......................................................................................... 5  
1   R E VI SI O N  HI S T O R Y  ................................................................................................... 6  
2   S T U D Y  O B J E C TI V E S  A N D  E N D P OI N T S  ................................................................... 6  
2. 1  
St u d y  O bj e cti v e s  ............................................................................................................ 6  
2. 1. 1  
Pri m ar y  O bj e cti v e  ................................................................................................................... 6  
2. 1. 2  
S e c o n d ar y  O bj e cti v e s  ............................................................................................................ 6  
2. 2  
St u d y  E n d p oi nt s  ............................................................................................................ 6  
2. 2. 1  
Pri m ar y  E n d p oi nt s  .................................................................................................................. 6  
2. 2. 2  
S e c o n d ar y  E n d p oi nt s  ............................................................................................................. 6  
3   S T U D Y  D E SI G N  .......................................................................................................... 7  
3. 1  
S u m m ar y  of  St u d y  D e si g n  ............................................................................................ 7  
3. 2  
D et er mi n ati o n  of  S a m pl e  Si z e  ...................................................................................... 9  
3. 3  
Tr e at m e nt s  ..................................................................................................................... 9  
3. 4  
R a n d o mi z ati o n  a n d  Bli n di n g  ........................................................................................ 9  
4   S T A TI S TI C A L  M E T H O D S  ......................................................................................... 1 0  
4. 1  
G e n er al  C o n si d er ati o n s  .............................................................................................. 1 0  
4. 2  
A dj u st m e nt s f or  C o v ari at e s  ........................................................................................ 1 0  
4. 3  
A n al y si s  S et s  ............................................................................................................... 1 0  
4. 3. 1  
M o difi e d I nt e nt -t o-Tr e at  ........................................................................................................ 1 0  
4. 3. 2  
P er -Pr ot o c ol  ......................................................................................................................... 1 1  
4. 3. 3  
S af et y  ................................................................................................................................... 1 1  
4. 3. 4  
P h ar m a c o ki n eti c s ( P K)  ......................................................................................................... 1 1  
4. 4  
B a s eli n e  a n d  P o st b a s eli n e  D efi niti o n  ........................................................................ 1 1  
4. 5  
H a n dli n g  of  Dr o p o ut s  or  Mi s si n g  D at a  ...................................................................... 1 1  
4. 6  
Tr e at m e nt  Gr o u p  C o m p ar a bilit y  ................................................................................. 1 1  
4. 6. 1  
P ati e nt  Di s p o siti o n  ............................................................................................................... 1 1  
4. 6. 2  
Pr ot o c ol  D e vi ati o n s  .............................................................................................................. 1 1  
4. 6. 3  
P ati e nt  C h ar a ct eri sti c s  ......................................................................................................... 1 2  
4. 6. 4  
Pri or  a n d  C o n c o mit a nt  T h er a p y  ........................................................................................... 1 2  
4. 7  
Effi c a c y  A n al y s e s  ........................................................................................................ 1 2  
4. 7. 1  
Pri m ar y  Effi c a c y  A n al y si s  ..................................................................................................... 1 3  
4. 7. 2  
S e c o n d ar y  Effi c a c y  A n al y s e s  ............................................................................................... 1 3  
4. 8  
S af et y  A n al y s e s  ........................................................................................................... 1 3  
4. 8. 1  
A d v er s e  E v e nt s  .................................................................................................................... 1 4  
4. 8. 2  
S eri o u s  A d v er s e  E v e nt s  ....................................................................................................... 1 4  
4. 8. 3  
Cli ni c al  L a b or at or y  E v al u ati o n  .............................................................................................. 1 5  
4. 8. 4  
Vit al  Si g n s  ............................................................................................................................ 1 6  
4. 8. 5  
El e ctr o c ar di o gr a m  ................................................................................................................ 1 6  
4. 9  
P D  A n al y s e s  ................................................................................................................. 1 6  
4. 1 0  
P K  A n al y s e s  .............................................................................................................. 1 6  
4. 1 0. 1  
M e a s ur e m e nt s  a n d  C oll e cti o n  S c h e d ul e  .............................................................................. 1 6  
4. 1 0. 2  
Bi o a n al yti c al  M et h o d s  .......................................................................................................... 1 6  
4. 1 0. 3  
Pl a s m a/ Ti s s u e  C o n c e ntr ati o n s  ............................................................................................ 1 7  


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
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C o nfi d e nti al  
4 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
4. 1 0. 4  
P ar a m et er  C al c ul ati o n  .......................................................................................................... 1 7  
4. 1 0. 5  
D at a  S u m m ari z ati o n  a n d  Pr e s e nt ati o n  ................................................................................ 1 7  
4. 1 0. 6  
St ati sti c al  A n al y si s  of  Pl a s m a/ Ti s s u e  C o n c e ntr ati o n s  .......................................................... 1 7  
4. 1 1  
I nt eri m  A n al y si s  a n d  D at a  M o nit ori n g .................................................................... 1 7  
4. 1 2  
H a n dli n g  of  Dr o p o ut s  or  Mi s si n g  D at a  ................................................................... 1 8  
4. 1 3  
S u b gr o u p  A n al y si s  ................................................................................................... 1 8  
4. 1 4  
M ulti pl e  C o m p ari s o n/ M ulti pli cit y  ............................................................................ 1 8  
5   C H A N G E S  T O  P R O T O C O L -S P E CI FI E D  A N A L Y S E S  ............................................. 1 8  
6   LI S T  O F  T A B L E S  A N D  FI G U R E S  ............................................................................ 1 8  
 
 
 


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
5 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
Gl o s s ar y  a n d  A b br e vi ati o n s  
 
A E  
A d v er s e  E v e nt  
A L T   
Al a ni n e  Tr a n s a mi n a s e  
A PI  
A cti v e  P h ar m a c e uti c al I n gr e di e nt  
A S T   
A s p art at e  Tr a n s a mi n a s e  
B L Q   
B el o w t h e  L o w er l e v el  of  Q u a ntifi c ati o n  
C F R   
C o d e  of  F e d er al  R e g ul ati o n s  
C O N S O R T   
C o n s oli d at e d  St a n d ar d s  of  R e p orti n g  Tri al s  
C R F   
C a s e  R e p ort  F or m  
C R P   
C -R e a cti v e  Pr ot ei n  
D P  
Dr u g  Pr o d u ct  
E C G   
El e ctr o c ar di o gr a m  
e C R F   
El e ctr o ni c  C a s e  R e p ort  F or m s  
F D A   
F o o d  a n d  Dr u g  A d mi ni str ati o n  
G C P   
G o o d  Cli ni c al  Pr a cti c e  
G L P   
G o o d  L a b or at or y  Pr a cti c e s  
G M P   
G o o d  M a n uf a ct uri n g  Pr a cti c e s  
H B s A g   
H e p atiti s  B  S urf a c e  A nti g e n  
HI V  
H u m a n I m m u n o d efi ci e n c y  Vir u s  
H R Q o L   
H e alt h -r el at e d  Q u alit y  of  Lif e 
I B 
I n v e sti g at or’ s  Br o c h ur e 
I C H  
I nt er n ati o n al  C o nf er e n c e  o n  H ar m o ni s ati o n  
I N D  
I n v e sti g ati o n al  N e w  Dr u g  A p pli c ati o n 
I C F 
I nf or m e d  C o n s e nt  F or m 
I R B 
I n stit uti o n al  R e vi e w  B o ar d 
I T T 
I nt e nt-T o -Tr e at  
M A D   
M ulti pl e  A s c e n di n g  D o s e  
M e d D R A   
M e di c al  Di cti o n ar y f or  R e g ul at or y  A cti viti e s  
mI T T   
M o difi e d I nt e nt -T o -Tr e at  
P D  
P h ar m a c o d y n a mi c s  
PI  
Pri n ci p al I n v e sti g at or  
P K  
P h ar m a c o ki n eti c s  
Q C  
Q u alit y  C o ntr ol  
S A E   
S eri o u s  A d v er s e  E v e nt  
S A P   
St ati sti c al  A n al y si s  Pl a n  
S F U   
S af et y  F oll o w -U p  
SI B D Q   
S h ort I nfl a m m at or y  B o w el  Di s e a s e  Q u e sti o n n air e  
S M C   
S af et y  M o nit ori n g  C o m mitt e e  
S O C   
S y st e m  Or g a n  Cl a s s  
S O P   
St a n d ar d  O p er ati n g  Pr o c e d ur e  
T E A E   
Tr e at m e nt -E m er g e nt  A d v er s e  E v e nt  
U C  
Ul c er ati v e  C oliti s  
U C EI S   
Ul c er ati v e  C oliti s  E n d o s c o pi c I n d e x  of  S e v erit y  
U L N   
U p p er  Li mit  of  N or m al  
 
 


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
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St atisti c al  A n al ysis  Pl a n  
1   
R E VI SI O N  HI S T O R Y  
 
S A P  V er si o n  1 . 0 w a s  cr e at e d  a n d  a p pr o v e d  pri or t o  a n y  u n bli n di n g  t o t h e  st u d y t e a m.  
 
S A P  V er si o n  2. 0  w a s  pl a n n e d t o  u p d at e  a  st ati sti ci a n  of  K C R N  R e s e ar c h  a n d  S e cti o n  6  Li st  of 
T a bl e s  a n d  Fi g ur e s . T F L  s h ell s  w er e  cr e at e d  f or t h e  1 st  c o h ort a n d  att a c h e d.   
 
 
2   
S T U D Y  O B J E C TI V E S  A N D  E N D P OI N T S  
 
2. 1   
St u d y  O bj e cti v e s  
 
2. 1. 1   Pri m ar y  O bj e cti v e  
 
T h e  pri m ar y  o bj e cti v e i s t o  a s s e s s t h e  effi c a c y  a n d  s af et y  of  m ulti pl e  or al  d o s e s  of  B B T -4 0 1 -1 S 
i n  p ati e nt s  wit h  a cti v e  U C. 
 
2. 1. 2   S e c o n d ar y  O bj e cti v e s  
 
T h e  s e c o n d ar y  o bj e cti v e s  ar e t o  a s s e s s t h e  pl a s m a  a n d ti s s u e  c o n c e ntr ati o n  of  m ulti pl e  or al 
d o s e s  of  B B T -4 0 1 -1 S i n  p ati e nt s  wit h  a cti v e  U C  a n d t o  e v al u at e t h e  eff e ct s  of  B B T -4 0 1 -1 S  o n 
bi o m ar k er s . 
 
2. 2   
St u d y  E n d p oi nt s  
 
2. 2. 1   Pri m ar y  E n d p oi nt s  
 
•   C h a n g e fr o m  b a s eli n e i n  T ot al  M a y o  S c or e  at  W e e k  8  
 
2. 2. 2   S e c o n d ar y  E n d p oi nt s  
 
•   C h a n g e fr o m  B a s eli n e i n  P arti al  M a y o  S c or e  at  W e e k  8   
•   C h a n g e fr o m  B a s eli n e i n  Hi st ol o gi c  A s s e s s m e nt  of  E n d o s c o pi c  Bi o p s y  at  W e e k  8  
•   C h a n g e fr o m  B a s eli n e i n  Ul c er ati v e  C oliti s  E n d o s c o pi c I n d e x  of  S e v erit y ( U C EI S)  S c or e 
at  W e e k  8  
•   C h a n g e fr o m  B a s eli n e i n  S h ort I nfl a m m at or y  B o w el  Di s e a s e  Q u e sti o n n air e ( SI B D Q)  at 
W e e k  8  
•  
N u m b er  a n d  S e v erit y  of  Tr e at m e nt  E m er g e nt  A d v er s e  E v e nt s ( T E A E s)  u p t o  W e e k  8  
•   C h a n g e fr o m  B a s eli n e i n  C o n c e ntr ati o n  of  Bi o m ar k er s ( C -r e a cti v e  pr ot ei n [ C R P], f e c al 
c al pr ot e cti n,  a n d f e c al l a ct of erri n)  at  W e e k  8  
•   Pl a s m a  a n d  Ti s s u e  C o n c e ntr ati o n  of  B B T -4 0 1 -1 S i n  P ati e nt s  wit h  A cti v e  U C  
 
 


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
7 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
3   
S T U D Y  D E SI G N  
 
3. 1   
S u m m ar y  of  St u d y  D e si g n  
 
T hi s r a n d o mi z e d,  pl a c e b o -c o ntr oll e d,  d o s e -e s c al ati o n,  m ulti c e nt er,  P h a s e  2  st u d y  c o n si st s  of 
t hr e e  c o h ort s  wit h  1 6-w e e k tr e at m e nt  p eri o d  p er  c o h ort t h at  will  b e  c o n d u ct e d  s e q u e nti all y.  T h e 
fir st  c o h ort  will r e c ei v e  4 0 0  m g  of  B B T-4 0 1 -1 S ( st arti n g  d o s e).  Effi c a c y,  s af et y,  a n d  P K  d at a  of 
t h e fir st  c o h ort  will  b e  u s e d t o  s el e ct t h e  d o s e  of t h e  s u b s e q u e nt  c o h ort.  F or t h e  1 st  or  2 n d 
c o h ort, if t h e  1 2t h  p ati e nt ( 7 5 %)  c o m pl et e s  Vi sit  4 ( W e e k  8),  u n bli n di n g  of  1 2  p ati e nt s  will  b e 
p erf or m e d  wit hi n  2  w e e k s  aft er  Vi sit  4 ( W e e k  8)  a n d t h e  u n bli n di n g i nf or m ati o n  will  b e  o nl y 
pr o vi d e d t o t h e  S p o n s or f or t h e  a n al y si s t o  d et er mi n e t h e  d o s e  of t h e  n e xt  c o h ort.  A  d o s e l e v el 
m a y  b e r e p e at e d  or  a d d e d  b a s e d  o n t h e r e s ult s  of t h e  pr e vi o u s  c o h ort( s).  
  
P ati e nt s  will r e c ei v e  a  d ail y  or al  d o s e  of  B B T  4 0 1 -1 S  or  pl a c e b o f or t h e  1 6  w e e k s.  W hil e 
p ati e nt s  w h o  ar e  a s si g n e d t o  A cti v e  Gr o u p  will r e c ei v e  B B T -4 0 1 -1 S f or t h e fir st  1 2  w e e k s  a n d 
t h e n  pl a c e b o f or t h e l a st  4  w e e k s,  p ati e nt s  w h o  ar e  a ssi g n e d t o  Pl a c e b o  Gr o u p  will r e c ei v e 
pl a c e b o f or t h e fir st  8  w e e k s  a n d t h e n  B B T -4 0 1 -1 S f or l a st  8  w e e k s.   
 
 
 
 


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
8 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
 
T h e  s c h e d ul e  of  a s s e s s m e nt s i s ill u str at e d i n  T a bl e  1.  
 
T a bl e  1 .  S c h e d ul e  of  A s s e s s m e nt s  
 
 
S cr e e ni n g  
Tr e at m e nt  P eri o d  
S F U  
Vi sit  N u m b er   
V 1  
V 2   
V 3   
V 4    
V 5    
V 6   
E T  
Vi sit  P eri o d   U p t o  W -4  
B a s eli n e   
W 4   
W 8   
W 1 2   
W 1 6   
N/ A  
W 2 fr o m  L D  
Vi sit  Wi n d o w   
N/ A  
Wit hi n  2 8 
d a y s fr o m 
V 1  
± 3 
d a y s  
± 3 
d a y s  
± 3 
d a y s  
± 3 
d a y s  
N/ A  
+  7  d a y s 
fr o m  L D 
I nf or m e d  C o n s e nt 
X  
  
  
  
  
  
 
 
D e m o gr a p hi c I nf or m ati o n  
X  
  
  
  
  
  
 
 
M e di c al/ m e di c ati o n  Hi st or y  
X  
X   
  
  
  
  
 
 
I n cl u si o n/ e x cl u si o n  Crit eri a 
X  
X   
  
  
  
  
 
 
Vit al  Si g n s  
X  
X   
X   
X   
X   
X   
X  
X  
P h y si c al  E x a mi n ati o n  
X  
X a   
X   
X   
X   
X   
X  
 
1 2 -l e a d  E C G 
X  
X 1   
X   
X   
X   
X   
X  
 
Cli ni c al  L a b  T e st s  a n d  S er u m 
Bi o m ar k er 2  
X  
X a   
X   
X   
X   
X   
X  
X  
E n d o s c o p y  ( bi o p s y) 
X  
  
  
X   
  
  
X 3  
 
R a n d o mi z ati o n  
 
X   
  
  
  
  
 
 
M a y o  S c or e  
X  
X   
X   
X   
X   
X   
X  
 
Ul c er ati v e  C oliti s  E n d o s c o pi c I n d e x  of 
S e v erit y  
X   
  
  
X   
  
  
X c  
 
S h ort I nfl a m m at or y  B o w el  Di s e a s e 
Q u e sti o n n air e  
 
X   
X   
X   
X   
X   
X  
 
F e c al  Bi o m ar k er 4  
 
X   
X   
X   
X   
X   
X  
 
Pl a s m a  P h ar m a c o ki n eti c s 5  
 
X   
X   
X    
  
  
 
 
Ti s s u e  C o n c e ntr ati o n 6  
X  
  
  
X   
  
  
X c 
 
Dr u g  Di s p e n si n g ( wit h  s u bj e ct  di ar y)   
 
X   
X   
X   
X   
  
 
 
Dr u g  R et ur n  a n d  C o m pli a n c e  
 
  
X   
X   
X   
X   
X  
 
A E  a n d  C o n c o mit a nt  M e di c ati o n  
 
X   
X   
X   
X   
X g   
X g  
X  
A E  =  a d v er s e  e v e nt;  E C G  =  el e ctr o c ar di o gr a m;  S F U  =  S af et y  F oll o w -U p;  V  =  Vi sit;  W  =  W e e k;  E T  =  E arl y 
T er mi n ati o n;  L D  =  L a st  D o s e  
 
 
 
1   W ai v e d if t h e  s cr e e ni n g  vi sit i s  c o n d u ct e d  wit hi n  1 0  d a y s  pri or t o  Vi sit  2 ( B a s eli n e).   
2    S er u m  c h e mi str y,  h e m at ol o g y,  c o a g ul ati o n t e st,  HI V  a n d  h e p atiti s  s cr e e n s,  s er u m  h C G ( w o m e n  wit h 
c hil d b e ari n g  p ot e nti al  o nl y),  a n d  s er u m  C R P ( n ot  m e a s ur e d  at  S F U).   
3   O nl y if  e arl y t er mi n ati o n  o c c ur s  b ef or e  Vi sit  4 ( W 8).   
4    F e c al  c al pr ot e cti n  a n d f e c al l a c t of erri n.  A  c oll e cti o n  c o nt ai n er  will  b e  di s p e n s e d t o  p ati e nt s  o n t h e 
pr e vi o u s  vi sit.   
5    Vi sit  2 ( B a s eli n e)  a n d  Vi sit  3 ( W 4):  pr e -d o s e  a n d  3  a n d  6  h o ur s  p o st -d o s e;  Vi sit  4 ( W 8):  pr e -d o s e  o nl y.  
6    D uri n g t h e  e n d o s c o p y (fl e xi bl e  pr o ct o si g m oi d o s c o p y/ c ol o n o s c o p y) f or  bi o p s y.  
g  R e vi e wi n g  a n y  c h a n g e s i n  s m o ki n g  h a bit s  of  s u bj e ct  d uri n g t h e  st u d y  p eri o d.  


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
9 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
 
3. 2   
D et er mi n ati o n  of  S a m pl e  Si z e  
 
A s t hi s i s  a n i niti al  d o s e -e s c al ati o n  st u d y, it i s  a p pr o pri at el y  b a s e d  o n  o nl y  a li mit e d  n u m b er  of 
p ati e nt s  i n   e a c h  d o s e  c o h ort.    T h e  si z e   of  t h e  st u d y  i s   n ot   b a s e d   o n   a n y  st ati sti c al   p o w er 
c al c ul ati o n s  a n d  n o f or m al  s a m pl e  si z e  c al c ul ati o n  h a s  b e e n  d o n e.  B a s e d  o n t h e  e x p eri e n c e fr o m 
t h e  pr e vi o u s  st u di e s  a n d t h e  u s e  of  a  s e q u e nti al  d o s e-e s c al ati o n  d e si g n f or t hi s  st u d y,  a t ot al  of 
4 8  p ati e nt s ( 1 6  p ati e nt s  p er  d o s e  c o h ort) i s  c o n si d er e d  a p pr o pri at e f or t h e  st u d y.  
 
3. 3   
Tr e at m e nt s  
 
P ati e nt s  will r e c ei v e  a  d ail y  or al  d o s e  of  B B T  4 0 1 -1 S  or  pl a c e b o f or t h e  1 6  w e e k s.  W hil e  p ati e nt s 
w h o  ar e  a s si g n e d t o  A cti v e  Gr o u p  will r e c ei v e  B B T -4 0 1 -1 S f or t h e fir st  1 2  w e e k s  a n d t h e n  pl a c e b o 
f or t h e l a st  4  w e e k s,  p ati e nt s  w h o  ar e  a s si g n e d t o  Pl a c e b o  Gr o u p  will r e c ei v e  pl a c e b o f or t h e fir st 
8  w e e k s  a n d t h e n  B B T -4 0 1 -1 S f or l a st  8  w e e k s.   
 
3. 4   
R a n d o mi z ati o n  a n d  Bli n di n g  
 
A t ot al  of  1 6  s u bj e ct s i n  e a c h  of  t h e  3  d o si n g  c o h ort s  will  b e r a n d o mi z e d t o  eit h er  a cti v e  or  pl a c e b o 
gr o u p i n  a  3: 1 r ati o ( 1 2  a cti v e  a n d  4  pl a c e b o)  u si n g t h e  el e ctr o ni c  d at a  c a pt ur e ( E D C)  s y st e m  i n 
w hi c h t h e r a n d o mi z ati o n  c o d e i s i nt e gr at e d .  
 
T h e r a n d o mi z ati o n  c o d e  will  b e  g e n er at e d  b y  a n  u n bli n d e d  st ati sti ci a n  w h o i s  n ot i n v ol v e d  wit h 
t h e  st u d y.  T h e  S p o n s or, i n v e sti g at or s,  p ati e nt s,  a n d  C R O  a n d  ot h er r el e v a nt  p er s o n n el i n v ol v e d 
wit h  t h e  c o n d u ct  of  t h e  st u d y,    wit h  t h e  e x c e pti o n  of  cli ni c al  s u p pl y  st aff  a n d  t h e  u n bli n d e d 
st ati sti ci a n,  will  b e  bli n d e d t o t h e i d e ntit y  of  st u d y  m e di c ati o n.  
 
F or t h e  1 st  or  2 n d  c o h ort, if t h e  1 2t h  p ati e nt  ( 7 5 %)  c o m pl et e s  Vi sit  4  ( W e e k  8), t h e  C R O  d at a 
m a n a g e m e nt ( D M) t e a m  c o nfir m  all  cli ni c al  d at a  of t h e  1 2  p ati e nt s  h a v e  n o i s s u e  a n d t h e n  o bt ai n 
t h e  writt e n  c o n se nt fr o m t h e  S p o n s or t o  br e a ki n g t h e  c o d e.  P er t h e r e q u e st  of t h e  C R O  D M t e a m, 
t h e  r a n d o mi z ati o n  c o d e s  of  t h e  1 2  p ati e nt s    will  b e  o p e n e d  vi a  t h e  u n bli n d e d  st ati sti ci a n  a n d 
n otifi e d t o t h e  S p o n s or f or t h e  a n al y si s t o  d et er mi n e t h e  n e xt  d o s e.  Aft er  c o nfir mi n g  all  cli ni c al 
d at a   of  r e m ai ni n g   4   p ati e nt s  f or  t h e   1 st   or   2 n d   c o h ort,  t h e  r a n d o mi z ati o n   c o d e s    will   b e 
s u b s e q u e ntl y  o p e n e d t o t h e  s p o n s or t hr o u g h t h e  s a m e  pr o c e d ur e s  st at e d  a b o v e.   
 
Aft er t h e l a st  p ati e nt  of l a st  c o h ort  c o m pl et e s t h e  S F U, t h e  C R O  D M t e a m  c o nfir m s t h e  w h ol e 
cli ni c al  d at a b a s e  h a s  n o  i s s u e  a n d  t h e n  r e q u e st s  t h e  d at a b a s e  l o c k  t o  t h e   S p o n s or.   P er  t h e 
S p o n s or’ s  a p pr o v al  o n t h e  d at a b a s e l o c k, t h e r a n d o mi z ati o n  c o d e  of  all  p ati e nt s  will  b e  o p e n e d 
vi a t h e  u n bli n d e d  st ati sti ci a n  a n d  n otifi e d t o t h e  C R O f or t h e  st ati sti c al  a n al y si s.   
 
Br e a ki n g  of t h e r a n d o mi z ati o n  c o d e  wit h o ut  s p o n s or’ s  p er mi s si o n i s  e x pr e s sl y f or bi d d e n  e x c e pt 
i n t h e  e v e nt  of  a  m e di c al  e m er g e n c y  w h er e t h e i d e ntit y  of t h e  st u d y  m e di c ati o n  m u st  b e  k n o w n i n 
or d er t o  pr o p erl y tr e at t h e  p at i e nt. I n t h e  e v e nt  of  a  m e di c al  e m er g e n c y, it i s r e q u e st e d t h at t h e 
i n v e sti g at or  m a k e  e v er y  eff ort t o  c o nt a ct t h e  st u d y  m o nit or  or  d e si g n e e  pri or t o  br e a ki n g t h e  c o d e.  
 


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
1 0 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
If t h e  bli n d i s  br o k e n  d u e t o t h e  m e di c al  e m er g e n c y, t h e  s u bj e ct  m u st  b e  e arl y t er mi n at e d;  a  writt e n 
e x pl a n ati o n  m u st  b e  pr e p ar e d i m m e di at el y.  
 
 
4   
S T A TI S TI C A L  M E T H O D S  
 
4. 1   
G e n er al  C o n si d er ati o n s  
 
T hi s  d o c u m e nt  d e s cri b e s  t h e  st ati sti c al  a n al y s e s  pl a n n e d  pri or  t o  fi n al  tr e at m e nt  a s si g n m e nt 
u n bli n di n g  of t h e  a g gr e g at e  d at a b a s e.  A n y  c h a n g e t o t h e  d at a  a n al y si s  m et h o d s  d e s cri b e d i n t h e 
pr ot o c ol  will  r e q uir e  a n  a m e n d m e nt  O N L Y if it  c h a n g e s  a  pri n ci p al f e at ur e  of t h e  pr ot o c ol.  A n y 
ot h er  c h a n g e  t o  t h e  d at a  a n al y si s    m et h o d s  d e s cri b e d  i n  t h e  pr ot o c ol  a n d  t h e  j u stifi c ati o n  f or 
m a ki n g t h e  c h a n g e  will  b e  d e s cri b e d i n t h e  cli ni c al  st u d y r e p ort ( C S R).  A d diti o n al  e x pl or at or y  or 
a d -h o c  a n al y s e s  of t h e  d at a  will  b e  c o n d u ct e d  a s  d e e m e d  a p pr o pri at e.  
 
All t e st s  of tr e at m e nt  eff e ct s  will  b e  c o n d u ct e d  at  a t w o -si d e d  al p h a l e v el  of  0. 0 5  u nl e s s  ot h er wi s e 
st at e d,  a n d  all  c o nfi d e n c e i nt er v al s ( CI’ s)  will  b e  gi v e n  at  a t w o -si d e d  9 5 % l e v el,  u nl e s s  ot h er wi s e 
st at e d.  St ati sti c al  a n al y si s  will  b e  p erf or m e d  u si n g  S A S  s oft w ar e ( S A S,  V er si o n  9. 1. 2  or  hi g h er).  
 
T h e f oll o wi n g  g e n er al t er m s  will  b e  u s e d  gl o b all y i n t h e  S A P:  
•   U nl e s s  ot h er wi s e  s p e cifi e d, t h e  st ati sti c al  a n al y s e s  will  b e r e p ort e d  u si n g  s u m m ar y t a bl e s 
a n d  d at a li sti n g s.   
•   C o nti n u o u s  v ari a bl e s    will   b e  s u m m ari z e d    wit h   n,    m e a n,  st a n d ar d   d e vi ati o n,    m e di a n, 
mi ni m u m,  a n d  m a xi m u m.   
•   C at e g ori c al  v ari a bl e s   will  b e  s u m m ari z e d  b y  c o u nt s  a n d  b y  p er c e nt a g e s  of  s u bj e ct s  i n 
c orr e s p o n di n g  c at e g ori e s.   
•   All  s u m m ar y t a bl e s  will  b e  pr e s e nt e d  b y tr e a t m e nt a n d/ or  c o h ort .  
•   I n di vi d u al  s u bj e ct  d at a  o bt ai n e d fr o m t h e  c a s e r e p ort f or m ( C R F s)  a n d  a n y  d eri v e d  d at a 
will  b e  pr e s e nt e d  b y  s u bj e ct i n  d at a li sti n g s.  D at a li sti n g s  will  b e  s ort e d  b y  s u bj e ct,  a n d 
vi sit  d at e  a n d ti m e, if  a p pli c a bl e.   
 
4. 2   
A dj u st m e nt s f or  C o v ari at e s  
 
T h er e  will  b e  n o  a dj u st m e nt f or  c o v ari at e s.   
 
4. 3   
A n al y si s  S et s  
 
4. 3. 1   M o difi e d I nt e nt -t o-Tr e at   
 
A  m o difi e d i nt e nt -t o-tr e at ( mI T T) s et  will  c o n si st  of  all r a n d o mi z e d  p ati e nt s  w h o  h a v e  r e c ei v ed  at 
l e a st  1  d o s e  of  st u d y  m e di c ati o n a n d  h a v e  at l e a st  1  p o st -b a s eli n e  effi c a c y  m e a s ur e m e nt . T h e 
mI T T  s et  will  b e t h e  pri m ar y  s et  u s e d f or  effi c a c y  a n al y s e s.  
 


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
1 1 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
4. 3. 2   P er -Pr ot o c ol   
 
T h e  p er -pr ot o c ol  s et  will  c o n si st  of  all  s u bj e ct s i n t h e  mI T T  w h o  d o  n ot  h a v e  pr e -d efi n e d  m aj or 
pr ot o c ol  d e vi ati o n s t h at  m a y  aff e ct t h e  pri m ar y  effi c a c y  e n d p oi nt  a n d  h a v e  c o m pl et e d  t h e st u d y 
u ntil  Vi sit  4 ( W e e k  8)  .   
 
4. 3. 3   S af et y   
 
T h e  s af et y  s et  will  c o n si st  of  all  s u bj e ct s  w h o  h a v e  r e c ei v e d  at  l e a st  1  d o s e  of  i n v e sti g ati o n al 
pr o d u ct.   T h e  s af et y  s et  will  b e t h e  pri m ar y  a n al y si s  d at a s et  u s e d f or  s af et y  a n al y s e s.   
 
4. 3. 4   P h ar m a c o ki n eti c s ( P K)  
 
T h e  P K  s et  will  c o n si st  of  all  s u bj e ct s  w h o  h a v e  r e c ei v e d  at l e a st  1  d o s e  of i n v e sti g ati o n al  pr o d u ct 
a n d  t h er e i s  at l e a st  1  P K  s a m pli n g.   T h e P K  s et  will  b e t h e  pri m ar y  a n al y si s  d at a s et  u s e d f or  P K  
a n al y s e s.   
 
 
4. 4   
B a s eli n e  a n d  P o st b a s eli n e  D efi niti o n  
 
U nl e s s  ot h er wi s e  s p e cifi e d, t h e  b a s eli n e  v al u e i s  d efi n e d  a s t h e l a st  v al u e  o bt ai n e d  b ef or e t h e 
d at e  a n d ti m e  of t h e fir st  d o s e  of  st u d y  dr u g.  P o st -b a s eli n e  v al u e s  ar e  d efi n e d  a s  v al u e  o bt ai n e d 
aft er t h e fir st  d o s e  of  st u d y  dr u g.  C h a n g e fr o m  b a s eli n e i s  d e fi n e d  a s  a  p o st-b a s eli n e  v al u e  mi n u s 
t h e  b a s eli n e  v al u e.  
 
4. 5   
H a n dli n g  of  Dr o p o ut s  or  Mi s si n g  D at a  
 
N o  a dj u st m e nt s f or  mi s si n g  d at a  a n d  n o i m p ut ati o n  m et h o d s  ar e  pl a n n e d f or t hi s  st u d y.  
 
