Conditions: Systemic Lupus Erythematosus SLE Lupus
Keywords: JBT-101 (also known as lenabasum) efficacy musculoskeletal disease randomized trial
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 109
Healthy volunteers: no

Brief summary:
The objective of this study is to evaluate the efficacy, safety, and tolerability of JBT-101 (also known as lenabasum) in systemic lupus erythematosus (SLE).

* One hundred adults with active joint disease and at least moderate pain will be enrolled in this study to evaluate treatment of their systemic lupus erythematosus (SLE) with JBT-101. JBT-101 is a synthetic endocannabinoid receptor type 2 (CB2) agonist and an activator of the body's normal processes, to resolve innate immune responses without immunosuppression.
* Participants will receive 2 doses of JBT-101 by mouth (three groups of varying doses) or, placebo, for 84 days and will continue to be followed for an additional 28 days. Participant visits to assess endpoints occur on Day 1, then every 2 weeks twice, then every 4 weeks three times, for a total of six visits.
* The change in maximum daily pain Numerical Rating Scale (NRS) score from Baseline (Visit 1) will be assessed at every visit.

Detailed description:

Arms:
arm 1: Eligible subjects will receive assigned study treatment of JBT-101 5 mg administered twice daily. arm 2: Eligible subjects will receive assigned study treatment of JBT-101 20 mg (A.M. Study Product) and 20 mg Placebo (P.M. Study Product). arm 3: Eligible subjects will receive assigned study treatment of JBT-101 20 mg (A.M. Study Product) and JBT-101 20 mg (P.M. Study Product). arm 4: Eligible subjects will receive assigned study treatment of Placebo (A.M.) and Placebo (P.M.) for (JBT-101).

Interventions: intervention 1: JBT-101 intervention 2: Placebo
Intervention descriptions: intervention 1: Participants will self-administer JBT-101 by mouth (orally), at prescribed dose and frequency per protocol, Days 1-84. Administration of dose(s) should be at least 8 hours apart. intervention 2: Participants will self-administer JBT-101 placebo by mouth (orally), at prescribed dose and frequency per protocol, Days 1-84. Administration of dose(s) should be at least 8 hours apart.

Protocol document:
Prot_000.pdf: 
 
 
C O N F I D E N T I A L 
 
 
 
Autoimmunity Centers of Excellence 
 
 
 
Protocol # ALE09 
 
 
A Phase 2, Double-blind, Randomized, Placebo-controlled Multicenter 
Study to Evaluate Efficacy, Safety, and Tolerability of JBT-101 in Systemic 
Lupus Erythematosus 
 
Short Title: JBT-101 in SLE 
 
 
 
BB-IND #132445 
 
Version 4.0: 05 October 2018  
 
 
IND Sponsor:  Division of Allergy, Immunology, and Transplantation (DAIT) 
 
National Institute of Allergy and Infectious Diseases (NIAID) 
 
National Institutes of Health (NIH) 
 
 
 
Confidentiality Statement 
The information contained within this document is not to be disclosed in any way without the prior permission of 
the Protocol Chair(s), or the Division of Allergy, Immunology and Transplantation; the National Institute of 
Allergy and Infectious Diseases; and the National Institutes of Health. 
 


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PROTOCOL CHAIRS 
 
Protocol Chairs 
 
Meggan Mackay, M.D. 
The Feinstein Institute for Medical Research 
350 Community Drive 
Manhasset, NY  11030 
Phone: 516-562-3838 
E-mail: mmackay@nshs.edu 
Robert Zurier, M.D. 
The Feinstein Institute for Medical Research 
350 Community Drive 
Manhasset, NY  11030 
Phone: 978-870-7352 
E-mail: robert.zurier@umassmed.edu 
 
 
Cynthia Aranow, M.D. 
The Feinstein Institute for Medical Research 
350 Community Drive 
Manhasset NY 11030 
Phone: 516-562-3837 
Fax:   516-562-2537 
E-mail: caranow@nshs.edu 
 
 
DAIT/NIAID, NIH 
 
Medical Monitor 
 
Regulatory Officer 
Linna Ding, MD, Ph.D. 
Division of Allergy, Immunology, and 
Transplantation 
National Institute of Allergy and Infectious 
Diseases 
National Institutes of Health 
5601 Fishers Lane, Room 7D46 
Rockville, MD  20852 
Phone: (240) 627-3524 
E-mail: linnad@niaid.nih.gov 
 
Maria-Concetta Veri, PhD 
Division of Allergy, Immunology, and 
Transplantation 
National Institute of Allergy and Infectious 
Diseases 
National Institutes of Health 
5601 Fishers Lane, Room 7B48 
Rockville, MD  20852 
Phone: 240-627-3572 
Fax: 301-480-1537 
E-mail: maria.veri@nih.gov 
 
 
 
Project Manager 
 
 
Jessica Springer, BSN, MPH/MPA 
Division of Allergy, Immunology, and 
Transplantation 
National Institute of Allergy and Infectious 
Diseases 
National Institutes of Health 
5601 Fishers Lane, Room 7D34 
Rockville, MD  20852 
Phone: (240) 627-3474 
E-mail: springerj@mail.nih.gov 
 
 


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DAIT-SACCC 
 
 
 
 
 
Senior Statistician 
Lynette Keyes-Elstein, DrPH 
DAIT-SACCC ADG Principal Investigator 
Rho Federal Systems Division, Inc. 
6330 Quadrangle Drive 
Rho Building 
Chapel Hill, NC  27517 
Phone:  919-595-6410 
Fax:  919-287-3039 
E-mail: lynette_keyes-
elstein@rhoworld.com  
 
Project Manager 
Laurie McLeod, CCRP 
Rho Federal Systems Division, Inc. 
6330 Quadrangle Drive 
Rho Building 
Chapel Hill, NC  27517 
Phone: 919-595-6601 
Fax: 919-287-3039 
E-mail: laurie_mcleod@rhoworld.com  
 
 
 


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INVESTIGATOR SIGNATURE PAGE 
Protocol: ALE09 
Version/Date: v4.0 / 05 October 2018 
Title: A Phase 2, Double-blind, Randomized, Placebo-controlled Multicenter Study to 
Evaluate Efficacy, Safety, and Tolerability of JBT-101 in Systemic Lupus Erythematosus 
Study Sponsor: The National Institute of Allergy and Infectious Diseases (NIAID) 
INSTRUCTIONS: The site Principal Investigator should print, sign, and date at the 
indicated location below.  A copy should be kept for your records and the original signature 
page sent. After signature, please return the original of this form by surface mail to:  
DAIT Regulatory Management Center (RMC) 
Pharmaceutical Product Development (PPD) 
3900 Paramount Parkway 
Morrisville, NC 27560 
I confirm that I have read the above protocol in the latest version.  I understand it, and I will 
work according to the principles of Good Clinical Practice (GCP) as described in the United 
States Code of Federal Regulations (CFR) – 45 CFR part 46 and 21 CFR parts 50, 56, and 
312, and in the International Conference on Harmonization (ICH) document Guidance for 
Industry: E6 Good Clinical Practice: Consolidated Guidance dated April 1996.  Further, I 
will conduct the study in keeping with local legal and regulatory requirements. 
As the site Principal Investigator, I agree to carry out the study by the criteria written in the 
protocol and understand that no changes can be made to this protocol without the written 
permission of the IRB and NIAID. 
 
____________________________________     
Site Principal Investigator  (Print) 
 
____________________________________                                      _________________ 
Site Principal Investigator (Signature)                                                          Date 


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PROTOCOL SYNOPSIS 
Title of the Protocol:  A Phase 2, Double-blind, Randomized, Placebo-controlled Multicenter Study to 
Evaluate Efficacy, Safety, and Tolerability of JBT-101 in Systemic Lupus Erythematosus 
ACE Protocol Number: ALE09 
Protocol Chair(s):  Meggan Mackay, M.D.  
IND Holder:  DAIT/NIAID, NIH  
Objectives:  To evaluate the efficacy, safety, tolerability, and biologic effects of JBT-101. The primary 
objective is to evaluate effect on inflammatory pain related to active musculoskeletal disease in SLE. 
Hypotheses/Estimates:  The hypothesis is that JBT-101 will provide clinical efficacy in SLE patients with at 
least moderate musculoskeletal disease activity by activation of pathways that resolve ongoing, adverse 
immune responses and inhibit inflammatory cytokine production associated with SLE.  
Study Arms:  four cohorts:  
JBT-101 5 mg q a.m. and JBT-101 5 mg q p.m. 
JBT-101 20 mg q a.m. and placebo q p.m. 
JBT-101 20 mg q a.m. and JBT-101 20 mg q p.m. 
Placebo q a.m. and placebo q p.m. 
Study Design:  One hundred eligible subjects will be randomized in a 1:1:1:1 ratio to one of four cohorts to 
receive either JBT-101 (three groups: 5 mg q a.m. and 5 mg q p.m., 20 mg q a.m. and placebo q p.m., 20 mg q 
a.m. and 20 mg q p.m.) or placebo for 84 days, then 28 days of follow-up. Subject visits to assess endpoints 
occur at six times: Days 1, 15 ± 3, 29 ± 3, 57 ± 3, 85 ± 3 and 113 ± 3. 
Endpoints: 
PRIMARY EFFICACY ENDPOINT: 
The primary endpoint for evaluation of the primary objective will be improvement in maximum daily pain 
NRS scores in the treated groups relative to the control after 12 weeks of treatment.  Longitudinal trends over 
the course of the treatment period will be modeled and used to estimate differences between means at baseline 
and Day 84 for each treatment group. 
SECONDARY EFFICACY ENDPOINTS: 
1. The 7-day average of maximum daily pain NRS scores prior to Visits 1 (Day 1), 3 (Day 29), 4 (Day 
57), 5 (Day 85), and 6 (Day 113) will be used to evaluate the number (%) of subjects with: 
 
Changes in pain categories from Visit 1 (Day 1) to Visits 3 (Day 29), 4 (Day 57), 5 (Day 85) 
and 6 (Day 113) (See Section 6.2.2.2 Pain Categories) 
 
Improvement of 30% from Visit 1 (Day 1) to Visits 3 (Day 29), 4 (Day 57), 5 (Day 85) and 6 
(Day 113) 
 
Improvement of 50% from Visit 1 (Day 1) to Visits 3 (Day 29), 4 (Day 57), 5 (Day 85) and 6 
(Day 113)   
 
Improvement of 75% from Visit 1 (Day 1) to Visits 3 (Day 29), 4 (Day 57), 5 (Day 85) and 6 
(Day 113)   
 
Improvement of 100% from Visit 1 (Day 1) to Visits 3 (Day 29), 4 (Day 57), 5 (Day 85) and 
6 (Day 113)   
2. Trends in active musculoskeletal disease activity over the duration of the treatment period (i.e. Visit 1 
(Day 1) through Visit 5 (Day 85)) will be evaluated longitudinally using multiple indices: 
 
Physician assessed tender joint count  
 
Physician assessed swollen joint count  
 
Presence or absence of arthritis on the SELENA SLEDAI  
 
Musculoskeletal domain of the BILAG 2004  
3. Persistence of trends in musculoskeletal disease activity after stopping treatment will be evaluated at 
Visit 6 (Day 113) 
4. Trends in overall SLE disease activity over the duration of the treatment period (i.e. Visit 1 (Day 1) 
through Visit 5 (Day 85)) will be evaluated longitudinally using multiple indices:  
 
SLE Responder Index , where a responder is defined as having all of the following:  
o ≥4 point reduction in SELENA-SLEDAI score,  
o no new BILAG A or no more than 1 new BILAG B domain score, and  


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o no deterioration from baseline in the Physician's Global Assessment defined as an 
increase of ≥0.3 points.  
 