4. 6   
Tr e at m e nt  Gr o u p  C o m p ar a bilit y  
 
4. 6. 1   P ati e nt  Di s p o siti o n  
 
S u bj e ct  di s p o siti o n i nf or m ati o n  will  b e  s u m m ari z e d f or  all  s u bj e ct s.  S u m m ari e s  will i n cl u d e: t h e 
n u m b er  of  s u bj e ct s i n  e a c h  a n al y si s  s et , t h e  n u m b er  of  s u bj e ct s  c o m pl et e d t h e  st u d y,  a n d t h e 
n u m b er  of  s u bj e ct s  di s c o nti n u e d  st u d y  a n d it s r e a s o n.  All  s u bj e ct s  r a n d o mi z e d i n t h e  st u d y  will 
b e i n cl u d e d i n t h e  s u m m ar y t a bl e.  P ati e nt  all o c ati o n  b y i n v e sti g at or  or  sit e  will  b e  s u m m ari z e d. 
P ati e nt  all o c ati o n  b y  i n v e sti g at or  or  sit e   will  al s o  b e  li st e d  a s   w ell.  All  s u bj e ct s  r a n d o mi z e d  t o 
pl a c e b o fr o m  e a c h  c o h ort  will  b e  p o ol e d  i n  Pl a c e b o  gr o u p  a n d  s u m m ari z e d  a s  a  pl a c e b o  gr o u p.  
 
4. 6. 2   Pr ot o c ol  D e vi ati o n s  
 


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S u m m ar y  a n d l i sti n g s  of  s u bj e ct s  wit h  si g nifi c a nt  pr ot o c ol  d e vi ati o n s  or  vi ol ati o n s  will  b e  pr o vi d e d. 
T h e f oll o wi n g li st  of  si g nifi c a nt  pr ot o c ol  vi ol ati o n s  will  b e  d et er mi n e d fr o m t h e  cli ni c al  d at a b a s e 
a n d fr o m t h e  st u d y  cli ni c al/ m e di c al  gr o u p:  
•   L a c k  of i nf or m e d  c o n s e nt  or l at e i nf or m e d  c o n s e nt  
•   Vi ol ati o n s  of i n cl u si o n/ e x cl u si o n  crit eri a  
•   Si g nifi c a nt  vi ol ati o n s  of  pr o hi bit e d  c o n c o mit a nt    m e di c ati o n  u s a g e  a s  d et er mi n e d  b y  t h e 
cli ni c al/ m e di c al  gr o u p  
•   Ot h er  si g nifi c a nt  pr ot o c ol  vi ol ati o n s  a s  d et er mi n e d  b y t h e  cli ni c al/ m e di c al  gr o u p  
 
4. 6. 3   P ati e nt  C h ar a ct eri sti c s  
 
T h e  f oll o wi n g  p ati e nt  c h ar a ct eri sti c s  at  b a s eli n e   will  b e  s u m m ari z e d  b y  tr e at m e nt  gr o u p  f or  all 
mI T T  p ati e n t s: 
•   D e m o gr a p hi c ( a g e,  g e n d er,  et h ni c  ori gi n,  h ei g ht,  w ei g ht,  B MI)   
•   M e di c al  hi st or y  a n d  Pr e -e xi sti n g  c o n diti o n   
 
M e di c al  hi st or y  a n d  pr e -e xi sti n g  c o n diti o n s    will  b e  s u m m ari z e d  b y  pr ef err e d  t er m  ( P T)    wit hi n 
s y st e m  or g a n  cl a s s ( S O C).   M e di c al  hi st or y i s  d efi n e d  a s ill n e s s( e s) t h at  e n d e d  pri or t o t h e  si g ni n g 
of i nf or m e d  c o n s e nt.  Pr e -e xi sti n g  c o n diti o n s  a n d  A E s  at  b a s eli n e  ar e t h o s e  A E s  o c c urri n g  d uri n g 
t h e  b a s eli n e/ s cr e e ni n g  vi sit s t h at ar e  Vi sit s  1  a n d  2.  
 
4. 6. 4   Pri or  a n d  C o n c o mit a nt  T h er a p y  
 
V er b ati m t er m s  o n  e C R F s  will  b e  m a p p e d t o  A n at o mi c al  T h er a p e uti c  C h e mi c al ( A T C)  cl a s s  a n d 
G e n eri c  Dr u g  N a m e s  u si n g t h e  W orl d  H e alt h  Or g a ni z ati o n ( W H O)  Dr u g  Di cti o n ar y  E n h a n c e d 
( W H O D D E)  B 2 f or m at,  M ar c h  1,  2 0 1 5 r el e a s e. 
 
Pri or  m e di c ati o n s  ar e  d efi n e d  a s  m e di c ati o n s  st art e d t o  b e  t a k e n  pri or t o t h e fir st a d mi ni str ati o n 
of t h e  st u d y  dr u g .  C o n c o mit a nt  m e di c ati o n s  ar e  d efi n e d  a s  m e di c ati o n s  st art e d  o n  or  aft er t h e 
d a y  of t h e fir st  a d mi ni str ati o n  of t h e  st u d y  dr u g  d uri n g t h e  st u d y.   
 
Pri or  a n d  c o n c o mit a nt  m e di c ati o n s  will  b e t a b ul at e d f or t h e  mI T T  s et  b y  W H O D D E  A T C l e v el  2 
cl a s sifi c ati o n s,  pr ef err e d t er m,  a n d tr e at m e nt. If  a  s u bj e ct r e p ort s t h e  s a m e  pr ef err e d t er m 
m ulti pl e ti m e s, t h e n t h e fr e q u e n c y  of t h at  pr ef err e d t er m  will  o nl y  b e i n cr e m e nt e d  b y  o n e.  A s 
wit h t h e  pr ef err e d t er m, if  a  s u bj e ct r e p ort s  m ulti pl e  m e di c ati o n s  wit hi n t h e  s a m e  A T C l e v el  2 
cl a s sifi c ati o n, t h e n t h e fr e q u e n c y  of t h at  A T C l e v el  2  cl a s sifi c ati o n  will  o nl y  b e i n cr e m e nt e d  b y 
o n e.  P er c e nt a g e s  will  b e  c al c ul at e d  u si n g  t h e t ot al  n u m b er  of  s u bj e ct s i n t h e  s af et y a n al y si s  s et . 
E a c h  s u m m ar y  will  b e  or d er e d  b y  d e s c e n di n g  or d er  of i n ci d e n c e  of  pr ef err e d t er m  wit hi n  e a c h 
A T C  cl a s s.  Pri or  a n d  c o n c o mit a nt  m e di c ati o n s  will  b e i n cl u d e d i n  a  d at a li sti n g.   
 
4. 7   
Effi c a c y  A n al y s e s  
 
U nl e s s  ot h er wi s e  s p e cifi e d,  all  effi c a c y  a n al y s e s  will  b e  b a s e d  o n t h e  mI T T  a n d  s u bj e ct s  will  b e 
a n al y z e d  a c c or di n g t o t h eir r a n d o mi z e d tr e at m e nt.  H o w e v er,  a d diti o n al 


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
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s e n siti vit y/ s u p pl e m e nt ar y  a n al y s e s  will  b e  c o n d u ct e d  u si n g t h e  P P  a n al y si s  s et f or  all  effi c a c y 
e n d p oi nt s.   
 
4. 7. 1   Pri m ar y  Effi c a c y  A n al y si s  
 
D e s cri pti v e  st ati sti c s  will  b e  pr e s e nt e d i n cl u di n g  m e a n,  st a n d ar d  d e vi ati o n  ( S D),  m e di a n,  m a x, 
a n d  mi n  b y tr e at m e nt  a n d  c o h ort  gr o u p  f or t h e  c h a n g e fr o m  b a s eli n e t o  W e e k  8 i n  T ot al  M a y o 
s c or e .  Al s o, t o  b ett er  a s s e s s t h e  diff er e n c e s  b et w e e n  e a c h  d o s e  a n d  t h e  pl a c e b o f or t h e  c h a n g e 
fr o m  b a s eli n e  t o    We e k  8  i n   T ot al    M a y o  s c or e ,  a    mi x e d    m o d el  r e p e at e d    m e a s ur e s  ( M M R M) 
a n al y si s  will  b e  p erf or m e d.  T h e  M M R M  m o d el  will i n cl u d e tr e at m e nt  ( w h et h er 1 st d o s e,  2 n d  d o s e, 
or  3 r d d o s e  v s . Pl a c e b o)  a n d t h e  b a s eli n e  s c or e  a s fi x e d  eff e ct s,  a n d  c e nt er  a s  a r a n d o m  eff e ct.  
R e stri ct e d  M a xi m u m  Li k eli h o o d ( R E M L)  wit h  a n  u n str u ct ur e d  v ari a n c e -c o v ari a n c e  m atri x  will  b e 
u s e d f or  e sti m ati o n i n t h e  M M R M  a n al y si s.  If t h e fit  of t h e  m o d el  wit h t h e  u n str u ct ur e d  c o v ari a n c e 
str u ct ur e   d o e s   n ot  c o n v er g e,  t h e  f oll o wi n g  c o v ari a n c e  str u ct ur e s    will   b e  tri e d  i n   or d er   u ntil 
c o n v er g e n c e i s r e a c h e d:  T o e plit z  wit h  h et er o g e n eit y,  a ut or e gr e s si v e  wit h  h et er o g e n eit y,  T o e plit z, 
a n d  a ut or e gr e s si v e.   E a c h  d o s e  will  b e  c o m p ar e d  wit h  pl a c e b o — m o d el -b a s e d  p oi nt  e sti m at e s f or 
t h e tr e at m e nt  eff e ct s  a n d  9 5 %  c o nfi d e n c e i nt er v al s ( CI s)  will  b e  c al c ul at e d. 
 
4. 7. 2   S e c o n d ar y  Effi c a c y  A n al y s e s  
 
T h e  s e c o n d ar y  effi c a c y  a n al y s e s  will  b e  b a s e d  o n t h e  mI T T  s et  o n t h e f oll o wi n g  e n d p oi nt s:  
•   C h a n g e fr o m  B a s eli n e  t o W e e k  8  i n  P arti al  M a y o  S c or e  
•   C h a n g e fr o m  B a s eli n e  t o W e e k  8  i n  Hi st ol o gi c  A s s e s s m e nt  of  E n d o s c o pi c  Bi o p s y  
•   C h a n g e fr o m  B a s eli n e  t o W e e k  8  i n  U C EI S  S c or e  
•   C h a n g e fr o m  B a s eli n e  t o W e e k  8  i n  SI B D Q  
 
F or  e a c h  s e c o n d ar y  effi c a c y  e n d p oi n t  d e s cri b e d  a b o v e,  d e s cri pti v e  st ati sti c s  will  b e  pr e s e nt e d 
b y tr e at m e nt  a n d  c o h ort  gr o u p i n cl u di n g  m e a n,  S D,  m e di a n,  m a x,  a n d  mi n .  Si mil ar t o t h e 
pri m ar y  effi c a c y  a n al y si s,  mi x e d  m o d el r e p e at e d  m e a s ur e s ( M M R M)  a n al y s e s  will  b e  p erf or m e d  
f or v ari o u s  s e c o n d ar y  effi c a c y  e n d p oi nt s  a s  n ot e d  a b o v e . 
 
4. 8   
S af et y  A n al y s e s  
 
T h e  s af et y  a n d t ol er a bilit y  of tr e at m e nt  will  b e  a s s e s s e d  b y  s u m m ari zi n g t h e f oll o wi n g:  
•   A E s  
•   Tr e at m e nt -e m er g e nt  a d v er s e  e v e nt s ( T E A E s)   
o   B y  P T  
o   B y  S O C  
o   B y  m a xi m u m  s e v erit y   
o   B y  c o n si d er e d t o  b e r el at e d t o i n v e sti g ati o n al  pr o d u c t b y i n v e sti g at or  
•   S eri o u s  A d v er s e  E v e nt s ( S A E s)  
•   A E l e a di n g t o  di s c o nti n u ati o n  
•   Vit al  si g n s  a n d  w ei g ht  
•   L a b or at or y  m e a s ur e m e nt s  


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•   El e ctr o c ar di o gr a m s ( E C G s)  
 
All  s af et y  a n al y s e s   will  b e  b a s e d  o n  t h e  s af et y  a n al y si s  s et .   A E  r at e s   will  b e  s u m m ari z e d  b y 
tr e at m e nt  gr o u p  a n d  o v er all,  a n d   will  b e  br o k e n  d o w n  b y  s e v erit y,  s eri o u s n e s s  a n d  r el ati o n  t o 
st u d y  dr u g.    P h y si c al  e x a mi n ati o n s,  vit al  si g n s,    E C G  a n d  st a n d ar d  l a b o r at or y  r e s ult s    will  b e 
s u m m ari z e d  wit h  m e a n s,  st a n d ar d  d e vi ati o n s,  m e di a n s  a n d r a n g e s f or  c o nti n u o u s  v ari a bl e s  a n d 
wit h  c o u nt s  a n d  p er c e nt a g e s f or  c at e g ori c al  v ari a bl e s.  St ati sti c al t e st s  ar e  n ot  pl a n n e d f or  s af et y.   
 
4. 8. 1   A d v er s e  E v e nt s  
 
A n    A E  i s  d efi n e d  a s  a n y  u nt o w ar d    m e di c al  o c c urr e n c e  i n  a  s u bj e ct    w h o  i s  a d mi ni st er e d  a 
m e di ci n al  pr o d u ct  a n d t h at  d o e s  n ot  n e c e s s aril y  h a v e  a  c a u s al r el ati o n s hi p t o t h e tr e at m e nt.  All 
A E s  will  b e i n cl u d e d i n t h e  d at a li sti n g s.  V er b ati m t er m s  o n  c a s e r e p ort f or m s  wi ll  b e  m a p p e d t o 
pr ef err e d  t er m s  a n d  s y st e m  or g a n  cl a s s e s  ( S O C)  u si n g  t h e    M e di c al   Di cti o n ar y  f or   R e g ul at or y 
A cti viti e s ( M e d D R A) ( v er si o n  1 9. 1).  
 
A   Tr e at m e nt   E m er g e nt   A d v er s e   E v e nt  ( T E A E)  i s  d efi n e d  a s  a n  a d v er s e  e v e nt  t h at  o c c ur s  or 
w or s e n s  o n  or  aft er t h e  fir st  d o s e  of  st u d y  dr u g.  T E A E  s u m m ar y  will  b e  di s pl a y e d  b y  c o h ort  a n d 
tr e at m e nt.  U nl e s s  ot h er wi s e  s p e cifi e d,  s u m m ari e s t h at  ar e  di s pl a y e d  b y  S O C  a n d  pr ef err e d t er m s 
will  b e  or d er e d  al p h a b eti c all y  b y  S O C,  a n d  wit hi n  e a c h  S O C,  pr ef err e d t er m s  will  al s o  b e  o r d er e d 
al p h a b eti c all y.  S u m m ari e s  of t h e f oll o wi n g t y p e s  will  b e  pr e s e nt e d:  
•   S u bj e ct i n ci d e n c e  of  T E A E s  b y  M e d D R A  S O C  a n d  pr ef err e d t er m.  
•   S u bj e ct i n ci d e n c e  of  T E A E s  b y  M e d D R A  S O C,  pr ef err e d t er m,  a n d  s e v erit y.  S e v erit y  will 
b e r e c or d e d  a s  d e e m e d  b y  i n v e sti g at or.  At  e a c h l e v el  of  s u bj e ct  s u m m ari z ati o n,  a  s u bj e ct 
i s  cl a s sifi e d  a c c or di n g t o t h e  hi g h e st  s e v erit y if t h e  s u bj e ct r e p ort e d  o n e  or  m or e  e v e nt s. 
•   S u bj e ct i n ci d e n c e  of  st u d y  dr u g r el at e d  T E A E s  b y  M e d D R A  S O C  a n d  pr ef err e d t er m.  
•   S u bj e ct i n ci d e n c e  of  T E A E s  b y  d e s c e n di n g i n ci d e n c e  of  pr ef err e d t er m s.  
•   S u bj e ct i n ci d e n c e  of  s eri o u s  T E A E s  b y  M e d D R A  S O C  a n d  pr ef err e d t er m, if  a p pli c a bl e.  
•   S u bj e ct i n ci d e n c e  of  T E A E l e a di n g t o  e arl y t er mi n ati o n  b y  M e d D R A  S O C  a n d  pr ef err e d 
t er m, if  a p pli c a bl e. 
 
F or  e a c h  s u bj e ct  a n d f or  e a c h  a d v er s e  e v e nt, t h e  d ur ati o n  of t h e  e v e nt  will  b e  c al c ul at e d  a s:  
D ur ati o n  of  A E  =  A E  st o p  d at e  - A E  st art  d at e  +  1  
 
T h e  d ur ati o n  of  A E s  will  b e  di s pl a y e d i n t h e  d at a li sti n g.   
 
4. 8. 2   S eri o u s  A d v er s e  E v e nt s  
 
A  s eri o u s  a d v er s e  e v e nt ( S A E) i s  a n y  A E  or  s u s p e ct e d  a d v er s e r e a cti o n t h at i n t h e  vi e w  of  eit h er 
t h e i n v e sti g at or  or  S p o n s or, r e s ult s i n  a n y  of t h e f oll o wi n g  o ut c o m e s:  
•   D e at h  
•   A lif e -t hr e at e ni n g  A E: it i s  d efi n e d  a s  a n  A E  or  s u s p e ct e d  a d v er s e r e a cti o n t h at i n t h e  vi e w 
of t h e i n v e sti g at or  or  S p o n s or, it s  o c c urr e n c e  pl a c e s t h e  p ati e nt  or  s u bj e ct  at i m m e di at e 


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ri s k  of  d e at h. It  d o e s  n ot i n cl u d e  a n  A E  or  s u s p e ct e d  a d v er s e r e a cti o n t h at,  h a d it  o c c urr e d 
i n  a  m or e  s e v er e f or m,  mi g ht  h a v e  c a u s e d  d e at h.  
•   I n p ati e nt  h os pit ali z ati o n  or  pr ol o n g ati o n  of  e xi sti n g  h o s pit ali z ati o n . 
•   A  p er si st e nt  or  si g nifi c a nt  i n c a p a cit y  or  s u b st a nti al  di sr u pti o n  of  t h e  a bilit y  t o  c o n d u ct 
n or m al lif e f u n cti o n.   
•   A  c o n g e nit al  a n o m al y/ birt h  d ef e ct . 
•   I m p ort a nt    m e di c al   e v e nt s  t h at    m a y   n ot   r e s ult  i n   d e at h,  lif e-t hr e at e ni n g,   or   r e q uir e 
h o s pit ali z ati o n    m a y   b e  c o n si d er e d   s eri o u s    w h e n,   b a s e d   u p o n   a p pr o pri at e    m e di c al 
j u d g m e nt, t h e y  m a y j e o p ar di z e t h e  p ati e nt  or  s u bj e ct  a n d  m a y r e q uir e  m e di c al  or  s ur gi c al 
i nt er v e nti o n t o  pr e v e nt  o n e  of  o ut c o m e s li st e d i n t h e  a b o v e  d efi niti o n. 
 
Lif e t hr e at e ni n g:    
A n  a d v er s e  e v e nt  o r  s u s p e ct e d  a d v er s e r e a cti o n i s  c o n si d er e d “lif e-t hr e at e ni n g” if, i n t h e  vi e w  of 
eit h er t h e i n v e sti g at or  or  s p o n s or, it s  o c c urr e n c e  pl a c e s t h e  p ati e nt  or  s u bj e ct  at i m m e di at e ri s k 
of  d e at h. It  d o e s  n ot i n cl u d e  a n  a d v er s e  e v e nt  or  s u s p e ct e d  a d v er s e r e a cti o n  t h at,  h a d it  o c c urr e d 
i n  a  m or e  s e v er e f or m,  mi g ht  h a v e  c a u s e d  d e at h. 
 
H o s pit ali z ati o n:   
A n y  a d v er s e  e v e nt l e a di n g t o  h o s pit ali z ati o n  or  pr ol o n g ati o n  of  h o s pit ali z ati o n  will  b e  c o n si d er e d 
a s ‘ s eri o u s’,  U N L E S S  at l e a st  o n e  of t h e f oll o wi n g  e x c e pti o n s i s  m et:  
•   t h e  a d mi s si o n r e s ult s i n  a  h o s pit al  st a y  of l e s s t h a n  2 4  h o ur s  O R 
•   t h e  a d mi s si o n i s  pr e-pl a n n e d (i. e.,  el e cti v e  or  s c h e d ul e d  s ur g er y  arr a n g e d  pri or t o t h e  st art 
of t h e  st u d y)  
 
H o w e v er,  it  s h o ul d  b e  n ot e d  t h at  i n v a si v e  tr e at m e nt  d uri n g  a n y   h o s pit ali z ati o n    m a y  f ulfill  t h e 
crit eri a  of ‘ m e di c all y i m p ort a nt’  a n d  a s  s u c h  m a y  b e r e p ort a bl e  a s  a  S A E  d e p e n d e nt  o n  cli ni c al 
j u d g m e nt. 
 
Di s a bilit y  m e a n s  a  s u b st a nti al  di sr u pti o n  of  a  p er s o n’ s  a bilit y t o  c o n d u ct  n or m al lif e f u n cti o n s.  
 
I m p ort a nt  m e di c al e v e nt:   
A s  g ui d a n c e  f or  d et er mi n ati o n  of  i m p ort a nt    m e di c al  e v e nt s  s e e  t h e  ‘ W H O    A d v er s e    R e a cti o n 
T er mi n ol o g y  –  Criti c al   T er m s  Li st’.   T h e s e  t er m s  eit h er  s e e  or    mi g ht  b e  i n di c ati v e  of  a  s eri o u s 
di s e a s e   st at e.    S u c h   r e p ort e d   e v e nt s    w arr a nt   s p e ci al   att e nti o n   b e c a u s e   of   t h eir   p o s si bl e 
a s s o ci ati o n  wit h  a  s eri o u s  di s e a s e  st at e  a n d  m a y l e a d t o  m or e  d e ci si v e  a cti o n t h a n  r e p ort s  o n 
ot h er t er m s.   
 
4. 8. 3   Cli ni c al  L a b or at or y  E v al u ati o n     
 
A b n or m al l a b or at or y fi n di n g s  wit h o ut  cli ni c al  si g nifi c a n c e ( b a s e d  o n t h e  i n v e sti g at or' s j u d g m e nt) 
s h o ul d  n ot  b e r e c or d e d  a s  a d v er s e  e v e nt s;  h o w e v er, l a b or at or y  v al u e  c h a n g e s r e q uiri n g t h er a p y 
or  a dj u st m e nt i n  pri or t h er a p y  ar e  c o n si d er e d  a s  a d v er s e  e v e nt s.  
A d v er s e  e v e nt s  will  b e r e vi e w e d  c o nti n u o u sl y t hr o u g h o ut t h e  st u d y.  
 


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L a b or at or y r e s ult s ( h e m at ol o g y,  s er u m  c h e mi str y  a n d  uri n al y si s)  will  b e  pr e s e nt e d i n  d at a li sti n g. 
A b n or m al  v al u e s   will  b e  fl a g g e d  a s  hi g h  or  l o w  r el ati v e  t o  t h e  l o c al  l a b  n or m al  r a n g e s,   w h er e 
a p pli c a bl e.  V al u e s t h at  ar e  d e e m e d  a s  a b n or m al,  cli ni c all y  si g n ifi c a nt  will  al s o  b e fl a g g e d.  
 
L a b or at or y  r e s ult s    will  b e  s u m m ari z e d  u si n g  d e s cri pti v e  st ati sti c s  at  b a s eli n e  a n d  p o st -d o s e. 
C h a n g e s fr o m  b a s eli n e  will  al s o  b e  s u m m ari z e d.  O nl y  n o n -mi s si n g  a s s e s s m e nt s  at  b a s eli n e  a n d 
p o st -d o s e  will  b e  a n al y z e d.   
 
A n y  cli n i c all y  si g nifi c a nt l a b  a b n or m aliti e s  will  b e  d et er mi n e d  b y t h e  Pri n ci p al I n v e sti g at or  a n d  will 
b e r e p ort e d i n t h e  A E t a bl e  s u m m ari e s.   
 
4. 8. 4   Vit al  Si g n s     
 
Vit al  si g n s  will  b e  s u m m ari z e d  u si n g  d e s cri pti v e  st ati sti c s  at  b a s eli n e  a n d  at  e a c h  p o st -d o s e ti m e 
p oi nt .  C h a n g e s fr o m  b a s eli n e  will  al s o  b e  s u m m ari z e d.  
 
4. 8. 5   El e ctr o c ar di o gr a m     
 
E C G  p ar a m et er s ( n u m eri c)  will  b e  s u m m ari z e d  u si n g  d e s cri pti v e  st ati sti c s  at  b a s eli n e  a n d  at 
e a c h  p o st -d o s e ti m e  p oi nt.  C h a n g e s fr o m  b a s eli n e  will  al s o  b e  s u m m ari z e d.   
  
4. 9   
P D  A n al y s e s  
 
N o f or m al  st ati sti c al  a n al y si s  of  P D  e n d p oi nt s (i. e.  bi o m ar k er s)  will  b e  p erf or m e d.  P D  d at a fr o m 
e a c h  a s s a y  will  b e li st e d.   
 
4. 1 0   P K  A n al y s e s  
 
4. 1 0. 1   
M e a s ur e m e nt s  a n d  C oll e cti o n  S c h e d ul e  
 
Pl a s m a : 
Bl o o d  s a m pl e s f or t h e  d et er mi n ati o n  of  pl a s m a  B B T -4 0 1 -1 S  c o n c e ntr ati o n s  will  b e  c oll e ct e d  at 
Vi sit  2 ( W e e k  0)  a n d  Vi sit  3 ( W e e k  4)  at  pr e d o s e  a n d  at  3  a n d  6  h o ur s  p o st d o s e  a n d  Vi sit  4 
( W e e k  8)  at  pr e d o s e.   
 
Ti s s u e:   
Ti s s u e  s a m pl e s  will  b e  c oll e ct e d  fr o m  d e s c e n di n g  c ol o n  a n d r e ct u m d uri n g  e n d o s c o p y 
pr o c e d ur e s  of  Vi sit  1 ( S cr e e ni n g)  a n d  Vi sit  4 ( W e e k  8).    
 
4. 1 0. 2   
Bi o a n al yti c al  M et h o d s  
 
Pl a s m a  a n d  ti s s u e  c o n c e ntr ati o n s  of   B B T -4 0 1 -1 S    will  b e  d et er mi n e d  u si n g  hi g h  p erf or m a n c e 
li q ui d  c hr o m at o gr a p h y-t a n d e m  m a s s  s p e ctr o m etr y ( H P L C  M S/ M S)  m et h o d s.  Pl a s m a  m et h o d  w a s 
v ali d at e d    wit h  r e s p e ct  t o  a c c ur a c y,  pr e ci si o n,  li n e arit y,  s e n siti vit y,  a n d  s p e cifi cit y  at    C el eri o n, 


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Li n c ol n,    N e br a s k a.    T h e   a n al yti c al  r a n g e  (l o w er  li mit   of   q u a ntit ati o n  [ L L O Q]  –   u p p er  li mit   of 
q u a ntit ati o n [ U L O Q]) f or  pl a s m a  B B T -4 0 1 -1 S  c o n c e ntr ati o n  i s  e xp e ct e d t o  b e  1. 0 0  –  1 0 0 0  n g/ m L.  
Ti s s u e  m et h o d  will  b e  q u alifi e d t o  d et e ct t h e  ti s s u e c o n c e ntr ati o n s  of  B B T -4 0 1 -1 S  at  1. 0 0  –  1 0 0 0 
n g/ g r a n g e  u si n g  bi o p s y  s a m pl e s  of  a p pr o xi m at el y  2 0  m g.  
 
 
4. 1 0. 3   
P l a s m a/ Ti s s u e C o n c e ntr ati o n s  
 
Pl a s m a  a n d  ti s s u e   B B T -4 0 1 -1 S   c o n c e ntr ati o n s   a s   d et er mi n e d   at  t h e   c oll e cti o n  ti m e s   a n d 
a n al y z e d  p er  t h e  bi o a n al yti c al    m et h o d s  d e s cri b e d  i n   S e cti o n 4. 1 0. 1  a n d   S e cti o n  4. 1 0 . 2   will  b e 
s u m m ari z e d.  
 
4. 1 0. 4   
P ar a m et er  C al c ul ati o n  
 
D u e t o li mit e d  s a m pli n g ti m e  p oi nt s t o  c al c ul at e  P K  p ar a m et er s, t h er e  will  b e  n o  P K  p ar a m et er 
c al c ul ati o n  s u c h  a s  T m a x ,  Cm a x ,  A U C f or  pl a s m a  or ti s s u e  c o n c e ntr ati o n.  
 
4. 1 0. 5   
D at a  S u m m ari z ati o n  a n d  Pr e s e nt ati o n  
 
Pl a s m a  a n d  ti s s u e c o n c e ntr ati o n s  of  B B T -4 0 1 -1 S  will  b e li st e d  b y ti m e  p oi nt  a n d  v i sit  s c h e d ul e 
( e. g.,  W 0,  W 4  et c),  r e s p e cti v el y, f or  all  s u bj e ct s w h o  r e c ei v e  a  d ail y  or al  d o s e  of  B B T  4 0 1-1 S . 
Pl a s m a  a n d  ti s s u e   c o n c e ntr ati o n s   of    B B T -4 0 1 -1 S    will   b e   pr e s e nt e d    wit h  t h e  s a m e  l e v el   of 
pr e ci si o n  a s  r e c ei v e d  fr o m  t h e  bi o a n al yti c al  l a b or at or y.    All    B L Q  a n d    mi s si n g  v al u e s    will  b e 
pr e s e nt e d  a s “ B L Q”  or “.”, r e s p e cti v el y, i n t h e  c o n c e ntr ati o n li sti n g s  a n d f o ot n ot e d  a c c or di n gl y.   
 
B B T -4 0 1 -1 S  p l a s m a a n d ti s s u e  c o n c e ntr ati o n s  will  b e li st e d  a n d  s u m m ari z e d  b y tr e at m e nt  ( d o s e 
gr o u p)  f or  all  s u bj e ct s, if  a p pr o pri at e.  S u m m ar y  st ati sti c s, i n cl u di n g  s a m pl e  si z e  ( n),  arit h m eti c 
m e a n  ( m e a n),  st a n d ar d  d e vi ati o n  ( S D),  c o effi ci e nt  of  v ari ati o n  ( C V %),    mi ni m u m,    m e di a n,  a n d 
m a xi m u m  will  b e  c al c ul at e d f or  B B T -4 0 1 -1 S  pl a s m a  a n d ti s s u e  c o n c e ntr ati o n s , if  a p pr o pri at e. T h e 
l e v el  of  pr e ci si o n f or  e a c h c o n c e ntr ati o n  st ati sti c  will  b e  pr e s e nt e d  a s f oll o w s:  mi ni m u m/ m a xi m u m , 
m e a n,  m e di a n  a n d  S D  i n  s a m e  pr e ci si o n  a s i n  bi o a n al yti c al  d at a,  n  will  b e  pr e s e nt e d  a s  a n i nt e g er 
a n d  C V %  will  b e  pr e s e nt e d t o  1  d e ci m al  pl a c e.  
 
4. 1 0. 6   
St ati sti c al  A n al y si s  of  Pl a s m a/ Ti s s u e  C o n c e ntr ati o n s  
 
N o  f or m al  st ati sti c al  a n al y si s  will  b e  p erf or m e d f or  pl a s m a/ti s s u e  c o n c e ntr ati o n s. 
 