SELENA SLEDAI score 
 
BILAG 2004 score 
 
Physician’s Global Assessment 
5. Persistence of trends in overall SLE disease activity after stopping treatment will be evaluated at Visit 
6 (Day 113) 
6. Trends in patient-reported outcomes over the duration of the treatment period (i.e. Visit 1 (Day 1) 
through Visit 5 (Day 85)) will be evaluated longitudinally using multiple indices: 
 
Lupus Activity Patient Global Assessment  
 
PROMIS-29 Short Form  
 
PROMIS Item Bank v2.0 - Cognitive Function 
7. Treatment Satisfaction Survey 
8. Persistence of trends in patient-reported outcomes after stopping treatment will be evaluated at Visit 6 
(Day 113) 
SAFETY ENDPOINTS: 
Safety will be evaluated by describing incidence of treatment emergent adverse events (TEAEs) from Visit 1 
(Day 1) through Visit 6 (Day 113). The TEAEs will be identified by monitoring subject-reported AEs, Adverse 
Events of Special Interest, vital signs, medical history, physical examination, blood and urine laboratory safety 
tests, 12-lead electrocardiograms, including QT/QTc measurements, and Addiction Research Center Inventory-
Marijuana scale. Analyses on the following specific events are planned. 
1. Any Grade 3 or higher AE or SAE that, in the opinion of the blinded site investigator, is at least 
“possibly related to study product. Unless noted otherwise, grading is defined by the National Cancer 
Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE) system version 4.0  
2. QTc prolongation > 500 msec total duration and > 60 msec from Visit 1 (Day 1) QTc interval prior to 
study drug administration 
3. Mild/moderate and severe disease flares by SELENA SLEDAI Flare Index  
4. BILAG 2004 disease flares, defined as one new BILAG A or two new BILAG B scores 
5. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3 x upper limit of normal and 
total bilirubin > 1.5 x the upper limit of normal (confirmed on repeat testing) 
6. Tolerability, assessed by incidence of discontinuation of study product due to TEAEs at least 
“possibly” related to study product from Visits 1 (Day 1) through 5 (Day 85) 
7. Psychotropic activity, assessed using the ARCI-M 
MECHANISTIC ENDPOINTS: 
1. Trends in C-reactive protein levels in the blood over the duration of the treatment period (i.e. Visit 1 
(Day 1) through Visit 5 (Day 85)) will be evaluated longitudinally 
2.  Persistence of trends in C-reactive protein levels after stopping treatment will be evaluated at Visit 6 
(Day 113) 
3. Trends in pro-inflammatory cytokine levels over the duration of the treatment period  (i.e. Visits 1 
(Day 1), 3 (Day 29) and 5 (Day 85)) will be evaluated longitudinally using multiple indices: 
 
Pro-inflammatory cytokines in serum 
i. IFN, IFN, IL-6, TNF, and IL-1  
ii. Expression of other cytokines will be explored  
 
Pro-inflammatory cytokines in whole blood with and without in vitro TLR stimulation  
i.  IFN, IFN, IL-6, TNF, and IL-1 in supernatant of stimulated and unstimulated 
whole blood cells 
 
Type 1 IFN gene signature in whole blood mRNA.    
4. Persistence of trends in biomarkers of inflammation after stopping treatment will be evaluated at Visit 
6 (Day 113) 
5. Changes in bioactive lipids in plasma from Visit 1 (Day 1) (pre and post dose) to Visit 2 (Day 15) will 
be evaluated longitudinally using multiple indices: 


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Title of the Protocol:  A Phase 2, Double-blind, Randomized, Placebo-controlled Multicenter Study to 
Evaluate Efficacy, Safety, and Tolerability of JBT-101 in Systemic Lupus Erythematosus 
 
Specialized Pro-resolving lipid Mediators (SPMs), including lipoxin A4  
 
Anti-inflammatory eicosanoids 
 
Pro-inflammatory eicosanoids 
6. Changes in plasma concentrations of JBT-101 and its metabolites from Visit 1 (Day 1) (pre and post 
dose) to Visit 2 (Day 15)  
 
EXPLORATORY ENDPOINTS: 
1. Fibromyalgia Symptom Scale score, from Visit 1 (Day 1) to Visits 5 (Day 85) and 6 (Day 113) 
Sample Size:  100 eligible subjects will be randomized within 24 months and followed for 112 days; the study 
duration is estimated to be 33 months. 
 
 
Lay Summary: 
One hundred adults with SLE and active joint disease with at least moderate pain will be 
enrolled in this study to evaluate the safety, efficacy, and mechanisms of action of JBT-101. 
JBT-101 is a synthetic endocannabinoid receptor type 2 (CB2) agonist and an activator of the 
body’s normal processes to resolve innate immune responses without immunosuppression.  
JBT-101 induces a class switch in production of lipid mediators to increase production of 
“Specialized Pro-resolving lipid Mediators” (SPMs) while reducing production of pro-
inflammatory mediators.  In turn, SPMs trigger a physiologic network to resolve 
inflammation and fibrosis, and, when present, increase clearance of pathogens.  With return 
to homeostasis, clinical benefit is expected to occur in people with SLE, for example, in 
those who have inflammation of the musculoskeletal system and associated pain.   
Subjects will be randomized to receive 2 daily oral doses of JBT-101 (three groups of 
varying doses; JBT-101 10 mg daily, JBT-101 20 mg daily or JBT-101 40 mg daily) or 
placebo for 84 days and will continue to be followed for an additional 28 days. Subject visits 
to assess endpoints occur on Day 1, then every 2 weeks twice, then every 4 weeks three 
times, for six total visits after randomization. The study will compare changes over time in 
daily measures of the maximum pain NRS in treated groups compared to the placebo group 
after 12 weeks of treatment. Studies are also planned to evaluate tolerability and 
inflammation.


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FLOW DIAGRAM OF PROTOCOL 
 
 


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ABBREVIATIONS 
 
βHCG 
β Human Chorionic Gonadotropin 
ACE 
Autoimmunity Centers of Excellence 
ACR 
American College of Rheumatology 
ADCT 
Autoimmune Diseases Clinical Trials 
AE 
Adverse event 
ARCI-M 
Addiction Research Center Inventory-Marijuana 
AUC 
Area under the curve 
b.i.d. 
Twice a day 
BILAG 
British Isles Lupus Activity Group 
BP 
Blood pressure 
CB1 
Cannabinoid type 1 receptor 
CB2 
Cannabinoid type 2 receptor 
CBC 
Complete blood count 
CFR 
Code of Federal Regulations 
Cmax 
Concentration maximum 
Corbus 
Corbus Pharmaceuticals Holdings, Inc. 
CRP 
C-reactive protein 
CTCAE 
Common Terminology Criteria for Adverse Events 
DAIT 
Division of Allergy, Immunology, and Transplantation 
DEA 
Drug Enforcement Administration 
DHHS 
Department of Health and Human Services 
DSMB 
Data and Safety Monitoring Board 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic data capture 
FDA 
Food and Drug Administration 
FIMR 
Feinstein Institute for Medical Research 
GCP 
Good Clinical Practice 
HED 
Human equivalent dose 
HIV 
Human Immunodeficiency Virus 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonization 
IFN 
Interferon 
IL 
Interleukin 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ITT 
Intention-to-Treat or Intent-to-Treat 
IVRS 
Interactive voice-response system 
NCI 
National Cancer Institute 
NIAID 
National Institute of Allergy and Infectious Diseases 
NIH 
National Institutes of Health 
NOAEL 
No observed adverse effect level 
NRS 
Numerical rating scale 


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NSAIDs 
Non-steroidal anti-inflammatory drugs 
P 
Pulse 
PBMC 
Peripheral blood mononuclear cells 
PI 
Principal Investigator 
PP 
Per Protocol 
PPD 
Purified protein derivative 
PK 
Pharmacokinetic 
PROMIS 
Patient-Reported Outcomes Measurement Information System 
q.d. 
Once per day 
QTc 
Corrected QT 
R 
Respiratory rate 
RhoFED 
Rho Federal Systems Division, Inc. 
RMANOVA 
Mixed models repeated measures analysis of variance 
SACCC 
Statistical and Clinical Coordinating Center 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAR 
Suspected Adverse Reaction 
SELENA 
Safety of Estrogen in Lupus: National Assessment 
SID 
Subject identification number 
SLE 
Systemic lupus erythematosus 
SLEDAI 
Systemic Lupus Erythematosus Disease Activity Index 
SP 
Safety Population 
SPMs 
Specialized Pro-resolving Lipid Mediators 
SUSAR 
Serious and Unexpected Suspected Adverse Reaction  
TEAE 
Treatment emergent adverse event 
TNFα 
Tumor necrosis factor α 
ULN 
Upper Limit of Normal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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TABLE OF CONTENTS 
PROTOCOL SYNOPSIS ........................................................................................................5 
FLOW DIAGRAM OF PROTOCOL ....................................................................................8 
TABLE OF CONTENTS ......................................................................................................11 
1 BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE .....................16 
1.1 
DISEASE BACKGROUND ............................................................................................16 
 
Description and Epidemiology of Disease .......................................................16 
1.1.1
 
Immunopathogenesis of Systemic Lupus Erythematosus .................................17 
1.1.2
 
Current Treatment of Active Musculoskeletal Involvement in Systemic 
1.1.3
Lupus Erythematosus .......................................................................................17 
1.2 
RATIONALE FOR JBT-101 .........................................................................................19 
 
Specialized Pro-resolving Lipid Mediators Induce Resolution of 
1.2.1
Inflammation, Infection, and Fibrotic Processes .............................................19 
 
Proposed Mechanism of Action of JBT-101, a Synthetic CB2 Agonist ...........20 
1.2.2
 
Summary of Biologic Effects of JBT-101 .........................................................21 
1.2.3
1.3 
SUMMARY OF PRE-CLINICAL AND CLINICAL STUDIES ..............................................22 
 
Animal and Human Biomaterials Safety Data .................................................22 
1.3.1
 
Animal Toxicokinetic Results ...........................................................................23 
1.3.2
 
Animal Metabolism ..........................................................................................23 
1.3.3
 
Clinical Studies ................................................................................................24 
1.3.4
1.4 
CURRENT LICENSING OF JBT-101 .............................................................................28 
1.5 
KNOWN AND POTENTIAL RISKS AND BENEFITS OF JBT-101 .....................................28 
 
Potential Risks .................................................................................................28 
1.5.1
 
Potential Benefits .............................................................................................30 
1.5.2
1.6 
RATIONALE FOR THE STUDY .....................................................................................30 
 
Rationale for the Inclusion and Exclusion Criteria .........................................31 
1.6.1
 
Rationale for the Treatment Arm .....................................................................32 
1.6.2
 
Rationale for the Control Arm .........................................................................33 
1.6.3
 
Rationale for Mechanistic Studies ...................................................................33 
1.6.4
2 STUDY OBJECTIVES AND PURPOSE .......................................................................34 
2.1 
PRIMARY OBJECTIVE(S) ............................................................................................34 
2.2 
SECONDARY OBJECTIVE(S) .......................................................................................34 
2.3 
EXPLORATORY OBJECTIVES ......................................................................................34 
3 STUDY DESIGN ...............................................................................................................35 
3.1 
DESCRIPTION OF STUDY DESIGN ...............................................................................35 
 
Stratification, Randomization, and Blinding ...................................................37 
3.1.1
 
Subject Completion and Replacement ....................................................38 
3.1.1.1
3.2 
DESCRIPTION OF ENDPOINTS .....................................................................................38 
 
Primary Efficacy Endpoint ..............................................................................38 
3.2.1
 
Secondary Efficacy Endpoints .........................................................................38 
3.2.2
 
Safety Endpoints...............................................................................................40 
3.2.3


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Mechanistic Endpoints .....................................................................................40 
3.2.4
 
Exploratory Endpoints .....................................................................................41 
3.2.5
4 SELECTION OF SUBJECTS ..........................................................................................41 
4.1 
INCLUSION CRITERIA ................................................................................................41 
4.2 
EXCLUSION CRITERIA ...............................................................................................42 
4.3 
CO-ENROLLMENT GUIDELINES ..................................................................................44 
4.4 
STRATEGIES FOR RECRUITMENT AND RETENTION ....................................................44 
5 TREATMENT OF SUBJECTS .......................................................................................45 
5.1 
DESCRIPTION OF STUDY PRODUCT ............................................................................45 
 
Product Description .........................................................................................45 
5.1.1
 
Packaging and Labeling of Study Product ......................................................45 
5.1.2
 
Storage and Handling of Study Product ..........................................................46 
5.1.3
5.2 
DOSAGE REGIMEN ....................................................................................................47 
5.3 
ADMINISTRATION OF STUDY PRODUCT .....................................................................47 
5.4 
MANAGEMENT PLAN FOR POTENTIAL RISKS ............................................................47 
 
Prevention of Potential Risks to Study Product ...............................................48 
5.4.1
 
Management of Potential Risks to Study Product............................................48 
5.4.2
5.5 
CONCURRENT MEDICATIONS AND THERAPY .............................................................49 
5.6 
PROHIBITED MEDICATIONS .......................................................................................50 
5.7 
PROCEDURES FOR MONITORING SUBJECT COMPLIANCE ...........................................50 
5.8 
TREATMENT DISCONTINUATION AND SUBJECT WITHDRAWAL .................................51 
 
Interruption of Dosing and Study Treatment Discontinuation ........................51 
5.8.1
 
Procedures for Discontinuation of Protocol-Specified Treatment 
5.8.1.1
Requirements ..........................................................................................51 
 
Subject Withdrawal from the Study..................................................................52 
5.8.2
 
Procedures for Subject Withdrawal from the Study ...............................52 
5.8.2.1
 
Safety Stopping Guidance ................................................................................52 
5.8.3
6 ASSESSMENT OF SAFETY AND EFFICACY ............................................................53 
6.1 
ASSESSMENTS OF ELIGIBILITY AND SAFETY .............................................................53 
 
Medical History and Use of Contraception .....................................................54 
6.1.1
 
Concomitant Medication and Treatment History ............................................54 
6.1.2
 
Physical Examination ......................................................................................54 
6.1.3
 
Vital Signs, Height and Weight Measurements ................................................54 
6.1.4
 
Disease Flares for Safety Assessment ..............................................................55 
6.1.5
 
SELENA SLEDAI (28 day assessment) ..................................................55 
6.1.5.1
 
BILAG 2004 ............................................................................................55 
6.1.5.2
 
Flare Definitions ....................................................................................56 
6.1.5.3
 
Blood and Urine Laboratory Safety Tests .......................................................56 
6.1.6
 
Electrocardiograms and QT/QTc Intervals .....................................................56 
6.1.7
 
ARCI-M Questionnaire ....................................................................................57 
6.1.8
 
Pregnancies......................................................................................................57 
6.1.9
 
Tuberculosis Screening ....................................................................................57 
6.1.10
6.2 
ASSESSMENTS OF EFFICACY .....................................................................................58 


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Primary Efficacy Variable: Maximum Daily Pain NRS Score ........................58 
6.2.1
 
Secondary Efficacy Variables ..........................................................................58 
6.2.2
 
Response Categories ..............................................................................58 
6.2.2.1
 
Pain Categories ......................................................................................59 
6.2.2.2
 
66/68 Joint Count ...................................................................................59 
6.2.2.3
 
Disease Activity ......................................................................................59 
6.2.2.4
 
Patient-reported Outcomes ..............................................................................60 
6.2.3
 