4. 1 1   I nt eri m  A n al y si s  a n d  D at a  M o nit ori n g 
 
T h er e  will  b e  n o f or m all y  pl a n n e d i nt eri m  a n al y s e s.  H o w e v er,  i n  or d er t o  s el e ct t h e  2 n d  c o h ort 
d o s e,  if  1 2t h  p ati e nt ( 7 5 %)  of  1 st  c o h ort  c o m pl et e s  Vi sit  4 ( W e e k  8),  u n bli n di n g  of  1 2  p ati e nt s  will 
b e  p erf or m e d  wit hi n  2  w e e k s  aft er  Vi sit  4.  T h e  u n bli n di n g i nf or m ati o n  will  b e  o nl y  pr o vi d e d t o t h e 
S p o n s or f or t h e  a n al y si s  d et er mi ni n g t h e  d o s e  of  n e xt  c o h ort.   Li k e wi s e,  aft er  1 2t h  p ati e nt  of  2 n d 
C o h ort  c o m pl et e s  Vi sit  4,  si mil ar  u n bli n di n g  of  2 n d  c o h ort  will  o c c ur i n  or d er t o  s el e ct t h e  d o s e f or 


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t h e  3r d  c o h ort.  T h e  a n al y si s  of t h e  u n bli n d e d  d at a  of  1 st  a n d/ or  2 n d  c o h ort  will  b e  a n al y z e d  b y  a 
t hir d-p art y i n d e p e n d e nt  st ati sti ci a n. I n cl u di n g t h e  st u d y  st ati sti ci a n,  m o st  of t h e  k e y  p er s o n n el  of 
t h e  st u d y  w h o  dir e ctl y  p arti ci p at e i n  c o n d u cti n g  of t h e  st u d y  s h o ul d  b e r e m ai n e d  bli n d e d.   
 
4. 1 2   H a n dli n g  of  Dr o p o ut s  or  Mi s si n g  D at a  
 
N o i m p ut ati o n s  will  b e  m a d e f or  mi s si n g  v a l u e s.  
 
4. 1 3   S u b gr o u p  A n al y si s  
 
T h er e  ar e  n o  pl a n n e d  s u b gr o u p  effi c a c y  a n al y s e s.   
 
4. 1 4   M ulti pl e  C o m p ari s o n/ M ulti pli cit y  
 
N o  a dj u st m e nt s f or  m ulti pli cit y  or  m ulti pl e t e sti n g  will  b e  m a d e.   
 
  
5   
C H A N G E S  T O  P R O T O C O L -S P E CI FI E D  A N A L Y S E S  
 
N o  c h a n g e s t o  pr ot o c ol -s p e cifi e d  a n al y s e s  ar e  pl a n n e d.  
 
 
6   
LI S T  O F  T A B L E S  A N D  FI G U R E S  
 
Li st  of  T a bl e s  
 
I C H 
H e a di n g  
T a bl e  
N u m b er  
T a bl e  D e s cri pti o n  
1 4. 1   
 
D E M O G R A P HI C  
  
1 4. 1. 1   
S u m m ar y  of  P ati e nt  Di s p o siti o n  ( All  P ati e nt s) 
  
1 4. 1. 2   
S u m m ar y  of  D e m o gr a p hi c  a n d  B a s eli n e  C h ar a ct eri sti c s  ( mI T T A n al y si s  s et ) 
  
1 4. 1. 3   
S u m m ar y  of  M e di c al  Hi st or y  ( mI T T A n al y si s  s et ) 
  
1 4. 1. 4   
S u m m ar y  of  Pri or  M e di c ati o n s  ( mI T T A n al y si s  s et ) 
  
1 4. 1. 5   
S u m m ar y  of  C o n c o mit a nt  M e di c ati o n s  ( mI T T A n al y si s  s et ) 
1 4. 2   
 
E F FI C A C Y  
1 4. 2. 1   
 
Pri m ar y  Effi c a c y  
  
1 4. 2. 1. 1   
S u m m ar y  of  C h a n g e  of  T ot al  M a y o  S c or e fr o m  B a s eli n e t o  W e e k  8 ( mI T T 
A n al y si s  s et ) 
  
1 4. 2. 1 . 2  
S u m m ar y  of  C h a n g e  of  T ot al  M a y o  S c or e fr o m  B a s eli n e t o  W e e k  8 ( P P  
A n al y si s  s et ) 
1 4. 2. 2   
 
S e c o n d ar y  Effi c a c y  
  
1 4. 2. 2. 1 . 1  S u m m ar y  of  C h a n g e  of  P arti al  M a y o  S c or e fr o m  B a s eli n e t o  W e e k  8 ( mI T T 
A n al y si s  s et ) 
  
1 4. 2. 2. 1 . 2  S u m m ar y  of  C h a n g e  of  P arti al  M a y o  S c or e fr o m  B a s eli n e t o  W e e k  8 ( P P  
A n al y si s  s et ) 


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B a s eli n e t o  W e e k  8 ( mI T T  A n al y si s  s et ) 
  
1 4. 2. 2. 2 . 2  S u m m ar y  of  C h a n g e  of  Hi st ol o gi c  A s s e s s m e nt  of  E n d o s c o pi c  Bi o p s y fr o m 
B a s eli n e t o  W e e k  8 ( P P  A n al y si s  s et ) 
  
1 4. 2. 2. 3 . 1  S u m m ar y  of  C h a n g e  of  Ul c er ati v e  C oliti s  E n d o s c o pi c I n d e x  of  S e v erit y ( U C EI S) 
S c or e fr o m  B a s eli n e t o  W e e k  8 ( mI T T  A n al y si s  s et ) 
  
1 4. 2. 2. 3 . 2  S u m m ar y  of  C h a n g e  of  Ul c er ati v e  C oliti s  E n d o s c o pi c I n d e x  of  S e v erit y ( U C EI S) 
S c or e fr o m  B a s eli n e t o  W e e k  8 ( P P  A n al y si s  s et ) 
  
1 4. 2. 2. 4 . 1  S u m m ar y  of  C h a n g e  of  S h ort I nfl a m m at or y  B o w el  Di s e a s e  Q u e sti o n n air e 
( SI B D Q) fr o m  B a s eli n e t o  W e e k  8 ( mI T T A n al y si s  s et ) 
  
1 4. 2. 2. 4 . 2  S u m m ar y  of  C h a n g e  of  S h ort I nfl a m m at or y  B o w el  Di s e a s e  Q u e sti o n n air e 
( SI B D Q) fr o m  B a s eli n e t o  W e ek  8 ( P P  A n al y si s  s et ) 
1 4. 2. 3   
 
E x pl or at or y  Effi c a c y  
  
1 4. 2. 3. 1   
S u m m ar y  of  C h a n g e  of  C o n c e ntr ati o n  of  Bi o m ar k er s fr o m  B a s eli n e t o  W e e k  8 
( mI T T A n al y si s  s et ) 
  
1 4. 2. 3. 2   
S u m m ar y  of  C h a n g e  of  C o n c e ntr ati o n  of  Bi o m ar k er s fr o m  B a s eli n e t o  W e e k  8 
(P P  A n al y si s  s et ) 
1 4. 3    
 
S A F E T Y  
1 4. 3. 1   
 
Di s pl a y  of  A d v er s e  E v e nt s  
  
1 4. 3. 1. 1   
O v er all  S u m m ar y  of  Tr e at m e nt -E m er g e nt  A d v er s e  E v e nt s  u p t o  W e e k  8 ( S af et y 
A n al y si s  s et ) 
  
1 4. 3. 1. 2   
S u m m ar y  of  Tr e at m e nt -E m er g e nt  A d v er s e  E v e nt s  u p t o  W e e k  8  b y  S y st e m 
Or g a n  Cl a s s  a n d  Pr ef err e d  T er m ( S af et y  A n al y si s  s et ) 
  
1 4. 3. 1. 3   
S u m m ar y  of  Tr e at m e nt -E m er g e nt  A d v er s e  E v e nt s  u p t o  W e e k  8  b y  S y st e m 
Or g a n  Cl a s s,  Pr ef err e d  T er m,  a n d  S e v erit y ( S af et y  A n al y s i s  s et) 
  
1 4. 3. 1. 4   
S u m m ar y  of  Tr e at m e nt -E m er g e nt  A d v er s e  E v e nt s  u p t o  W e e k  8  b y  S y st e m 
Or g a n  Cl a s s,  Pr ef err e d  T er m,  a n d  R el ati o n s hi p t o  St u d y  Dr u g ( S af et y  A n al y si s 
s et ) 
  
1 4. 3. 1. 5   
S u m m ar y  of  Tr e at m e nt -E m er g e nt  S eri o u s  A d v er s e  E v e nt s  u p t o  W e e k  8  b y 
S y st e m  Or g a n  Cl a s s  a n d  Pr e f err e d  T er m ( S af et y A n al y si s  s et ) 
  
1 4. 3. 1. 6   
S u m m ar y  of  Tr e at m e nt -E m er g e nt  A d v er s e  E v e nt s  u p t o  W e e k  8  L e a di n g t o 
St u d y  Di s c o nti n u ati o n  b y  S y st e m  Or g a n  Cl a s s  a n d  Pr ef err e d  T er m ( S af et y 
A n al y si s  s et ) 
1 4. 3. 2   
 
L a b or at or y  T e sti n g s  
  
1 4. 3. 2. 1   
S u m m ar y  of  V al u e s  a n d  C h a n g e s  of  H e m at ol o g y  P ar a m et er s  b y  Vi sit ( S af et y 
A n al y si s  s et ) 
  
1 4. 3. 2. 2   
S u m m ar y  of  V al u e s  a n d  C h a n g e s  of  C h e mi str y  P ar a m et er s  b y  Vi sit ( S af et y 
A n al y si s  s et ) 
1 4. 3. 3   
 
Vit al  Si g n s,  E C G  D at a,  P h y si c al  E x a mi n ati o n   
  
1 4. 3. 3 . 1  
S u m m ar y  of  Vit al  Si g n  P ar a m et er s  b y  Vi sit ( S af et y  A n al y si s  s et ) 
  
1 4. 3. 3. 2   
S u m m ar y  of  El e ctr o c ar di o gr a m  P ar a m et er s  b y  Vi sit ( S af et y  A n al y si s  s et ) 
  
1 4. 3. 3. 3   
S u m m ar y  of  P h y si c al  E x a mi n ati o n  b y  Vi sit ( S af et y  A n al y si s  s et ) 
1 4. 4    
 
P h ar m a c o ki n eti c s  
1 4. 4 . 1  
 
Pl a s m a  C o n c e ntr ati o n  
  
1 4. 4 . 1. 1  
Pl a s m a  B B T -4 0 1 -1 S  C o n c e ntr ati o n s ( n g/ m L)  F oll o wi n g t h e  A d mi ni str ati o n  of 
B B T -4 0 1 -1 S  or  Pl a c e b o  ( P K  A n al y si s  s et) 
1 4. 4 . 2  
 
Ti s s u e  C o n c e ntr ati o n  
  
1 4. 4. 2 . 1  
Ti s s u e  B B T -4 0 1 -1 S  C o n c e ntr ati o n s ( n g/ g )  F oll o wi n g t h e  A d mi ni str ati o n  of B B T -
4 0 1 -1 S  or  Pl a c e b o  ( P K  A n al y si s  s et) 


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
2 0 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
 
Li st  of  D at a  Li sti n g s  
 
I C H 
H e a di n g  
Li sti n g 
N u m b er  
Li sti n g  D e s cri pti o n  
1 6. 2   
 
P A TI E N T  D A T A  LI S TI N G S  
1 6. 2. 1   
 
Di s c o nti n u e d  P ati e nt s  
  
1 6. 2. 1. 1   
P ati e nt  Di s p o siti o n  
1 6. 2. 2   
 
Pr ot o c ol  D e vi ati o n s  
  
1 6. 2. 2. 1   
I n cl u si o n/ E x cl u si o n  Crit eri a  Fi n di n g s –  D e vi ati o n s  
1 6. 2. 3   
 
P ati e nt s  E x cl u d e d fr o m t h e  E ffi c a c y  S u m m ar y  
1 6. 2. 4   
 
D e m o gr a p hi c s  a n d  B a s eli n e  C h ar a ct eri sti c s  
  
1 6. 2. 4. 1   
D e m o gr a p hi c s  a n d  B a s eli n e  C h ar a ct eri sti c s  
  
1 6. 2. 4. 2   
M e di c al  Hi st or y  
  
1 6. 2. 4. 3   
Pri or  a n d  C o n c o mit a nt  M e di c ati o n s  
1 6. 2. 5   
 
C o m pli a n c e  a n d/ or  Dr u g  A d mi ni str ati o n  D at a  
  
1 6. 2. 5. 1. 1   
St u d y  Dr u g  A d mi ni str ati o n  a n d  L o g   
1 6. 2. 6   
 
I n di vi d u al E ffi c a c y R e s p o n s e  D at a  
  
1 6. 2. 6. 1   
T ot al  M a y o  S c or e   
  
1 6. 2. 6. 2   
P arti al  M a y o  S c or e  
  
1 6. 2. 6. 3   
Hi st ol o gi c  A s s e s s m e nt  of  E n d o s c o pi c  Bi o p s y  
  
1 6. 2. 6. 4   
Ul c er ati v e  C oliti s  E n d o s c o pi c I n d e x  of  S e v erit y  
  
1 6. 2. 6. 5   
S h ort I nfl a m m at or y  B o w el  Di s e a s e  Q u e sti o n n air e   
  
1 6. 2. 6. 6   
Bi o m ar k er s   
1 6. 2. 7   
 
A d v er s e  E v e nt s  Li sti n g s  
  
1 6. 2. 7. 1   
A d v er s e  E v e nt s  
  
1 6. 2. 7. 2   
S eri o u s  A d v er s e  E v e nt s  
  
1 6. 2. 7. 3   
A d v er s e  E v e nt s  L e a di n g t o  P er m a n e nt  Wit h dr a w al  of  St u d y  Tr e at m e nt  or 
Di s c o nti n u ati o n fr o m t h e  St u d y   
  
1 6. 2. 7. 4   
A d v er s e  E v e nt s  L e a di n g t o  D e at h  
1 6. 2. 8   
 
I n di vi d u al  L a b  M e a s ur e s 
  
1 6. 2. 8. 1   
H e m at ol o g y  
  
1 6. 2. 8. 2   
C h e mi str y   
  
1 6. 2. 8. 3   
Vit al  Si g n s  
  
1 6. 2. 8. 4   
El e ctr o c ar di o gr a m  
  
1 6. 2. 8. 5   
P h y si c al  E x a mi n ati o n  
1 6. 2. 9   
 
P h ar m a c o ki n eti c s  
  
1 6. 2. 9. 1   
I n di vi d u al  Pl a s m a C o n c e ntr ati o n  D at a   
  
1 6. 2. 9. 2   
I n di vi d u al Ti s s u e  C o n c e ntr ati o n  D at a   
1 6. 2. 1 0   
 
Ot h er  Mi s c ell a n e o u s  D at a  
  
1 6. 2. 1 0 . 1  
R a n d o mi z ati o n  
  
1 6. 2. 1 0 . 2  
I P 
  
1 6. 2. 1 0 . 3    
I n v e sti g at or  Si g n at ur e  
 
 
 


C o nfi d e nti al  
1 /6 1   
 
  
v 2. 1  Fi n al , 2 2  J u l 2 0 2 0  
 
 
 
T A B L E S,  FI G U R E S,  A N D  LI S TI N G S  S H E L L S  
 
 
 
St u d y  Titl e:   A  R a n d o mi z e d,  D o u bl e -bli n d,  Pl a c e b o -
c o ntr oll e d,  P h a s e  2 a  St u d y t o  E v al u at e t h e 
Effi c a c y  a n d  S af et y  of  B B T -4 0 1 -1 S i n  P ati e nt s 
wit h  A cti v e  Ul c er ati v e  C oliti s  
   
S p o n s or:   Bri d g e  Bi ot h er a p e uti c s, I n c.  
 
C’ s  T o w er  # 3 0 3  
5 8,  P a n g y o -r o  2 5 5  b e o n-gil,  B u n d a n g -g u   
 S e o n g n a m -si,  G y e o n g gi -d o,  R e p u bli c  of  K or e a  
   
U S  R e pr e s e nt ati v e:   K C R N  R e s e ar c h , L L C . 
  2 0 2 5 1  C e nt ur y  B o ul e v ar d  S uit e  3 2 5  
G er m a nt o w n,  M D  2 0 8 7 4  
   
Pr ot o c ol  N u m b er:   B B T 4 0 1 -U C -U S 0 2  
Pr oj e ct  C o d e :  B B T 4 0 1 P 2 A  
   
V er si o n :  2 .1  Fi n al  
D at e :  2 2  J u l 2 0 2 0  


C o nfi d e nti al  
2 /6 1   
  
  
v 2. 1  Fi n al , 2 2  J u l 2 0 2 0  
T a bl es  a n d  Listi n gs  t o  B e  G e n e r at e d 
 
I C H H e a di n g  
T a bl e  
N u m b e r  
T a bl e  D es c ri pti o n  
1 4. 1   
 
D E M O G R A P HI C  
 
1 4. 1. 1   
S u m m ar y  of  P ati e nt  Dis p ositi o n  ( All  P ati e nts) 
 
1 4. 1. 2   
S u m m ar y  of  D e m o gr a p hi c  a n d  B as eli n e  C h ar a ct eristi cs ( mI T T  A n al ysis s et)  
 
1 4. 1. 3   
S u m m ar y  of  M e di c al  Hist or y ( mI T T  A n al ysis s et)  
 
1 4. 1. 4   
S u m m ar y  of  Pri or  M e di c ati o ns ( mI T T  A n al ysis s et)  
 
1 4. 1. 5   
S u m m ar y  of  C o n c o mit a nt  M e di c ati o ns ( mI T T  A n al ysis s et)  
1 4. 2   
 
E F FI C A C Y  
1 4. 2. 1   
 
P ri m a r y  Effi c a c y  
 
1 4. 2. 1. 1   
S u m m ar y  of  C h a n g e  of  T ot al  M a y o  S c or e fr o m  B as eli n e t o  W e e k  8 ( mI T T  A n al ysis s et)  
 
1 4. 2. 1. 2   
S u m m ar y  of  C h a n g e  of  T ot al  M a y o  S c or e fr o m  B as eli n e t o  W e e k  8 ( P P  A n al ysis s et)  
1 4. 2. 2   
 
S e c o n d a r y  Effi c a c y  
 
1 4. 2. 2. 1. 1   
S u m m ar y  of  C h a n g e  of  P arti al  M a y o  S c or e fr o m  B as eli n e t o  W e e k  8 ( mI T T  A n al ysis s et)  
 
1 4. 2. 2. 1. 2   
S u m m ar y  of  C h a n g e  of  P arti al  M a y o  S c or e fr o m  B as eli n e t o  W e e k  8 ( P P  A n al ysis s et)  
 
1 4. 2. 2. 2. 1   
S u m m ar y  of  C h a n g e  of  Hist ol o gi c  Ass ess m e nt  of  E n d os c o pi c  Bi o ps y fr o m  B as eli n e t o  W e e k  8 ( mI T T  A n al ysis s et)  
 
1 4. 2. 2. 2. 2   
S u m m ar y  of  C h a n g e  of  Hist ol o g i c  Ass ess m e nt  of  E n d os c o pi c  Bi o ps y fr o m  B as eli n e t o  W e e k  8 ( P P  A n al ysis s et) 
 
1 4. 2. 2. 3. 1   
S u m m ar y  of  C h a n g e  of  Ul c er ati v e  C olitis  E n d os c o pi c I n d e x  of  S e v erit y ( U C EI S)  S c or e fr o m  B as eli n e t o  W e e k  8 ( mI T T 
A n al ysis s et)  
 
1 4. 2. 2. 3. 2   
S u m m ar y  of  C h a n g e  of  Ul c er ati v e  C olitis  E n d os c o pi c I n d e x  of  S e v erit y ( U C EI S)  S c or e fr o m  B as eli n e t o  W e e k  8 ( P P 
A n al ysis s et)  
 
1 4. 2. 2. 4. 1   
S u m m ar y  of  C h a n g e  of  S h ort I nfl a m m at or y  B o w el  Dis e as e  Q u esti o n n air e ( SI B D Q) fr o m  B as eli n e t o  W e e k  8 ( mI T T 
A n al ysis s et)  
 
1 4. 2. 2. 4. 2   
S u m m ar y  of  C h a n g e  of  S h ort I nfl a m m at or y  B o w el  Dis e as e  Q u esti o n n air e ( SI B D Q) fr o m  B as eli n e t o  W e e k  8 ( P P 
A n al ysis s et)  
1 4. 2. 3   
 
E x pl o r at o r y  Effi c a c y  
 
1 4. 2. 3. 1   
S u m m ar y  of  C h a n g e  of  C o n c e ntr ati o n  of  Bi o m ar k ers fr o m  B as eli n e t o  W e e k  8 ( mI T T  A n al ysis s et)  
 
1 4. 2. 3. 2   
S u m m ar y  of  C h a n g e  of  C o n c e ntr ati o n  of  Bi o m ar k ers fr o m  B as eli n e t o  W e e k  8 ( P P  A n al ysis s et)  
1 4. 3    
 
S A F E T Y  
1 4. 3. 1   
 
Dis pl a y  of  A d v e rs e  E v e nts  
 
1 4. 3. 1. 1   
O v er all  S u m m ar y  of  Tr e at m e nt -E m er g e nt  A d v ers e  E v e nts  u p t o  W e e k  8  ( S af et y  A n al ysis s et) 
 
1 4. 3. 1. 2   
S u m m ar y  of  Tr e at m e nt -E m er g e nt  A d v ers e  E v e nts  u p t o  W e e k  8  b y  S yst e m  Or g a n  Cl ass  a n d  Pr ef err e d  T er m ( S af et y 
A n al ysis s et)  
 
1 4. 3. 1. 3   
S u m m ar y  of  Tr e at m e nt -E m er g e nt  A d v ers e  E v e nts  u p t o  W e e k  8  b y  S yst e m  Or g a n  Cl ass,  Pr ef err e d  T er m,  a n d  S e v erit y 
( S af et y  A n al ysis s et) 


C o nfi d e nti al  
3 /6 1   
  
  
v 2. 1  Fi n al , 2 2  J u l 2 0 2 0  
 
1 4. 3. 1. 4   
S u m m ar y  of  Tr e at m e nt -E m er g e nt  A d v ers e  E v e nts  u p t o  W e e k  8  b y  S yst e m  Or g a n  Cl ass,  Pr ef err e d  T er m,  a n d 
R el ati o ns hi p t o  St u d y  Dr u g ( S af et y  A n al ysis s et)  
 
1 4. 3. 1. 5   
S u m m ar y  of  Tr e at m e nt -E m er g e nt  S er i o us  A d v ers e  E v e nts  u p t o  W e e k  8  b y  S yst e m  Or g a n  Cl ass  a n d  Pr ef err e d  T er m 
( S af et y  A n al ysis s et) 
 
1 4. 3. 1. 6   
S u m m ar y  of  Tr e at m e nt -E m er g e nt  A d v ers e  E v e nts  u p t o  W e e k  8  L e a di n g t o  St u d y  Dis c o nti n u ati o n  b y  S yst e m  Or g a n  Cl ass 
a n d  Pr ef err e d  T er m ( S af et y  A n al ysis  s et) 
1 4. 3. 2   
 
L a b o r at o r y  T esti n gs  
 
1 4. 3. 2. 1   
S u m m ar y  of  V al u es  a n d  C h a n g es  of  H e m at ol o g y  P ar a m et ers  b y  Visit ( S af et y  A n al ysis s et)  
 
1 4. 3. 2. 2   
S u m m ar y  of  V al u es  a n d  C h a n g es  of  C h e mistr y  P ar a m et ers  b y  Visit ( S af et y  A n al ysis s et)  
1 4. 3. 3   
 
Vit al  Si g ns,  E C G  D at a,  P h ysi c al  E x a mi n ati o n   
 
1 4. 3. 3 . 1  
S u m m ar y  of  Vit al  Si g n  P ar a m et ers  b y  Visit ( S af et y  A n al ysis s et)  
 
1 4. 3. 3. 2   
S u m m ar y  of  El e ctr o c ar di o gr a m  P ar a m et ers  b y  Visit ( S af et y  A n al ysis s et)  
 
1 4. 3. 3. 3   
S u m m ar y  of  P h ysi c al  E x a mi n ati o n  b y  Visit ( S af et y  A n al ysis s et)  
1 4. 4    
 
P h a r m a c o ki n eti cs  
1 4. 4. 1   
 
Pl as m a  C o n c e nt r ati o n  
 
1 4. 4. 1. 1   
Pl as m a  B B T -4 0 1 -1 S  C o n c e ntr ati o ns ( n g/ m L)  F oll o wi n g t h e  A d mi nistr ati o n  of  B B T -4 0 1 -1 S  or  Pl a c e b o  ( P K  A n al ysis s et) 
1 4. 4. 2   
 
Tiss u e  C o n c e nt r ati o n  
 
1 4. 4. 2. 1   
Tiss u e  B B T -4 0 1 -1 S  C o n c e ntr ati o ns ( n g/ g)  F oll o wi n g t h e  A d mi nistr ati o n  of  B B T -4 0 1 -1 S  or  Pl a c e b o  ( P K  A n al ysis s et) 
 
 


C o nfi d e nti al  
4 /6 1   
  
  
v 2. 1  Fi n al , 2 2  J u l 2 0 2 0  
I C H  H e a di n g  
Listi n g  N u m b e r  
Listi n g  D es c ri pti o n  
1 6. 2   
 
P A TI E N T  D A T A  LI S TI N G S  
1 6. 2. 1   
 
Dis c o nti n u e d  P ati e nts  
 
1 6. 2. 1. 1  
P ati e nt  Dis p ositi o n  
1 6. 2. 2   
 
P r ot o c ol  D e vi ati o ns  
 
1 6. 2. 2. 1  
I n cl usi o n/ E x cl usi o n  Crit eri a  Fi n di n gs –  D e vi ati o ns  
1 6. 2. 3   
 
P ati e nts  E x cl u d e d f r o m t h e  E ffi c a c y  S u m m a r y  
1 6. 2. 4   
 
D e m o g r a p hi c s  a n d  B as eli n e  C h a r a ct e risti cs  
 
1 6. 2. 4. 1  
D e m o gr a p hi cs  a n d  B as eli n e  C h ar a ct eristi cs  
 
1 6. 2. 4. 2  
M e di c al  Hist or y  
 
1 6. 2. 4. 3  
Pri or  a n d  C o n c o mit a nt  M e di c ati o ns  
1 6. 2. 5   
 
C o m pli a n c e  a n d/ o r  D r u g  A d mi nist r ati o n  D at a  
 
1 6. 2. 5. 1. 1   
St u d y  Dr u g  A d mi nistr ati o n  a n d  L o g   
1 6. 2. 6   
 
I n di vi d u al E ffi c a c y R es p o ns e  D at a  
 
1 6. 2. 6. 1  
T ot al  M a y o  S c or e   
 
1 6. 2. 6. 2  
P arti al  M a y o  S c or e  
 
1 6. 2. 6. 3  
Hist ol o gi c  Ass ess m e nt  of  E n d os c o pi c  Bi o ps y  
 
1 6. 2. 6. 4  
Ul c er ati v e  C olitis  E n d os c o pi c I n d e x  of  S e v erit y  
 
1 6. 2. 6. 5  
S h ort I nfl a m m at or y  B o w el  Dis e as e  Q u esti o n n air e   
 
1 6. 2. 6. 6  
Bi o m ar k ers   
1 6. 2. 7   
 
A d v e rs e  E v e nts  Listi n gs  
 
1 6. 2. 7. 1  
A d v ers e  E v e nts  
 
1 6. 2. 7. 2  
S eri o us  A d v ers e  E v e nts  
 
1 6. 2. 7. 3  
A d v ers e  E v e nts  L e a di n g t o  P er m a n e nt  Wit h dr a w al  of  St u d y  Tr e at m e nt  or  Dis c o nti n u ati o n fr o m t h e  St u d y   
 
1 6. 2. 7. 4  
A d v ers e  E v e nts  L e a di n g t o  D e at h  
1 6. 2. 8   
 
I n di vi d u al  L a b  M e as u r es  
 
1 6. 2. 8. 1  
H e m at ol o g y  
 
1 6. 2. 8. 2  
C h e mistr y   
 
1 6. 2. 8. 3  
Vit al  Si g ns  
 
1 6. 2. 8. 4  
El e ctr o c ar di o gr a m  
 
1 6. 2. 8. 5  
P h ysi c al  E x a mi n ati o n  
1 6. 2. 9   
 
P h a r m a c o ki n eti cs  
 
1 6. 2. 9. 1  
I n di vi d u al  Pl as m a  C o n c e ntr ati o n  D at a  
 
1 6. 2. 9. 2  
I n di vi d u al  Tiss u e  C o n c e ntr ati o n  D at a  
1 6. 2. 1 0   
 
Ot h e r  Mis c ell a n e o us  D at a  
 
1 6. 2. 1 0. 1  
R a n d o mi z ati o n  
 
1 6. 2. 1 0. 2  
I P 
 
1 6. 2. 1 0. 3     
I n v esti g at or  Si g n at ur e  


 
C o nfi d e nti al  
5 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
< T y p e   o f   A n a l y s i s   i . e .   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
 
T a b l e   1 4 . 1 . 1  
S u m m a r y   o f   P a t i e n t   D i s p o s i t i o n    
A l l   P a t i e n t s  
 
 
P l a c e b o  
B B T - 4 0 1 - 1 S     
A l l   S u b j e c t s  
 
n   %  
n   %  
n   %  
 
 
 
 
S c r e e n e d  
x x    
x x  
X X  
 
 
 
 
R a n d o m i z e d    
X X    
X X    
X X    
      S i t e   N u m b e r   0 1  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
      S i t e   N u m b e r   0 2  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
      …  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
 
 
 
M o d i f i e d   I n t e n t - t o - T r e a t   ( m I T T )  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
P e r - P r o t o c o l  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
S a f e t y  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
P h a r m a c o k i n e t i c s   ( P K )  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
 
 
 
D o s e d   [ 1 ]  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
 
 
 
C o m p l e t e d   I n i t i a l   8 - W e e k   T r e a t m e n t  
 
 
 
      Y e s  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
      N o  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
 
 
 
I f   N o ,   R e a s o n   f o r   E a r l y   T e r m i n a t i o n   o f   I n i t i a l   8 - W e e k   T r e a t m e n t   
 
 
 
      S u b j e c t ’ s   r e q u e s t   o r   r e q u e s t   o f   l e g a l   r e p r e s e n t a t i v e  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
      P e r   P r i n c i p a l   I n v e s t i g a t o r ,   c o n t i n u a t i o n   w o u l d   b e      
      d e t r i m e n t a l   t o   s u b j e c t ’ s   w e l l - b e i n g  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
      S p o n s o r   r e q u e s t  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
      W i t h d r a w a l   o f   c o n s e n t  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
      S i g n i f i c a n t   P r o t o c o l   D e v i a t i o n  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
      N o n - c o m p l i a n c e   w i t h   t h e   p r o t o c o l   o r   s t u d y   d r u g  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
      C l i n i c a l   P r o g r e s s i o n  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
      A d v e r s e   E v e n t  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
      L o s t   t o   f o l l o w - u p  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
      D e a t h  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
      O t h e r  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
 
 
 
C o m p l e t e d   V i s i t   6   ( W e e k   1 6 )  
 
 
 
      Y e s  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
      N o  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
[ 1 ]   ‘ D o s e d ’   i s   d e f i n e d   a s   a l l   r a n d o m i z e d   p a t i e n t s   w h o   r e c e i v e d   a t   l e a s t   o n e   d o s e   o f   s t u d y   m e d i c a t i o n .  
 
N o t e :   P e r c e n t a g e s   a r e   b a s e d   o n   t h e   n u m b e r   o f   s u b j e c t s   r a n d o m i z e d .  


 
C o nfi d e nti al  
6 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - d i s p - f a s >   D D M M M Y Y Y   H H : M M : S S   -   D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y  
< P a t h / P r o g r a m   N a m e >      
P a g e   1   o f   X                            
 
 
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 1 . 2  
S u m m a r y   o f   D e m o g r a p h i c   a n d   B a s e l i n e   C h a r a c t e r i s t i c s    
m I T T   A n a l y s i s   s e t  
 
 
P l a c e b o    
B B T - 4 0 1 - 1 S  
O v e r a l l  
 
( N = X X )  
( N = X X )  
( N = X X )  
 
 
 
 
A g e   ( Y e a r s )  
 
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X . X X )  
X X . X   ( X . X X )  
X X . X   ( X . X X )  
    M e d i a n  
X X . X  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
X X ,   X X  
 
 
 
 
G e n d e r ,   n   ( % )  
 
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
X X   ( X X )  
    M a l e  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    F e m a l e  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
 
 
 
 
E t h n i c i t y ,   n   ( % )  
 
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
X X   ( X X )  
    H i s p a n i c    
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    N o n - H i s p a n i c    
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
 
 
 
 
R a c e ,   n   ( % )  
 
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
X X   ( X X )  
    B l a c k   o r   A f r i c a n   A m e r i c a n  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    N a t i v e   A m e r i c a n   I n d i a n   o r   N a t i v e   A l a s k a n  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    N a t i v e   H a w a i i a n   o r   O t h e r   P a c i f i c   I s l a n d e r  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    A s i a n  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    W h i t e  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    O t h e r  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
 
 
 
 
H e i g h t   ( c m )  
 
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    M e d i a n  
X X . X  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
X X ,   X X  
 
 
 
 
W e i g h t   ( k g )  
 
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    M e d i a n  
X X . X  
X X . X  
X X . X  


 
C o nfi d e nti al  
7 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
X X ,   X X  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                                
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
P a g e   1   o f   X    
 
 


 
C o nfi d e nti al  
8 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 1 . 3  
S u m m a r y   o f   M e d i c a l   H i s t o r y    
m I T T   A n a l y s i s   s e t  
 
S y s t e m   O r g a n   C l a s s  
P l a c e b o    
B B T - 4 0 1 - 1 S  
O v e r a l l  
    P r e f e r r e d   T e r m  
( N = X X )  
( N = X X )  
( N = X X )  
 
 
 
 
S u b j e c t s   w i t h   A n y   r e p o r t e d   M e d i c a l   H i s t o r y   a n d   P r e -
e x i s t i n g   C o n d i t i o n s   [ 1 ]  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
 
 
 
 
S y s t e m   O r g a n   C l a s s   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    …  
 
 
 
 
 
 
 
S y s t e m   O r g a n   C l a s s   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    …  
 
 
 
S y s t e m   O r g a n   C l a s s   3  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
 
 
 
 
… .  
 
 
 
 
 
 
 
 
 
 
 
[ 1 ]  M e d i c a l   h i s t o r y   i s   d e f i n e d   a s   i l l n e s s ( e s )   t h a t   e n d e d   p r i o r   t o   t h e   s i g n i n g   o f   i n f o r m e d   c o n s e n t .   P r e - e x i s t i n g  
c o n d i t i o n s   a n d   A E s   a t   b a s e l i n e   a r e   t h o s e   A E s   o c c u r r i n g   d u r i n g   t h e   b a s e l i n e / s c r e e n i n g   v i s i t s   t h a t   a r e   V i s i t s   1   a n d   2 .  
N o t e   1 :   M e d i c a l   h i s t o r y   a n d   P r e - e x i s t i n g   C o n d i t i o n s   w e r e   c o d e d   u s i n g   t h e   M e d D R A   v e r s i o n   2 3 . 0 .  
N o t e   2 :   S u b j e c t s   w i t h   o n e   o r   m o r e   r e c o r d s   w i t h i n   a   l e v e l   o f   M e d D R A   a r e   c o u n t e d   o n l y   o n c e   i n   t h a t   l e v e l .  
 
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S             D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                              
< P a t h / P r o g r a m   N a m e >      
P a g e   1   o f   X    
  
 


 
C o nfi d e nti al  
9 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 1 . 4  
S u m m a r y   o f   P r i o r   M e d i c a t i o n s    
m I T T   A n a l y s i s   s e t  
 
T h e r a p e u t i c   S u b c l a s s i f i c a t i o n   [ A T C 2 ]  
P l a c e b o    
B B T - 4 0 1 - 1 S  
O v e r a l l  
    P r e f e r r e d   M e d i c a t i o n   N a m e  
( N = X X )  
( N = X X )  
( N = X X )  
 
 
 
 
S u b j e c t s   w i t h   A n y   P r i o r   M e d i c a t i o n   [ 1 ]  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
 
 
 
 
T h e r a p e u t i c   S u b c l a s s   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   M e d i c a t i o n   N a m e   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   M e d i c a t i o n   N a m e   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    …  
 
 
 
T h e r a p e u t i c   S u b c l a s s   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   M e d i c a t i o n   N a m e   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   M e d i c a t i o n   N a m e   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    …  
 
 
 
T h e r a p e u t i c   S u b c l a s s   3  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   M e d i c a t i o n   N a m e   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   M e d i c a t i o n   N a m e   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
 
 
 
 
… .  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[ 1 ]  P r i o r   m e d i c a t i o n s   a r e   d e f i n e d   a s   m e d i c a t i o n s   s t a r t e d   t o   b e   t a k e n   p r i o r   t o   t h e   f i r s t   a d m i n i s t r a t i o n   o f   t h e   s t u d y  
d r u g .  
N o t e   1 :   W H O   D r u g   D i c t i o n a r y   E n h a n c e d   ( W H O D D E )   B 3   f o r m a t   ( 0 1 M A R 2 0 2 0   r e l e a s e )   w a s   u s e d   t o   c o d e   m e d i c a t i o n   n a m e s .  
N o t e   2 :   I f   a   s u b j e c t   r e p o r t s   s a m e   p r e f e r   t e r m   m u l t i p l e   t i m e s ,   t h e   f r e q u e n c y   o f   t h a t   p r e f e r r e d   t e r m   w i l l   o n l y   b e  
i n c r e m e n t e d   b y   o n e .   S a m e   a s   p r e f e r r e d   t e r m ,   i f   a   s u b j e c t   r e p o r t s   m u l t i p l e   m e d i c a t i o n s   w i t h i n   t h e   s a m e   A T C   l e v e l   2  
c l a s s i f i c a t i o n ,   t h e n   t h e   f r e q u e n c y   o f   t h a t   A T C   l e v e l   2   c l a s s i f i c a t i o n   w i l l   o n l y   b e   i n c r e m e n t e d   b y   o n e .  
 
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S             D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                              
< P a t h / P r o g r a m   N a m e >      
P a g e   1   o f   X    
 
 
 


 
C o nfi d e nti al  
1 0 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 1 . 5  
S u m m a r y   o f   C o n c o m i t a n t   M e d i c a t i o n s    
m I T T   A n a l y s i s   s e t  
 
T h e r a p e u t i c   S u b c l a s s i f i c a t i o n   [ A T C 2 ]  
P l a c e b o    
B B T - 4 0 1 - 1 S  
O v e r a l l  
    P r e f e r r e d   M e d i c a t i o n   N a m e  
( N = X X )  
( N = X X )  
( N = X X )  
 
 
 
 
S u b j e c t s   w i t h   A n y   C o n c o m i t a n t   M e d i c a t i o n   [ 1 ]  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
 
 
 
 
T h e r a p e u t i c   S u b c l a s s   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   M e d i c a t i o n   N a m e   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   M e d i c a t i o n   N a m e   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    …  
 
 
 
T h e r a p e u t i c   S u b c l a s s   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   M e d i c a t i o n   N a m e   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   M e d i c a t i o n   N a m e   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    …  
 
 
 
T h e r a p e u t i c   S u b c l a s s   3  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   M e d i c a t i o n   N a m e   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   M e d i c a t i o n   N a m e   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
 
 
 
 
… .  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[ 1 ]  C o n c o m i t a n t   m e d i c a t i o n s   a r e   d e f i n e d   a s   m e d i c a t i o n s   s t a r t e d   o n   o r   a f t e r   t h e   d a y   o f   t h e   f i r s t   a d m i n i s t r a t i o n   o f   t h e  
s t u d y   d r u g   d u r i n g   t h e   s t u d y .  
N o t e   1 :   W H O   D r u g   D i c t i o n a r y   E n h a n c e d   ( W H O D D E )   B 3   f o r m a t   ( 0 1 M A R 2 0 2 0   r e l e a s e )   w a s   u s e d   t o   c o d e   m e d i c a t i o n   n a m e s .  
N o t e   2 :   I f   a   s u b j e c t   r e p o r t s   s a m e   p r e f e r   t e r m   m u l t i p l e   t i m e s ,   t h e   f r e q u e n c y   o f   t h a t   p r e f e r r e d   t e r m   w i l l   o n l y   b e  
i n c r e m e n t e d   b y   o n e .   S a m e   a s   p r e f e r r e d   t e r m ,   i f   a   s u b j e c t   r e p o r t s   m u l t i p l e   m e d i c a t i o n s   w i t h i n   t h e   s a m e   A T C   l e v e l   2  
c l a s s i f i c a t i o n ,   t h e n   t h e   f r e q u e n c y   o f   t h a t   A T C   l e v e l   2   c l a s s i f i c a t i o n   w i l l   o n l y   b e   i n c r e m e n t e d   b y   o n e .  
 
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S             D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                              
< P a t h / P r o g r a m   N a m e >      
P a g e   1   o f   X    
 
 
 
 


 
C o nfi d e nti al  
1 1 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 2 . 1 . 1 . 1  
S u m m a r y   o f   C h a n g e   o f   T o t a l   M a y o   S c o r e   f r o m   B a s e l i n e   t o   W e e k   8    
m I T T   A n a l y s i s   s e t  
 
 
P l a c e b o  
B B T - 4 0 1 - 1 S  
S t u d y   V i s i t  
( N = X X )  
( N = X X )  
 
 
 
B a s e l i n e  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
C h a n g e   f r o m   B a s e l i n e   t o   W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
    L S   M e a n   ( S E )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    P - V a l u e ,   A c t i v e   v s   P l a c e b o  
 
0 . X X X  
    L S   M e a n   D i f f e r e n c e   ( S E )  
 
X X . X   ( X X . X X )  
    9 5 %   C I   f o r   D i f f e r e n c e s  
 
( X X . X ,   X X . X )  
 
 
 
 
 
 
N o t e :   L e a s t   S q u a r e s   m e a n s ,   p - v a l u e s   w e r e   f r o m   M M R M   m o d e l   w i t h   t r e a t m e n t   a n d   b a s e l i n e   s c o r e   a s   f i x e d   e f f e c t s ,   a n d   c e n t e r  
a s   r a n d o m   e f f e c t .   R e s t r i c t e d   M a x i m u m   L i k e l i h o o d   ( R E M L )   w i t h   a n   u n s t r u c t u r e d   v a r i a n c e - c o v a r i a n c e   m a t r i x   i s   u s e d   f o r  
e s t i m a t i o n   i n   t h e   M M R M   a n a l y s i s .  
 
 


 
C o nfi d e nti al  
1 2 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 2 . 1 . 1 . 2  
S u m m a r y   o f   C h a n g e   o f   T o t a l   M a y o   S c o r e   f r o m   B a s e l i n e   t o   W e e k   8    
P P   A n a l y s i s   s e t  
 
 
P l a c e b o  
B B T - 4 0 1 - 1 S  
S t u d y   V i s i t  
( N = X X )  
( N = X X )  
 
 
 
B a s e l i n e  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
C h a n g e   f r o m   B a s e l i n e   t o   W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
    L S   M e a n   ( S E )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    P - V a l u e ,   A c t i v e   v s   P l a c e b o  
 
0 . X X X  
    L S   M e a n   D i f f e r e n c e   ( S E )  
 
X X . X   ( X X . X X )  
    9 5 %   C I   f o r   D i f f e r e n c e s  
 
( X X . X ,   X X . X )  
 
 
 
 
 
 
N o t e :   L e a s t   S q u a r e s   m e a n s ,   p - v a l u e s   w e r e   f r o m   M M R M   m o d e l   w i t h   t r e a t m e n t   a n d   b a s e l i n e   s c o r e   a s   f i x e d   e f f e c t s ,   a n d   c e n t e r  
a s   r a n d o m   e f f e c t .   R e s t r i c t e d   M a x i m u m   L i k e l i h o o d   ( R E M L )   w i t h   a n   u n s t r u c t u r e d   v a r i a n c e - c o v a r i a n c e   m a t r i x   i s   u s e d   f o r  
e s t i m a t i o n   i n   t h e   M M R M   a n a l y s i s .  
 
 
 


 
C o nfi d e nti al  
1 3 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 2 . 2 . 1 . 1  
S u m m a r y   o f   C h a n g e   o f   P a r t i a l   M a y o   S c o r e   f r o m   B a s e l i n e   t o   W e e k   8    
m I T T   A n a l y s i s   s e t  
 
 
P l a c e b o  
B B T - 4 0 1 - 1 S  
S t u d y   V i s i t  
( N = X X )  
( N = X X )  
 
 
 
B a s e l i n e  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
C h a n g e   f r o m   B a s e l i n e   t o   W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
    L S   M e a n   ( S E )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    P - V a l u e ,   A c t i v e   v s   P l a c e b o  
 
0 . X X X  
    L S   M e a n   D i f f e r e n c e   ( S E )  
 
X X . X   ( X X . X X )  
    9 5 %   C I   f o r   D i f f e r e n c e s  
 
( X X . X ,   X X . X )  
 
 
 
 
 
 
N o t e :   L e a s t   S q u a r e s   m e a n s ,   p - v a l u e s   w e r e   f r o m   M M R M   m o d e l   w i t h   t r e a t m e n t   a n d   b a s e l i n e   s c o r e   a s   f i x e d   e f f e c t s ,   a n d   c e n t e r  
a s   r a n d o m   e f f e c t .   R e s t r i c t e d   M a x i m u m   L i k e l i h o o d   ( R E M L )   w i t h   a n   u n s t r u c t u r e d   v a r i a n c e - c o v a r i a n c e   m a t r i x   i s   u s e d   f o r  
e s t i m a t i o n   i n   t h e   M M R M   a n a l y s i s .  
 
 


 
C o nfi d e nti al  
1 4 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 2 . 2 . 1 . 2  
S u m m a r y   o f   C h a n g e   o f   P a r t i a l   M a y o   S c o r e   f r o m   B a s e l i n e   t o   W e e k   8    
P P   A n a l y s i s   s e t  
 
 
P l a c e b o  
B B T - 4 0 1 - 1 S  
S t u d y   V i s i t  
( N = X X )  
( N = X X )  
 
 
 
B a s e l i n e  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
C h a n g e   f r o m   B a s e l i n e   t o   W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
    L S   M e a n   ( S E )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    P - V a l u e ,   A c t i v e   v s   P l a c e b o  
 
0 . X X X  
    L S   M e a n   D i f f e r e n c e   ( S E )  
 
X X . X   ( X X . X X )  
    9 5 %   C I   f o r   D i f f e r e n c e s  
 
( X X . X ,   X X . X )  
 
 
 
 
 
 
N o t e :   L e a s t   S q u a r e s   m e a n s ,   p - v a l u e s   w e r e   f r o m   M M R M   m o d e l   w i t h   t r e a t m e n t   a n d   b a s e l i n e   s c o r e   a s   f i x e d   e f f e c t s ,   a n d   c e n t e r  
a s   r a n d o m   e f f e c t .   R e s t r i c t e d   M a x i m u m   L i k e l i h o o d   ( R E M L )   w i t h   a n   u n s t r u c t u r e d   v a r i a n c e - c o v a r i a n c e   m a t r i x   i s   u s e d   f o r  
e s t i m a t i o n   i n   t h e   M M R M   a n a l y s i s .  
 
 


 
C o nfi d e nti al  
1 5 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 2 . 2 . 2 . 1  
S u m m a r y   o f   C h a n g e   o f   H i s t o l o g i c   A s s e s s m e n t   o f   E n d o s c o p i c   B i o p s y   f r o m   B a s e l i n e   t o   W e e k   8    
m I T T   A n a l y s i s   s e t  
 
 
P l a c e b o  
B B T - 4 0 1 - 1 S  
S t u d y   V i s i t  
( N = X X )  
( N = X X )  
S p e c i m e n   R e g i o n   o f   O r i g i n   : X X X X X X X X  
 
 
L a b o r a t o r y   T e s t :     X X X X X X X X X  
 
 
 
 
 
B a s e l i n e  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
C h a n g e   f r o m   B a s e l i n e   t o   W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
    L S   M e a n   ( S E )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    P - V a l u e ,   A c t i v e   v s   P l a c e b o  
 
0 . X X X  
    L S   M e a n   D i f f e r e n c e   ( S E )  
 
X X . X   ( X X . X X )  
    9 5 %   C I   f o r   D i f f e r e n c e s  
 
( X X . X ,   X X . X )  
 
 
 
 
 
 
N o t e :   L e a s t   S q u a r e s   m e a n s ,   p - v a l u e s   w e r e   f r o m   M M R M   m o d e l   w i t h   t r e a t m e n t   a n d   b a s e l i n e   s c o r e   a s   f i x e d   e f f e c t s ,   a n d   c e n t e r  
a s   r a n d o m   e f f e c t .   R e s t r i c t e d   M a x i m u m   L i k e l i h o o d   ( R E M L )   w i t h   a n   u n s t r u c t u r e d   v a r i a n c e - c o v a r i a n c e   m a t r i x   i s   u s e d   f o r  
e s t i m a t i o n   i n   t h e   M M R M   a n a l y s i s .  
 
P r o g r a m m i n g   N o t e :   S t a r t   a   n e w   p a g e   f o r   e a c h   l a b o r a t o r y   t e s t .  
 
 


 
C o nfi d e nti al  
1 6 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 2 . 2 . 2 . 2  
S u m m a r y   o f   C h a n g e   o f   H i s t o l o g i c   A s s e s s m e n t   o f   E n d o s c o p i c   B i o p s y   f r o m   B a s e l i n e   t o   W e e k   8    
P P   A n a l y s i s   s e t  
 
P l a c e b o  
B B T - 4 0 1 - 1 S  
S t u d y   V i s i t  
( N = X X )  
( N = X X )  
 
 
 
S p e c i m e n   R e g i o n   o f   O r i g i n   : X X X X X X X X  
 
 
L a b o r a t o r y   T e s t :     X X X X X X X X X  
 
 
 
B a s e l i n e  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
C h a n g e   f r o m   B a s e l i n e   t o   W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
    L S   M e a n   ( S E )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    P - V a l u e ,   A c t i v e   v s   P l a c e b o  
 
0 . X X X  
    L S   M e a n   D i f f e r e n c e   ( S E )  
 
X X . X   ( X X . X X )  
    9 5 %   C I   f o r   D i f f e r e n c e s  
 
( X X . X ,   X X . X )  
 
 
 
 
 
 
N o t e :   L e a s t   S q u a r e s   m e a n s ,   p - v a l u e s   w e r e   f r o m   M M R M   m o d e l   w i t h   t r e a t m e n t   a n d   b a s e l i n e   s c o r e   a s   f i x e d   e f f e c t s ,   a n d   c e n t e r  
a s   r a n d o m   e f f e c t .   R e s t r i c t e d   M a x i m u m   L i k e l i h o o d   ( R E M L )   w i t h   a n   u n s t r u c t u r e d   v a r i a n c e - c o v a r i a n c e   m a t r i x   i s   u s e d   f o r  
e s t i m a t i o n   i n   t h e   M M R M   a n a l y s i s .  
 
P r o g r a m m i n g   N o t e :   S t a r t   a   n e w   p a g e   f o r   e a c h   l a b o r a t o r y   t e s t .  
 
 


 
C o nfi d e nti al  
1 7 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 2 . 2 . 3 . 1  
S u m m a r y   o f   C h a n g e   o f   U l c e r a t i v e   C o l i t i s   E n d o s c o p i c   I n d e x   o f   S e v e r i t y   ( U C E I S )   S c o r e   f r o m   B a s e l i n e   t o   W e e k   8    
m I T T   A n a l y s i s   s e t  
 
 
P l a c e b o  
B B T - 4 0 1 - 1 S  
S t u d y   V i s i t  
( N = X X )  
( N = X X )  
 
 
 
B a s e l i n e  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
C h a n g e   f r o m   B a s e l i n e   t o   W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
    L S   M e a n   ( S E )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    P - V a l u e ,   A c t i v e   v s   P l a c e b o  
 
0 . X X X  
    L S   M e a n   D i f f e r e n c e   ( S E )  
 
X X . X   ( X X . X X )  
    9 5 %   C I   f o r   D i f f e r e n c e s  
 
( X X . X ,   X X . X )  
 
 
 
 
 
 
N o t e :   L e a s t   S q u a r e s   m e a n s ,   p - v a l u e s   w e r e   f r o m   M M R M   m o d e l   w i t h   t r e a t m e n t   a n d   b a s e l i n e   s c o r e   a s   f i x e d   e f f e c t s ,   a n d   c e n t e r  
a s   r a n d o m   e f f e c t .   R e s t r i c t e d   M a x i m u m   L i k e l i h o o d   ( R E M L )   w i t h   a n   u n s t r u c t u r e d   v a r i a n c e - c o v a r i a n c e   m a t r i x   i s   u s e d   f o r  
e s t i m a t i o n   i n   t h e   M M R M   a n a l y s i s .  
 
 


 
C o nfi d e nti al  
1 8 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 2 . 2 . 3 . 2  
S u m m a r y   o f   C h a n g e   o f   U l c e r a t i v e   C o l i t i s   E n d o s c o p i c   I n d e x   o f   S e v e r i t y   ( U C E I S )   S c o r e   f r o m   B a s e l i n e   t o   W e e k   8    
P P   A n a l y s i s   s e t  
 
 
P l a c e b o  
B B T - 4 0 1 - 1 S  
S t u d y   V i s i t  
( N = X X )  
( N = X X )  
 
 
 
B a s e l i n e  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
C h a n g e   f r o m   B a s e l i n e   t o   W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
    L S   M e a n   ( S E )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    P - V a l u e ,   A c t i v e   v s   P l a c e b o  
 
0 . X X X  
    L S   M e a n   D i f f e r e n c e   ( S E )  
 
X X . X   ( X X . X X )  
    9 5 %   C I   f o r   D i f f e r e n c e s  
 
( X X . X ,   X X . X )  
 
 
 
 
 
 
N o t e :   L e a s t   S q u a r e s   m e a n s ,   p - v a l u e s   w e r e   f r o m   M M R M   m o d e l   w i t h   t r e a t m e n t   a n d   b a s e l i n e   s c o r e   a s   f i x e d   e f f e c t s ,   a n d   c e n t e r  
a s   r a n d o m   e f f e c t .   R e s t r i c t e d   M a x i m u m   L i k e l i h o o d   ( R E M L )   w i t h   a n   u n s t r u c t u r e d   v a r i a n c e - c o v a r i a n c e   m a t r i x   i s   u s e d   f o r  
e s t i m a t i o n   i n   t h e   M M R M   a n a l y s i s .  
 
 
 


 
C o nfi d e nti al  
1 9 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 2 . 2 . 4 . 1  
S u m m a r y   o f   C h a n g e   o f   S h o r t   I n f l a m m a t o r y   B o w e l   D i s e a s e   Q u e s t i o n n a i r e   ( S I B D Q )   f r o m   B a s e l i n e   t o   W e e k   8    
m I T T   A n a l y s i s   s e t  
 
 
P l a c e b o  
B B T - 4 0 1 - 1 S  
S t u d y   V i s i t  
( N = X X )  
( N = X X )  
 
 
 
S I B D Q   Q u e s t i o n   # :   x x x x x x  
 
 
 
 
 
B a s e l i n e  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
C h a n g e   f r o m   B a s e l i n e   t o   W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
    L S   M e a n   ( S E )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    P - V a l u e ,   A c t i v e   v s   P l a c e b o  
 
0 . X X X  
    L S   M e a n   D i f f e r e n c e   ( S E )  
 
X X . X   ( X X . X X )  
    9 5 %   C I   f o r   D i f f e r e n c e s  
 
( X X . X ,   X X . X )  
 
 
 
 
 
 
N o t e :   L e a s t   S q u a r e s   m e a n s ,   p - v a l u e s   w e r e   f r o m   M M R M   m o d e l   w i t h   t r e a t m e n t   a n d   b a s e l i n e   s c o r e   a s   f i x e d   e f f e c t s ,   a n d   c e n t e r  
a s   r a n d o m   e f f e c t .   R e s t r i c t e d   M a x i m u m   L i k e l i h o o d   ( R E M L )   w i t h   a n   u n s t r u c t u r e d   v a r i a n c e - c o v a r i a n c e   m a t r i x   i s   u s e d   f o r  
e s t i m a t i o n   i n   t h e   M M R M   a n a l y s i s .  
 
P r o g r a m m i n g   N o t e :   S t a r t   a   n e w   p a g e   f o r   e a c h   q u e s t i o n .  
 
 


 
C o nfi d e nti al  
2 0 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 2 . 2 . 4 . 2  
S u m m a r y   o f   C h a n g e   o f   S h o r t   I n f l a m m a t o r y   B o w e l   D i s e a s e   Q u e s t i o n n a i r e   ( S I B D Q )   f r o m   B a s e l i n e   t o   W e e k   8    
P P   A n a l y s i s   s e t  
 
 
P l a c e b o  
B B T - 4 0 1 - 1 S  
S t u d y   V i s i t  
( N = X X )  
( N = X X )  
 
 
 
S I B D Q   Q u e s t i o n   # :   x x x x x x  
 
 
 
 
 
B a s e l i n e  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
C h a n g e   f r o m   B a s e l i n e   t o   W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
    L S   M e a n   ( S E )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    P - V a l u e ,   A c t i v e   v s   P l a c e b o  
 
0 . X X X  
    L S   M e a n   D i f f e r e n c e   ( S E )  
 
X X . X   ( X X . X X )  
    9 5 %   C I   f o r   D i f f e r e n c e s  
 
( X X . X ,   X X . X )  
 
 
 
 
 
 
N o t e :   L e a s t   S q u a r e s   m e a n s ,   p - v a l u e s   w e r e   f r o m   M M R M   m o d e l   w i t h   t r e a t m e n t   a n d   b a s e l i n e   s c o r e   a s   f i x e d   e f f e c t s ,   a n d   c e n t e r  
a s   r a n d o m   e f f e c t .   R e s t r i c t e d   M a x i m u m   L i k e l i h o o d   ( R E M L )   w i t h   a n   u n s t r u c t u r e d   v a r i a n c e - c o v a r i a n c e   m a t r i x   i s   u s e d   f o r  
e s t i m a t i o n   i n   t h e   M M R M   a n a l y s i s .  
 
P r o g r a m m i n g   N o t e :   S t a r t   a   n e w   p a g e   f o r   e a c h   q u e s t i o n .  
 
 


 
C o nfi d e nti al  
2 1 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 2 . 3 . 1  
S u m m a r y   o f   C h a n g e   o f   C o n c e n t r a t i o n   o f   B i o m a r k e r s   f r o m   B a s e l i n e   t o   W e e k   8  
m I T T   A n a l y s i s   s e t  
 
 
P l a c e b o  
B B T - 4 0 1 - 1 S  
S t u d y   V i s i t  
( N = X X )  
( N = X X )  
 
B i o m a r k e r   # 1  
 
 
 
B a s e l i n e  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
C h a n g e   f r o m   B a s e l i n e   t o   W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
    L S   M e a n   ( S E )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    P - V a l u e ,   A c t i v e   v s   P l a c e b o  
 
0 . X X X  
    L S   M e a n   D i f f e r e n c e   ( S E )  
 
X X . X   ( X X . X X )  
    9 5 %   C I   f o r   D i f f e r e n c e s  
 
( X X . X ,   X X . X )  
 
 
 
B i o m a r k e r   # 2  
…  
 
 
 
N o t e :   L e a s t   S q u a r e s   m e a n s ,   p - v a l u e s   w e r e   f r o m   M M R M   m o d e l   w i t h   t r e a t m e n t   a n d   b a s e l i n e   s c o r e   a s   f i x e d   e f f e c t s ,   a n d   c e n t e r  
a s   r a n d o m   e f f e c t .   R e s t r i c t e d   M a x i m u m   L i k e l i h o o d   ( R E M L )   w i t h   a n   u n s t r u c t u r e d   v a r i a n c e - c o v a r i a n c e   m a t r i x   i s   u s e d   f o r  
e s t i m a t i o n   i n   t h e   M M R M   a n a l y s i s .  
 
P r o g r a m m i n g   N o t e :   S t a r t   a   n e w   p a g e   f o r   e a c h   b i o m a r k e r .  
 


 
C o nfi d e nti al  
2 2 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 2 . 3 . 2  
S u m m a r y   o f   C h a n g e   o f   C o n c e n t r a t i o n   o f   B i o m a r k e r s   f r o m   B a s e l i n e   t o   W e e k   8    
P P   A n a l y s i s   s e t  
 
 
P l a c e b o  
B B T - 4 0 1 - 1 S  
S t u d y   V i s i t  
( N = X X )  
( N = X X )  
 
B i o m a r k e r   # 1  
 
 
 
B a s e l i n e  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
C h a n g e   f r o m   B a s e l i n e   t o   W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
    L S   M e a n   ( S E )  
X X . X   ( X X . X X )  
X X . X   ( X X . X X )  
    P - V a l u e ,   A c t i v e   v s   P l a c e b o  
 
0 . X X X  
    L S   M e a n   D i f f e r e n c e   ( S E )  
 
X X . X   ( X X . X X )  
    9 5 %   C I   f o r   D i f f e r e n c e s  
 
( X X . X ,   X X . X )  
 
 
 
B i o m a r k e r   # 2  
…  
 
 
 
N o t e :   L e a s t   S q u a r e s   m e a n s ,   p - v a l u e s   w e r e   f r o m   M M R M   m o d e l   w i t h   t r e a t m e n t   a n d   b a s e l i n e   s c o r e   a s   f i x e d   e f f e c t s ,   a n d   c e n t e r  
a s   r a n d o m   e f f e c t .   R e s t r i c t e d   M a x i m u m   L i k e l i h o o d   ( R E M L )   w i t h   a n   u n s t r u c t u r e d   v a r i a n c e - c o v a r i a n c e   m a t r i x   i s   u s e d   f o r  
e s t i m a t i o n   i n   t h e   M M R M   a n a l y s i s .  
 
P r o g r a m m i n g   N o t e :   S t a r t   a   n e w   p a g e   f o r   e a c h   b i o m a r k e r .   T h i s   s h o u l d   i n c l u d e   C - r e a c t i v e   p r o t e i n   [ C R P ] ,   f e c a l  
c a l p r o t e c t i n ,   a n d   f e c a l   l a c t o f e r r i n .  
 
 


 
C o nfi d e nti al  
2 3 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 3 . 1 . 1  
O v e r a l l   S u m m a r y   o f   T r e a t m e n t - E m e r g e n t   A d v e r s e   E v e n t s   u p   t o   W e e k   8  
S a f e t y   A n a l y s i s   S e t  
 
 
P l a c e b o  
B B T - 4 0 1 - 1 S  
O v e r a l l  
 
( N = X X )  
( N = X X )  
( N = X X )  
 
 
 
 
N u m b e r   o f   P a t i e n t s   w i t h   a t   L e a s t   1   T E A E   u p   t o   W e e k   8   
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
 
 
 
 
N u m b e r   o f   P a t i e n t s   w i t h   a t   L e a s t   1   S e r i o u s   T E A E   u p   t o  
W e e k   8  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
 
 
 
 
N u m b e r   o f   P a t i e n t s   w i t h   a t   L e a s t   1   T E A E   u p   t o   W e e k   8  
L e a d i n g   t o   S t u d y   D i s c o n t i n u a t i o n  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
 
 
 
 
N u m b e r   o f   P a t i e n t s   w i t h   T E A E s   b y   W o r s t   S e v e r i t y  
 
 
 
    M i l d  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    M o d e r a t e  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    S e v e r e  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
 
 
 
 
N u m b e r   o f   P a t i e n t s   w i t h   T E A E s   b y   W o r s t   R e l a t i o n s h i p   
 
 
 
    N o t   R e l a t e d  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P o s s i b l y   R e l a t e d  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r o b a b l y   R e l a t e d  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    R e l a t e d  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
N o t e   1 :   A   T r e a t m e n t   E m e r g e n t   A d v e r s e   E v e n t   ( T E A E )   i s   d e f i n e d   a s   a n   a d v e r s e   e v e n t   t h a t   o c c u r s   o r   w o r s e n s   o n   o r   a f t e r   t h e  
f i r s t   d o s e   o f   s t u d y   d r u g .  
N o t e   2 :   I f   a   p a t i e n t   e x p e r i e n c e d   m o r e   t h a n   1   e v e n t   i n   a   c a t e g o r y ,   t h e n   t h a t   p a t i e n t   i s   c o u n t e d   o n l y   o n c e   i n   t h a t  
c a t e g o r y  
N o t e   3 :   M e d D R A   D i c t i o n a r y   ( V e r s i o n   2 3 . 0 )   w a s   u s e d   f o r   c o d i n g   a d v e r s e   e v e n t s .  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S             D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                               
< P a t h / P r o g r a m   N a m e >      
P a g e   1   o f   X    
 
 


 
C o nfi d e nti al  
2 4 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 3 . 1 . 2  
S u m m a r y   o f   T r e a t m e n t - E m e r g e n t   A d v e r s e   E v e n t s   u p   t o   W e e k   8   b y   S y s t e m   O r g a n   C l a s s   a n d   P r e f e r r e d   T e r m    
S a f e t y   A n a l y s i s   s e t  
 
S y s t e m   O r g a n   C l a s s  
P l a c e b o  
B B T - 4 0 1 - 1 S  
O v e r a l l  
    P r e f e r r e d   T e r m  
( N = X X )  
( N = X X )  
( N = X X )  
 
 
 
 
S u b j e c t s   w i t h   A n y   T E A E s   u p   t o   W e e k   8  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
 
 
 
 
S y s t e m   O r g a n   C l a s s   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    …  
 
 
 
 
 
 
 
S y s t e m   O r g a n   C l a s s   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    …  
 
 
 
 
S y s t e m   O r g a n   C l a s s   3  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N o t e   1 :   A   T r e a t m e n t   E m e r g e n t   A d v e r s e   E v e n t   ( T E A E )   i s   d e f i n e d   a s   a n   a d v e r s e   e v e n t   t h a t   o c c u r s   o r   w o r s e n s   o n   o r   a f t e r   t h e  
f i r s t   d o s e   o f   s t u d y   d r u g .  
N o t e   2 :   S u b j e c t s   w i t h   o n e   o r   m o r e   a d v e r s e   e v e n t s   w i t h i n   a   l e v e l   o f   M e d D R A   t e r m   i s   c o u n t e d   o n l y   o n c e   i n   t h a t   l e v e l .  
N o t e   3 :   S y s t e m   O r g a n   C l a s s   ( S O C )   t e r m s   a r e   s o r t e d   u s i n g   a l p h a b e t i c a l   o r d e r .   W i t h i n   e a c h   S O C ,   p r e f e r r e d   t e r m s   a r e   s o r t e d  
u s i n g   a l p h a b e t i c a l   o r d e r .  
N o t e   4 :     M e d D R A   D i c t i o n a r y   ( V e r s i o n   2 3 . 0 )   w a s   u s e d   f o r   c o d i n g   a d v e r s e   e v e n t s .  
 