Lupus Activity Patient Global Assessment .............................................60 
6.2.3.1
 
PROMIS Forms ......................................................................................60 
6.2.3.2
 
Fibromyalgia Symptom Scale .................................................................61 
6.2.3.3
 
Treatment Satisfaction Survey .........................................................................61 
6.2.4
6.3 
MECHANISTIC STUDIES .............................................................................................61 
 
Biomarkers of Inflammation ............................................................................61 
6.3.1
 
C-reactive Protein ..................................................................................61 
6.3.1.1
 
Pro-Inflammatory Cytokines ..................................................................61 
6.3.1.2
 
Type 1 IFN gene signature...................................................................62 
6.3.1.3
 
Metabolipidomic Profile ..................................................................................62 
6.3.2
 
JBT-101 Plasma Concentrations and Metabolites ..........................................62 
6.3.3
 
Optional Unspecified Future Studies ...............................................................62 
6.3.4
 
Blood Draw Prioritization ...............................................................................62 
6.3.5
6.4 
EVALUATIONS BY STUDY VISIT ................................................................................63 
 
Screening Period ..............................................................................................63 
6.4.1
 
Evaluation of Eligibility and Randomization .........................................65 
6.4.1.1
 
Treatment Period .............................................................................................65 
6.4.2
 
Visit 1 (Day 1) ........................................................................................65 
6.4.2.1
 
Visit 2 (Day 15 ± 3 days) ........................................................................67 
6.4.2.2
 
Visit 3 (Day 29 ± 3 days) ........................................................................67 
6.4.2.3
 
Visit 4 (Day 57 ± 3 days) ........................................................................69 
6.4.2.4
 
Visit 5 (Day 85 ± 3 days) ........................................................................70 
6.4.2.5
 
Visit 6 (Day 113 ± 3 days) ......................................................................71 
6.4.2.6
 
Early Withdrawal Visit ...........................................................................72 
6.4.2.7
 
Visit Windows...................................................................................................73 
6.4.3
 
Unscheduled Visits ...........................................................................................74 
6.4.4
7 SAFETY MONITORING AND REPORTING .............................................................78 
7.1 
OVERVIEW ................................................................................................................78 
7.2 
DEFINITIONS .............................................................................................................78 
 
Adverse Event (AE) ..........................................................................................78 
7.2.1
 
Suspected Adverse Reaction (SAR) ........................................................78 
7.2.1.1
 
Unexpected Adverse Event ...............................................................................78 
7.2.2
 
Serious Adverse Event (SAE) ...........................................................................79 
7.2.3
 
Adverse Events of Special Interest (AESI) .......................................................79 
7.2.4
7.3 
COLLECTION AND RECORDING OF ADVERSE EVENTS ...............................................80 
 
Collection Period .............................................................................................80 
7.3.1
 
Collecting Adverse Events ...............................................................................80 
7.3.2


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Recording Adverse Events ...............................................................................80 
7.3.3
7.4 
GRADING AND ATTRIBUTION OF ADVERSE EVENTS ..................................................81 
 
Grading Criteria ..............................................................................................81 
7.4.1
 
Attribution Definitions .....................................................................................82 
7.4.2
7.5 
REPORTING OF SERIOUS ADVERSE EVENTS AND ADVERSE EVENTS .........................82 
 
Reporting of Serious Adverse Events to DAIT/NIAID .....................................82 
7.5.1
 
Reporting AESIs to DAIT/NIAID .....................................................................83 
7.5.2
 
Reporting to Health Authority .........................................................................83 
7.5.3
 
Annual Reporting ...................................................................................83 
7.5.3.1
 
Expedited Safety Reporting ....................................................................84 
7.5.3.2
 
Reporting of Adverse Events to IRBs ...............................................................85 
7.5.4
 
Reporting of Safety Information (AEs, SAEs and AESIs) to Corbus ...............85 
7.5.5
7.6 
PREGNANCY REPORTING ...........................................................................................85 
7.7 
REPORTING OF OTHER SAFETY INFORMATION ..........................................................86 
7.8 
REVIEW OF SAFETY INFORMATION ...........................................................................86 
 
Medical Monitor Review ..................................................................................86 
7.8.1
 
DSMB Review ..................................................................................................86 
7.8.2
 
Planned DSMB Reviews .........................................................................86 
7.8.2.1
 
Ad hoc DSMB Reviews ...........................................................................86 
7.8.2.2
8 STATISTICAL CONSIDERATIONS AND ANALYTICAL PLAN ...........................87 
8.1 
SAMPLE SIZE AND POWER .........................................................................................87 
8.2 
ANALYSIS POPULATIONS ..........................................................................................91 
 
Modified Intent-to-Treat Population ................................................................91 
8.2.1
 
Per Protocol Population ..................................................................................91 
8.2.2
 
Safety Population .............................................................................................91 
8.2.3
 
PK Population ..................................................................................................91 
8.2.4
8.3 
DESCRIPTION OF THE ANALYSES ...............................................................................91 
 
Subject Disposition ..........................................................................................92 
8.3.1
 
Efficacy Analysis ..............................................................................................92 
8.3.2
 
Primary Efficacy Analysis ......................................................................92 
8.3.2.1
 
Secondary Efficacy Analyses ..................................................................94 
8.3.2.2
 
Safety Analyses .................................................................................................94 
8.3.3
 
Adverse events ........................................................................................94 
8.3.3.1
 
Laboratory safety outcomes ...................................................................95 
8.3.3.2
 
Electrocardiograms and QT/QTc intervals ............................................95 
8.3.3.3
 
ARCI-M questionnaire ...........................................................................95 
8.3.3.4
 
Plasma Concentrations of JBT-101 and Metabolites ......................................95 
8.3.4
 
Mechanistic Analyses .......................................................................................96 
8.3.5
8.4 
INTERIM ANALYSIS ...................................................................................................96 
8.5 
OTHER STATISTICAL CONSIDERATIONS ....................................................................96 
8.6 
COVARIATES .............................................................................................................96 
8.7 
MULTI-CENTER STUDIES ...........................................................................................96 
8.8 
MULTIPLE COMPARISONS AND MULTIPLICITY ..........................................................96 
8.9 
EXAMINATION OF SUBGROUPS ..................................................................................97 
8.10 
CHANGES TO THE STATISTICAL ANALYSIS PLAN ......................................................97 


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8.11 
MISSING DATA ..........................................................................................................97 
9 ACCESS TO SOURCE DATA AND DOCUMENTS ...................................................97 
10 DATA COLLECTION, QUALITY CONTROL AND QUALITY ASSURANCE .....98 
11 ETHICAL CONSIDERATIONS AND COMPLIANCE WITH GOOD CLINICAL 
PRACTICE .........................................................................................................99 
11.1 
COMPLIANCE WITH GOOD CLINICAL PRACTICES ......................................................99 
11.2 
INSTITUTIONAL REVIEW BOARD ...............................................................................99 
11.3 
INFORMED CONSENT .................................................................................................99 
11.4 
DATA AND SAFETY MONITORING BOARD ...............................................................100 
11.5 
STUDY TERMINATION .............................................................................................100 
12 FINANCING AND INSURANCE .................................................................................100 
13 PUBLICATION POLICY ..............................................................................................100 
14 APPENDICES .................................................................................................................101 
14.1 
APPENDIX A: REPRODUCTIVE POTENTIAL AND EFFECTIVE METHODS OF 
CONTRACEPTION ....................................................................................................101 
14.2 
APPENDIX B: FIBROMYALGIA SYMPTOM SCALE .....................................................102 
14.3 
APPENDIX C: LUPUS ACTIVITY PATIENT’S GLOBAL ASSESSMENT ..........................103 
14.4 
APPENDIX D: ARCI-M QUESTIONNAIRE (PRE-DOSE) ............................................104 
14.5 
APPENDIX E: ARCI-M QUESTIONNAIRE (POST-DOSE) ...........................................105 
14.6 
APPENDIX F: PROMIS-29 SHORT FORM ................................................................106 
14.7 
APPENDIX G: PROMIS ITEM BANK V2.0 - COGNITIVE FUNCTION ..........................110 
14.8 
APPENDIX H: TREATMENT SATISFACTION SURVEY (PARTICIPANT) ........................115 
14.9 
APPENDIX I: PARTICIPANT DRUG SCREENING MATERIALS .....................................116 
14.10 APPENDIX J: PARTICIPANT DAILY PAIN NRS MATERIALS ......................................117 
15 REFERENCES ................................................................................................................119 


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1 BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE 
1.1 Disease Background 
 
Description and Epidemiology of Disease 
1.1.1
Systemic lupus erythematosus (SLE) is a chronic and serious illness that has no cure and for 
which current therapeutic strategies have limited efficacy and significant toxicities. 
SLE is a prototypical autoimmune disease with a wide array of clinical manifestations, 
including rash, photosensitivity, oral ulcers, arthritis, pleuritis, pericarditis, kidney problems, 
seizures and psychosis, and blood cell abnormalities [1]. Patients with SLE have an increased 
frequency of related autoimmune problems, such as Sjögren’s syndrome and 
antiphospholipid syndrome (i.e., clotting problems, strokes, fetal loss) that require additional 
treatments. SLE may occur with other autoimmune conditions, such as thyroiditis, hemolytic 
anemia, and idiopathic thrombocytopenia purpura. Accelerated atherosclerosis among SLE 
patients is responsible for premature mortality [2, 3]. 
The musculoskeletal system is the most commonly involved system in SLE, with reported 
incidences of 69-95% in different series [4-6]. Arthritis is the most commonly reported of all 
11 American College of Rheumatology (ACR) criteria for the diagnosis of SLE [1]. In 
addition, arthritis is the first manifestation of SLE in about 60-70% of patients [1, 7]. After 
five years of disease, joint involvement affects about 85% of patients [1]. Tendon 
inflammation, manifesting as tendonitis, tenosynovitis or tendon rupture, has been well 
described in SLE, occurring in 23-44% of patients [8-10]. A small percentage of SLE 
patients develop Jaccoud’s arthropathy due to recurrent episodes of inflammation resulting in 
ligamentous laxity and joint subluxation. In addition to joint symptoms, generalized myalgia 
is frequently associated with SLE, occurring in as many as 80% of SLE cases [10]. This 
myalgia characteristically affects the deltoids and quadriceps and occurs during disease 
flares. 
Musculoskeletal involvement in SLE is associated with pain. Chronic pain is a common 
entity for most SLE patients, resulting in a significant reduction in quality of life and 
productivity [11-14]. In focus groups of SLE patients, pain was the most frequently identified 
health issue, occurring in > 85% of patients [15]. Indeed, SLE patients have higher visual 
analogue pain scores than patients with rheumatoid arthritis [16]. Satisfaction of SLE patients 
with their medical care is inversely related to their level of pain [17]. 
In addition to pain caused by active musculoskeletal inflammation, SLE patients may 
experience pain from concurrent fibromyalgia. About 16-32% of SLE patients also meet 
criteria for fibromyalgia [18]. 
Improvement in patient-reported pain in SLE is associated with improvement in patient 
overall health [19]. Pain responders have greater improvement in Medical Outcome Study 


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Short Form-36 Survey scores, patient global health assessment scores, and Physician’s 
Global Assessment, compared to non-responders [19].  
 
Immunopathogenesis of Systemic Lupus Erythematosus  
1.1.2
SLE is a disease characterized at a molecular level by loss of tolerance resulting in 
autoreactive B and T cells, abnormally primed dendritic cells, autoantibody production [20, 
21], generation of immune complexes, and their deposition in tissues. The characteristic 
serologic feature of SLE is autoantibodies against one’s own nucleic acid or DNA- or RNA-
binding nuclear proteins [22]. These immune complexes have been shown to activate innate 
immune responses through toll-like receptors, Fcγ receptors and complement [23-25]. 
Chronic activation of innate immune responses by immune complexes in SLE can lead to 
production of pro-inflammatory cytokines such as type 1 interferons (IFNs), with subsequent 
local activation of dendritic cells, presentation of self-antigen, and perpetuation of 
autoimmunity. Interferons, particularly the type 1 IFNα, are implicated in the pathogenesis of 
SLE [26]. Many patients with SLE display up-regulation of type 1 IFN-inducible genes, 
referred to as the “type 1 IFN gene signature”, and some have elevated serum levels of IFNα 
[27-29]. Elevated serum and tissue levels of multiple other pro-inflammatory cytokines, 
including IFNα, interleukin (IL)-1, IL-2, IL-6, IL-10, IL-12, IL-18, IFNγ, BAFF and tumor 
necrosis factor α (TNFα) have been implicated in the immune-pathogenesis of SLE [30-34]. 
These molecules mediate tissue destruction and contribute to breaking tolerance through 
effects on further B cell activation, auto-antibody production and expression of costimulatory 
molecules on lymphocytes[30, 35, 36] . Specifically, plasma levels of IL-6 have been 
correlated with lupus arthritis [37]. 
This self-amplifying cycle of ongoing activation of innate immune responses and subsequent 
perpetuation of autoimmunity underpins the immunopathogenesis of SLE. As a consequence, 
SLE is a disease characterized at the tissue level by chronic inflammation, which causes local 
pain, tissue damage, and organ dysfunction. This immune pathology can translate clinically 
to ongoing joint and periarticular inflammation with chronic musculoskeletal pain [38]. 
 
Current Treatment of Active Musculoskeletal Involvement in Systemic 
1.1.3
Lupus Erythematosus 
Treatments approved by the FDA specifically for the treatment of SLE include only 
hydroxychloroquine, corticosteroids, aspirin, and most recently, belimumab [39, 40]. As an 
indicator of the dearth of new treatments for SLE, belimumab was the first treatment 
approved for SLE in 50 years [39].  
Traditional treatment strategies for active joint involvement in SLE generally begin with the 
use of non-steroidal anti-inflammatory drugs (NSAIDs), anti-malarial drugs, and non-
narcotic analgesic drugs, then escalate with symptom severity to include corticosteroids or 
other immunosuppressive drugs and narcotic analgesic drugs  [41]. These therapies can be 
limited in their efficacy and associated with toxicities [42-44]. Nonsteroidal anti-
inflammatory drugs are relatively contraindicated in SLE patients with renal disease. 


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Potential toxicities of NSAIDs, including enhanced photosensitivity, aseptic meningitis, 
gastrointestinal irritation, ulcers, bleeding and renal toxicity limit their use in SLE patients. 
Hydroxychloroquine, an antimalarial agent which modulates the innate immune system, is 
commonly used to limit exposure to corticosteroids and to target constitutional and 
musculoskeletal features of disease. While its safety profile is relatively non-toxic and there 
is evidence that it decreases organ damage and prolongs states of remission, the acute 
therapeutic effect of hydroxychloroquine is mild [45]. 
Corticosteroids and/or immunosuppressive agents are used for joint involvement in SLE 
patients that is refractory to NSAIDs and anti-malarial treatments [46], even though the 
patients are at risk for developing cumulative toxicities from exposure to these drugs. For 
example, avascular necrosis is an extremely painful and debilitating problem that is 
associated with corticosteroid use and occurs in approximately 37% of SLE patients [47]. 
Other potentially devastating side effects of corticosteroids include infection, weight gain, 
osteoporosis, cataracts, and diabetes. The pro-atherogenic effects (hypertension, 
dyslipidemia, metabolic syndrome) of steroids are particularly disturbing, given the 
accelerated atherosclerosis associated with SLE [2, 3]. Immunosuppressive medications such 
as azathioprine, methotrexate, mycophenolic acid, leflunomide, cyclophosphamide, 
cyclosporine used to treat joint involvement in SLE are associated with multiple toxicities. 
Common toxicities include infections (some with fatal outcomes), hepatic, bone marrow and 
renal impairment, and infertility. Infection is a major contributor to morbidity and mortality 
in SLE [48-51]. 
Narcotic analgesia can afford relief of pain from joint involvement, but complications of 
narcotic analgesics, including somnolence, constipation, addiction/dependence, fatigue and 
nausea, can be formidable. There is a rapidly increasing awareness of the dramatic rise in 
opioid-related abuse, addiction and overdose-related deaths [52]. 
Directly relevant to the treatment of active musculoskeletal disease in SLE are four recent 
treat-to-target recommendations in SLE from an international task force [53]. In redacted 
version, these four recommendations are: the treatment target should be remission of organ 
manifestations; factors such as pain that negatively influence health-related quality of life 
should be addressed; maintenance treatment should aim for the lowest glucocorticoid dose 
needed to control disease; and relevant therapies adjuvant to any immunomodulation should 
be considered to control comorbidity in SLE. 
Clearly, there is a significant unmet need for improved treatment of joint involvement and 
associated pain in patients with SLE who are refractory to NSAIDS and anti-malarial 
therapy, to resolve joint inflammation, improve pain, and avoid or reduce the risk of infection 
and the need for systemic corticosteroid therapy, immunosuppressive medications, and/or 
chronic narcotic analgesia. 


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1.2 Rationale for JBT-101 
 
Specialized Pro-resolving Lipid Mediators Induce Resolution of 
1.2.1
Inflammation, Infection, and Fibrotic Processes 
Inflammation normally resolves. Physiologic resolution of innate immune responses occurs 
when naturally-occurring counter-regulatory processes are sufficient to overcome the pro-
inflammatory milieu [54-57]. The key up-stream event in resolution of innate immune 
responses is “class switch” of bioactive lipid mediators from pro-inflammatory mediators, 
such as leukotriene B4 and prostaglandin E2, to specialized pro-resolving lipid mediators 
(SPMs), including lipoxins, resolvins, maresins, and protectins [58]. The SPMs initiate 
resolution of innate immune responses, including resolution of inflammation, bacterial 
infection, and fibrotic processes, thereby restoring homeostasis [54-57].  
Resolution of innate immune responses is an active and orchestrated process that is not the 
same as anti-inflammation or immunosuppression [54]. Resolution of immune responses 
incorporates multiple pathways to restore homeostasis [54-57] including: 
 Increase in production of SPMs and anti-inflammatory eicosanoids, with a 
concomitant decrease in production of pro-inflammatory eicosanoids [54-57] 
 Increase in production of IL-10 [59], an anti-inflammatory cytokine, coupled with a 
decrease in production of pro-inflammatory cytokines [60, 61], pro-fibrotic growth 
factors [62, 63], and extracellular matrix [64] 
 Increase in influx of non-inflammatory macrophages [65, 66], with a decrease in 
influx and accumulation of inflammatory cells and pro-fibrotic myofibroblasts [63, 
65, 67] in inflamed tissues. This includes inhibition of adhesion molecule expression, 
chemokine production, and migration of inflammatory cells into tissues [67-70] 
 Increase in apoptosis of inflammatory cells, including neutrophils [70-72] and pro-
fibrotic cells, including fibroblasts [73], in involved tissues 
 Increase in autophagy in inflammatory cells [60] 
 Increase in clearance of apoptotic cells and cellular debris by non-inflammatory 
macrophages [67, 70, 72] 
 Increase in bacterial clearance. SPMs stimulate production of bactericidal peptides 
[74], enhance phagocytosis and killing of bacteria by neutrophils and macrophages 
[71, 75-77] and enhance the antibacterial effects of antibiotics [78] 
 Subsequent increase in migration of non-inflammatory macrophages out of 
previously inflamed tissues through efferent lymph [67], completing the return to 
homeostasis 
The cumulative effect is that class switch of eicosanoids to increase production of SPMs 
results in activation of a naturally occurring, broad-reaching, physiologic network that 
resolves innate immune responses, including inflammation, infection, and fibrotic processes, 
restoring homeostasis without immunosuppression. 


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Proposed Mechanism of Action of JBT-101, a Synthetic CB2 Agonist 
1.2.2
JBT-101, a fully synthetic endocannabinoid-mimic, is proposed to activate the resolution 
machinery of innate immune responses, through cannabinoid type 2 receptor (CB2)-mediated 
responses. The endocannabinoid system consists of endocannabinoids, CB receptors, and the 
machinery dedicated to endocannabinoid synthesis, cellular uptake, and degradation. The 
resolution machinery of innate immune responses and the endocannabinoid system have 
many common characteristics. Both are naturally occurring, primitive, and conserved 
biologic networks whose inherent purpose is to restore homeostasis following times of stress 
[79-82]. Receptors and natural ligands in both systems can be expressed on demand upon cell 
activation. Both systems use ligands that are synthesized from membrane phospholipids such 
as arachidonic acid and docosahexaenoic acid during calcium-activated biosynthetic 
pathways [83, 84]. Ligands for both systems act in an autocrine and paracrine fashion [85, 
86]. 
There are two main endocannabinoid receptor subtypes: cannabinoid receptor type 1 (CB1), 
mainly expressed in the central and peripheral nervous system, and CB2, mainly distributed 
throughout immune and hematopoietic cells [87-89]. Cell surface expression of CB2 is 
rapidly up-regulated on multiple immune cell types during immune responses [90-92]. 
Expression of CB2 on immune cells is 10-100 times greater than CB1 expression [88]. 
JBT-101 is a full agonist of CB2, with limited ability to cross the blood-brain barrier [93] and 
activate CB1 in the brain, through which psychoactivity of cannabinoids is mediated. The 
composition of JBT-101 that will be used in this trial has a 12 times greater affinity for CB2 
than CB1 [94]. 
Based on human and animal model data and other pre-clinical studies, JBT-101 is proposed 
to be an upstream activator of the resolution machinery of innate immune responses inducing 
a class switch in production of bioactive eicosanoids to favor SPMs. This class switch in 
eicosanoids is expected to initiate a naturally-occurring, physiologic biologic network that 
will resolve chronic inflammation, without immunosuppression. Clinical benefit is expected 
with return of homeostasis, including improvement in signs and symptoms of active SLE, 
including multiple measures of active musculoskeletal inflammation, and a reduction in 
disease flares. Because its proposed mechanism of action does not include 
immunosuppression or narcotic analgesia, treatment with JBT-101 is expected to be safe 
enough and well tolerated for long-term use in SLE. To our knowledge, there are no other 
therapies in development for SLE at this time that are designed to induce class switch of 
bioactive eicosanoids to increase SPMs and resolve inflammation in SLE, emphasizing the 
uniqueness of JBT-101 as a potential treatment for SLE. In addition to its expected clinical 
benefit based on this novel mechanism of action, JBT-101 is expected to have an acceptable 
safety profile, based in part on its relative specificity for CB2, limited penetration of the 
blood-brain barrier penetration, and lack of psychoactivity associated with CB1/ 
tetrahydrocannabinol agonists/mimetics. As of January 2017, JBT-101 has been tested in a 
clinical trial in Systemic Sclerosis (SSc), and there are two ongoing clinical trials in 
inflammatory myositis and cystic fibrosis. No serious adverse events attributed to JBT-101 in 
these 3 clinical trials have been reported. There is no reason to suspect that a SLE population 


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will be at greater risk for potential JBT-101 toxicity than any of these 3 immune-
compromised populations. 
 
Summary of Biologic Effects of JBT-101 
1.2.3
The biologic effects of JBT-101 that are relevant to the treatment of SLE are outlined here, 
and data in support of these effects can be found in more detail in the Investigator’s Brochure 
(IB) for JBT-101. In humans, human cells, and/or animal models of inflammation, JBT-101 
increases production of the SPM lipoxin A4 and anti-inflammatory eicosanoids such as 
PGD2 and PGJ2, while decreasing production of pro-inflammatory eicosanoids and pro-
inflammatory cytokines that have been implicated in SLE, including IFNα, IL-6, and IL-1β 
[62, 63, 95-101]. In other animal models of disease, JBT-101 inhibits tissue inflammation 
and edema, as well as tissue damage caused by inflammation [62, 63, 95, 96, 98, 101]. Of 
significance, JBT-101 inhibits lung inflammation and fibrosis, when administered in both 
preventative and therapeutic manners in rodent models [63, 102]. In one animal model of 
prolonged and excessive lung inflammation induced by persistent infection, JBT-101 restores 
resolution of lung inflammation to normal, improves bacterial clearance, lessens associated 
weight loss, and improves survival, without immunosuppression [102]. JBT-101 also 
prevents development of inflammation and fibrosis in the skin in animal models [62, 101]. 
JBT-101 has direct effects on fibroblasts that may reduce fibrosis, including inhibition of 
TGFβ and collagen production [62, 63]. 
The human equivalent dose (HED), based on body surface area, of effective/ active doses in 
rodent models were between about 0.5 - 60 mg per day total daily dose, with a median HED 
of about 5 mg per day (difficulties in translating doses in animal models to human equivalent 
doses are acknowledged). 
Potentially relevant to the treatment of SLE and inflammatory arthritis in SLE, preliminary 
studies done by the Protocol Chairs and collaborators have demonstrated that JBT-101 
reduces production of IFNα and IFNγ by peripheral blood mononuclear cells (PBMC) from 
healthy volunteers and from patients with SLE ex vivo. In summary, the results showed: 
 JBT-101 reduced release of IFNα and IFNγ from PBMC from both healthy volunteers 
and five SLE patients, when those PBMC were stimulated with CpG DNA (for IFNα 
production) or phytohemagglutinin (for IFNγ production), p < 0.05 (see Figure 1). 
 In a dose-dependent manner, JBT-101 reduced levels of IFNα mRNA in PBMC from 
an SLE patient, when those PBMC were stimulated with CpG DNA, p < 0.05 [101]. 
 When added to SLE PBMC stimulated with CpG DNA ex vivo, 30 μM JBT-101 
reduced IFNα production in 7/9 (78%) of subjects, with inhibition in those seven 
subjects ranging from 42% to 97%. Similarly, when added to SLE PBMC stimulated 
with phytohemagglutinin ex vivo, 30 μM JBT-101 reduced IFNγ production in 5/6 
(83%) of subjects, with inhibition in those five subjects ranging from 48% to 85%. 
Suppression of both IFNα and IFNγ production was independent of Systemic Lupus 
Erythematosus Disease Activity Index (SLEDAI) scores [101]. 


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Figure 1. JBT-101 decreases IFN 
production by ex vivo stimulated PBMC 
from SLE patients  
Legend: Panel A. PBMC were isolated from 
five SLE patients and stimulated with 
phytohemagglutinin without or with 30 uM 
JBT-101. IFNγ release from these PBMC was 
reduced 63.5 +/- 13.9% (mean +/- SD) by 
addition of JBT-101 (p = 0.001 versus 
untreated, stimulated control cells by student t 
test).  
Panel B. PBMC were isolated from five SLE 
patients and stimulated with CpG DNA 
without or with 30 uM JBT-101. IFNα release 
from these PBMC was reduced by JBT-101 (p 
< 0.001 vs untreated, stimulated control cells 
by student t test).  
In support of these findings in PBMC from 
SLE patients, JBT-101 decreased production of IFNα by PBMC from dermatomyositis 
patients [100].  
In addition, in support of potential benefit of JBT-101 in musculoskeletal inflammation in 
SLE, JBT-101 at doses equivalent to 0.5 mg every other day in humans inhibited adjuvant-
induced arthritis in rodents, with prevention of pannus formation, bone destruction, and joint 
ankylosis, accompanied by a significant improvement in a composite clinical score that 
included joint swelling and pain [96]. JBT-101 also inhibited the development of serositis 
induced by toll-like receptor activation of cells within the mouse peritoneal cavity [98]. 
1.3 Summary of Pre-Clinical and Clinical Studies 
See the IB for JBT-101 for details of design and findings in non-clinical and previous clinical 
studies. Certain information relevant to safety and trial design is summarized below. 
 