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S             D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                              
< P a t h / P r o g r a m   N a m e >      
P a g e   1   o f   X    
 
 
 
 


 
C o nfi d e nti al  
2 5 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 3 . 1 . 3  
S u m m a r y   o f   T r e a t m e n t - E m e r g e n t   A d v e r s e   E v e n t s   u p   t o   W e e k   8   b y   S y s t e m   O r g a n   C l a s s ,   P r e f e r r e d   T e r m ,   a n d  
S e v e r i t y  
S a f e t y   A n a l y s i s   S e t  
 
S y s t e m   O r g a n   C l a s s  
 
P l a c e b o  
B B T - 4 0 1 - 1 S   
O v e r a l l  
P r e f e r r e d   T e r m  
S e v e r i t y  
( N = X X )  
( N = X X )  
( N = X X )  
 
 
 
 
 
S u b j e c t s   w i t h   A n y   T E A E s   u p   t o   W e e k   8   
 
 
 
 
 
M i l d  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
M o d e r a t e  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
S e v e r e  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
 
 
 
 
S y s t e m   O r g a n   C l a s s   1  
 
 
 
 
 
M i l d  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
M o d e r a t e  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
S e v e r e  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
    P r e f e r r e d   T e r m   1  
 
 
 
 
 
M i l d  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
M o d e r a t e  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
S e v e r e  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
    P r e f e r r e d   T e r m   2  
 
 
 
 
 
M i l d  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
M o d e r a t e  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
S e v e r e  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N o t e   1 :   A   T r e a t m e n t   E m e r g e n t   A d v e r s e   E v e n t   ( T E A E )   i s   d e f i n e d   a s   a n   a d v e r s e   e v e n t   t h a t   o c c u r s   o r   w o r s e n s   o n   o r   a f t e r   t h e  
f i r s t   d o s e   o f   s t u d y   d r u g .  
N o t e   2 :   S u b j e c t s   w i t h   o n e   o r   m o r e   a d v e r s e   e v e n t s   w i t h i n   a   l e v e l   o f   M e d D R A   t e r m   i s   c o u n t e d   o n l y   o n c e   i n   t h a t   l e v e l   u s i n g  
t h e   m o s t   s e v e r e   i n c i d e n t .  
N o t e   3 :   S y s t e m   O r g a n   C l a s s   ( S O C )   t e r m s   a r e   s o r t e d   u s i n g   a l p h a b e t i c a l   o r d e r .   W i t h i n   e a c h   S O C ,   p r e f e r r e d   t e r m s   a r e   s o r t e d  
u s i n g   a l p h a b e t i c a l   o r d e r .  
N o t e   4 :   M e d D R A   D i c t i o n a r y   ( V e r s i o n   2 3 . 0 )   w a s   u s e d   f o r   c o d i n g   a d v e r s e   e v e n t s .  
 
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S             D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                              
< P a t h / P r o g r a m   N a m e >      
P a g e   1   o f   X    
 
 
 
 


 
C o nfi d e nti al  
2 6 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 3 . 1 . 4  
S u m m a r y   o f   T r e a t m e n t - E m e r g e n t   A d v e r s e   E v e n t s   u p   t o   W e e k   8   b y   S y s t e m   O r g a n   C l a s s ,   P r e f e r r e d   T e r m ,   a n d  
R e l a t i o n s h i p   t o   S t u d y   D r u g  
S a f e t y   A n a l y s i s   S e t  
 
S y s t e m   O r g a n   C l a s s  
 
P l a c e b o  
B B T - 4 0 1 - 1 S   
O v e r a l l  
P r e f e r r e d   T e r m  
R e l a t i o n s h i p   
( N = X X )  
( N = X X )  
( N = X X )  
 
 
 
 
 
S u b j e c t s   w i t h   A n y   T E A E s   u p   t o   W e e k   8   
 
 
 
 
 
R e l a t e d  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
N o t   R e l a t e d     
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
O v e r a l l  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
 
 
 
 
S y s t e m   O r g a n   C l a s s   1  
 
 
 
 
 
R e l a t e d  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
N o t   R e l a t e d     
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
O v e r a l l  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
    P r e f e r r e d   T e r m   1  
 
 
 
 
 
R e l a t e d  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
N o t   R e l a t e d     
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
O v e r a l l  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
    P r e f e r r e d   T e r m   2  
 
 
 
 
 
R e l a t e d  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
N o t   R e l a t e d     
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
O v e r a l l  
X X   ( X X . X )   
X X   ( X X . X )   
X X   ( X X . X )  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N o t e   1 :   A   T r e a t m e n t   E m e r g e n t   A d v e r s e   E v e n t   ( T E A E )   i s   d e f i n e d   a s   a n   a d v e r s e   e v e n t   t h a t   o c c u r s   o r   w o r s e n s   o n   o r   a f t e r   t h e  
f i r s t   d o s e   o f   s t u d y   d r u g .  
N o t e   2 :   S u b j e c t s   w i t h   o n e   o r   m o r e   a d v e r s e   e v e n t s   w i t h i n   a   l e v e l   o f   M e d D R A   t e r m   i s   c o u n t e d   o n l y   o n c e   i n   t h a t   l e v e l   u s i n g  
t h e   m o s t   r e l a t e d   i n c i d e n t .  
N o t e   3 :   S y s t e m   O r g a n   C l a s s   ( S O C )   t e r m s   a r e   s o r t e d   u s i n g   a l p h a b e t i c a l   o r d e r .   W i t h i n   e a c h   S O C ,   p r e f e r r e d   t e r m s   a r e   s o r t e d  
u s i n g   a l p h a b e t i c a l   o r d e r .  
N o t e   4 :   M e d D R A   D i c t i o n a r y   ( V e r s i o n   2 3 . 0 )   w a s   u s e d   f o r   c o d i n g   a d v e r s e   e v e n t s .  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S             D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                               
< P a t h / P r o g r a m   N a m e >      
P a g e   1   o f   X    
 
 
 
 
 


 
C o nfi d e nti al  
2 7 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 3 . 1 . 5  
S u m m a r y   o f   T r e a t m e n t - E m e r g e n t   S e r i o u s   A d v e r s e   E v e n t s   u p   t o   W e e k   8   b y   S y s t e m   O r g a n   C l a s s   a n d   P r e f e r r e d   T e r m    
S a f e t y   A n a l y s i s   s e t  
 
S y s t e m   O r g a n   C l a s s  
P l a c e b o  
B B T - 4 0 1 - 1 S  
O v e r a l l  
    P r e f e r r e d   T e r m  
( N = X X )  
( N = X X )  
( N = X X )  
 
 
 
 
S u b j e c t s   w i t h   A n y   S e r i o u s   T E A E s   u p   t o   W e e k   8  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
 
 
 
 
S y s t e m   O r g a n   C l a s s   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    …  
 
 
 
 
 
 
 
S y s t e m   O r g a n   C l a s s   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    …  
 
 
 
 
S y s t e m   O r g a n   C l a s s   3  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N o t e   1 :   A   T r e a t m e n t   E m e r g e n t   A d v e r s e   E v e n t   ( T E A E )   i s   d e f i n e d   a s   a n   a d v e r s e   e v e n t   t h a t   o c c u r s   o r   w o r s e n s   o n   o r   a f t e r   t h e  
f i r s t   d o s e   o f   s t u d y   d r u g .  
N o t e   2 :   S u b j e c t s   w i t h   o n e   o r   m o r e   a d v e r s e   e v e n t s   w i t h i n   a   l e v e l   o f   M e d D R A   t e r m   i s   c o u n t e d   o n l y   o n c e   i n   t h a t   l e v e l .  
N o t e   3 :   S y s t e m   O r g a n   C l a s s   ( S O C )   t e r m s   a r e   s o r t e d   u s i n g   a l p h a b e t i c a l   o r d e r .   W i t h i n   e a c h   S O C ,   p r e f e r r e d   t e r m s   a r e   s o r t e d  
u s i n g   a l p h a b e t i c a l   o r d e r .  
N o t e   4 :     M e d D R A   D i c t i o n a r y   ( V e r s i o n   2 3 . 0 )   w a s   u s e d   f o r   c o d i n g   a d v e r s e   e v e n t s .  
 
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S             D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                              
< P a t h / P r o g r a m   N a m e >      
P a g e   1   o f   X    
  
 


 
C o nfi d e nti al  
2 8 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 3 . 1 . 6  
S u m m a r y   o f   T r e a t m e n t - E m e r g e n t   A d v e r s e   E v e n t s   u p   t o   W e e k   8   L e a d i n g   t o   S t u d y   D i s c o n t i n u a t i o n   b y   S y s t e m   O r g a n  
C l a s s   a n d   P r e f e r r e d   T e r m    
S a f e t y   A n a l y s i s   s e t  
 
S y s t e m   O r g a n   C l a s s  
P l a c e b o  
B B T - 4 0 1 - 1 S  
O v e r a l l  
    P r e f e r r e d   T e r m  
( N = X X )  
( N = X X )  
( N = X X )  
 
 
 
 
S u b j e c t s   w i t h   A n y   T E A E s   u p   t o   W e e k   8   L e a d i n g   t o   S t u d y  
D i s c o n t i n u a t i o n  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
 
 
 
 
S y s t e m   O r g a n   C l a s s   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    …  
 
 
 
 
 
 
 
S y s t e m   O r g a n   C l a s s   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    …  
 
 
 
 
S y s t e m   O r g a n   C l a s s   3  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   1  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
    P r e f e r r e d   T e r m   2  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N o t e   1 :   A   T r e a t m e n t   E m e r g e n t   A d v e r s e   E v e n t   ( T E A E )   i s   d e f i n e d   a s   a n   a d v e r s e   e v e n t   t h a t   o c c u r s   o r   w o r s e n s   o n   o r   a f t e r   t h e  
f i r s t   d o s e   o f   s t u d y   d r u g .  
N o t e   2 :   S u b j e c t s   w i t h   o n e   o r   m o r e   a d v e r s e   e v e n t s   w i t h i n   a   l e v e l   o f   M e d D R A   t e r m   i s   c o u n t e d   o n l y   o n c e   i n   t h a t   l e v e l .  
N o t e   3 :   S y s t e m   O r g a n   C l a s s   ( S O C )   t e r m s   a r e   s o r t e d   u s i n g   a l p h a b e t i c a l   o r d e r .   W i t h i n   e a c h   S O C ,   p r e f e r r e d   t e r m s   a r e   s o r t e d  
u s i n g   a l p h a b e t i c a l   o r d e r .  
N o t e   4 :     M e d D R A   D i c t i o n a r y   ( V e r s i o n   2 3 . 0 )   w a s   u s e d   f o r   c o d i n g   a d v e r s e   e v e n t s .  
 
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S             D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                              
< P a t h / P r o g r a m   N a m e >      
P a g e   1   o f   X    
 
 
 
 


 
C o nfi d e nti al  
2 9 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 3 . 2 . 1  
S u m m a r y   o f   V a l u e s   a n d   C h a n g e s   o f   H e m a t o l o g y   P a r a m e t e r s   b y   V i s i t  
S a f e t y   A n a l y s i s   S e t  
 
L a b o r a t o r y   G r o u p :   X X X X X X X X X  
L a b o r a t o r y   T e s t :     X X X X X X X X X   ( U n i t )  
 
P l a c e b o  
B B T - 4 0 1 - 1 S  
O v e r a l l  
S t u d y   V i s i t  
( N = X X )  
( N = X X )  
( N = X X )  
 
 
 
 
B a s e l i n e  
 
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    M e d i a n  
X X . X  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
X X ,   X X  
 
 
 
 
V i s i t   X X  
 
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    M e d i a n  
X X . X  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
X X ,   X X  
 
 
 
 
V i s i t   X X   -   C h a n g e   f r o m   B a s e l i n e  
 
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    M e d i a n  
X X . X  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
X X ,   X X  
 
 
 
 
… .  
 
 
 
 
 
 
 
 
 
 
 
 
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S             D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                               
< P a t h / P r o g r a m   N a m e >      
P a g e   1   o f   X    
 
 


 
C o nfi d e nti al  
3 0 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 3 . 2 . 2  
S u m m a r y   o f   V a l u e s   a n d   C h a n g e s   o f   C h e m i s t r y   P a r a m e t e r s   b y   V i s i t  
S a f e t y   A n a l y s i s   S e t  
 
L a b o r a t o r y   G r o u p :   X X X X X X X X X  
L a b o r a t o r y   T e s t :     X X X X X X X X X   ( U n i t )  
 
P l a c e b o  
B B T - 4 0 1 - 1 S  
O v e r a l l  
S t u d y   V i s i t  
( N = X X )  
( N = X X )  
( N = X X )  
 
 
 
 
B a s e l i n e  
 
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    M e d i a n  
X X . X  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
X X ,   X X  
 
 
 
 
V i s i t   X X  
 
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    M e d i a n  
X X . X  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
X X ,   X X  
 
 
 
 
V i s i t   X X   -   C h a n g e   f r o m   B a s e l i n e  
 
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    M e d i a n  
X X . X  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
X X ,   X X  
 
 
 
 
 
 
 
 
… .  
 
 
 
 
 
 
 
 
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S             D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                               
< P a t h / P r o g r a m   N a m e >      
P a g e   1   o f   X    
 
 


 
C o nfi d e nti al  
3 1 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
 
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 3 . 3 . 1  
S u m m a r y   o f   V i t a l   S i g n   P a r a m e t e r s   b y   V i s i t  
S a f e t y   A n a l y s i s   S e t  
 
V i t a l   S i g n s   P a r a m e t e r :     X X X X X X X X X   ( U n i t )  
 
P l a c e b o  
B B T - 4 0 1 - 1 S  
O v e r a l l  
S t u d y   V i s i t  
( N = X X )  
( N = X X )  
( N = X X )  
 
 
 
 
B a s e l i n e  
 
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    M e d i a n  
X X . X  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
X X ,   X X  
 
 
 
 
V i s i t   X X  
 
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    M e d i a n  
X X . X  
X X . X  
X X . X  
 
 
 
 
V i s i t   X X   -   C h a n g e   f r o m   B a s e l i n e  
 
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    M e d i a n  
X X . X  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
X X ,   X X  
 
 
 
 
 
 
 
 
… .  
 
 
 
… .  
 
 
 
 
 
 
 
 
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S             D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                               
< P a t h / P r o g r a m   N a m e >      
P a g e   1   o f   X    
 
 


 
C o nfi d e nti al  
3 2 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 3 . 3 . 2  
S u m m a r y   o f   E l e c t r o c a r d i o g r a m   P a r a m e t e r s   b y   V i s i t  
S a f e t y   A n a l y s i s   S e t  
 
E l e c t r o c a r d i o g r a m   P a r a m e t e r :     X X X X X X X X X   ( U n i t )  
 
P l a c e b o  
B B T - 4 0 1 - 1 S  
O v e r a l l  
S t u d y   V i s i t  
( N = X X )  
( N = X X )  
( N = X X )  
 
 
 
 
B a s e l i n e  
 
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    M e d i a n  
X X . X  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
X X ,   X X  
 
 
 
 
V i s i t   X X  
 
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    M e d i a n  
X X . X  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
X X ,   X X  
 
 
 
 
V i s i t   X X   -   C h a n g e   f r o m   B a s e l i n e  
 
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    M e d i a n  
X X . X  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
X X ,   X X  
 
 
 
 
 
 
 
 
… .  
 
 
 
 
 
 
 
 
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S             D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                               
< P a t h / P r o g r a m   N a m e >      
P a g e   1   o f   X    
 
 


 
C o nfi d e nti al  
3 3 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 3 . 3 . 3  
S u m m a r y   o f   P h y s i c a l   E x a m i n a t i o n   b y   V i s i t  
S a f e t y   A n a l y s i s   S e t  
 
B o d y   C a t e g o r y :   x x x x x x x x x x  
S t u d y   V i s i t  
 
 
 
    B o d y   C a t e g o r y  
P l a c e b o  
B B T - 4 0 1 - 1 S  
O v e r a l l  
        S t a t u s   [ 1 ]  
( N = X X )  
( N = X X )  
( N = X X )  
 
 
 
 
B a s e l i n e  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
        N C S  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
        C S  
 
 
 
 
 
 
 
V i s i t   X X  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
        N C S  
X X   ( X X . X )  
X X   ( X X . X )  
X X   ( X X . X )  
        C S  
 
 
 
 
 
 
 
 
 
 
 
… .  
 
 
 
 
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S             D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                               
< P a t h / P r o g r a m   N a m e >      
P a g e   1   o f   X    
 
 


 
C o nfi d e nti al  
3 4 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
 
T a b l e   1 4 . 4 . 1 . 1  
P l a s m a   B B T - 4 0 1 - 1 S   C o n c e n t r a t i o n s   ( n g / m L )   F o l l o w i n g   t h e   A d m i n i s t r a t i o n   o f   B B T - 4 0 1 - 1 S   o r   P l a c e b o  
  
P K   A n a l y s i s   S e t   
 
 
 
P l a c e b o  
B B T - 4 0 1 - 1 S  
S t u d y   V i s i t  
( N = X X )  
( N = X X )  
 
 
 
B a s e l i n e   P r e - d o s e  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    C o e f f i c i e n t   o f   V a r i a n c e   ( C V   % )  
X X . X  
X X . X  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
B a s e l i n e   3 H   P o s t   d o s e  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    C o e f f i c i e n t   o f   V a r i a n c e   ( C V   % )  
X X . X  
X X . X  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
B a s e l i n e   6 H   P o s t   d o s e  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    C o e f f i c i e n t   o f   V a r i a n c e   ( C V   % )  
X X . X  
X X . X  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
 
 
 
… .  
 
 
 
 
 
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S             D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                               
 
< P a t h / P r o g r a m   N a m e >                                                                                                                                                                               P a g e   1   o f   X      
 
 
 


 
C o nfi d e nti al  
3 5 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
 
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
< D M C   o r   F i n a l   A n a l y s i s >  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
T a b l e   1 4 . 4 . 2 . 1  
T i s s u e   B B T - 4 0 1 - 1 S   C o n c e n t r a t i o n s   ( n g / g )   F o l l o w i n g   t h e   A d m i n i s t r a t i o n   o f   B B T - 4 0 1 - 1 S   o r   P l a c e b o  
P K   A n a l y s i s   S e t  
 
P l a c e b o  
B B T - 4 0 1 - 1 S  
S t u d y   V i s i t  
( N = X X )  
( N = X X )  
 
 
 
C o l o n   S c r e e n i n g  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    C o e f f i c i e n t   o f   V a r i a n c e   ( C V   % )  
X X . X  
X X . X  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
R e c t u m   S c r e e n i n g  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    C o e f f i c i e n t   o f   V a r i a n c e   ( C V   % )  
X X . X  
X X . X  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
C o l o n   W e e k   8  
 
 
    n   ( m i s s i n g )  
X X   ( X X )  
X X   ( X X )  
    M e a n   ( S D )  
X X . X ( X . X X )  
X X . X ( X . X X )  
    C o e f f i c i e n t   o f   V a r i a n c e   ( C V   % )  
X X . X  
X X . X  
    M e d i a n  
X X . X  
X X . X  
    M i n ,   M a x  
X X ,   X X  
X X ,   X X  
 
 
 
 
 
 
… .  
 
 
 
 
 
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S             D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                             
< P a t h / P r o g r a m   N a m e >                                                                                                                                                                               P a g e   1   o f   X     
 
 
 
 


 
C o nfi d e nti al  
3 6 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 1 . 1    
P a t i e n t   D i s p o s i t i o n  
 
S u b j e c t  
I D  
R a n d o m i z e d  
( Y e s / N o )  
C o h o r t   T r e a t m e n t   D o s e d  
( Y e s / N o )  
A n a l y s i s  
P o p u l a t i o n  
D i d   t h e   s u b j e c t   c o m p l e t e  
i n i t i a l   8 - w e e k  
t r e a t m e n t ?   ( Y e s / N o )  
I f   N o ,   w h a t   w a s  
t h e   r e a s o n   f o r  
e a r l y   t e r m i n a t i o n  
o f   i n i t i a l   8 - w e e k  
t r e a t m e n t ?  
D i d   t h e   s u b j e c t  
c o m p l e t e   V i s i t  
6   ( W e e k   1 6 ) ?  
( Y e s / N o )  
x x - y y y   
Y e s / N o   
x x x   
x x x   
Y e s / N o   
m I T T / P P / S A F / P K   
Y e s / N o  
x x x x  
Y e s / N o  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                                
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
P a g e   1   o f   X    
 
 
 


 
C o nfi d e nti al  
3 7 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 2 . 1    
I n c l u s i o n / E x c l u s i o n   C r i t e r i a   F i n d i n g s   –   D e v i a t i o n s  
 
S u b j e c t   I D  
C r i t e r i a   T y p e    
C r i t e r i a   D e t a i l s  
V a l u e    
x x - y y y  
I n c l u s i o n / E x c l u s i o n  
x x x x x x x x x x x x x x x x x x x x x x x x x x  
Y e s / N o  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                                
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
P a g e   1   o f   X    
 
P r o g r a m m i n g   n o t e :  
1 .   O n l y   i n c l u d e   s u b j e c t s   w h o   a n s w e r   N o   t o   a n y   i n c l u s i o n   C r i t e r i a   o r   a n s w e r   Y e s   t o   a n y   E x c l u s i o n   C r i t e r i a .  
2 .   F o r   e a c h   s u b j e c t ,   o n l y   d i s p l a y   i n c l u s i o n   C r i t e r i a   w i t h   a n s w e r   =   N o   a n d   E x c l u s i o n   C r i t e r i a   w i t h   a n s w e r   =   Y e s .  
 
 


 
C o nfi d e nti al  
3 8 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 4 . 1    
D e m o g r a p h i c s   a n d   B a s e l i n e   C h a r a c t e r i s t i c s  
  
 
S u b j e c t   I D   
C o h o r t   
T r e a t m e n t   A g e ( Y e a r s )   G e n d e r  
E t h n i c i t y  
R a c e  
x x - y y y   
x x x   
x x x   
x x  
M / F  
x x x x  
x x x x  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                                
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
P a g e   1   o f   X    
 
 
 


 
C o nfi d e nti al  
3 9 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 4 . 2    
M e d i c a l   H i s t o r y  
 
 
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                                
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
P a g e   1   o f   X    
 
 
 
S u b j e c t  
I D  
C o h o r t /  
T r e a t m e n t  
B o d y   S y s t e m /  
C a t e g o r y  
D e s c r i p t i o n   o f   M e d i c a l  
H i s t o r y  
D a t e   o f   O n s e t  
D a t e   o f   R e s o l u t i o n  
x x - y y y   
x x x / x x x x   
x x x x x x  
x x x x x x x x x x x x x  
D D - M M M - Y Y Y Y  
D D - M M M - Y Y Y Y / O n g o i n g  
S u b j e c t  
I D  
C o h o r t /  
T r e a t m e n t  
D o e s   t h e  
s u b j e c t  
h a v e  
a s s e s s e d  
M a y o   S c o r e  
p r e v i o u s l y ?  
( Y e s / N o )  
M a y o   S c o r e  
T y p e / S c o r e / D a t
e   o f   A s s e s s e d  
D o e s   t h e  
s u b j e c t   h a v e  
e x p e r i e n c e d  
a n y  
h o s p i t a l i z a t
i o n s   d u e   t o  
U C ?   ( Y e s / N o )  
D a t e   o f  
H o s p i t a l i z a
t i o n /  
T r e a t m e n t s  
R e c e i v e d  
D o e s   t h e   s u b j e c t  
c u r r e n t l y   h a v e  
a n y  
e x t r a i n t e s t i n a l  
m a n i f e s t a t i o n s  
o f   U C ?   ( Y e s / N o )  
S i t e s   
E x t r a i n t e s t i
n a l  
M a n i f e s t a t i o
n s  
x x - y y y   
x x x / x x x x   
Y e s / N o   
x x x x x / x x x / D D -
M M M - Y Y  
Y e s / N o   
D D - M M M -
Y Y / x x x x x x  
 
Y e s / N o  
x x x / x x
x / x x x  
x x x x x  
S u b j e c t  
I D  
C o h o r t /  
T r e a t m e n t  
H i s t o r y   o f  
A l c o h o l i s m   a n d  
D r u g   A b u s e ?  
( y e s / N o )  
I f   ‘ Y e s ,  
d e s c r i b e  
y e a r  
S m o k i n g  
S t a t u s  
I f   ‘ C u r r e n t  
s m o k e r ’ ,   h o w  
m a n y   c i g a r e t t e s  
s m o k e d   i n   a   d a y  
W e e k l y   A l c o h o l  
C o n s u m p t i o n  
H a s   t h e   s u b j e c t  
t a k e n   a n y  
m e d i c a t i o n s   a n d / o r  
U C   t h e r a p i e s  
w i t h i n   3   m o n t h s  
p r i o r   t o   V 1  
( S c r e e n i n g ) ?  
( Y e s / N o )  
x x - y y y   
x x x / x x x x   
Y e s / N o  
x x x x x x x   
 
x x  
T y p e / a m o u n t / u n i t   
  Y e s / N o  


 
C o nfi d e nti al  
4 0 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 4 . 3    
P r i o r   a n d   C o n c o m i t a n t   M e d i c a t i o n s  
  
 
S u b j e c t  
I D  
C o h o r t /  
T r e a t m e n t  
M e d i c a t i o n   N a m e   
S t a r t   D a t e        S t o p   D a t e   
D o s e   D o s e  
F o r m  
U n i t   R o u t e   F r e q u e n c y   I n d i c a t i o n  
x x - y y y   
x x x / x x x   
x x  
D D - M M M -
Y Y Y Y    
D D - M M M -
Y Y Y Y / O n g o i n g  
 
x x x x   x x x x   
x x x x   x x x x   
x x x x   
x x x x  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                                
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
P a g e   1   o f   X    
 
 
 
 
 


 
C o nfi d e nti al  
4 1 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 5 . 1    
S t u d y   D r u g   A d m i n i s t r a t i o n   a n d   L o g  
  
 
S u b j e c t  
I D  
C o h o r t  
/ T r e a t m e n t  
V i s i t   D a t e   o f   I P  
R e t u r n e d  
N u m b e r   o f  
b o t t l e s  
r e t u r n e d  
N u m b e r   o f   d a y s   t h a t   I P  
d o s i n g   s h o u l d   b e   t a k e n  
d u r i n g   p r e v i o u s   t r e a t m e n t  
p e r i o d   ( f r o m   l a s t   v i s i t  
d a t e   t o   l a s t   d o s i n g   d a t e )  
N u m b e r   o f   d a y s   t h a t  
I P   d o s i n g   w a s  
m i s s e d   d u r i n g  
p r e v i o u s   t r e a t m e n t  
p e r i o d  
P a t i e n t  
C o m p l i a n c e  
( % )  
x x - y y y   
x x x / x x x   
x x x x   
D D - M M M -
Y Y Y Y / N o t  
D o n e    
 
x x x  
x x x x  
x x x x  
x x x x  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                                
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
P a g e   1   o f   X    
 
 
 


 
C o nfi d e nti al  
4 2 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 6 . 1    
T o t a l   M a y o   S c o r e  
  
 
S u b j e c t   I D   
C o h o r t  
/ T r e a t m e n t  
V i s i t   
D a t e   o f   L o c a l   R e a d  
S c o r e   A s s e s s e d      
 
L o c a l   R e a d  
S c o r e  
C e n t r a l   R e a d  
S c o r e  
E v i d e n c e   o f   U C  
e x t e n d i n g   p r o x i m a l  
t o   t h e   r e c t u m ?  
T o t a l   M a y o  
S c o r e  
x x - y y y  
x x x / x x x   
x x x x   
D D - M M M - Y Y Y Y / N o t   D o n e  
 
x x x x x   
x x x x x  
x x x x x  
x x x x x  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                                       D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                         
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
                    P a g e   1   o f   X  
 
 
 
 


 
C o nfi d e nti al  
4 3 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 6 . 2    
P a r t i a l   M a y o   S c o r e  
  
 
S u b j e c t   I D   
C o h o r t  
/ T r e a t m e n t  
V i s i t   
D a t e   o f  
A s s e s s m e n t  
S t o o l  
F r e q u e n c y  
R e c t a l  
B l e e d i n g  
P h y s i c i a n ’ s  
G l o b a l  
A s s e s s m e n t  
P a r t i a l   M a y o   S c o r e  
x x - y y y   
x x x / x x x  
x x x x   
D D - M M M - Y Y Y Y / N o t  
D o n e    
 
x x x x x x   
x x x x x x  
x x x x x x  
x x x x  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                                       D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                        
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
                  P a g e   1   o f   X    
 
 
 


 
C o nfi d e nti al  
4 4 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 6 . 3    
H i s t o l o g i c   A s s e s s m e n t   o f   E n d o s c o p i c   B i o p s y  
  
 
S u b j e c t  
I D  
C o h o r t  
/ T r e a t m e n t  
V i s i t   
D a t e  
S p e c i m e n   R e g i o n   o f   O r i g i n     
L a b o r a t o r y   T e s t   
R e s u l t s  
x x - y y y   
x x x / x x x   
x x x x   
D D - M M M - Y Y Y Y  
 
 
x x x x  
x x x x x  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                       D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                               
< P a t h / P r o g r a m   N a m e >       
      
  
                             
  
  
  
  
  
                              P a g e   1   o f   X    
 
P r o g r a m m i n g   n o t e :  
F o r   r e s u l t s ,   p r e s e n t   b o t h   n u m e r i c a l   a n d   c h a r a c t e r   v a l u e s   i f   a v a i l a b l e .  
 