Animal and Human Biomaterials Safety Data 
1.3.1
A nonclinical safety program was designed to support the development of JBT-101 and 
consisted of safety pharmacology, general toxicology, reproductive and developmental, and 
genotoxicity studies conducted with JBT-101. 
Safety pharmacology and general toxicology studies up to 6 and 9 months’ duration in rats 
and dogs identified central nervous system/neurobehavioral effects in rats and/or dogs. JBT-
101-related convulsions were observed in rat and dog studies, but this adverse finding was 
considered to be related to procedures during animal handling and dosing, and the JBT-101 
systemic exposure by Cmax at No-Observed Adverse Effect Levels in these studies were 
determined to be ≥5× in rats and ≥1.7× in dogs related to clinical exposure at a human dose 
0
100
200
300
0
30
AjA  mM
IFN (pg/ml)
0
200
400
600
800
0
30
AjA  mM
IFN (pg/ml)
A
B
JBT-101. mM
JBT-101. mM


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of 20 mg (b.i.d.) JBT-101. Specifically, the lowest dose where seizures were observed in rats 
was 4 mg/kg/day. The highest dose being used in this study is approximately 0.67 
mg/kg/day. In addition, JBT-101 did not have any effect on seizure threshold in animals. 
There were no other treatment-related clinical, macroscopic or microscopic findings 
indicating organ toxicity in any of the repeat dose studies. In the in vitro human ether a-go-go 
(hERG) assay, the approximate half maximal inhibitory concentration (IC50) value for 
inhibition of the potassium current by JBT-101 was 7 µM (2800 ng/mL), 5× higher than 
clinical Cmax exposure value at a human dose of 20 mg (b.i.d.) JBT-101. In addition, there 
were no adverse cardiovascular effects occurred in vivo in anaesthetized dogs, or on 
cardiovascular parameters in dogs after repeat administration of JBT-101 up to 10 mg/kg 
BID for 9 months.  In a physical dependence rat study, JBT-101 did not exhibit drug 
dependence lability. Furthermore, JBT-101 was not teratogenic in the rat embryofetal 
development study and a pilot rabbit embryofetal development study (i.e., Segment 2 
studies). In a reproductive and developmental rat study (i.e., Segment 1), JBT-101 had no 
effect on male and female fertility. JBT-101 was not mutagenic or clastogenic in in vitro or 
in vivo genotoxicity studies. 
 
Animal Toxicokinetic Results 
1.3.2
Toxicokinetic results from the 2-week once a day (q.d.) dose studies in rats and dogs and the 
2-week and 13-week studies of the rat three times a day and dog b.i.d. studies demonstrated 
that: 
 JBT-101 exposure increased in a linear fashion with increases in dose. 
 JBT-101 exposure was comparable in males and females in both species. 
 JBT-101 exposure was comparable after the first and 14th doses in the 2-week q.d. 
dose studies, indicating an absence of accumulation or time-dependency to 
pharmacokinetic (PK) measurements. In the 13-week study in rats, no change in Cmax 
was observed between days 14 and 98 of treatment, whereas there was between a 10-
20% accumulation of JBT-101 based on AUC between days 14 and 91 of treatment. 
In the 13-week study in dogs, there was no change in Cmax observed between days 14 
and 91 and no change in JBT-101 AUC levels was observed between days 14 and 98 
of treatment. 
 
Animal Metabolism 
1.3.3
Studies of metabolism in animals have shown that: 
 JBT-101 binds tightly to plasma proteins, with binding of ≥ 97% in rat, dog, and 
human plasma.  
 JBT-101 undergoes limited metabolism. The percent of unchanged JBT-101 
remaining after a 2-hour incubation in vitro was 103%, 90%, 86%, and 83% for rat, 
dog, monkey, and human hepatocytes, respectively. 


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 JBT-101 is not a substrate for cytochrome P450 and displayed no inhibition of 
CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5 at concentrations of up to 
50 µM. Because the half maximal inhibitory concentration values for JBT-101 were 
greater than 50 µM for all P450 isozymes, there appears to be no cytochrome P450 
inhibition at pharmacological study product levels. 
 
Clinical Studies 
1.3.4
As of January 2017, 117 healthy volunteers and 19 subjects with neuropathic pain have 
received JBT-101 through participation in two Phase 1 clinical trials, three mechanism of 
action studies, and one Phase 2 clinical trial in refractory neuropathic pain under different 
Investigational New Drug Applications (INDs) and sponsors (no longer active), for 
indications/investigational purposes not being considered in this IND. Subjects received up to 
240 mg total daily dose and were dosed up to seven days in total, up to three times a day. 
Subjects were ages 18-77 years of age. Details of the study designs can be found in the IB for 
JBT-101.  
As of April 2017, 42 subjects (27 JBT-101, 15 placebo) with diffuse cutaneous systemic 
sclerosis (SSc) were enrolled in trial JBT101-SSc-001, and 36 of 38 subjects that completed 
double blind treatment enrolled in the one-year open-label extension.  Eighty-five subjects 
with cystic fibrosis (61 JBT-101, 24 placebo) were enrolled in trial JBT101-CF-001.  
Twenty-two subjects (~11 JBT-101, 11 placebo) with skin-predominant dermatomyositis are 
actively being enrolled in trial JBT-101-DM-001.  
All of the data used for analyses of the pharmacokinetic and metabolism studies and safety 
measures was derived from the completed Phase 1 (CT-3-01, CPL7075-001-01) and Phase 2 
studies (CPL7075/102/02/02/001.1, JBT101-SSc-001). 
Details of pharmacokinetic and metabolism findings in the completed Phase 1 and Phase 2 
clinical trials can be found in the IB for JBT-101. Key pharmacokinetics and metabolism 
findings include: 
 JBT-101 was rapidly absorbed from the gastrointestinal tract. 
 Mean Cmax values increased approximately proportional to the increase in dose for 
single doses from 10 to 240 mg and multiple doses from 20 to 80 mg per day. 
 Mean AUC0-inf values also increased approximately proportional to the increase in 
dose for single doses from 10 to 240 mg. For multiple doses from 20 to 80 mg per 
day, AUC0-24h values increased slightly greater than the increase in dose. The mean ± 
SD AUC0- INF for JBT-101 was 35,025 ± 5784 ng·hr/ml for 80 mg three times a day. 
 Subjects ≥ 65 years old had an average AUC0-24h about 15% greater than that of the 
younger subjects. 
 The fraction absorbed, mean clearance divided by fraction absorbed, and volume of 
distribution tended to increase slightly with dose in multiple dose studies. 
 For multiple doses, Tmax occurred at around 3 hours. 


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 The average half-life ranged from 3.7 to 5.6 hours for single doses. 
 There were no effects of the fed state at 20 and 40 mg doses. 
 Following JBT-101 administration at 20-40 mg b.i.d. for 7 days in humans, the only 
observable plasma metabolite of JBT-101 was a glucuronide metabolite [103], which 
represented 9% of total JBT-101 present in the plasma. 
The safety findings in each completed individual clinical trial can be found in detail in the IB 
for JBT-101. In summary, key safety findings from the two Phase 1 trials (CT-3-01, 
CPL7075-100-01) and two Phase 2 trials (CPL7075/02/01/001.1, JBT101-SSc-001) are: 
 Maximum Tolerated Dose is 180 mg total daily dose 
 No deaths and no serious, severe or unexpected AEs related to JBT-101 occurred in 
any of the studies  
 One of 27 (3.7%) JBT-101-treated subjects in the SSc trial (JBT101-SSc-001) 
withdrew due to a TEAE of moderate dizziness. 
 Mild to moderate AEs consistent with CB1/CB2 agonists occurred at higher doses, 
especially > 150 mg/day total daily dose 
 In pooled safety data, TEAEs that occurred in ≥ 5% of 88 JBT-101-treated subjects 
who received doses within the estimated therapeutic range of ≤ 60 mg total daily dose 
were dizziness (n = 10, 11%), dry mouth (n = 5, 5.6%), arthralgias (n = 6, 6.8%), GI 
disturbances (n = 6, 6.8%)  and fatigue (n=9, 10.2%). Note that the majority of 
subjects with GI complaints (6/6), fatigue (8/9) and arthralgias (6/6) were in the SSc 
trial and all of these symptoms are common in SSc. 
 In pooled safety data of all trials (n = 150 total) and all doses of JBT-101, which 
included 71 subjects who received JBT-101 at doses higher than the estimated 
therapeutic range, TEAEs that were observed in two or more subjects ≥ 5% of the 
time included mild dizziness (21.3%), moderate dizziness (10%), mild somnolence 
(6%), mild nausea (12%), mild dry mouth (8%), and mild fatigue (5.3%) (Table 27 of 
the Investigator Brochure for JBT-101). These AEs were consistent with CB1/CB2 
agonist class effects and showed a dose-response. Most AEs occurred in the highest 
frequency in subjects who received ≥ 150 mg total daily dose of JBT-101. Adverse 
events that were reported in ≥ 5% of placebo-treated subjects were headache 
(5.7%).There were no AEs or laboratory abnormalities that indicated 
immunosuppression or an increase in rate of infection. 
 Changes from baseline in blood pressure (BP) and pulse rate (P) in subjects treated 
with JBT-101 were generally similar to those treated with placebo, although in 
multiple dosing studies in healthy volunteers, BP recordings that were considered 
intermittent hypotension occurred more frequently subjects ≥ 65 years of age than in 
subjects ≥ 18 and ≤ 45 years of age (4/6 versus 0/18, respectively). 
 No clinically relevant changes in physical examination findings were observed. 


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 No clinically relevant changes in electrocardiograms (ECGs) or QT/corrected QT 
interval (QTc) intervals were observed. In the multiple dosing studies, subjects ≥ 18 
and ≤ 45 years of age had no abnormal ECG findings and no differences in mean 
changes in QTc intervals between subjects treated with JBT-101 versus placebo. In 
subjects who received high doses (≥ 180 mg total daily dose JBT-101) and were ≥ 65 
years of age, three of six subjects who received JBT-101 had prolongation of QTc 
intervals ≥ 30 msec from baseline on Day 1, with no prolongation exceeding 39 msec 
and no QTc exceeding 500 msec. The maximum QTc observed was 487 msec. None 
of these changes were considered clinically significant. The longest prolongation of 
QTc, as of July 2017, with JBT-101 has occurred in a healthy subject who received 
placebo. 
 There were no notable changes in hematology or chemistry values from baseline. 
Individual changes in liver and renal function tests were few and small in magnitude. 
No food or age effects were observed in the laboratory hematology and chemistry 
values. 
In formal testing, there was no psychoactivity, effect on mood, or effect on 
attention/cognition at doses up to 80 mg total daily dose. The efficacy findings in the 
completed Phase 2 trials (CPL7075/02/01/001.1, JBT101-SSc-001) as of July 2017 can be 
summarized as follows: 
o JBT-101 reduced neuropathic pain significantly compared to placebo [104] 
 In JBT101-SSc-001, evidence of efficacy was observed across multiple outcomes, 
including the Combined Response Index in diffuse cutaneous SSc, the modified 
Rodnan Skin Score, Physician Global Assessment, Patient Global Assessment, the 
Health Assessment Questionnaire-Disability Index, a systemic sclerosis skin 
symptom questionnaire, and the 5D-Itch questionnaire 
 In JBT101-SSc-001, multiple different glucuronide metabolites of JBT-101 were 
observed in the plasma at < 10% with one glucuronide metabolite present at >10% at 
all doses. An open-label extension to the JBT101-SSc-001 study is ongoing, with 36 
subjects enrolled as of July 2017. All subjects in the open-label extension receive 
JBT-101 20 mg once or twice per day, for up to 12 months. As of July 2017, total 
duration of double blind placebo controlled and open-label extension dosing with 
JBT-101 was median 234 days (range 28, 295 days). All 36 subjects had at least one 
open-label extension visit ≥ 28 days post baseline.  Adverse events (AEs, n = 88) 
occurred in 28/36 (78%) subjects in the open-label extension.  Most AEs were mild 
(55/88, 62%) or moderate (30/88, 34%) in severity and unrelated to JBT-101 (75/88, 
85%).  The AEs that occurred in ≥ 10% of subjects (n, % of subjects) were mild 
fatigue (5, 14%) and mild/moderate upper respiratory tract infection (4, 11%). 
 
Study JBT101-CF-001 is a double-blind, placebo-controlled, randomised Phase 2 study 
conducted at 21 centres in the US and Europe. JBT-101 was administered at 1 mg once per 
day or 5 mg once per day for 28 days, escalating to 20 mg once per day or 20 mg twice per 


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day for an additional 56 days in subjects with cystic fibrosis. Eight-five subjects were dosed 
with study medication, the last subject has completed the trial, and it is estimated that 
~61 subjects received JBT-101 and ~24 subjects received placebo throughout the trial. 
Safety data is summarized as follows: 
• 
The majority of spontaneously reported adverse events were mild to moderate in 
JBT-101 treated subjects.  The most frequent adverse event reported during JBT-
101 treatment was mild dry mouth.  
• 
Four of 61 (6.6%) of JBT-101 subjects withdrew following a TEAE, of which two 
were considered related to JBT-101 including mild lack of cognitive clarity, and a 
moderate feeling unmotivated. One of 24 (4.2%) of the placebo subjects withdrew 
following mild difficulty focusing, mild lack of cognitive clarity  
• 
Triplet ECGs with QT/QTc interval measurements were done throughout the trial 
and showed no significant changes from baseline and similar findings in subjects 
who received JBT-101 and placebo. 
• 
Overall, changes from baseline in the ARCI-M were similar in subjects who 
received JBT-101 and placebo. 
JBT-101-treated subjects exhibited clear reductions in inflammatory biomarkers in the 
sputum including total cells, neutrophils, eosinophils, macrophages, lymphocytes, 
interleukin-8, neutrophil elastase, and IgG in sputum.  The number of new pulmonary 
exacerbations (commencement of new systemic antibiotic) per individual per 12 weeks 
(event rate) was 0.28 for JBT-101 vs. 0.60 for placebo (54% reduction).  The event rate per 
12 weeks of new pulmonary exacerbations treated with IV antibiotics was 0.09 for JBT-101 
(all doses combined) vs. 0.26 for placebo (65% reduction) and was lowest with JBT-101 20 
mg b.i.d. (80% reduction).No unexpected SAEs were reported; most SAEs are acute 
infectious pulmonary exacerbation of cystic fibrosis. 
Study JBT101-DM-001 is a double-blind, placebo-controlled, randomised Phase 2 study 
being conducted at one centre in the US. JBT-101 or placebo is administered at 20 mg 
once per day for 28 days, escalating to 20 mg twice per day for an additional 56 days in 
subjects with skin-predominant dermatomyositis. As of July 2017, 22 subjects have been 
dosed with study product, and it is estimated that ~11 subjects received JBT-101 and ~11 
subjects have received placebo. Safety data are summarized as follows: 
• 
The study has not completed enrolment and remains blinded. 
• 
Following their review of blinded safety data, a Safety Monitoring Committee 
recommended no change to the protocol or safety monitoring plan. 
• 
There have been no serious, severe, or unexpected AEs. Most AEs have been mild 
in severity. 
An open label extension of the study has started and as of July 2017, 11 patients have 
enrolled. 


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1.4 Current Licensing of JBT-101 
JBT-101 has not been approved for any indication. 
1.5 Known and Potential Risks and Benefits of JBT-101 
 
Potential Risks 
1.5.1
Expected AEs in clinical studies with JBT-101 include those related to active SLE, JBT-101, 
and common events in the general population. Expected AEs related to active SLE include 
any new or worsening signs and symptoms of mucocutaneous disease, serositis, 
musculoskeletal disease, peripheral or central nervous system disease, renal disease (and 
accompanying systemic hypertension and reduction in renal function), hematologic 
cytopenias (autoimmune hemolytic anemia, leukopenia, thrombocytopenia), depression and 
anxiety and/or signs of constitutional disease such as lymphadenopathy, fever and weight 
loss. Other expected AEs related to active SLE also include mild to severe infections related 
either to disease or immunosuppressive medications, medically significant elevations in acute 
phase reactants such as total globulins, CRP, sedimentation rate, and anti-dsDNA or other 
antibody levels, medically significant reductions in complement levels, and mild normocytic 
anemia. Additional anticipated risks of JBT-101 specific to SLE patients would include 
worsening xerostomia in patients with dry mouth from associated sicca syndrome. Many 
patients with SLE also demonstrate cognitive impairment and/or depression that may worsen 
or become apparent during a disease flare. 
Expected AEs related to JBT-101 are via CB receptors. CB1/CB2 agonists can produce AEs 
in humans, and many of these may be caused by the activation of central CB1 rather than of 
CB2 or peripheral CB1. Adverse effects most often observed, at least in other published 
clinical trials, have been dizziness/light-headedness, dry mouth, tiredness/fatigue, muscle 
weakness, myalgia (muscle pain) and palpitations [105]. Other less frequently reported side 
effects of CB1/CB2 agonists include disorientation, feeling of drunkenness, ‘high sensation’, 
mental clouding and/or altered time perception, impairment of memory or ability to 
concentrate, tremor, balance impairment or lack of coordination, nausea/feeling sick, 
vomiting, hypotension, blurred vision, constipation or diarrhea, confusion, 
dysphoria/depression, disorientation, paranoia and hallucinations [105]. Any of these AEs 
potentially could be seen with JBT-101 exposure. 
As of July 2017, a number of the AEs associated with CB1/CB2 agonists have been reported 
in subjects exposed to JBT-101 and future subjects are at risk for these same AEs. As seen in 
pooled safety data from the 2 Phase 1 studies and 2 Phase 2 completed clinical trials, AEs 
that occurred in ≥ 5% of JBT-101 treated subjects were fatigue, dry mouth, arthralgias, 
dizziness, nausea and vomiting.  Many of the other AEs listed as class effects of CB1/CB2 
agonists have been reported by JBT-101-treated subjects, albeit at frequencies lower than 5% 
as of July 2017 (see Tables 17, 18 and 20 in the Investigator Brochure for JBT-101). JBT-
101 is a full agonist of CB2, with little evidence of psychotropic activity at likely therapeutic 
doses, because of limited ability to cross the blood-brain barrier and reduced affinity for 


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CB1. Psychotropic activity of JBT-101 will be tested formally with the ARCI-M 
questionnaire [106]. 
Prolongations of QTc interval to less than 500 msec total and up to 39 msec prolongation 
from pre-treatment baseline were observed in a previous Phase 1 study, and all of these 
prolongations were judged not clinically significant. They were observed in some subjects ≥ 
65 years of age exposed to JBT-101 at a total daily dose greater than or equal to 180 mg for 
seven days. The QTc changes were also observed on ECGs not done using standard 
techniques to measure QT/QTc intervals. For this reason, to ensure safety of subjects, the 
QT/QTc interval will be measured at time points before, during and after treatment, and 
maximum doses of JBT-101 to be tested in this study will not exceed 40 mg/day (given as 20 
mg b.i.d.). In the JBT101-SSc-001 study, assessment of ECGs and corrected QT intervals 
using standard techniques revealed no clinically significant prolongation of corrected QT 
intervals or other significant electrocardiogram findings.  
Studies of human reproduction have not been performed with JBT-101. It is not known if 
JBT-101 can cause fetal harm when administered to pregnant women or if it can negatively 
affect reproductive capacity. Women of childbearing potential should avoid becoming 
pregnant and should not be breastfeeding at the start of the study, during the study, and for 28 
days after the last dose of study drug. 
Expected AEs in a general population include events such as mild changes in vital signs, sore 
throats, mild skin, upper or lower respiratory tract, or genitourinary infections requiring 
topical or oral antibiotics, asymptomatic bacteriuria, headaches, nausea, mild rashes, and 
minor accidents. Mild abnormalities in laboratory testing of CBC testing, platelets, 
differential cell counts, metabolic panels including liver function tests and electrolytes, and 
urinalyses are expected to occur in a general population. 
Abrupt discontinuation of treatment with JBT-101 has not been shown to cause any harmful 
effects in previous studies; therefore, study product may be stopped without tapering or 
adding additional treatments. If a subject has received clinical benefit from JBT-101, then 
his/her disease activity may or may not worsen after discontinuation of JBT-101. To reduce 
this risk of disease flare, subjects will continue their standard-of-care medication throughout 
the study and during the follow-up period. Subjects will have follow-up safety evaluation and 
testing of disease activity 28 ± 3 days after the end of the planned active treatment period or 
after withdrawal or discontinuation of study product. 
Subjects will be instructed to call the site investigator or treating physician if they experience 
an AE (whether or not they determine it to be related to the study) and may be evaluated for 
potential toxicity at an unscheduled visit. 
Please see the IB for JBT-101 for further information about risk. 


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Potential Benefits 
1.5.2
No physical, psychological, social, legal, or any other benefits are claimed for individual 
SLE subjects who chose to participate in this study. Based on biologic effects of JBT-101 
and other preferential CB2 agonists in in vitro and in vivo models of inflammation and 
various diseases, it is reasonable to test JBT-101 for evidence of efficacy in SLE in this 
study. The information that will come from this study will address effects of JBT-101 on 
efficacy, safety, tolerability, and biomarkers of inflammation in SLE subjects. This 
information will be used in decision making about whether to progress JBT-101 to future 
pivotal clinical studies, as a step toward approval by regulatory agencies for treatment of 
SLE.  
1.6 Rationale for the Study 
There remains significant unmet medical need for the treatment of active musculoskeletal 
disease in SLE that is refractory to treatment with NSAIDS and anti-malarial agents and 
necessitates the addition of corticosteroids, immunosuppressive medications and/or narcotic 
analgesia. A double-blind, randomized, placebo-controlled design will be used to reduce bias 
in assessment of safety, tolerability, and efficacy of JBT-101 in SLE subjects with active 
musculoskeletal disease.  JBT-101 and placebo will be administered in addition to current 
standard of care that the subject is receiving, to reduce risk of precipitating disease flares by 
stopping standard-of-care treatments.  There is limited metabolism of JBT-101, and JBT-101 
has no impact on multiple cytochrome P450 systems, an observation that reduces the 
likelihood of adverse drug-drug actions in SLE patients on complex treatment programs. 
The hypothesis is that JBT-101 will provide clinical efficacy in SLE patients with at least 
moderate musculoskeletal disease activity by activation of pathways that resolve ongoing, 
adverse immune responses and inhibit inflammatory cytokine production associated with 
SLE. JBT-101 is expected to decrease production of pro-inflammatory cytokines implicated 
in the pathogenesis of SLE, such as IFNα, IL-6, and IL-1β. Further, JBT-101 is expected to 
activate apoptosis in activated immune cells and induce clearance of apoptotic cells 
(efferocytosis) and cellular debris by non-inflammatory macrophages. Through these 
mechanisms, JBT-101 is expected to provide efficacy in active musculoskeletal inflammation 
in SLE, without immunosuppression. 
For the primary efficacy analysis, inflammatory pain will be measured daily using the 
maximum pain numerical rating scale (NRS), and longitudinal changes will be evaluated 
after 12 weeks (end of treatment). Other efficacy outcomes include categorical change in 
pain (improvement, no change, worsening), the number (%) of subjects achieving a 30% (or 
50%, 75% or 100%) reduction in maximum pain from baseline to end of treatment, and SLE 
disease activity measures, including number of tender and swollen joints on 66/68 joint 
count, presence versus absence of arthritis by Safety of Estrogen in Lupus: National 
Assessment (SELENA) SLEDAI and score in the musculoskeletal domain of the British Isles 
Lupus Activity Group (BILAG) 2004, the SLE Responder Index and its domains (SELENA 
SLEDAI assessment, BILAG 2004 assessment, and Physician’s Global Assessment), and 
disease flares. Efficacy also will be assessed with patient-reported outcomes [Lupus Activity 
Patient Global Assessment and Patient-Reported Outcomes Measurement Information 


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System (PROMIS)-29 Short Form, PROMIS Item Bank v2.0 - Cognitive Function test, and 
Treatment Satisfaction Survey]. Changes from baseline in secondary efficacy outcomes are 
expected to occur and be in the direction of improvement, although the changes are not 
expected to reach statistical significance at p < 0.05 after 84 days exposure in this first trial in 
relatively small numbers of SLE patients. In contrast, changes in the metabolipidomic profile 
and stimulated whole blood cytokine expression are expected within days, and changes in 
biomarkers of inflammation, such as C-reactive protein (CRP) and type I IFN gene 
expression, are expected to happen within a few weeks.  
Safety assessments include patient-reported AEs, vital signs, physical examinations, 
complete blood count (CBC) with cell differential, metabolic panel, urinalysis, and 12-lead 
ECGs for QT/QTc intervals. Blood for JBT-101 concentrations and metabolites, biomarkers 
of inflammation, metabolipidomic profiles, cytokine expression in serum and stimulated 
whole blood, and analysis of type 1 IFN gene expression will also be collected. Confirmation 
of the lack of psychotropic properties of oral JBT-101 will be done using the Addiction 
Research Center Inventory-Marijuana (ARCI-M) questionnaire. 
The mechanism of action of JBT-101 will be evaluated by measuring metabolipidomic 
profiles, to determine whether JBT-101 increases SPMs, especially lipoxin A4, and anti-
inflammatory eicosanoids, both in absolute amounts and relative to pro-inflammatory 
eicosanoid mediators. The downstream consequences of this activity on biologic pathways 
relevant to disease pathology in SLE will be tested, looking for decreased expression of 
cytokines and gene transcripts that are elevated during inflammation in SLE. 
This is a first-in-SLE study of JBT-101. The data from this study will provide information on 
whether the benefit: risk profile in SLE supports further clinical development and 
progression to future pivotal clinical testing. The data will support selection of optimal dose 
and dose regimen of JBT-101 in future SLE studies. 
 