 
C o nfi d e nti al  
4 5 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 6 . 4    
U l c e r a t i v e   C o l i t i s   E n d o s c o p i c   I n d e x   o f   S e v e r i t y  
  
 
S u b j e c t  
I D  
C o h o r t  
/ T r e a t m e n t  
V i s i t   
D a t e   o f  
A s s e s s m e n t  
V a s c u l a r  
P a t t e r n  
B l e e d i n g   
E r o s i o n s   a n d   U l c e r s   
S c o r e  
x x - y y y   
x x x / x x x   
x x x x   
D D - M M M - Y Y Y Y / N o t  
D o n e    
 
x x x x x x  
x x x x x x   
x x x x x x  
x x x x  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >     D r a f t - D D M M M Y Y Y   H H : M M : S S     D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y          
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
      P a g e   1   o f   X   
 
 
 
 


 
C o nfi d e nti al  
4 6 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 6 . 5    
S h o r t   I n f l a m m a t o r y   B o w e l   D i s e a s e   Q u e s t i o n n a i r e  
  
 
S u b j e c t  
I D  
C o h o r t  
/ T r e a t m e n t  
V i s i t   D a t e   a n d  
T i m e   o f  
A s s e s s m e n t  
Q 1 :   H o w   o f t e n   h a s  
t h e   f e e l i n g   o f  
f a t i g u e   o r   b e i n g  
t i r e d   a n d   w o r n  
o u t   b e e n   a  
p r o b l e m   f o r   y o u  
d u r i n g   t h e  p a s t   2  
w e e k s ?  
Q 2 :   H o w   o f t e n  
d u r i n g   t h e   l a s t   2  
w e e k s   h a v e   y o u  
d e l a y e d   o r  
c a n c e l e d   a   s o c i a l  
e n g a g e m e n t  
b e c a u s e   o f   y o u r  
b o w e l   p r o b l e m ?  
Q 3 :   H o w   m u c h  
d i f f i c u l t y   h a v e   y o u  
h a d ,   a s   a   r e s u l t   o f  
y o u r   b o w e l   p r o b l e m s ,  
d o i n g   l e i s u r e   o r  
s p o r t s   a c t i v i t i e s  
y o u   w o u l d   h a v e   l i k e d  
t o   h a v e   d o n e   d u r i n g  
t h e   p a s t   2   w e e k s ?  
Q 4 :   H o w   o f t e n  
d u r i n g   t h e   l a s t   2  
w e e k s   h a v e   y o u  
b e e n   t r o u b l e d   b y  
p a i n   i n   t h e  
a b d o m e n ?  
Q 5 :   H o w   o f t e n  
d u r i n g   t h e  
l a s t   2   w e e k s  
h a v e   y o u   f e l t  
d e p r e s s e d   o r  
d i s c o u r a g e d ?    
x x - y y y   
x x x / x x x   
x x x x   x x x x x   
x x x x x x  
x x x x x x  
x x x x x x  
 
x x x x x x  
x x x x x x  
 
S u b j e c t  
I D  
C o h o r t  
/ T r e a t m e n t  
V i s i t   D a t e   a n d  
T i m e   o f  
A s s e s s m e n t  
Q 6 :   O v e r a l l ,   i n  
t h e   l a s t   2   w e e k s ,  
h o w   m u c h   o f   a  
p r o b l e m   h a v e   y o u  
h a d   w i t h   p a s s i n g  
l a r g e   a m o u n t s   o f  
g a s ?  
Q 7 :   O v e r a l l ,   i n  
t h e   l a s t   2   w e e k s ,  
h o w   m u c h   o f   a  
p r o b l e m   h a v e   y o u  
h a d   m a i n t a i n i n g  
o r   g e t t i n g   t o ,  
t h e   w e i g h t   y o u  
w o u l d   l i k e   t o   b e  
a t ?  
 
Q 8 :   H o w   o f t e n  
d u r i n g   t h e   l a s t   2  
w e e k s   h a v e   y o u  
f e l t   r e l a x e d   a n d  
f r e e   o f   t e n s i o n ?  
Q 9 :   H o w   m u c h   o f   t h e  
t i m e   d u r i n g   t h e   l a s t  
2   w e e k s   h a v e   y o u  
b e e n   t r o u b l e d   b y   a  
f e e l i n g   o f   h a v i n g   t o  
g o   t o   t h e   b a t h r o o m  
e v e n   t h o u g h   y o u r  
b o w e l s   w e r e   e m p t y ?  
Q 1 0 :   H o w   m u c h  
o f   t h e   t i m e  
d u r i n g  t h e   l a s t  
2   w e e k s   h a v e  
y o u   f e l t   a n g r y  
a s   a   r e s u l t   o f  
y o u r   b o w e l  
p r o b l e m ?      
x x - y y y   
x x x / x x x   
x x x x   x x x x x   
x x x x x x  
x x x x x x  
x x x x x x  
 
x x x x x x  
x x x x x x  
 
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                                 D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                      
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
            P a g e   1   o f   X    
 
P r o g r a m m i n g   n o t e :  
F o r   e a c h   q u e s t i o n ,   p r e s e n t   b o t h   n u m e r i c a l   a n d   c h a r a c t e r   r e s p o n s e s   i f   a v a i l a b l e .  
 
 


 
C o nfi d e nti al  
4 7 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 6 . 6    
B i o m a r k e r  
  
 
S u b j e c t   I D   
C o h o r t  
/ T r e a t m e n t  
V i s i t   
B i o m a r k e r  
P a r a m e t e r  
D a t e   o f   S a m p l e  
R e s u l t s  
x x - y y y   
x x x / x x x  
x x x x   
x x x x    
D D - M M M - Y Y Y Y / N o t   D o n e    
x x x x x  
 
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >       D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                                
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
                P a g e   1   o f   X   
 
P r o g r a m m i n g   n o t e :   t h i s   s h o u l d   i n c l u d e   C - r e a c t i v e   p r o t e i n   [ C R P ] ,   f e c a l   c a l p r o t e c t i n ,   a n d   f e c a l   l a c t o f e r r i n .  
 
 


 
C o nfi d e nti al  
4 8 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 7 . 1    
A d v e r s e   E v e n t s  
  
 
S u b j e c t  
I D  
C o h o r t  
/ T r e a t m e n t  
A E  
T e r m  
D e s c r i p t i o n   S e v e r i t y    D a t e   o f  
O n s e t /  
R e s o l u t i o n  
O u t c o m e
 
 
A c t i o n  
t a k e n  
w i t h  
S t u d y  
D r u g  
R e l a t e d n e s s   I s   t h e  
a d v e r s e  
e v e n t  
s e r i o u s ?  
( Y e s / N o )  
S e r i o u s n e s s  
C r i t e r i a  
D a t e   o f  
D e a t h  
x x - y y y   
x x x / x x x   
x x x x   
x x x x x x x x   
x x x x     
D D - M M M - Y Y Y Y /  
D D - M M M - Y Y Y Y /  
O n g o i n g  
 
x x x x x x x
 
 
x x x x x x x   
x x x x x   
Y e s / N o   
x x x x x x   
D D - M M M -
Y Y Y Y  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                               D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                        
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
        P a g e   1   o f   X    
 
 
 


 
C o nfi d e nti al  
4 9 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 7 . 2    
S e r i o u s   A d v e r s e   E v e n t s  
  
 
S u b j e c t  
I D  
C o h o r t  
/ T r e a t m e n t  
A E   T e r m   D e s c r i p t i o n   
S e v e r i t y     D a t e   o f  
O n s e t /  
R e s o l u t i o n  
O u t c o m e
 
 
A c t i o n  
t a k e n  
w i t h  
S t u d y  
D r u g  
R e l a t e d n e s s   I s   t h e  
a d v e r s e  
e v e n t  
s e r i o u s ?  
( Y e s / N o )  
S e r i o u s n e s s  
C r i t e r i a  
D a t e   o f  
D e a t h  
x x - y y y   
x x x / x x x   
x x x x   
x x x x x x x x   
x x x x     
D D - M M M - Y Y Y Y /  
D D - M M M - Y Y Y Y /  
O n g o i n g  
 
x x x x x x x
 
 
x x x x x x x   x x x x x   
Y e s / N o   
x x x x x x   
D D - M M M -
Y Y Y Y  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                                   D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                     
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
              P a g e   1   o f   X    
 
 
 


 
C o nfi d e nti al  
5 0 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 7 . 3    
A d v e r s e   E v e n t s   L e a d i n g   t o   P e r m a n e n t   W i t h d r a w a l   o f   S t u d y   T r e a t m e n t   o r   D i s c o n t i n u a t i o n   f r o m   t h e   S t u d y  
  
 
S u b j e c t  
I D  
C o h o r t  
/ T r e a t m e n t  
A E   T e r m   
D e s c r i p t i o n   
S e v e r i t y     D a t e   o f  
O n s e t /  
R e s o l u t i o n  
O u t c o m e
 
 
A c t i o n  
t a k e n  
w i t h  
S t u d y  
D r u g  
R e l a t e d n e s s   I s   t h e  
a d v e r s e  
e v e n t  
s e r i o u s ?  
( Y e s / N o )  
S e r i o u s n e s s  
C r i t e r i a  
D a t e   o f  
D e a t h  
x x - y y y   
x x x / x x x   
x x x x   
x x x x x x x x   
x x x x     
D D - M M M - Y Y Y Y /  
D D - M M M - Y Y Y Y /  
O n g o i n g  
 
x x x x x x x
 
 
x x x x x x x   x x x x x   
Y e s / N o   
x x x x x x   
D D - M M M -
Y Y Y Y  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                             D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                           
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
              P a g e   1   o f   X    
 
 
 


 
C o nfi d e nti al  
5 1 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 7 . 4    
A d v e r s e   E v e n t s   L e a d i n g   t o   D e a t h  
  
 
S u b j e c t  
I D  
C o h o r t  
/ T r e a t m e n t  
A E  
T e r m  
D e s c r i p t i o n   S e v e r i t y    D a t e   o f  
O n s e t /  
R e s o l u t i o n  
O u t c o m e
 
 
A c t i o n  
t a k e n  
w i t h  
S t u d y  
D r u g  
R e l a t e d n e s s   I s   t h e  
a d v e r s e  
e v e n t  
s e r i o u s ?  
( Y e s / N o )  
S e r i o u s n e s s  
C r i t e r i a  
D a t e   o f  
D e a t h  
P r i m a r y  
C a u s e  
o f  
D e a t h  
x x - y y y   
x x x / x x x   
x x x x   x x x x x x x x   
x x x x     
D D - M M M - Y Y Y Y /  
D D - M M M - Y Y Y Y /  
O n g o i n g  
 
x x x x x x x
 
 
x x x x x x x   x x x x x   
Y e s / N o   
x x x x x x   
D D - M M M -
Y Y Y Y  
x x x x x  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                             D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                           
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
            P a g e   1   o f   X    
 
 
 


 
C o nfi d e nti al  
5 2 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 8 . 1  
H e m a t o l o g y  
  
 
S u b j e c t  
I D  
C o h o r t  
/ T r e a t m e n t  
V i s i t   
D a t e   o f   S a m p l e   
L a b o r a t o r y  
P a r a m e t e r ( U n i t )  
R e s u l t s
 
 
E v a l u a t i o n   ( N C S / C S )  
x x - y y y   
x x x / x x x   
x x x x   
D D - M M M - Y Y Y Y / N o t  
D o n e    
 
x x x x    
x x x x  
N C S / C S  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                                       D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :  
D D M M M Y Y Y Y                                
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
      P a g e   1   o f   X   
 
 
 


 
C o nfi d e nti al  
5 3 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 8 . 2  
C h e m i s t r y  
  
 
S u b j e c t  
I D  
C o h o r t  
/ T r e a t m e n t  
V i s i t   
D a t e   o f   S a m p l e   
L a b o r a t o r y  
P a r a m e t e r ( U n i t )  
R e s u l t s
 
 
E v a l u a t i o n   ( N C S / C S )  
x x - y y y   
x x x / x x x   
x x x x   
D D - M M M - Y Y Y Y / N o t   D o n e     x x x x    
 
x x x x  
N C S / C S  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                 D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                                
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
    P a g e   1   o f   X    
 
 
 


 
C o nfi d e nti al  
5 4 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
 
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 8 . 4  
V i t a l   S i g n s  
  
 
S u b j e c t   I D   
C o h o r t  
/ T r e a t m e n t  
V i s i t   
D a t e   o f   A s s e s s m e n t   
P a r a m e t e r   ( U n i t )  
R e s u l t s  
 
x x - y y y   
x x x / x x x  
x x x x  
D D - M M M - Y Y Y Y / N o t   D o n e     x x x x    
 
x x x x  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                                       D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                         
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
                  P a g e   1   o f   X    
 
 
 


 
C o nfi d e nti al  
5 5 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 8 . 5  
E l e c t r o c a r d i o g r a m  
  
 
S u b j e c t  
I D  
C o h o r t  
/ T r e a t m e n t  
V i s i t   
D a t e   a n d   T i m e   o f   E C G   
P a r a m e t e r ( U n i t )   
R e s u l t s
 
 
O v e r a l l  
I n t e r p r e t a t i o n  
I f   ‘ N C S ’   o r   C S ’ ,   t h e n  
d e s c r i b e  
x x - y y y   
x x x / x x x   
x x x x   
D D - M M M -
Y Y Y Y / H H : M M / N o t  
D o n e / W a i v e d   p e r  
p r o t o c o l    
 
x x x x    
x x x x  
x x x x x  
x x x x x  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                                       D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                            
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
                  P a g e   1   o f   X    
 
 
 


 
C o nfi d e nti al  
5 6 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 8 . 6  
P h y s i c a l   E x a m i n a t i o n  
  
 
S u b j e c t  
I D  
C o h o r t  
/ T r e a t m e n t  
V i s i t   
D a t e   o f  
P h y s i c a l  
E x a m i n a t i o n  
B o d y   C a t e g o r y   
S t a t u s ( N C S / C S )
 
 
A b n o r m a l   F i n d i n g  
x x - y y y   
x x x / x x x   
x x x x   
D D - M M M -
Y Y Y Y / N o t  
D o n e / W a i v e d  
p e r   p r o t o c o l  
   
x x x x x x x    
N C S / C S  
x x x x x x x x x x x x x x x x  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                                       D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :  
D D M M M Y Y Y Y                                
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
        P a g e   1   o f   X    
 
 
 


 
C o nfi d e nti al  
5 7 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 9 . 1  
I n d i v i d u a l   P l a s m a   C o n c e n t r a t i o n   D a t a  
  
 
S u b j e c t  
I D  
C o h o r t  
/ T r e a t m e n t  
V i s i t   
D a t e   o f  
S a m p l i n g  
T i m e   P o i n t  
T i m e   o f   S a m p l i n g  
R e s u l t s  
x x - y y y   
x x x / x x x   
x x x x   
D D - M M M -
Y Y Y Y / N o t   D o n e    
P r e - d o s e / 3 H   P o s t  
d o s e / 6 H   P o s t   d o s e  
 
H H : M M / N o t   D o n e  
x x x x  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                               D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                       
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
      P a g e   1   o f   X    
 
 
 


 
C o nfi d e nti al  
5 8 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 9 . 2  
I n d i v i d u a l   T i s s u e   C o n c e n t r a t i o n   D a t a  
  
 
S u b j e c t   I D   
C o h o r t  
/ T r e a t m e n t  
V i s i t  
D a t e   o f   S a m p l i n g  
R e s u l t s  
x x - y y y   
x x x / x x x  
C o l o n   S c r e e n i n g / R e c t u m   S c r e e n i n g / C o l o n  
W e e k   8   / R e c t u m   W e e k   8  
 
D D - M M M - Y Y Y Y / N o t   D o n e     
x x x x  
 
 
 


 
C o nfi d e nti al  
5 9 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 1 0 . 1  
R a n d o m i z a t i o n  
  
 
S u b j e c t  
I D  
W h i c h   c o h o r t   i s   t h e  
s u b j e c t   i n ?  
 
I s   t h i s   s u b j e c t   e l i g i b l e   t o   p a r t i c i p a t e  
i n   t h i s   s t u d y ?   ( Y e s / N o )  
I f   Y e s ,   R a n d o m i z a t i o n   C o d e  
x x - y y y   
x x x  
Y e s / N o  
x x x x  
 
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                                 D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                               
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
                  P a g e   1   o f   X    
 
 
 


 
C o nfi d e nti al  
6 0 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 1 0 . 2  
I P  
  
 
S u b j e c t  
I D  
C o h o r t  
/ T r e a t m e n t  
V i s i t   
D o s e ( m g / d a y )   
I P   C o d e   
D a t e   a n d   T i m e   o f   I P  
A d m i n i s t r a t i o n   a t   S i t e  
D a t e   o f   I P  
D i s t r i b u t e d  
R e - d i s t r i b u t e d   I P  
C o d e s  
x x - y y y   
x x x / x x x   
x x x x   
x x x    
x x x  
D D - M M M - Y Y Y Y / H H : M M / N o t   D o n e   
D D - M M M - Y Y Y Y / N o t  
D o n e  
 
x x x x / N o n e  
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                                       D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                            
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
                  P a g e   1   o f   X    
 
 
 


 
C o nfi d e nti al  
6 1 /6 1   
  
  
  v 2. 1  Dr aft , 2 2  J u l 2 0 2 0  
B r i d g e   B i o t h e r a p e u t i c s ,   I n c .  
 
C o n f i d e n t i a l  
P R O T O C O L :   B B T 4 0 1 - U C - U S 0 2  
 
< D M C   o r   F i n a l   A n a l y s i s >  
D r a f t   V e r s i o n   ( t o   m e n t i o n   o n l y   i f   n o t   f i n a l )  
 
L i s t i n g   1 6 . 2 . 1 0 . 3  
I n v e s t i g a t o r   S i g n a t u r e  
  
 
S u b j e c t   I D  
C o h o r t  
/ T r e a t m e n t  
D i d   y o u   ( P r i n c i p a l   I n v e s t i g a t o r )  
r e v i e w   a l l   t h e   s t u d y   i n f o r m a t i o n ?  
( Y e s / N o )  
N a m e  
D a t e  
T y p e  
x x - y y y  
x x x / x x x  
Y e s / N o  
x x x x  
x x x x  
x x x x  
 
O u t p u t   I D :   < U n i q u e   O u t p u t   i d   i . e .   t - e n r o l >                     D r a f t - D D M M M Y Y Y   H H : M M : S S         D A T E   O F   D A T A B A S E   E X T R A C T I O N :   D D M M M Y Y Y Y                              
< P a t h / P r o g r a m   N a m e >       
  
  
  
  
  
  
  
  
  
  
  
  
  P a g e   1   o f   X    


3 1  J ul  2 0 2 0
3 1  J ul  2 0 2 0


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
3 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
T A B L E  O F  C O N T E N T S  
 
Gl o s s ar y  a n d  A b br e vi ati o n s  .......................................................................................... 5  
1   R E VI SI O N  HI S T O R Y  ................................................................................................... 6  
2   S T U D Y  O B J E C TI V E S  A N D  E N D P OI N T S  ................................................................... 6  
2. 1  
St u d y  O bj e cti v e s  ............................................................................................................ 6  
2. 1. 1  
Pri m ar y  O bj e cti v e  ................................................................................................................... 6  
2. 1. 2  
S e c o n d ar y  O bj e cti v e s  ............................................................................................................ 6  
2. 2  
St u d y  E n d p oi nt s  ............................................................................................................ 6  
2. 2. 1  
Pri m ar y  E n d p oi nt s  .................................................................................................................. 6  
2. 2. 2  
S e c o n d ar y  E n d p oi nt s  ............................................................................................................. 6  
3   S T U D Y  D E SI G N  .......................................................................................................... 7  
3. 1  
S u m m ar y  of  St u d y  D e si g n  ............................................................................................ 7  
3. 2  
D et er mi n ati o n  of  S a m pl e  Si z e  ...................................................................................... 9  
3. 3  
Tr e at m e nt s  ..................................................................................................................... 9  
3. 4  
R a n d o mi z ati o n  a n d  Bli n di n g  ........................................................................................ 9  
4   S T A TI S TI C A L  M E T H O D S  ......................................................................................... 1 0  
4. 1  
G e n er al  C o n si d er ati o n s  .............................................................................................. 1 0  
4. 2  
A dj u st m e nt s f or  C o v ari at e s  ........................................................................................ 1 0  
4. 3  
A n al y si s  S et s  ............................................................................................................... 1 0  
4. 3. 1  
M o difi e d I nt e nt -t o-Tr e at  ........................................................................................................ 1 0  
4. 3. 2  
P er -Pr ot o c ol  ......................................................................................................................... 1 1  
4. 3. 3  
S af et y  ................................................................................................................................... 1 1  
4. 3. 4  
P h ar m a c o ki n eti c s ( P K)  ......................................................................................................... 1 1  
4. 4  
B a s eli n e  a n d  P o st b a s eli n e  D efi niti o n  ........................................................................ 1 1  
4. 5  
H a n dli n g  of  Dr o p o ut s  or  Mi s si n g  D at a  ...................................................................... 1 1  
4. 6  
Tr e at m e nt  Gr o u p  C o m p ar a bilit y  ................................................................................. 1 1  
4. 6. 1  
P ati e nt  Di s p o siti o n  ............................................................................................................... 1 1  
4. 6. 2  
Pr ot o c ol  D e vi ati o n s  .............................................................................................................. 1 1  
4. 6. 3  
P ati e nt  C h ar a ct eri sti c s  ......................................................................................................... 1 2  
4. 6. 4  
Pri or  a n d  C o n c o mit a nt  T h er a p y  ........................................................................................... 1 2  
4. 7  
Effi c a c y  A n al y s e s  ........................................................................................................ 1 2  
4. 7. 1  
Pri m ar y  Effi c a c y  A n al y si s  ..................................................................................................... 1 3  
4. 7. 2  
S e c o n d ar y  Effi c a c y  A n al y s e s  ............................................................................................... 1 3  
4. 8  
S af et y  A n al y s e s  ........................................................................................................... 1 3  
4. 8. 1  
A d v er s e  E v e nt s  .................................................................................................................... 1 4  
4. 8. 2  
S eri o u s  A d v er s e  E v e nt s  ....................................................................................................... 1 4  
4. 8. 3  
Cli ni c al  L a b or at or y  E v al u ati o n  .............................................................................................. 1 5  
4. 8. 4  
Vit al  Si g n s  ............................................................................................................................ 1 6  
4. 8. 5  
El e ctr o c ar di o gr a m  ................................................................................................................ 1 6  
4. 9  
P D  A n al y s e s  ................................................................................................................. 1 6  
4. 1 0  
P K  A n al y s e s  .............................................................................................................. 1 6  
4. 1 0. 1  
M e a s ur e m e nt s  a n d  C oll e cti o n  S c h e d ul e  .............................................................................. 1 6  
4. 1 0. 2  
Bi o a n al yti c al  M et h o d s  .......................................................................................................... 1 6  
4. 1 0. 3  
Pl a s m a/ Ti s s u e  C o n c e ntr ati o n s  ............................................................................................ 1 7  


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
4 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
4. 1 0. 4  
P ar a m et er  C al c ul ati o n  .......................................................................................................... 1 7  
4. 1 0. 5  
D at a  S u m m ari z ati o n  a n d  Pr e s e nt ati o n  ................................................................................ 1 7  
4. 1 0. 6  
St ati sti c al  A n al y si s  of  Pl a s m a/ Ti s s u e  C o n c e ntr ati o n s  .......................................................... 1 7  
4. 1 1  
I nt eri m  A n al y si s  a n d  D at a  M o nit ori n g .................................................................... 1 7  
4. 1 2  
H a n dli n g  of  Dr o p o ut s  or  Mi s si n g  D at a  ................................................................... 1 8  
4. 1 3  
S u b gr o u p  A n al y si s  ................................................................................................... 1 8  
4. 1 4  
M ulti pl e  C o m p ari s o n/ M ulti pli cit y  ............................................................................ 1 8  
5   C H A N G E S  T O  P R O T O C O L -S P E CI FI E D  A N A L Y S E S  ............................................. 1 8  
6   LI S T  O F  T A B L E S  A N D  FI G U R E S  ............................................................................ 1 8  
 
 
 


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
5 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
Gl o s s ar y  a n d  A b br e vi ati o n s  
 
A E  
A d v er s e  E v e nt  
A L T   
Al a ni n e  Tr a n s a mi n a s e  
A PI  
A cti v e  P h ar m a c e uti c al I n gr e di e nt  
A S T   
A s p art at e  Tr a n s a mi n a s e  
B L Q   
B el o w t h e  L o w er l e v el  of  Q u a ntifi c ati o n  
C F R   
C o d e  of  F e d er al  R e g ul ati o n s  
C O N S O R T   
C o n s oli d at e d  St a n d ar d s  of  R e p orti n g  Tri al s  
C R F   
C a s e  R e p ort  F or m  
C R P   
C -R e a cti v e  Pr ot ei n  
D P  
Dr u g  Pr o d u ct  
E C G   
El e ctr o c ar di o gr a m  
e C R F   
El e ctr o ni c  C a s e  R e p ort  F or m s  
F D A   
F o o d  a n d  Dr u g  A d mi ni str ati o n  
G C P   
G o o d  Cli ni c al  Pr a cti c e  
G L P   
G o o d  L a b or at or y  Pr a cti c e s  
G M P   
G o o d  M a n uf a ct uri n g  Pr a cti c e s  
H B s A g   
H e p atiti s  B  S urf a c e  A nti g e n  
HI V  
H u m a n I m m u n o d efi ci e n c y  Vir u s  
H R Q o L   
H e alt h -r el at e d  Q u alit y  of  Lif e 
I B 
I n v e sti g at or’ s  Br o c h ur e 
I C H  
I nt er n ati o n al  C o nf er e n c e  o n  H ar m o ni s ati o n  
I N D  
I n v e sti g ati o n al  N e w  Dr u g  A p pli c ati o n 
I C F 
I nf or m e d  C o n s e nt  F or m 
I R B 
I n stit uti o n al  R e vi e w  B o ar d 
I T T 
I nt e nt-T o -Tr e at  
M A D   
M ulti pl e  A s c e n di n g  D o s e  
M e d D R A   
M e di c al  Di cti o n ar y f or  R e g ul at or y  A cti viti e s  
mI T T   
M o difi e d I nt e nt -T o -Tr e at  
P D  
P h ar m a c o d y n a mi c s  
PI  
Pri n ci p al I n v e sti g at or  
P K  
P h ar m a c o ki n eti c s  
Q C  
Q u alit y  C o ntr ol  
S A E   
S eri o u s  A d v er s e  E v e nt  
S A P   
St ati sti c al  A n al y si s  Pl a n  
S F U   
S af et y  F oll o w -U p  
SI B D Q   
S h ort I nfl a m m at or y  B o w el  Di s e a s e  Q u e sti o n n air e  
S M C   
S af et y  M o nit ori n g  C o m mitt e e  
S O C   
S y st e m  Or g a n  Cl a s s  
S O P   
St a n d ar d  O p er ati n g  Pr o c e d ur e  
T E A E   
Tr e at m e nt -E m er g e nt  A d v er s e  E v e nt  
U C  
Ul c er ati v e  C oliti s  
U C EI S   
Ul c er ati v e  C oliti s  E n d o s c o pi c I n d e x  of  S e v erit y  
U L N   
U p p er  Li mit  of  N or m al  
 
 


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
6 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
1   
R E VI SI O N  HI S T O R Y  
 
S A P  V er si o n  1 . 0 w a s  cr e at e d  a n d  a p pr o v e d  pri or t o  a n y  u n bli n di n g  t o t h e  st u d y t e a m.  
 
S A P  V er si o n  2. 0  w a s  pl a n n e d t o  u p d at e  a  st ati sti ci a n  of  K C R N  R e s e ar c h  a n d  S e cti o n  6  Li st  of 
T a bl e s  a n d  Fi g ur e s . T F L  s h ell s  w er e  cr e at e d  f or t h e  1 st  c o h ort a n d  att a c h e d.   
 
 
2   
S T U D Y  O B J E C TI V E S  A N D  E N D P OI N T S  
 
2. 1   
St u d y  O bj e cti v e s  
 
2. 1. 1   Pri m ar y  O bj e cti v e  
 
T h e  pri m ar y  o bj e cti v e i s t o  a s s e s s t h e  effi c a c y  a n d  s af et y  of  m ulti pl e  or al  d o s e s  of  B B T -4 0 1 -1 S 
i n  p ati e nt s  wit h  a cti v e  U C. 
 
2. 1. 2   S e c o n d ar y  O bj e cti v e s  
 
T h e  s e c o n d ar y  o bj e cti v e s  ar e t o  a s s e s s t h e  pl a s m a  a n d ti s s u e  c o n c e ntr ati o n  of  m ulti pl e  or al 
d o s e s  of  B B T -4 0 1 -1 S i n  p ati e nt s  wit h  a cti v e  U C  a n d t o  e v al u at e t h e  eff e ct s  of  B B T -4 0 1 -1 S  o n 
bi o m ar k er s . 
 
2. 2   
St u d y  E n d p oi nt s  
 
2. 2. 1   Pri m ar y  E n d p oi nt s  
 
•   C h a n g e fr o m  b a s eli n e i n  T ot al  M a y o  S c or e  at  W e e k  8  
 
2. 2. 2   S e c o n d ar y  E n d p oi nt s  
 
•   C h a n g e fr o m  B a s eli n e i n  P arti al  M a y o  S c or e  at  W e e k  8   
•   C h a n g e fr o m  B a s eli n e i n  Hi st ol o gi c  A s s e s s m e nt  of  E n d o s c o pi c  Bi o p s y  at  W e e k  8  
•   C h a n g e fr o m  B a s eli n e i n  Ul c er ati v e  C oliti s  E n d o s c o pi c I n d e x  of  S e v erit y ( U C EI S)  S c or e 
at  W e e k  8  
•   C h a n g e fr o m  B a s eli n e i n  S h ort I nfl a m m at or y  B o w el  Di s e a s e  Q u e sti o n n air e ( SI B D Q)  at 
W e e k  8  
•  
N u m b er  a n d  S e v erit y  of  Tr e at m e nt  E m er g e nt  A d v er s e  E v e nt s ( T E A E s)  u p t o  W e e k  8  
•   C h a n g e fr o m  B a s eli n e i n  C o n c e ntr ati o n  of  Bi o m ar k er s ( C -r e a cti v e  pr ot ei n [ C R P], f e c al 
c al pr ot e cti n,  a n d f e c al l a ct of erri n)  at  W e e k  8  
•   Pl a s m a  a n d  Ti s s u e  C o n c e ntr ati o n  of  B B T -4 0 1 -1 S i n  P ati e nt s  wit h  A cti v e  U C  
 
 


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
7 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
3   
S T U D Y  D E SI G N  
 
3. 1   
S u m m ar y  of  St u d y  D e si g n  
 
T hi s r a n d o mi z e d,  pl a c e b o -c o ntr oll e d,  d o s e -e s c al ati o n,  m ulti c e nt er,  P h a s e  2  st u d y  c o n si st s  of 
t hr e e  c o h ort s  wit h  1 6-w e e k tr e at m e nt  p eri o d  p er  c o h ort t h at  will  b e  c o n d u ct e d  s e q u e nti all y.  T h e 
fir st  c o h ort  will r e c ei v e  4 0 0  m g  of  B B T-4 0 1 -1 S ( st arti n g  d o s e).  Effi c a c y,  s af et y,  a n d  P K  d at a  of 
t h e fir st  c o h ort  will  b e  u s e d t o  s el e ct t h e  d o s e  of t h e  s u b s e q u e nt  c o h ort.  F or t h e  1 st  or  2 n d 
c o h ort, if t h e  1 2t h  p ati e nt ( 7 5 %)  c o m pl et e s  Vi sit  4 ( W e e k  8),  u n bli n di n g  of  1 2  p ati e nt s  will  b e 
p erf or m e d  wit hi n  2  w e e k s  aft er  Vi sit  4 ( W e e k  8)  a n d t h e  u n bli n di n g i nf or m ati o n  will  b e  o nl y 
pr o vi d e d t o t h e  S p o n s or f or t h e  a n al y si s t o  d et er mi n e t h e  d o s e  of t h e  n e xt  c o h ort.  A  d o s e l e v el 
m a y  b e r e p e at e d  or  a d d e d  b a s e d  o n t h e r e s ult s  of t h e  pr e vi o u s  c o h ort( s).  
  
P ati e nt s  will r e c ei v e  a  d ail y  or al  d o s e  of  B B T  4 0 1 -1 S  or  pl a c e b o f or t h e  1 6  w e e k s.  W hil e 
p ati e nt s  w h o  ar e  a s si g n e d t o  A cti v e  Gr o u p  will r e c ei v e  B B T -4 0 1 -1 S f or t h e fir st  1 2  w e e k s  a n d 
t h e n  pl a c e b o f or t h e l a st  4  w e e k s,  p ati e nt s  w h o  ar e  a ssi g n e d t o  Pl a c e b o  Gr o u p  will r e c ei v e 
pl a c e b o f or t h e fir st  8  w e e k s  a n d t h e n  B B T -4 0 1 -1 S f or l a st  8  w e e k s.   
 
 
 
 


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
8 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
 
T h e  s c h e d ul e  of  a s s e s s m e nt s i s ill u str at e d i n  T a bl e  1.  
 