Rationale for the Inclusion and Exclusion Criteria 
1.6.1
The target population is adults with SLE who have active musculoskeletal disease (arthritis 
or tendonitis) with significant inflammatory pain, despite treatment with an anti-malarial 
drug unless intolerant of an anti-malarial drug, and who are on stable doses of prednisone ≤ 
10 mg daily or equivalent for at least 14 days prior to dosing with study product. To reduce 
risk to subjects in this first-in-SLE study, subjects will be excluded who have severe organ 
damage, severe disease activity and/or require > 10 mg day oral prednisone or equivalent for 
treatment.  Additionally, patients with a recent or current history of substance abuse or those 
with chronic pain requiring narcotic analgesia will be excluded in order to limit confounding 
effects of these substances on our endpoints. Subjects will be > 18 and ≤ 70 years of age at 
the time of signing the Informed Consent Form. Adults are selected as the target population, 
because neither toxicology studies in juvenile animals nor safety or efficacy assessments in 
children with SLE have been done yet. 
Subjects with fibromyalgia are not excluded from the study. Given that up to about one-third 
of SLE patients have concomitant fibromyalgia, exclusion of SLE subjects with fibromyalgia 


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from this study is impractical and would delay and jeopardize completion of study 
enrollment.  Multiple steps have been included in the trial design to account for the potential 
impact of pain from fibromyalgia on study results.  To ensure that a significant component of 
the subjects daily pain NRS score is from inflammatory pain from joint/tendon involvements, 
subjects will be required to have arthritis and/or tendonitis on SELENA SLEDAI assessment 
or B score in the musculoskeletal domain of the BILAG 2004 assessment.  The presence or 
absence of fibromyalgia and its severity will be assessed using the Fibromyalgia Symptom 
Score [107].  The absence versus presence of fibromyalgia (Fibromyalgia Symptom Score < 
13 versus ≥ 13 at Screening) will be used as a stratification variable at randomization and in 
subset analyses of the efficacy outcomes. 
 
Rationale for the Treatment Arm 
1.6.2
The JBT-101 doses selected for this study are within the range of doses that were well 
tolerated in previous Phase 1 and 2 studies and in a recently completed clinical trial in SSc, 
all sponsored by Corbus Pharmaceuticals Holdings, Inc.  The JBT-101 oral doses selected 
for this study are 5 mg b.i.d., 20 mg q.d., and 20 mg b.i.d. Parallel dose assignment to 
JBT-101 in doses up to 20 mg b.i.d. is supported by a previous multiple ascending dose study 
and a Phase 2 study in humans in which JBT-101 doses up to 40 mg b.i.d. showed acceptable 
safety profiles and were well-tolerated. In a recently completed study of JBT-101 in 
systemic sclerosis and ongoing studies in dermatomyositis and cystic fibrosis 
(sponsored by Corbus) using similar doses to those proposed in this clinical trial (5 
mg-40 mg daily), JBT-101 has been well tolerated with no severe AEs attributable to 
JBT-101. Each dose is expected have an acceptable safety profile, be well-tolerated, and 
provide clinical benefit, based on previous animal or human testing and the nature of the 
inflammatory components of SLE. Based on preclinical data and early higher dose clinical 
data, it is expected that any safety risk and clinical efficacy of JBT-101 in humans will be 
related to exposure. Based on extrapolation from animal models of inflammation, 5 mg q.d. 
was estimated to be about the median dose required for efficacy in humans. However, 
information from the cystic fibrosis study and from a cutaneous model of E. coli- induced 
inflammation [101] suggests that 5 mg b.i.d. may be more effective than the 5 mg q.d. dose:  
 The 5 mg q.d. dose has some but more limited effects than 20 mg b.i.d. on biomarkers 
in the sputum in cystic fibrosis patients, with biologic effects of 20 mg b.i.d. ≥ 20 mg 
q.d. and > 5 mg q.d. doses  
 In a human model of innate immune responses (E. coli- induced cutaneous 
inflammation) the 5 mg b.i.d. dosing demonstrates the expected mechanism of action 
by enhancing resolution of inflammation.  Some activities such as induction of 
Specialized Pro-resolving lipid Mediators are less with 5 mg b.i.d. than with 20 mg 
b.i.d. whereas other activities such as inhibition of neutrophil infiltration in the skin 
are equal  
Since the 5 mg b.i.d. dose does not pose any safety issues, we plan to use 5 mg b.i.d. as the 
low dose arm. The JBT-101 20 mg dose is expected to provide maximal or near maximal 
levels of clinical benefit, and the JBT-101 20 mg b.i.d. dose is expected to provide 
maximal/plateau levels of clinical benefit. Inclusion of the JBT-101 20 mg q.d. and 20 mg 


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b.i.d. doses is expected to maximize opportunity to detect clinical efficacy, safety signals, 
evidence of biologic activity, and effects on biomarkers in this study. Finally, the availability 
of data from three different doses of JBT-101 will facilitate the exploratory modeling of 
relationships between plasma concentrations of JBT-101 and efficacy outcomes, SAEs, 
biomarkers of inflammation, and levels of certain SPMs. 
The 84 days duration of dosing is supported by findings in 13-week toxicology studies in 
rats and dogs. This study will provide data on safety, tolerability, plasma concentrations, 
and clinical efficacy of JBT-101 over a longer exposure than in a shorter study.  
In support of oral administration q.d. or b.i.d. without regard to fed/fasted state, JBT-101 is 
well absorbed from the gastrointestinal tract and exhibits dose proportional PK at the doses to 
be tested in this study.  Based on PK results in previous clinical trials, Tmax is expected to be 
between 2.7 to 3.5 hours for the 5 and 20 mg doses in the current trial, which supports the 
timing of 3 hours post dosing as an estimate of time of maximal plasma concentrations.  The 
average terminal chemical half-life of JBT-101 in subjects who received 10 mg or 20 mg q.d. 
in previous studies ranges from 3.7 to 4.4 hours and the biologic effects of JBT-101 are 
longer, which supports q.d. and b.i.d. testing.  Doses to be tested in this study have not shown 
a significant food effect in a prior clinical study, which supports dosing without regard to fed 
state. 
 
Rationale for the Control Arm 
1.6.3
Inclusion of a placebo cohort in this study is important to control for variations in disease 
activity and AEs that occur commonly in SLE as a result of their disease, co-morbid illness 
and/or adverse effects of prescribed medications.  Because of the relatively short duration of 
the study and maintenance of the subject’s existing medications for musculoskeletal disease 
activity and pain, the inclusion of a placebo cohort does not impose undue risk on these 
subjects.  To limit risk of increasing disease activity in a placebo-controlled trial, patients 
with a BILAG A in any organ system at Screening or Visit 1 (Day 1) will be excluded, 
because those individuals should receive a new treatment for that severely active organ 
system.  Subjects will be maintained on their SLE medications from Screening throughout 
Visit 6 (Day 113), to reduce a risk of disease flare precipitated by discontinuation of 
medications to meet entry criteria.  Stopping rules will limit the risk of AEs due to severe 
increases in disease activity. 
 
Rationale for Mechanistic Studies 
1.6.4
The rationale for the mechanistic studies is to validate the preclinical studies and investigate 
the in vivo effects of JBT-101 on pathways that promote ongoing inflammatory responses 
and those that promote resolution of inflammation. Pre-clinical studies done in vitro using 
healthy control and SLE PBMC and in animal models suggest that the drug’s anti-
inflammatory properties are mediated by inhibition of pro-inflammatory cytokines such as 
IL-1β, IL-6, IFNα and IFNγ and by increased production of prostaglandins and other 
bioactive lipids that facilitate the resolution of inflammation. All of these cytokines have 
been implicated in the pro-inflammatory milieu that is associated with SLE. Additionally, 


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although JBT-101 has not been demonstrated previously to have an effect on TNFα we plan 
to verify this in the planned mechanistic studies, which will be completed using stored 
specimens should the clinical results warrant further study. In addition to supplying more 
information that will enhance our understanding of the mechanism of action, it is possible 
that the mechanistic studies will identify a surrogate biomarker for response that is more 
sensitive and specific than currently accepted disease activity measures. This has significant 
potential importance for the design of a Phase III study. 
2 STUDY OBJECTIVES AND PURPOSE  
2.1 Primary Objective(s) 
The primary objective of this trial is to evaluate efficacy of JBT-101 for treatment of 
inflammatory pain related to active musculoskeletal disease in SLE. 
For evaluation of this objective, the primary efficacy analysis will compare longitudinal 
changes in daily measures of the maximum pain NRS in treated groups compared to the 
placebo group after 12 weeks of treatment.  
2.2 Secondary Objective(s) 
The secondary objectives are to: 
1. Evaluate efficacy of JBT-101 in active musculoskeletal disease in SLE 
2. Evaluate efficacy of JBT-101 in overall disease activity in SLE 
3. Evaluate efficacy of JBT-101 in patient-reported outcomes in SLE 
4. Evaluate the safety and tolerability of JBT-101 in subjects with SLE 
5. Evaluate the effects of JBT-101 on biomarkers of inflammation in SLE 
6. Evaluate the effects of JBT-101 on bioactive lipids in SLE 
7. Evaluate JBT-101 plasma concentrations and metabolites in SLE 
2.3 Exploratory Objectives 
The exploratory objectives of this trial are: 
1. Explore impact of JBT-101 on symptoms of fibromyalgia 
2. Explore relationships between JBT-101 plasma concentrations and efficacy, SAEs, 
biomarkers of inflammation, and certain SPMs, including lipoxin A4 


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3 STUDY DESIGN 
3.1 Description of Study Design 
This study is a randomized, double-blind, placebo-controlled, multi-center clinical trial to test 
the efficacy, safety, and tolerability of JBT-101 compared to placebo for the treatment of 
SLE, to evaluate JBT-101’s impact on SPMs and biomarkers of inflammation in SLE, and to 
determine JBT-101 plasma concentrations and metabolites in SLE subjects. The target 
population is SLE subjects ≥ 18 and ≤ 70 years of age with active musculoskeletal disease 
(arthritis and/or tendonitis) and 7-day average of maximal daily pain NRS score ≥ 4 of 10 (at 
least moderate pain) at Screening. If applicable, subjects must be on stable doses of 
corticosteroids ≤ 10 mg daily prednisone or equivalent prior to assessment of screening daily 
pain NRS score and non-increasing doses of other immunosuppressive medications for at 
least 3 months. Additionally, subjects must be on a stable dose of any anti-malarial drug for 
at least 3 months prior to screening or have a history of intolerance, contraindication, or 
unwillingness to take an anti-malarial drug.  
One hundred eligible subjects will be randomized in a 1:1:1:1 ratio to one of four cohorts to 
receive assigned study treatment (see Table 1 below).  On Days 1-84, study product (JBT-
101 or matching placebo) will be self-administered orally b.i.d., with at least 8 hours between 
doses and without regard to fed state.  Randomized eligible subjects will take the 1st dose of 
study medication in the clinic at Visit 1 (Day 1) (See Section 5.3, Administration of Study 
Product).  
Table 1. Randomization Cohorts 
Cohort 
Approximate 
n 
  
Days 1-84 
A.M. Study Product 
P.M. Study Product 
1 
25 
JBT-101 5 mg 
JBT-101 5 mg 
2 
25 
JBT-101 20 mg 
Placebo 
3 
25 
JBT-101 20 mg 
JBT-101 20 mg 
4 
25 
Placebo 
Placebo 
 
Written informed consent must be obtained prior to the subject undergoing any study-related 
procedure, including screening tests and washout periods for prohibited medications, when 
applicable. During the screening period, subjects will be evaluated by the site investigator or 
qualified designee to assess eligibility for randomization into the study. Screening will take 
place over multiple days. The subject must report maximum daily pain NRS scores for seven 
days following the initial visit in the clinic, to ascertain whether eligibility criteria are met 
with a 7-day average of maximum daily pain NRS score ≥ 4 of 10. 
Subjects will report maximum daily pain NRS scores using an interactive voice-response e-
diary system (IVRS), which can be accessed by any phone that supports tone dialing. At the 
Screening visit, subjects will be registered and provided with credentials allowing access to 
the IVRS. Subjects will be instructed on how to record maximum daily pain NRS score, 