T a bl e  1 .  S c h e d ul e  of  A s s e s s m e nt s  
 
 
S cr e e ni n g  
Tr e at m e nt  P eri o d  
S F U  
Vi sit  N u m b er   
V 1  
V 2   
V 3   
V 4    
V 5    
V 6   
E T  
Vi sit  P eri o d   U p t o  W -4  
B a s eli n e   
W 4   
W 8   
W 1 2   
W 1 6   
N/ A  
W 2 fr o m  L D  
Vi sit  Wi n d o w   
N/ A  
Wit hi n  2 8 
d a y s fr o m 
V 1  
± 3 
d a y s  
± 3 
d a y s  
± 3 
d a y s  
± 3 
d a y s  
N/ A  
+  7  d a y s 
fr o m  L D 
I nf or m e d  C o n s e nt 
X  
  
  
  
  
  
 
 
D e m o gr a p hi c I nf or m ati o n  
X  
  
  
  
  
  
 
 
M e di c al/ m e di c ati o n  Hi st or y  
X  
X   
  
  
  
  
 
 
I n cl u si o n/ e x cl u si o n  Crit eri a 
X  
X   
  
  
  
  
 
 
Vit al  Si g n s  
X  
X   
X   
X   
X   
X   
X  
X  
P h y si c al  E x a mi n ati o n  
X  
X a   
X   
X   
X   
X   
X  
 
1 2 -l e a d  E C G 
X  
X 1   
X   
X   
X   
X   
X  
 
Cli ni c al  L a b  T e st s  a n d  S er u m 
Bi o m ar k er 2  
X  
X a   
X   
X   
X   
X   
X  
X  
E n d o s c o p y  ( bi o p s y) 
X  
  
  
X   
  
  
X 3  
 
R a n d o mi z ati o n  
 
X   
  
  
  
  
 
 
M a y o  S c or e  
X  
X   
X   
X   
X   
X   
X  
 
Ul c er ati v e  C oliti s  E n d o s c o pi c I n d e x  of 
S e v erit y  
X   
  
  
X   
  
  
X c  
 
S h ort I nfl a m m at or y  B o w el  Di s e a s e 
Q u e sti o n n air e  
 
X   
X   
X   
X   
X   
X  
 
F e c al  Bi o m ar k er 4  
 
X   
X   
X   
X   
X   
X  
 
Pl a s m a  P h ar m a c o ki n eti c s 5  
 
X   
X   
X    
  
  
 
 
Ti s s u e  C o n c e ntr ati o n 6  
X  
  
  
X   
  
  
X c 
 
Dr u g  Di s p e n si n g ( wit h  s u bj e ct  di ar y)   
 
X   
X   
X   
X   
  
 
 
Dr u g  R et ur n  a n d  C o m pli a n c e  
 
  
X   
X   
X   
X   
X  
 
A E  a n d  C o n c o mit a nt  M e di c ati o n  
 
X   
X   
X   
X   
X g   
X g  
X  
A E  =  a d v er s e  e v e nt;  E C G  =  el e ctr o c ar di o gr a m;  S F U  =  S af et y  F oll o w -U p;  V  =  Vi sit;  W  =  W e e k;  E T  =  E arl y 
T er mi n ati o n;  L D  =  L a st  D o s e  
 
 
 
1   W ai v e d if t h e  s cr e e ni n g  vi sit i s  c o n d u ct e d  wit hi n  1 0  d a y s  pri or t o  Vi sit  2 ( B a s eli n e).   
2    S er u m  c h e mi str y,  h e m at ol o g y,  c o a g ul ati o n t e st,  HI V  a n d  h e p atiti s  s cr e e n s,  s er u m  h C G ( w o m e n  wit h 
c hil d b e ari n g  p ot e nti al  o nl y),  a n d  s er u m  C R P ( n ot  m e a s ur e d  at  S F U).   
3   O nl y if  e arl y t er mi n ati o n  o c c ur s  b ef or e  Vi sit  4 ( W 8).   
4    F e c al  c al pr ot e cti n  a n d f e c al l a c t of erri n.  A  c oll e cti o n  c o nt ai n er  will  b e  di s p e n s e d t o  p ati e nt s  o n t h e 
pr e vi o u s  vi sit.   
5    Vi sit  2 ( B a s eli n e)  a n d  Vi sit  3 ( W 4):  pr e -d o s e  a n d  3  a n d  6  h o ur s  p o st -d o s e;  Vi sit  4 ( W 8):  pr e -d o s e  o nl y.  
6    D uri n g t h e  e n d o s c o p y (fl e xi bl e  pr o ct o si g m oi d o s c o p y/ c ol o n o s c o p y) f or  bi o p s y.  
g  R e vi e wi n g  a n y  c h a n g e s i n  s m o ki n g  h a bit s  of  s u bj e ct  d uri n g t h e  st u d y  p eri o d.  


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
9 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
 
3. 2   
D et er mi n ati o n  of  S a m pl e  Si z e  
 
A s t hi s i s  a n i niti al  d o s e -e s c al ati o n  st u d y, it i s  a p pr o pri at el y  b a s e d  o n  o nl y  a li mit e d  n u m b er  of 
p ati e nt s  i n   e a c h  d o s e  c o h ort.    T h e  si z e   of  t h e  st u d y  i s   n ot   b a s e d   o n   a n y  st ati sti c al   p o w er 
c al c ul ati o n s  a n d  n o f or m al  s a m pl e  si z e  c al c ul ati o n  h a s  b e e n  d o n e.  B a s e d  o n t h e  e x p eri e n c e fr o m 
t h e  pr e vi o u s  st u di e s  a n d t h e  u s e  of  a  s e q u e nti al  d o s e-e s c al ati o n  d e si g n f or t hi s  st u d y,  a t ot al  of 
4 8  p ati e nt s ( 1 6  p ati e nt s  p er  d o s e  c o h ort) i s  c o n si d er e d  a p pr o pri at e f or t h e  st u d y.  
 
3. 3   
Tr e at m e nt s  
 
P ati e nt s  will r e c ei v e  a  d ail y  or al  d o s e  of  B B T  4 0 1 -1 S  or  pl a c e b o f or t h e  1 6  w e e k s.  W hil e  p ati e nt s 
w h o  ar e  a s si g n e d t o  A cti v e  Gr o u p  will r e c ei v e  B B T -4 0 1 -1 S f or t h e fir st  1 2  w e e k s  a n d t h e n  pl a c e b o 
f or t h e l a st  4  w e e k s,  p ati e nt s  w h o  ar e  a s si g n e d t o  Pl a c e b o  Gr o u p  will r e c ei v e  pl a c e b o f or t h e fir st 
8  w e e k s  a n d t h e n  B B T -4 0 1 -1 S f or l a st  8  w e e k s.   
 
3. 4   
R a n d o mi z ati o n  a n d  Bli n di n g  
 
A t ot al  of  1 6  s u bj e ct s i n  e a c h  of  t h e  3  d o si n g  c o h ort s  will  b e r a n d o mi z e d t o  eit h er  a cti v e  or  pl a c e b o 
gr o u p i n  a  3: 1 r ati o ( 1 2  a cti v e  a n d  4  pl a c e b o)  u si n g t h e  el e ctr o ni c  d at a  c a pt ur e ( E D C)  s y st e m  i n 
w hi c h t h e r a n d o mi z ati o n  c o d e i s i nt e gr at e d .  
 
T h e r a n d o mi z ati o n  c o d e  will  b e  g e n er at e d  b y  a n  u n bli n d e d  st ati sti ci a n  w h o i s  n ot i n v ol v e d  wit h 
t h e  st u d y.  T h e  S p o n s or, i n v e sti g at or s,  p ati e nt s,  a n d  C R O  a n d  ot h er r el e v a nt  p er s o n n el i n v ol v e d 
wit h  t h e  c o n d u ct  of  t h e  st u d y,    wit h  t h e  e x c e pti o n  of  cli ni c al  s u p pl y  st aff  a n d  t h e  u n bli n d e d 
st ati sti ci a n,  will  b e  bli n d e d t o t h e i d e ntit y  of  st u d y  m e di c ati o n.  
 
F or t h e  1 st  or  2 n d  c o h ort, if t h e  1 2t h  p ati e nt  ( 7 5 %)  c o m pl et e s  Vi sit  4  ( W e e k  8), t h e  C R O  d at a 
m a n a g e m e nt ( D M) t e a m  c o nfir m  all  cli ni c al  d at a  of t h e  1 2  p ati e nt s  h a v e  n o i s s u e  a n d t h e n  o bt ai n 
t h e  writt e n  c o n se nt fr o m t h e  S p o n s or t o  br e a ki n g t h e  c o d e.  P er t h e r e q u e st  of t h e  C R O  D M t e a m, 
t h e  r a n d o mi z ati o n  c o d e s  of  t h e  1 2  p ati e nt s    will  b e  o p e n e d  vi a  t h e  u n bli n d e d  st ati sti ci a n  a n d 
n otifi e d t o t h e  S p o n s or f or t h e  a n al y si s t o  d et er mi n e t h e  n e xt  d o s e.  Aft er  c o nfir mi n g  all  cli ni c al 
d at a   of  r e m ai ni n g   4   p ati e nt s  f or  t h e   1 st   or   2 n d   c o h ort,  t h e  r a n d o mi z ati o n   c o d e s    will   b e 
s u b s e q u e ntl y  o p e n e d t o t h e  s p o n s or t hr o u g h t h e  s a m e  pr o c e d ur e s  st at e d  a b o v e.   
 
Aft er t h e l a st  p ati e nt  of l a st  c o h ort  c o m pl et e s t h e  S F U, t h e  C R O  D M t e a m  c o nfir m s t h e  w h ol e 
cli ni c al  d at a b a s e  h a s  n o  i s s u e  a n d  t h e n  r e q u e st s  t h e  d at a b a s e  l o c k  t o  t h e   S p o n s or.   P er  t h e 
S p o n s or’ s  a p pr o v al  o n t h e  d at a b a s e l o c k, t h e r a n d o mi z ati o n  c o d e  of  all  p ati e nt s  will  b e  o p e n e d 
vi a t h e  u n bli n d e d  st ati sti ci a n  a n d  n otifi e d t o t h e  C R O f or t h e  st ati sti c al  a n al y si s.   
 
Br e a ki n g  of t h e r a n d o mi z ati o n  c o d e  wit h o ut  s p o n s or’ s  p er mi s si o n i s  e x pr e s sl y f or bi d d e n  e x c e pt 
i n t h e  e v e nt  of  a  m e di c al  e m er g e n c y  w h er e t h e i d e ntit y  of t h e  st u d y  m e di c ati o n  m u st  b e  k n o w n i n 
or d er t o  pr o p erl y tr e at t h e  p at i e nt. I n t h e  e v e nt  of  a  m e di c al  e m er g e n c y, it i s r e q u e st e d t h at t h e 
i n v e sti g at or  m a k e  e v er y  eff ort t o  c o nt a ct t h e  st u d y  m o nit or  or  d e si g n e e  pri or t o  br e a ki n g t h e  c o d e.  
 


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If t h e  bli n d i s  br o k e n  d u e t o t h e  m e di c al  e m er g e n c y, t h e  s u bj e ct  m u st  b e  e arl y t er mi n at e d;  a  writt e n 
e x pl a n ati o n  m u st  b e  pr e p ar e d i m m e di at el y.  
 
 
4   
S T A TI S TI C A L  M E T H O D S  
 
4. 1   
G e n er al  C o n si d er ati o n s  
 
T hi s  d o c u m e nt  d e s cri b e s  t h e  st ati sti c al  a n al y s e s  pl a n n e d  pri or  t o  fi n al  tr e at m e nt  a s si g n m e nt 
u n bli n di n g  of t h e  a g gr e g at e  d at a b a s e.  A n y  c h a n g e t o t h e  d at a  a n al y si s  m et h o d s  d e s cri b e d i n t h e 
pr ot o c ol  will  r e q uir e  a n  a m e n d m e nt  O N L Y if it  c h a n g e s  a  pri n ci p al f e at ur e  of t h e  pr ot o c ol.  A n y 
ot h er  c h a n g e  t o  t h e  d at a  a n al y si s    m et h o d s  d e s cri b e d  i n  t h e  pr ot o c ol  a n d  t h e  j u stifi c ati o n  f or 
m a ki n g t h e  c h a n g e  will  b e  d e s cri b e d i n t h e  cli ni c al  st u d y r e p ort ( C S R).  A d diti o n al  e x pl or at or y  or 
a d -h o c  a n al y s e s  of t h e  d at a  will  b e  c o n d u ct e d  a s  d e e m e d  a p pr o pri at e.  
 
All t e st s  of tr e at m e nt  eff e ct s  will  b e  c o n d u ct e d  at  a t w o -si d e d  al p h a l e v el  of  0. 0 5  u nl e s s  ot h er wi s e 
st at e d,  a n d  all  c o nfi d e n c e i nt er v al s ( CI’ s)  will  b e  gi v e n  at  a t w o -si d e d  9 5 % l e v el,  u nl e s s  ot h er wi s e 
st at e d.  St ati sti c al  a n al y si s  will  b e  p erf or m e d  u si n g  S A S  s oft w ar e ( S A S,  V er si o n  9. 1. 2  or  hi g h er).  
 
T h e f oll o wi n g  g e n er al t er m s  will  b e  u s e d  gl o b all y i n t h e  S A P:  
•   U nl e s s  ot h er wi s e  s p e cifi e d, t h e  st ati sti c al  a n al y s e s  will  b e r e p ort e d  u si n g  s u m m ar y t a bl e s 
a n d  d at a li sti n g s.   
•   C o nti n u o u s  v ari a bl e s    will   b e  s u m m ari z e d    wit h   n,    m e a n,  st a n d ar d   d e vi ati o n,    m e di a n, 
mi ni m u m,  a n d  m a xi m u m.   
•   C at e g ori c al  v ari a bl e s   will  b e  s u m m ari z e d  b y  c o u nt s  a n d  b y  p er c e nt a g e s  of  s u bj e ct s  i n 
c orr e s p o n di n g  c at e g ori e s.   
•   All  s u m m ar y t a bl e s  will  b e  pr e s e nt e d  b y tr e a t m e nt a n d/ or  c o h ort .  
•   I n di vi d u al  s u bj e ct  d at a  o bt ai n e d fr o m t h e  c a s e r e p ort f or m ( C R F s)  a n d  a n y  d eri v e d  d at a 
will  b e  pr e s e nt e d  b y  s u bj e ct i n  d at a li sti n g s.  D at a li sti n g s  will  b e  s ort e d  b y  s u bj e ct,  a n d 
vi sit  d at e  a n d ti m e, if  a p pli c a bl e.   
 
4. 2   
A dj u st m e nt s f or  C o v ari at e s  
 
T h er e  will  b e  n o  a dj u st m e nt f or  c o v ari at e s.   
 
4. 3   
A n al y si s  S et s  
 
4. 3. 1   M o difi e d I nt e nt -t o-Tr e at   
 
A  m o difi e d i nt e nt -t o-tr e at ( mI T T) s et  will  c o n si st  of  all r a n d o mi z e d  p ati e nt s  w h o  h a v e  r e c ei v ed  at 
l e a st  1  d o s e  of  st u d y  m e di c ati o n a n d  h a v e  at l e a st  1  p o st -b a s eli n e  effi c a c y  m e a s ur e m e nt . T h e 
mI T T  s et  will  b e t h e  pri m ar y  s et  u s e d f or  effi c a c y  a n al y s e s.  
 


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4. 3. 2   P er -Pr ot o c ol   
 
T h e  p er -pr ot o c ol  s et  will  c o n si st  of  all  s u bj e ct s i n t h e  mI T T  w h o  d o  n ot  h a v e  pr e -d efi n e d  m aj or 
pr ot o c ol  d e vi ati o n s t h at  m a y  aff e ct t h e  pri m ar y  effi c a c y  e n d p oi nt  a n d  h a v e  c o m pl et e d  t h e st u d y 
u ntil  Vi sit  4 ( W e e k  8)  .   
 
4. 3. 3   S af et y   
 
T h e  s af et y  s et  will  c o n si st  of  all  s u bj e ct s  w h o  h a v e  r e c ei v e d  at  l e a st  1  d o s e  of  i n v e sti g ati o n al 
pr o d u ct.   T h e  s af et y  s et  will  b e t h e  pri m ar y  a n al y si s  d at a s et  u s e d f or  s af et y  a n al y s e s.   
 
4. 3. 4   P h ar m a c o ki n eti c s ( P K)  
 
T h e  P K  s et  will  c o n si st  of  all  s u bj e ct s  w h o  h a v e  r e c ei v e d  at l e a st  1  d o s e  of i n v e sti g ati o n al  pr o d u ct 
a n d  t h er e i s  at l e a st  1  P K  s a m pli n g.   T h e P K  s et  will  b e t h e  pri m ar y  a n al y si s  d at a s et  u s e d f or  P K  
a n al y s e s.   
 
 
4. 4   
B a s eli n e  a n d  P o st b a s eli n e  D efi niti o n  
 
U nl e s s  ot h er wi s e  s p e cifi e d, t h e  b a s eli n e  v al u e i s  d efi n e d  a s t h e l a st  v al u e  o bt ai n e d  b ef or e t h e 
d at e  a n d ti m e  of t h e fir st  d o s e  of  st u d y  dr u g.  P o st -b a s eli n e  v al u e s  ar e  d efi n e d  a s  v al u e  o bt ai n e d 
aft er t h e fir st  d o s e  of  st u d y  dr u g.  C h a n g e fr o m  b a s eli n e i s  d e fi n e d  a s  a  p o st-b a s eli n e  v al u e  mi n u s 
t h e  b a s eli n e  v al u e.  
 
4. 5   
H a n dli n g  of  Dr o p o ut s  or  Mi s si n g  D at a  
 
N o  a dj u st m e nt s f or  mi s si n g  d at a  a n d  n o i m p ut ati o n  m et h o d s  ar e  pl a n n e d f or t hi s  st u d y.  
 
4. 6   
Tr e at m e nt  Gr o u p  C o m p ar a bilit y  
 
4. 6. 1   P ati e nt  Di s p o siti o n  
 
S u bj e ct  di s p o siti o n i nf or m ati o n  will  b e  s u m m ari z e d f or  all  s u bj e ct s.  S u m m ari e s  will i n cl u d e: t h e 
n u m b er  of  s u bj e ct s i n  e a c h  a n al y si s  s et , t h e  n u m b er  of  s u bj e ct s  c o m pl et e d t h e  st u d y,  a n d t h e 
n u m b er  of  s u bj e ct s  di s c o nti n u e d  st u d y  a n d it s r e a s o n.  All  s u bj e ct s  r a n d o mi z e d i n t h e  st u d y  will 
b e i n cl u d e d i n t h e  s u m m ar y t a bl e.  P ati e nt  all o c ati o n  b y i n v e sti g at or  or  sit e  will  b e  s u m m ari z e d. 
P ati e nt  all o c ati o n  b y  i n v e sti g at or  or  sit e   will  al s o  b e  li st e d  a s   w ell.  All  s u bj e ct s  r a n d o mi z e d  t o 
pl a c e b o fr o m  e a c h  c o h ort  will  b e  p o ol e d  i n  Pl a c e b o  gr o u p  a n d  s u m m ari z e d  a s  a  pl a c e b o  gr o u p.  
 
4. 6. 2   Pr ot o c ol  D e vi ati o n s  
 


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S u m m ar y  a n d l i sti n g s  of  s u bj e ct s  wit h  si g nifi c a nt  pr ot o c ol  d e vi ati o n s  or  vi ol ati o n s  will  b e  pr o vi d e d. 
T h e f oll o wi n g li st  of  si g nifi c a nt  pr ot o c ol  vi ol ati o n s  will  b e  d et er mi n e d fr o m t h e  cli ni c al  d at a b a s e 
a n d fr o m t h e  st u d y  cli ni c al/ m e di c al  gr o u p:  
•   L a c k  of i nf or m e d  c o n s e nt  or l at e i nf or m e d  c o n s e nt  
•   Vi ol ati o n s  of i n cl u si o n/ e x cl u si o n  crit eri a  
•   Si g nifi c a nt  vi ol ati o n s  of  pr o hi bit e d  c o n c o mit a nt    m e di c ati o n  u s a g e  a s  d et er mi n e d  b y  t h e 
cli ni c al/ m e di c al  gr o u p  
•   Ot h er  si g nifi c a nt  pr ot o c ol  vi ol ati o n s  a s  d et er mi n e d  b y t h e  cli ni c al/ m e di c al  gr o u p  
 
4. 6. 3   P ati e nt  C h ar a ct eri sti c s  
 
T h e  f oll o wi n g  p ati e nt  c h ar a ct eri sti c s  at  b a s eli n e   will  b e  s u m m ari z e d  b y  tr e at m e nt  gr o u p  f or  all 
mI T T  p ati e n t s: 
•   D e m o gr a p hi c ( a g e,  g e n d er,  et h ni c  ori gi n,  h ei g ht,  w ei g ht,  B MI)   
•   M e di c al  hi st or y  a n d  Pr e -e xi sti n g  c o n diti o n   
 
M e di c al  hi st or y  a n d  pr e -e xi sti n g  c o n diti o n s    will  b e  s u m m ari z e d  b y  pr ef err e d  t er m  ( P T)    wit hi n 
s y st e m  or g a n  cl a s s ( S O C).   M e di c al  hi st or y i s  d efi n e d  a s ill n e s s( e s) t h at  e n d e d  pri or t o t h e  si g ni n g 
of i nf or m e d  c o n s e nt.  Pr e -e xi sti n g  c o n diti o n s  a n d  A E s  at  b a s eli n e  ar e t h o s e  A E s  o c c urri n g  d uri n g 
t h e  b a s eli n e/ s cr e e ni n g  vi sit s t h at ar e  Vi sit s  1  a n d  2.  
 
4. 6. 4   Pri or  a n d  C o n c o mit a nt  T h er a p y  
 
V er b ati m t er m s  o n  e C R F s  will  b e  m a p p e d t o  A n at o mi c al  T h er a p e uti c  C h e mi c al ( A T C)  cl a s s  a n d 
G e n eri c  Dr u g  N a m e s  u si n g t h e  W orl d  H e alt h  Or g a ni z ati o n ( W H O)  Dr u g  Di cti o n ar y  E n h a n c e d 
( W H O D D E)  B 2 f or m at,  M ar c h  1,  2 0 1 5 r el e a s e. 
 
Pri or  m e di c ati o n s  ar e  d efi n e d  a s  m e di c ati o n s  st art e d t o  b e  t a k e n  pri or t o t h e fir st a d mi ni str ati o n 
of t h e  st u d y  dr u g .  C o n c o mit a nt  m e di c ati o n s  ar e  d efi n e d  a s  m e di c ati o n s  st art e d  o n  or  aft er t h e 
d a y  of t h e fir st  a d mi ni str ati o n  of t h e  st u d y  dr u g  d uri n g t h e  st u d y.   
 
Pri or  a n d  c o n c o mit a nt  m e di c ati o n s  will  b e t a b ul at e d f or t h e  mI T T  s et  b y  W H O D D E  A T C l e v el  2 
cl a s sifi c ati o n s,  pr ef err e d t er m,  a n d tr e at m e nt. If  a  s u bj e ct r e p ort s t h e  s a m e  pr ef err e d t er m 
m ulti pl e ti m e s, t h e n t h e fr e q u e n c y  of t h at  pr ef err e d t er m  will  o nl y  b e i n cr e m e nt e d  b y  o n e.  A s 
wit h t h e  pr ef err e d t er m, if  a  s u bj e ct r e p ort s  m ulti pl e  m e di c ati o n s  wit hi n t h e  s a m e  A T C l e v el  2 
cl a s sifi c ati o n, t h e n t h e fr e q u e n c y  of t h at  A T C l e v el  2  cl a s sifi c ati o n  will  o nl y  b e i n cr e m e nt e d  b y 
o n e.  P er c e nt a g e s  will  b e  c al c ul at e d  u si n g  t h e t ot al  n u m b er  of  s u bj e ct s i n t h e  s af et y a n al y si s  s et . 
E a c h  s u m m ar y  will  b e  or d er e d  b y  d e s c e n di n g  or d er  of i n ci d e n c e  of  pr ef err e d t er m  wit hi n  e a c h 
A T C  cl a s s.  Pri or  a n d  c o n c o mit a nt  m e di c ati o n s  will  b e i n cl u d e d i n  a  d at a li sti n g.   
 
4. 7   
Effi c a c y  A n al y s e s  
 
U nl e s s  ot h er wi s e  s p e cifi e d,  all  effi c a c y  a n al y s e s  will  b e  b a s e d  o n t h e  mI T T  a n d  s u bj e ct s  will  b e 
a n al y z e d  a c c or di n g t o t h eir r a n d o mi z e d tr e at m e nt.  H o w e v er,  a d diti o n al 


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s e n siti vit y/ s u p pl e m e nt ar y  a n al y s e s  will  b e  c o n d u ct e d  u si n g t h e  P P  a n al y si s  s et f or  all  effi c a c y 
e n d p oi nt s.   
 
4. 7. 1   Pri m ar y  Effi c a c y  A n al y si s  
 
D e s cri pti v e  st ati sti c s  will  b e  pr e s e nt e d i n cl u di n g  m e a n,  st a n d ar d  d e vi ati o n  ( S D),  m e di a n,  m a x, 
a n d  mi n  b y tr e at m e nt  a n d  c o h ort  gr o u p  f or t h e  c h a n g e fr o m  b a s eli n e t o  W e e k  8 i n  T ot al  M a y o 
s c or e .  Al s o, t o  b ett er  a s s e s s t h e  diff er e n c e s  b et w e e n  e a c h  d o s e  a n d  t h e  pl a c e b o f or t h e  c h a n g e 
fr o m  b a s eli n e  t o    We e k  8  i n   T ot al    M a y o  s c or e ,  a    mi x e d    m o d el  r e p e at e d    m e a s ur e s  ( M M R M) 
a n al y si s  will  b e  p erf or m e d.  T h e  M M R M  m o d el  will i n cl u d e tr e at m e nt  ( w h et h er 1 st d o s e,  2 n d  d o s e, 
or  3 r d d o s e  v s . Pl a c e b o)  a n d t h e  b a s eli n e  s c or e  a s fi x e d  eff e ct s,  a n d  c e nt er  a s  a r a n d o m  eff e ct.  
R e stri ct e d  M a xi m u m  Li k eli h o o d ( R E M L)  wit h  a n  u n str u ct ur e d  v ari a n c e -c o v ari a n c e  m atri x  will  b e 
u s e d f or  e sti m ati o n i n t h e  M M R M  a n al y si s.  If t h e fit  of t h e  m o d el  wit h t h e  u n str u ct ur e d  c o v ari a n c e 
str u ct ur e   d o e s   n ot  c o n v er g e,  t h e  f oll o wi n g  c o v ari a n c e  str u ct ur e s    will   b e  tri e d  i n   or d er   u ntil 
c o n v er g e n c e i s r e a c h e d:  T o e plit z  wit h  h et er o g e n eit y,  a ut or e gr e s si v e  wit h  h et er o g e n eit y,  T o e plit z, 
a n d  a ut or e gr e s si v e.   E a c h  d o s e  will  b e  c o m p ar e d  wit h  pl a c e b o — m o d el -b a s e d  p oi nt  e sti m at e s f or 
t h e tr e at m e nt  eff e ct s  a n d  9 5 %  c o nfi d e n c e i nt er v al s ( CI s)  will  b e  c al c ul at e d. 
 
4. 7. 2   S e c o n d ar y  Effi c a c y  A n al y s e s  
 
T h e  s e c o n d ar y  effi c a c y  a n al y s e s  will  b e  b a s e d  o n t h e  mI T T  s et  o n t h e f oll o wi n g  e n d p oi nt s:  
•   C h a n g e fr o m  B a s eli n e  t o W e e k  8  i n  P arti al  M a y o  S c or e  
•   C h a n g e fr o m  B a s eli n e  t o W e e k  8  i n  Hi st ol o gi c  A s s e s s m e nt  of  E n d o s c o pi c  Bi o p s y  
•   C h a n g e fr o m  B a s eli n e  t o W e e k  8  i n  U C EI S  S c or e  
•   C h a n g e fr o m  B a s eli n e  t o W e e k  8  i n  SI B D Q  
 
F or  e a c h  s e c o n d ar y  effi c a c y  e n d p oi n t  d e s cri b e d  a b o v e,  d e s cri pti v e  st ati sti c s  will  b e  pr e s e nt e d 
b y tr e at m e nt  a n d  c o h ort  gr o u p i n cl u di n g  m e a n,  S D,  m e di a n,  m a x,  a n d  mi n .  Si mil ar t o t h e 
pri m ar y  effi c a c y  a n al y si s,  mi x e d  m o d el r e p e at e d  m e a s ur e s ( M M R M)  a n al y s e s  will  b e  p erf or m e d  
f or v ari o u s  s e c o n d ar y  effi c a c y  e n d p oi nt s  a s  n ot e d  a b o v e . 
 
4. 8   
S af et y  A n al y s e s  
 
T h e  s af et y  a n d t ol er a bilit y  of tr e at m e nt  will  b e  a s s e s s e d  b y  s u m m ari zi n g t h e f oll o wi n g:  
•   A E s  
•   Tr e at m e nt -e m er g e nt  a d v er s e  e v e nt s ( T E A E s)   
o   B y  P T  
o   B y  S O C  
o   B y  m a xi m u m  s e v erit y   
o   B y  c o n si d er e d t o  b e r el at e d t o i n v e sti g ati o n al  pr o d u c t b y i n v e sti g at or  
•   S eri o u s  A d v er s e  E v e nt s ( S A E s)  
•   A E l e a di n g t o  di s c o nti n u ati o n  
•   Vit al  si g n s  a n d  w ei g ht  
•   L a b or at or y  m e a s ur e m e nt s  


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•   El e ctr o c ar di o gr a m s ( E C G s)  
 
All  s af et y  a n al y s e s   will  b e  b a s e d  o n  t h e  s af et y  a n al y si s  s et .   A E  r at e s   will  b e  s u m m ari z e d  b y 
tr e at m e nt  gr o u p  a n d  o v er all,  a n d   will  b e  br o k e n  d o w n  b y  s e v erit y,  s eri o u s n e s s  a n d  r el ati o n  t o 
st u d y  dr u g.    P h y si c al  e x a mi n ati o n s,  vit al  si g n s,    E C G  a n d  st a n d ar d  l a b o r at or y  r e s ult s    will  b e 
s u m m ari z e d  wit h  m e a n s,  st a n d ar d  d e vi ati o n s,  m e di a n s  a n d r a n g e s f or  c o nti n u o u s  v ari a bl e s  a n d 
wit h  c o u nt s  a n d  p er c e nt a g e s f or  c at e g ori c al  v ari a bl e s.  St ati sti c al t e st s  ar e  n ot  pl a n n e d f or  s af et y.   
 
4. 8. 1   A d v er s e  E v e nt s  
 
A n    A E  i s  d efi n e d  a s  a n y  u nt o w ar d    m e di c al  o c c urr e n c e  i n  a  s u bj e ct    w h o  i s  a d mi ni st er e d  a 
m e di ci n al  pr o d u ct  a n d t h at  d o e s  n ot  n e c e s s aril y  h a v e  a  c a u s al r el ati o n s hi p t o t h e tr e at m e nt.  All 
A E s  will  b e i n cl u d e d i n t h e  d at a li sti n g s.  V er b ati m t er m s  o n  c a s e r e p ort f or m s  wi ll  b e  m a p p e d t o 
pr ef err e d  t er m s  a n d  s y st e m  or g a n  cl a s s e s  ( S O C)  u si n g  t h e    M e di c al   Di cti o n ar y  f or   R e g ul at or y 
A cti viti e s ( M e d D R A) ( v er si o n  1 9. 1).  
 
A   Tr e at m e nt   E m er g e nt   A d v er s e   E v e nt  ( T E A E)  i s  d efi n e d  a s  a n  a d v er s e  e v e nt  t h at  o c c ur s  or 
w or s e n s  o n  or  aft er t h e  fir st  d o s e  of  st u d y  dr u g.  T E A E  s u m m ar y  will  b e  di s pl a y e d  b y  c o h ort  a n d 
tr e at m e nt.  U nl e s s  ot h er wi s e  s p e cifi e d,  s u m m ari e s t h at  ar e  di s pl a y e d  b y  S O C  a n d  pr ef err e d t er m s 
will  b e  or d er e d  al p h a b eti c all y  b y  S O C,  a n d  wit hi n  e a c h  S O C,  pr ef err e d t er m s  will  al s o  b e  o r d er e d 
al p h a b eti c all y.  S u m m ari e s  of t h e f oll o wi n g t y p e s  will  b e  pr e s e nt e d:  
•   S u bj e ct i n ci d e n c e  of  T E A E s  b y  M e d D R A  S O C  a n d  pr ef err e d t er m.  
•   S u bj e ct i n ci d e n c e  of  T E A E s  b y  M e d D R A  S O C,  pr ef err e d t er m,  a n d  s e v erit y.  S e v erit y  will 
b e r e c or d e d  a s  d e e m e d  b y  i n v e sti g at or.  At  e a c h l e v el  of  s u bj e ct  s u m m ari z ati o n,  a  s u bj e ct 
i s  cl a s sifi e d  a c c or di n g t o t h e  hi g h e st  s e v erit y if t h e  s u bj e ct r e p ort e d  o n e  or  m or e  e v e nt s. 
•   S u bj e ct i n ci d e n c e  of  st u d y  dr u g r el at e d  T E A E s  b y  M e d D R A  S O C  a n d  pr ef err e d t er m.  
•   S u bj e ct i n ci d e n c e  of  T E A E s  b y  d e s c e n di n g i n ci d e n c e  of  pr ef err e d t er m s.  
•   S u bj e ct i n ci d e n c e  of  s eri o u s  T E A E s  b y  M e d D R A  S O C  a n d  pr ef err e d t er m, if  a p pli c a bl e.  
•   S u bj e ct i n ci d e n c e  of  T E A E l e a di n g t o  e arl y t er mi n ati o n  b y  M e d D R A  S O C  a n d  pr ef err e d 
t er m, if  a p pli c a bl e. 
 
F or  e a c h  s u bj e ct  a n d f or  e a c h  a d v er s e  e v e nt, t h e  d ur ati o n  of t h e  e v e nt  will  b e  c al c ul at e d  a s:  
D ur ati o n  of  A E  =  A E  st o p  d at e  - A E  st art  d at e  +  1  
 
T h e  d ur ati o n  of  A E s  will  b e  di s pl a y e d i n t h e  d at a li sti n g.   
 
4. 8. 2   S eri o u s  A d v er s e  E v e nt s  
 
A  s eri o u s  a d v er s e  e v e nt ( S A E) i s  a n y  A E  or  s u s p e ct e d  a d v er s e r e a cti o n t h at i n t h e  vi e w  of  eit h er 
t h e i n v e sti g at or  or  S p o n s or, r e s ult s i n  a n y  of t h e f oll o wi n g  o ut c o m e s:  
•   D e at h  
•   A lif e -t hr e at e ni n g  A E: it i s  d efi n e d  a s  a n  A E  or  s u s p e ct e d  a d v er s e r e a cti o n t h at i n t h e  vi e w 
of t h e i n v e sti g at or  or  S p o n s or, it s  o c c urr e n c e  pl a c e s t h e  p ati e nt  or  s u bj e ct  at i m m e di at e 


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ri s k  of  d e at h. It  d o e s  n ot i n cl u d e  a n  A E  or  s u s p e ct e d  a d v er s e r e a cti o n t h at,  h a d it  o c c urr e d 
i n  a  m or e  s e v er e f or m,  mi g ht  h a v e  c a u s e d  d e at h.  
•   I n p ati e nt  h os pit ali z ati o n  or  pr ol o n g ati o n  of  e xi sti n g  h o s pit ali z ati o n . 
•   A  p er si st e nt  or  si g nifi c a nt  i n c a p a cit y  or  s u b st a nti al  di sr u pti o n  of  t h e  a bilit y  t o  c o n d u ct 
n or m al lif e f u n cti o n.   
•   A  c o n g e nit al  a n o m al y/ birt h  d ef e ct . 
•   I m p ort a nt    m e di c al   e v e nt s  t h at    m a y   n ot   r e s ult  i n   d e at h,  lif e-t hr e at e ni n g,   or   r e q uir e 
h o s pit ali z ati o n    m a y   b e  c o n si d er e d   s eri o u s    w h e n,   b a s e d   u p o n   a p pr o pri at e    m e di c al 
j u d g m e nt, t h e y  m a y j e o p ar di z e t h e  p ati e nt  or  s u bj e ct  a n d  m a y r e q uir e  m e di c al  or  s ur gi c al 
i nt er v e nti o n t o  pr e v e nt  o n e  of  o ut c o m e s li st e d i n t h e  a b o v e  d efi niti o n. 
 
Lif e t hr e at e ni n g:    
A n  a d v er s e  e v e nt  o r  s u s p e ct e d  a d v er s e r e a cti o n i s  c o n si d er e d “lif e-t hr e at e ni n g” if, i n t h e  vi e w  of 
eit h er t h e i n v e sti g at or  or  s p o n s or, it s  o c c urr e n c e  pl a c e s t h e  p ati e nt  or  s u bj e ct  at i m m e di at e ri s k 
of  d e at h. It  d o e s  n ot i n cl u d e  a n  a d v er s e  e v e nt  or  s u s p e ct e d  a d v er s e r e a cti o n  t h at,  h a d it  o c c urr e d 
i n  a  m or e  s e v er e f or m,  mi g ht  h a v e  c a u s e d  d e at h. 
 
H o s pit ali z ati o n:   
A n y  a d v er s e  e v e nt l e a di n g t o  h o s pit ali z ati o n  or  pr ol o n g ati o n  of  h o s pit ali z ati o n  will  b e  c o n si d er e d 
a s ‘ s eri o u s’,  U N L E S S  at l e a st  o n e  of t h e f oll o wi n g  e x c e pti o n s i s  m et:  
•   t h e  a d mi s si o n r e s ult s i n  a  h o s pit al  st a y  of l e s s t h a n  2 4  h o ur s  O R 
•   t h e  a d mi s si o n i s  pr e-pl a n n e d (i. e.,  el e cti v e  or  s c h e d ul e d  s ur g er y  arr a n g e d  pri or t o t h e  st art 
of t h e  st u d y)  
 
H o w e v er,  it  s h o ul d  b e  n ot e d  t h at  i n v a si v e  tr e at m e nt  d uri n g  a n y   h o s pit ali z ati o n    m a y  f ulfill  t h e 
crit eri a  of ‘ m e di c all y i m p ort a nt’  a n d  a s  s u c h  m a y  b e r e p ort a bl e  a s  a  S A E  d e p e n d e nt  o n  cli ni c al 
j u d g m e nt. 
 
Di s a bilit y  m e a n s  a  s u b st a nti al  di sr u pti o n  of  a  p er s o n’ s  a bilit y t o  c o n d u ct  n or m al lif e f u n cti o n s.  
 
I m p ort a nt  m e di c al e v e nt:   
A s  g ui d a n c e  f or  d et er mi n ati o n  of  i m p ort a nt    m e di c al  e v e nt s  s e e  t h e  ‘ W H O    A d v er s e    R e a cti o n 
T er mi n ol o g y  –  Criti c al   T er m s  Li st’.   T h e s e  t er m s  eit h er  s e e  or    mi g ht  b e  i n di c ati v e  of  a  s eri o u s 
di s e a s e   st at e.    S u c h   r e p ort e d   e v e nt s    w arr a nt   s p e ci al   att e nti o n   b e c a u s e   of   t h eir   p o s si bl e 
a s s o ci ati o n  wit h  a  s eri o u s  di s e a s e  st at e  a n d  m a y l e a d t o  m or e  d e ci si v e  a cti o n t h a n  r e p ort s  o n 
ot h er t er m s.   
 
4. 8. 3   Cli ni c al  L a b or at or y  E v al u ati o n     
 
A b n or m al l a b or at or y fi n di n g s  wit h o ut  cli ni c al  si g nifi c a n c e ( b a s e d  o n t h e  i n v e sti g at or' s j u d g m e nt) 
s h o ul d  n ot  b e r e c or d e d  a s  a d v er s e  e v e nt s;  h o w e v er, l a b or at or y  v al u e  c h a n g e s r e q uiri n g t h er a p y 
or  a dj u st m e nt i n  pri or t h er a p y  ar e  c o n si d er e d  a s  a d v er s e  e v e nt s.  
A d v er s e  e v e nt s  will  b e r e vi e w e d  c o nti n u o u sl y t hr o u g h o ut t h e  st u d y.  
 


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L a b or at or y r e s ult s ( h e m at ol o g y,  s er u m  c h e mi str y  a n d  uri n al y si s)  will  b e  pr e s e nt e d i n  d at a li sti n g. 
A b n or m al  v al u e s   will  b e  fl a g g e d  a s  hi g h  or  l o w  r el ati v e  t o  t h e  l o c al  l a b  n or m al  r a n g e s,   w h er e 
a p pli c a bl e.  V al u e s t h at  ar e  d e e m e d  a s  a b n or m al,  cli ni c all y  si g n ifi c a nt  will  al s o  b e fl a g g e d.  
 
L a b or at or y  r e s ult s    will  b e  s u m m ari z e d  u si n g  d e s cri pti v e  st ati sti c s  at  b a s eli n e  a n d  p o st -d o s e. 
C h a n g e s fr o m  b a s eli n e  will  al s o  b e  s u m m ari z e d.  O nl y  n o n -mi s si n g  a s s e s s m e nt s  at  b a s eli n e  a n d 
p o st -d o s e  will  b e  a n al y z e d.   
 
A n y  cli n i c all y  si g nifi c a nt l a b  a b n or m aliti e s  will  b e  d et er mi n e d  b y t h e  Pri n ci p al I n v e sti g at or  a n d  will 
b e r e p ort e d i n t h e  A E t a bl e  s u m m ari e s.   
 
4. 8. 4   Vit al  Si g n s     
 
Vit al  si g n s  will  b e  s u m m ari z e d  u si n g  d e s cri pti v e  st ati sti c s  at  b a s eli n e  a n d  at  e a c h  p o st -d o s e ti m e 
p oi nt .  C h a n g e s fr o m  b a s eli n e  will  al s o  b e  s u m m ari z e d.  
 
4. 8. 5   El e ctr o c ar di o gr a m     
 
E C G  p ar a m et er s ( n u m eri c)  will  b e  s u m m ari z e d  u si n g  d e s cri pti v e  st ati sti c s  at  b a s eli n e  a n d  at 
e a c h  p o st -d o s e ti m e  p oi nt.  C h a n g e s fr o m  b a s eli n e  will  al s o  b e  s u m m ari z e d.   
  
4. 9   
P D  A n al y s e s  
 
N o f or m al  st ati sti c al  a n al y si s  of  P D  e n d p oi nt s (i. e.  bi o m ar k er s)  will  b e  p erf or m e d.  P D  d at a fr o m 
e a c h  a s s a y  will  b e li st e d.   
 
4. 1 0   P K  A n al y s e s  
 
4. 1 0. 1   
M e a s ur e m e nt s  a n d  C oll e cti o n  S c h e d ul e  
 
Pl a s m a : 
Bl o o d  s a m pl e s f or t h e  d et er mi n ati o n  of  pl a s m a  B B T -4 0 1 -1 S  c o n c e ntr ati o n s  will  b e  c oll e ct e d  at 
Vi sit  2 ( W e e k  0)  a n d  Vi sit  3 ( W e e k  4)  at  pr e d o s e  a n d  at  3  a n d  6  h o ur s  p o st d o s e  a n d  Vi sit  4 
( W e e k  8)  at  pr e d o s e.   
 
Ti s s u e:   
Ti s s u e  s a m pl e s  will  b e  c oll e ct e d  fr o m  d e s c e n di n g  c ol o n  a n d r e ct u m d uri n g  e n d o s c o p y 
pr o c e d ur e s  of  Vi sit  1 ( S cr e e ni n g)  a n d  Vi sit  4 ( W e e k  8).    
 
4. 1 0. 2   
Bi o a n al yti c al  M et h o d s  
 
Pl a s m a  a n d  ti s s u e  c o n c e ntr ati o n s  of   B B T -4 0 1 -1 S    will  b e  d et er mi n e d  u si n g  hi g h  p erf or m a n c e 
li q ui d  c hr o m at o gr a p h y-t a n d e m  m a s s  s p e ctr o m etr y ( H P L C  M S/ M S)  m et h o d s.  Pl a s m a  m et h o d  w a s 
v ali d at e d    wit h  r e s p e ct  t o  a c c ur a c y,  pr e ci si o n,  li n e arit y,  s e n siti vit y,  a n d  s p e cifi cit y  at    C el eri o n, 


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Li n c ol n,    N e br a s k a.    T h e   a n al yti c al  r a n g e  (l o w er  li mit   of   q u a ntit ati o n  [ L L O Q]  –   u p p er  li mit   of 
q u a ntit ati o n [ U L O Q]) f or  pl a s m a  B B T -4 0 1 -1 S  c o n c e ntr ati o n  i s  e xp e ct e d t o  b e  1. 0 0  –  1 0 0 0  n g/ m L.  
Ti s s u e  m et h o d  will  b e  q u alifi e d t o  d et e ct t h e  ti s s u e c o n c e ntr ati o n s  of  B B T -4 0 1 -1 S  at  1. 0 0  –  1 0 0 0 
n g/ g r a n g e  u si n g  bi o p s y  s a m pl e s  of  a p pr o xi m at el y  2 0  m g.  
 
 
4. 1 0. 3   
P l a s m a/ Ti s s u e C o n c e ntr ati o n s  
 
Pl a s m a  a n d  ti s s u e   B B T -4 0 1 -1 S   c o n c e ntr ati o n s   a s   d et er mi n e d   at  t h e   c oll e cti o n  ti m e s   a n d 
a n al y z e d  p er  t h e  bi o a n al yti c al    m et h o d s  d e s cri b e d  i n   S e cti o n 4. 1 0. 1  a n d   S e cti o n  4. 1 0 . 2   will  b e 
s u m m ari z e d.  
 
4. 1 0. 4   
P ar a m et er  C al c ul ati o n  
 
D u e t o li mit e d  s a m pli n g ti m e  p oi nt s t o  c al c ul at e  P K  p ar a m et er s, t h er e  will  b e  n o  P K  p ar a m et er 
c al c ul ati o n  s u c h  a s  T m a x ,  Cm a x ,  A U C f or  pl a s m a  or ti s s u e  c o n c e ntr ati o n.  
 
4. 1 0. 5   
D at a  S u m m ari z ati o n  a n d  Pr e s e nt ati o n  
 
Pl a s m a  a n d  ti s s u e c o n c e ntr ati o n s  of  B B T -4 0 1 -1 S  will  b e li st e d  b y ti m e  p oi nt  a n d  v i sit  s c h e d ul e 
( e. g.,  W 0,  W 4  et c),  r e s p e cti v el y, f or  all  s u bj e ct s w h o  r e c ei v e  a  d ail y  or al  d o s e  of  B B T  4 0 1-1 S . 
Pl a s m a  a n d  ti s s u e   c o n c e ntr ati o n s   of    B B T -4 0 1 -1 S    will   b e   pr e s e nt e d    wit h  t h e  s a m e  l e v el   of 
pr e ci si o n  a s  r e c ei v e d  fr o m  t h e  bi o a n al yti c al  l a b or at or y.    All    B L Q  a n d    mi s si n g  v al u e s    will  b e 
pr e s e nt e d  a s “ B L Q”  or “.”, r e s p e cti v el y, i n t h e  c o n c e ntr ati o n li sti n g s  a n d f o ot n ot e d  a c c or di n gl y.   
 
B B T -4 0 1 -1 S  p l a s m a a n d ti s s u e  c o n c e ntr ati o n s  will  b e li st e d  a n d  s u m m ari z e d  b y tr e at m e nt  ( d o s e 
gr o u p)  f or  all  s u bj e ct s, if  a p pr o pri at e.  S u m m ar y  st ati sti c s, i n cl u di n g  s a m pl e  si z e  ( n),  arit h m eti c 
m e a n  ( m e a n),  st a n d ar d  d e vi ati o n  ( S D),  c o effi ci e nt  of  v ari ati o n  ( C V %),    mi ni m u m,    m e di a n,  a n d 
m a xi m u m  will  b e  c al c ul at e d f or  B B T -4 0 1 -1 S  pl a s m a  a n d ti s s u e  c o n c e ntr ati o n s , if  a p pr o pri at e. T h e 
l e v el  of  pr e ci si o n f or  e a c h c o n c e ntr ati o n  st ati sti c  will  b e  pr e s e nt e d  a s f oll o w s:  mi ni m u m/ m a xi m u m , 
m e a n,  m e di a n  a n d  S D  i n  s a m e  pr e ci si o n  a s i n  bi o a n al yti c al  d at a,  n  will  b e  pr e s e nt e d  a s  a n i nt e g er 
a n d  C V %  will  b e  pr e s e nt e d t o  1  d e ci m al  pl a c e.  
 
4. 1 0. 6   
St ati sti c al  A n al y si s  of  Pl a s m a/ Ti s s u e  C o n c e ntr ati o n s  
 
N o  f or m al  st ati sti c al  a n al y si s  will  b e  p erf or m e d f or  pl a s m a/ti s s u e  c o n c e ntr ati o n s. 
 
4. 1 1   I nt eri m  A n al y si s  a n d  D at a  M o nit ori n g 
 
T h er e  will  b e  n o f or m all y  pl a n n e d i nt eri m  a n al y s e s.  H o w e v er,  i n  or d er t o  s el e ct t h e  2 n d  c o h ort 
d o s e,  if  1 2t h  p ati e nt ( 7 5 %)  of  1 st  c o h ort  c o m pl et e s  Vi sit  4 ( W e e k  8),  u n bli n di n g  of  1 2  p ati e nt s  will 
b e  p erf or m e d  wit hi n  2  w e e k s  aft er  Vi sit  4.  T h e  u n bli n di n g i nf or m ati o n  will  b e  o nl y  pr o vi d e d t o t h e 
S p o n s or f or t h e  a n al y si s  d et er mi ni n g t h e  d o s e  of  n e xt  c o h ort.   Li k e wi s e,  aft er  1 2t h  p ati e nt  of  2 n d 
C o h ort  c o m pl et e s  Vi sit  4,  si mil ar  u n bli n di n g  of  2 n d  c o h ort  will  o c c ur i n  or d er t o  s el e ct t h e  d o s e f or 


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
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C o nfi d e nti al  
1 8 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
t h e  3r d  c o h ort.  T h e  a n al y si s  of t h e  u n bli n d e d  d at a  of  1 st  a n d/ or  2 n d  c o h ort  will  b e  a n al y z e d  b y  a 
t hir d-p art y i n d e p e n d e nt  st ati sti ci a n. I n cl u di n g t h e  st u d y  st ati sti ci a n,  m o st  of t h e  k e y  p er s o n n el  of 
t h e  st u d y  w h o  dir e ctl y  p arti ci p at e i n  c o n d u cti n g  of t h e  st u d y  s h o ul d  b e r e m ai n e d  bli n d e d.   
 
4. 1 2   H a n dli n g  of  Dr o p o ut s  or  Mi s si n g  D at a  
 
N o i m p ut ati o n s  will  b e  m a d e f or  mi s si n g  v a l u e s.  
 
4. 1 3   S u b gr o u p  A n al y si s  
 
T h er e  ar e  n o  pl a n n e d  s u b gr o u p  effi c a c y  a n al y s e s.   
 
4. 1 4   M ulti pl e  C o m p ari s o n/ M ulti pli cit y  
 
N o  a dj u st m e nt s f or  m ulti pli cit y  or  m ulti pl e t e sti n g  will  b e  m a d e.   
 
  
5   
C H A N G E S  T O  P R O T O C O L -S P E CI FI E D  A N A L Y S E S  
 
N o  c h a n g e s t o  pr ot o c ol -s p e cifi e d  a n al y s e s  ar e  pl a n n e d.  
 
 
6   
LI S T  O F  T A B L E S  A N D  FI G U R E S  
 
Li st  of  T a bl e s  
 
I C H 
H e a di n g  
T a bl e  
N u m b er  
T a bl e  D e s cri pti o n  
1 4. 1   
 
D E M O G R A P HI C  
  
1 4. 1. 1   
S u m m ar y  of  P ati e nt  Di s p o siti o n  ( All  P ati e nt s) 
  
1 4. 1. 2   
S u m m ar y  of  D e m o gr a p hi c  a n d  B a s eli n e  C h ar a ct eri sti c s  ( mI T T A n al y si s  s et ) 
  
1 4. 1. 3   
S u m m ar y  of  M e di c al  Hi st or y  ( mI T T A n al y si s  s et ) 
  
1 4. 1. 4   
S u m m ar y  of  Pri or  M e di c ati o n s  ( mI T T A n al y si s  s et ) 
  
1 4. 1. 5   
S u m m ar y  of  C o n c o mit a nt  M e di c ati o n s  ( mI T T A n al y si s  s et ) 
1 4. 2   
 
E F FI C A C Y  
1 4. 2. 1   
 
Pri m ar y  Effi c a c y  
  
1 4. 2. 1. 1   
S u m m ar y  of  C h a n g e  of  T ot al  M a y o  S c or e fr o m  B a s eli n e t o  W e e k  8 ( mI T T 
A n al y si s  s et ) 
  
1 4. 2. 1 . 2  
S u m m ar y  of  C h a n g e  of  T ot al  M a y o  S c or e fr o m  B a s eli n e t o  W e e k  8 ( P P  
A n al y si s  s et ) 
1 4. 2. 2   
 
S e c o n d ar y  Effi c a c y  
  
1 4. 2. 2. 1 . 1  S u m m ar y  of  C h a n g e  of  P arti al  M a y o  S c or e fr o m  B a s eli n e t o  W e e k  8 ( mI T T 
A n al y si s  s et ) 
  
1 4. 2. 2. 1 . 2  S u m m ar y  of  C h a n g e  of  P arti al  M a y o  S c or e fr o m  B a s eli n e t o  W e e k  8 ( P P  
A n al y si s  s et ) 


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
1 9 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
  
1 4. 2. 2. 2 . 1  S u m m ar y  of  C h a n g e  of  Hi st ol o gi c  A s s e s s m e nt  of  E n d o s c o pi c  Bi o p s y fr o m 
B a s eli n e t o  W e e k  8 ( mI T T  A n al y si s  s et ) 
  
1 4. 2. 2. 2 . 2  S u m m ar y  of  C h a n g e  of  Hi st ol o gi c  A s s e s s m e nt  of  E n d o s c o pi c  Bi o p s y fr o m 
B a s eli n e t o  W e e k  8 ( P P  A n al y si s  s et ) 
  
1 4. 2. 2. 3 . 1  S u m m ar y  of  C h a n g e  of  Ul c er ati v e  C oliti s  E n d o s c o pi c I n d e x  of  S e v erit y ( U C EI S) 
S c or e fr o m  B a s eli n e t o  W e e k  8 ( mI T T  A n al y si s  s et ) 
  
1 4. 2. 2. 3 . 2  S u m m ar y  of  C h a n g e  of  Ul c er ati v e  C oliti s  E n d o s c o pi c I n d e x  of  S e v erit y ( U C EI S) 
S c or e fr o m  B a s eli n e t o  W e e k  8 ( P P  A n al y si s  s et ) 
  
1 4. 2. 2. 4 . 1  S u m m ar y  of  C h a n g e  of  S h ort I nfl a m m at or y  B o w el  Di s e a s e  Q u e sti o n n air e 
( SI B D Q) fr o m  B a s eli n e t o  W e e k  8 ( mI T T A n al y si s  s et ) 
  
1 4. 2. 2. 4 . 2  S u m m ar y  of  C h a n g e  of  S h ort I nfl a m m at or y  B o w el  Di s e a s e  Q u e sti o n n air e 
( SI B D Q) fr o m  B a s eli n e t o  W e ek  8 ( P P  A n al y si s  s et ) 
1 4. 2. 3   
 
E x pl or at or y  Effi c a c y  
  
1 4. 2. 3. 1   
S u m m ar y  of  C h a n g e  of  C o n c e ntr ati o n  of  Bi o m ar k er s fr o m  B a s eli n e t o  W e e k  8 
( mI T T A n al y si s  s et ) 
  
1 4. 2. 3. 2   
S u m m ar y  of  C h a n g e  of  C o n c e ntr ati o n  of  Bi o m ar k er s fr o m  B a s eli n e t o  W e e k  8 
(P P  A n al y si s  s et ) 
1 4. 3    
 
S A F E T Y  
1 4. 3. 1   
 
Di s pl a y  of  A d v er s e  E v e nt s  
  
1 4. 3. 1. 1   
O v er all  S u m m ar y  of  Tr e at m e nt -E m er g e nt  A d v er s e  E v e nt s  u p t o  W e e k  8 ( S af et y 
A n al y si s  s et ) 
  
1 4. 3. 1. 2   
S u m m ar y  of  Tr e at m e nt -E m er g e nt  A d v er s e  E v e nt s  u p t o  W e e k  8  b y  S y st e m 
Or g a n  Cl a s s  a n d  Pr ef err e d  T er m ( S af et y  A n al y si s  s et ) 
  
1 4. 3. 1. 3   
S u m m ar y  of  Tr e at m e nt -E m er g e nt  A d v er s e  E v e nt s  u p t o  W e e k  8  b y  S y st e m 
Or g a n  Cl a s s,  Pr ef err e d  T er m,  a n d  S e v erit y ( S af et y  A n al y s i s  s et) 
  
1 4. 3. 1. 4   
S u m m ar y  of  Tr e at m e nt -E m er g e nt  A d v er s e  E v e nt s  u p t o  W e e k  8  b y  S y st e m 
Or g a n  Cl a s s,  Pr ef err e d  T er m,  a n d  R el ati o n s hi p t o  St u d y  Dr u g ( S af et y  A n al y si s 
s et ) 
  
1 4. 3. 1. 5   
S u m m ar y  of  Tr e at m e nt -E m er g e nt  S eri o u s  A d v er s e  E v e nt s  u p t o  W e e k  8  b y 
S y st e m  Or g a n  Cl a s s  a n d  Pr e f err e d  T er m ( S af et y A n al y si s  s et ) 
  
1 4. 3. 1. 6   
S u m m ar y  of  Tr e at m e nt -E m er g e nt  A d v er s e  E v e nt s  u p t o  W e e k  8  L e a di n g t o 
St u d y  Di s c o nti n u ati o n  b y  S y st e m  Or g a n  Cl a s s  a n d  Pr ef err e d  T er m ( S af et y 
A n al y si s  s et ) 
1 4. 3. 2   
 
L a b or at or y  T e sti n g s  
  
1 4. 3. 2. 1   
S u m m ar y  of  V al u e s  a n d  C h a n g e s  of  H e m at ol o g y  P ar a m et er s  b y  Vi sit ( S af et y 
A n al y si s  s et ) 
  
1 4. 3. 2. 2   
S u m m ar y  of  V al u e s  a n d  C h a n g e s  of  C h e mi str y  P ar a m et er s  b y  Vi sit ( S af et y 
A n al y si s  s et ) 
1 4. 3. 3   
 
Vit al  Si g n s,  E C G  D at a,  P h y si c al  E x a mi n ati o n   
  
1 4. 3. 3 . 1  
S u m m ar y  of  Vit al  Si g n  P ar a m et er s  b y  Vi sit ( S af et y  A n al y si s  s et ) 
  
1 4. 3. 3. 2   
S u m m ar y  of  El e ctr o c ar di o gr a m  P ar a m et er s  b y  Vi sit ( S af et y  A n al y si s  s et ) 
  
1 4. 3. 3. 3   
S u m m ar y  of  P h y si c al  E x a mi n ati o n  b y  Vi sit ( S af et y  A n al y si s  s et ) 
1 4. 4    
 
P h ar m a c o ki n eti c s  
1 4. 4 . 1  
 
Pl a s m a  C o n c e ntr ati o n  
  
1 4. 4 . 1. 1  
Pl a s m a  B B T -4 0 1 -1 S  C o n c e ntr ati o n s ( n g/ m L)  F oll o wi n g t h e  A d mi ni str ati o n  of 
B B T -4 0 1 -1 S  or  Pl a c e b o  ( P K  A n al y si s  s et) 
1 4. 4 . 2  
 
Ti s s u e  C o n c e ntr ati o n  
  
1 4. 4. 2 . 1  
Ti s s u e  B B T -4 0 1 -1 S  C o n c e ntr ati o n s ( n g/ g )  F oll o wi n g t h e  A d mi ni str ati o n  of B B T -
4 0 1 -1 S  or  Pl a c e b o  ( P K  A n al y si s  s et) 


                        Gi vi n g  Fl e xi bilit y t o  Dr u g  D e v el o p m e nt     
                                     
              B B T 4 0 1 P 2 A  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
  
  
  
  
  
  
  
 
C o nfi d e nti al  
2 0 /2 0   
v 2. 1  Fi n al , 2 2  J ul 2 0 2 0  
St atisti c al  A n al ysis  Pl a n  
 
Li st  of  D at a  Li sti n g s  
 
I C H 
H e a di n g  
Li sti n g 
N u m b er  
Li sti n g  D e s cri pti o n  
1 6. 2   
 
P A TI E N T  D A T A  LI S TI N G S  
1 6. 2. 1   
 
Di s c o nti n u e d  P ati e nt s  
  
1 6. 2. 1. 1   
P ati e nt  Di s p o siti o n  
1 6. 2. 2   
 
Pr ot o c ol  D e vi ati o n s  
  
1 6. 2. 2. 1   
I n cl u si o n/ E x cl u si o n  Crit eri a  Fi n di n g s –  D e vi ati o n s  
1 6. 2. 3   
 
P ati e nt s  E x cl u d e d fr o m t h e  E ffi c a c y  S u m m ar y  
1 6. 2. 4   
 
D e m o gr a p hi c s  a n d  B a s eli n e  C h ar a ct eri sti c s  
  
1 6. 2. 4. 1   
D e m o gr a p hi c s  a n d  B a s eli n e  C h ar a ct eri sti c s  
  
1 6. 2. 4. 2   
M e di c al  Hi st or y  
  
1 6. 2. 4. 3   
Pri or  a n d  C o n c o mit a nt  M e di c ati o n s  
1 6. 2. 5   
 
C o m pli a n c e  a n d/ or  Dr u g  A d mi ni str ati o n  D at a  
  
1 6. 2. 5. 1. 1   
St u d y  Dr u g  A d mi ni str ati o n  a n d  L o g   
1 6. 2. 6   
 
I n di vi d u al E ffi c a c y R e s p o n s e  D at a  
  
1 6. 2. 6. 1   
T ot al  M a y o  S c or e   
  
1 6. 2. 6. 2   
P arti al  M a y o  S c or e  
  
1 6. 2. 6. 3   
Hi st ol o gi c  A s s e s s m e nt  of  E n d o s c o pi c  Bi o p s y  
  
1 6. 2. 6. 4   
Ul c er ati v e  C oliti s  E n d o s c o pi c I n d e x  of  S e v erit y  
  
1 6. 2. 6. 5   
S h ort I nfl a m m at or y  B o w el  Di s e a s e  Q u e sti o n n air e   
  
1 6. 2. 6. 6   
Bi o m ar k er s   
1 6. 2. 7   
 
A d v er s e  E v e nt s  Li sti n g s  
  
1 6. 2. 7. 1   
A d v er s e  E v e nt s  
  
1 6. 2. 7. 2   
S eri o u s  A d v er s e  E v e nt s  
  
1 6. 2. 7. 3   
A d v er s e  E v e nt s  L e a di n g t o  P er m a n e nt  Wit h dr a w al  of  St u d y  Tr e at m e nt  or 
Di s c o nti n u ati o n fr o m t h e  St u d y   
  
1 6. 2. 7. 4   
A d v er s e  E v e nt s  L e a di n g t o  D e at h  
1 6. 2. 8   
 
I n di vi d u al  L a b  M e a s ur e s 
  
1 6. 2. 8. 1   
H e m at ol o g y  
  
1 6. 2. 8. 2   
C h e mi str y   
  
1 6. 2. 8. 3   
Vit al  Si g n s  
  
1 6. 2. 8. 4   
El e ctr o c ar di o gr a m  
  
1 6. 2. 8. 5   
P h y si c al  E x a mi n ati o n  
1 6. 2. 9   
 
P h ar m a c o ki n eti c s  
  
1 6. 2. 9. 1   
I n di vi d u al  Pl a s m a C o n c e ntr ati o n  D at a   
  
1 6. 2. 9. 2   
I n di vi d u al Ti s s u e  C o n c e ntr ati o n  D at a   
1 6. 2. 1 0   
 
Ot h er  Mi s c ell a n e o u s  D at a  
  
1 6. 2. 1 0 . 1  
R a n d o mi z ati o n  
  
1 6. 2. 1 0 . 2  
I P 
  
1 6. 2. 1 0 . 3    
I n v e sti g at or  Si g n at ur e