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including directions for recording scores at about the same time every day, preferably before 
bedtime. Subjects who are found to be eligible after the screening evaluation will return for 
Visit 1 (Day 1) within 42 days of the initial screening visit. Subject eligibility will be 
confirmed prior to randomization.  Randomized subjects will be instructed to continue to 
record their maximum daily pain NRS score through Visit 6 (Day 113).  
There will be six additional study visits; Visits 1-6 on Days 1, 15  ± 3, 29 ± 3, 57 ± 3, 85 ± 3 
and 113 ± 3, respectively. Treatment occurs from Visits 1-5 (Days 1-85), and Visit 6 (Day 
113) is a follow-up visit 28 ± 3 days after treatment ends. The 3 day window at Visits is 
included in case of holidays or unusual circumstances, and it is expected that most if not all 
visits will be on the targeted day.  Vital signs, AEs, prior/concomitant medications, and blood 
for laboratory safety tests will be evaluated at Visits 1-6 (Days 1-113).  On Visit 1 (Day 1), 
Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85) and Visit 6 (Day 113), subjects will also 
have a physical exam, urinalysis, and other assessments for evaluation of disease status 
including patient reported outcomes. Psychoactivity of JBT-101 will be assessed using the 
ARCI-M questionnaire at Visit 1 (Day 1), Visit 3 (Day 29) and Visit 5 (Day 85).  Twelve-
lead ECGs and QT/QTc intervals will be assessed at Screening and at Visit 1 (Day 1) and 
Visit 5 (Day 85).  At Visit 1 (Day 1), the ARCI-M questionnaire and QT/QTc intervals will 
be assessed both before and 2.5 to 3.5 hours after the first dose of JBT-101, when plasma 
concentrations of JBT-101 should be about maximal. Study personnel will record the 
subject’s interval medical history, assess AEs and medication use, and collect samples for 
safety, pharmacokinetic, and mechanistic assessments (see Flow Diagram of Protocol and 
Section 6, Assessments of Safety and Efficacy; Table 3, Schedule of Events for the specific 
assessment schedule). Subjects will return study drug bottles for a pill count, and new bottles 
will be dispensed, as appropriate.  
For therapeutic stability, subjects should remain on their current treatment regimen for SLE 
from Screening through Visit 6 (Day 113), unless the site investigator or other treating 
physician judges that a change in therapy is needed to provide best medical care for the 
subject. If a subject experiences an increase in disease activity of SLE during participation in 
the study, he/she should be treated with standard of care for that increase in activity.  If 
medically appropriate, some drugs that would interfere with evaluation of efficacy should be 
withheld for specified durations prior to certain study visits.  See Section 5.6, Prohibited 
Medications for details.  
Concomitant therapies taken for the long term treatment of pre-existing conditions other than 
SLE may be continued during the study provided they are in accordance with the exclusion 
criteria (Section 4.2, Exclusion Criteria). It is preferred that these medications be stabilized 
before entry and continued wherever practical without variation of dose or regimen during 
the study.  Concomitant medications and new medications should be administered at the 
discretion of the site investigator or treating physician in order to provide the subject with the 
best possible medical care. Because of the unavailability of toxicology data or clinical 
experience of JBT-101 in combination with many therapeutic agents, it is recommended that 
changes in ongoing treatments or introduction of new therapies are kept to a minimum. The 
benefit: risk to the subject should be carefully assessed and consideration given to the timing 
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Because this is an early study and no efficacy has been demonstrated in SLE, there are no 
plans to provide the subject with open-label JBT-101 after the study period. If they so 
choose, subjects may continue to be seen in the site investigator’s clinical practice. 
About 150 individuals will be screened to identify 100 eligible subjects, for a screen failure 
rate of about 33%. The number of subjects enrolled may be expanded by up to nine 
additional subjects, if these additional eligible subjects have signed the Informed Consent 
Form and are actively engaged in the screening process at the time 100 subjects have been 
randomized into the study.  
About 15 sites in the United States will participate in this trial. The target enrollment of 100 
eligible subjects will take place over about 24 months, for a recruitment rate of about 0.28 
subjects per site per month. The feasibility of this plan is judged acceptable, based on expert 
input from the Protocol Chairs and their collaborators. 
The planned total duration of an individual subject’s participation in the study is about 112 
Days (84 days treatment and 28 days follow-up), plus Screening, unless the subject 
withdraws prematurely. (See Section 5.8, Treatment Discontinuation and Subject 
Withdrawal.) Once 80% of planned sites are activated, the entire study is expected to take 
24-30 months to complete. 
 
Stratification, Randomization, and Blinding 
3.1.1
Eligible subjects will be randomized in a 1:1:1:1 ratio to one of four cohorts: 5 mg JBT-101 
b.i.d., 20 mg JBT-101 q.d., 20 mg JBT-101 b.i.d., or placebo (see Section 3.1, Description of 
Study Design, Table 1). Subjects will be stratified by 7-day average of maximum daily pain 
NRS score ≤ 6 versus > 6 and Fibromyalgia Symptom Scale Score < 13 versus ≥ 13 at 
Screening.  
To maintain the study blind, JBT-101 and placebo capsules and their packaging will be 
identical. All subjects will receive b.i.d dosing to maintain blinding to treatment assignment. 
In general, clinical staff, including the investigators, will be blinded to the treatment 
assignments until completion of the study.  In addition, they will not have access to any 
mechanistic data, and mechanistic laboratory staff will not have access to any clinical results 
until completion of the study. The success of blinding will be formally tested using a 
Treatment Satisfaction Survey that asks each study subject and corresponding site 
investigator to guess the study group assignment for that subject at the end of active 
treatment and then comparing these responses to what would be expected by chance. 
Unblinding must be approved by the study Medical Monitor unless an immediate life 
threatening condition has developed and the Medical Monitor is not accessible.  The site 
investigator will notify the protocol chair(s) and the DAIT- Statistical and Clinical 
Coordinating Center (SACCC) of the unblinding event on the next business day. The 
emergency unblinding will also be reported to the Data and Safety Monitoring Board 
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A full account of the event will be recorded, including the date and time of the unblinding, 
the reason for the decision to unblind, and the name of the individual who made the decision 
and the names of the Medical Monitor and others who were notified. The reasons for 
unblinding of a participant’s treatment will be included in the final study report. 
An individual’s treatment assignment will be unblinded if the subject experiences a suspected 
adverse reaction that is serious and unexpected (see Section 7.2.1,  Adverse Event and 
Section 7.2.1.1 Suspected Adverse Reaction and Section 7.2.2, Unexpected Adverse Event) or 
other protocol-specific event(s) determined by DAIT/NIAID to warrant unblinding. 
 Subject Completion and Replacement 
3.1.1.1
A subject is considered to have completed the study if he/she has completed Visit 6 (Day 
113). 
Randomized subjects who never initiate treatment may be withdrawn and will not count 
towards the accrual of 100 eligible subjects.  
3.2 Description of Endpoints  
See Section 6, Assessment of Safety and Efficacy, for detailed descriptions of endpoint 
measures, and Section 8, Statistical Considerations and Analytical Plan, for planned 
analyses. 
 
Primary Efficacy Endpoint 
3.2.1
The primary endpoint for evaluation of the primary objective will be improvement in 
maximum daily pain NRS scores in the treated groups relative to the control after 12 weeks 
of treatment.  Longitudinal trends over the course of the treatment period will be modeled 
and used to estimate differences between means at baseline and Day 84 for each treatment 
group. 
 
Secondary Efficacy Endpoints 
3.2.2
1. The 7-day average of maximum daily pain NRS scores prior to Visits 1, 3, 4, 5, and 6 
will be used to evaluate the number (%) of subjects with: 
 Changes in pain categories from Visit 1 (Day 1)  to Visits 3 (Day 29), 4 (Day 
57), 5 (Day 85) and 6 (Day 113) (See Section 6.2.2.2 Pain Categories) 
 Improvement of 30% from Visit 1 (Day 1)  to Visits 3 (Day 29), 4 (Day 57), 5 
(Day 85) and 6 (Day 113) 
 Improvement of 50% from Visit 1 (Day 1)  to Visits 3 (Day 29), 4 (Day 57), 5 
(Day 85) and 6 (Day 113)   
 Improvement of 75% from Visit 1 (Day 1)  to Visits 3 (Day 29), 4 (Day 57), 5 
(Day 85) and 6 (Day 113)   


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 Improvement of 100% from Visit 1 (Day 1)  to Visits 3 (Day 29), 4 (Day 57), 
5 (Day 85) and 6 (Day 113)   
2. Trends in active musculoskeletal disease activity over the duration of the treatment 
period (i.e. Visit 1 (Day 1) through Visit 5 (Day 85)) will be evaluated longitudinally 
using multiple indices: 
 Physician assessed tender joint count  
 Physician assessed swollen joint count  
 Presence or absence of arthritis on the SELENA SLEDAI  
 Musculoskeletal domain of the BILAG 2004  
3. Persistence of trends in musculoskeletal disease activity after stopping treatment will 
be evaluated at Visit 6 (Day 113). 
4. Trends in overall SLE disease activity over the duration of the treatment period (i.e. 
Visit 1 (Day 1) through Visit 5 (Day 85)) will be evaluated longitudinally using 
multiple indices:  
 SLE Responder Index, where a responder is defined as having all of the 
following:  
o ≥4 point reduction in SELENA-SLEDAI score,  
o no new BILAG A or no more than 1 new BILAG B domain score, and  
o no deterioration from baseline in the Physician's Global Assessment 
defined as an increase of ≥0.3 points.  
 SELENA SLEDAI score 
 BILAG 2004 score 
 Physician’s Global Assessment 
5. Persistence of trends in overall SLE disease activity after stopping treatment will be 
evaluated at Visit 6 (Day 113). 
6. Trends in patient-reported outcomes over the duration of the treatment period (i.e. 
Visit 1 (Day 1) through Visit 5 (Day 85)) will be evaluated longitudinally using 
multiple indices: 
 Lupus Activity Patient Global Assessment  
 PROMIS-29 Short Form  
 PROMIS Item Bank v2.0 - Cognitive Function 
7. Treatment Satisfaction Survey 
8. Persistence of trends in patient-reported outcomes after stopping treatment will be 
evaluated at Visit 6 (Day 113). 


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Safety Endpoints 
3.2.3
Safety will be evaluated by describing incidence of treatment-emergent adverse events 
(TEAEs) from Visit 1 (Day 1) through 6. TEAEs will be identified by monitoring subject-
reported AEs, vital signs, medical history, physical exams, blood and urine safety tests, 12-
lead electrocardiograms, and the ARCI-M. Analyses on the following specific events are 
planned.   
1. Any Grade 3 or higher AE or SAE that, in the opinion of the blinded site investigator, 
is at least possibly related to study product. Unless noted otherwise, grading is 
defined by the National Cancer Institute (NCI) - Common Terminology Criteria for 
Adverse Events (CTCAE) system version 4.0.  
2. QTc prolongation > 500 msec total duration and > 60 msec from Visit 1 (Day 1) QTc 
interval prior to study drug administration 
3. Mild/moderate and severe disease flares by SELENA SLEDAI Flare Index  
4. BILAG 2004 disease flares, defined as one new BILAG A or two new BILAG B 
scores 
5. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3 x upper 
limit of normal and total bilirubin > 1.5 x the upper limit of normal (confirmed on 
repeat testing) 
6. Tolerability, assessed by incidence of discontinuation of study product due to TEAEs 
at least possibly related to study product from Visits 1 (Day 1) through 5 (Day 85) 
7. Psychotropic activity, assessed using the ARCI-M 
 
Mechanistic Endpoints 
3.2.4
1. Trends in C-reactive protein levels in the blood over the duration of the treatment 
period (i.e. Visit 1 (Day 1) through Visit 5 (Day 85)) will be evaluated longitudinally 
2. Persistence of trends in C-reactive protein levels after stopping treatment will be 
evaluated at Visit 6 (Day 113) 
3. Trends in pro-inflammatory cytokine levels over the duration of the treatment period  
(i.e. Visits 1 (Day 1), 3 (Day 29) and 5(Day 85)) will be evaluated longitudinally 
using multiple indices: 
 Pro-inflammatory cytokines in serum 
i. IFN, IFN, IL-6, TNF, and IL-1  
ii. Expression of other cytokine will be explored  
 Pro-inflammatory cytokines in whole blood with and without in vitro TLR 
stimulation 
i.  IFN, IFN, IL-6, TNF, and IL-1 in supernatant of stimulated and 
unstimulated whole blood cells  
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4. Persistence of trends in biomarkers of inflammation after stopping treatment will be 
evaluated at Visit 6 (Day 113) 
5. Changes in bioactive lipids in plasma from Visit 1 (Day 1) (pre and post dose) to 
Visit 2 (Day 15) will be evaluated longitudinally using multiple indices: 
 Specialized Pro-resolving lipid Mediators (SPMs), including lipoxin A4  
 Anti-inflammatory eicosanoids 
 Pro-inflammatory eicosanoids 
6. Changes in plasma concentrations of JBT-101 and its metabolites from Visit 1 (Day 
1) (pre and post dose) to Visit 2 (Day 15) 
 
Exploratory Endpoints 
3.2.5
1. Changes in Fibromyalgia Symptom Scale score, from Visit 1 (Day 1)  to Visits 5 
(Day 85) and 6 (Day 113) 
4 SELECTION OF SUBJECTS 
The target population is adults with SLE who have active musculoskeletal disease (arthritis 
or tendonitis) with significant inflammatory pain, despite treatment with an anti-malarial 
drug unless intolerant of an anti-malarial drug, and who are on stable doses of prednisone ≤ 
10 mg daily or equivalent for at least 14 days prior to assessment of 7-day average of 
maximum daily pain NRS score at Screening and 42 days prior to Visit 1 (Day 1). 
Women and minorities will be recruited. Based on the demographics of this disease and the 
sites that will be used, it is anticipated that approximately 90% of the study population will 
be women and 60-75% will be African American and Hispanic or Asian. Urban sites will be 
included, to increase opportunities to enroll minority subjects. Pregnant and lactating women 
will be excluded from the study because of the unknown effects of JBT-101 on the fetus. 
Subjects < 18 years of age will be excluded, because there are no toxicology studies in 
juvenile animals and no safety, tolerability, and efficacy data in adults with SLE. 
4.1 Inclusion Criteria 
Individuals who meet ALL of the following criteria at Screening are eligible for enrollment: 
1. Fulfill the updated ACR 1997 Revised Criteria for the Classification of Systemic Lupus 
Erythematosus [108] 
2. ≥ 18 and ≤ 70 years of age at the time the Informed Consent Form is signed  
3. At least 3 months treatment with an anti-malarial drug such as hydroxychloroquine or a 
history of intolerance, contraindication, or unwillingness to take an anti-malarial drug 
4. Meets the SELENA SLEDAI definition of arthritis [109] or moderate arthritis or 
tendonitis that has not improved over the last month (i.e. BILAG B on the updated 
BILAG 2004 [110]) 


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5. Seven-day average of maximum of daily pain NRS scores ≥ 4 out of 10 during screening 
with continued reporting of pain NRS scores on at least 67% of days between the 
Screening visit and randomization.  
6. Overlap with polymyositis, systemic sclerosis, Sjögren’s syndrome, or rheumatoid 
arthritis is allowed, if, in the site investigator’s judgment, the predominant clinical 
features are those of SLE 
7. Not expected by the site investigator to require a change in potential disease-modifying 
treatments for SLE from Screening through Visit 6 (Day 113) 
8. Willing to not start or stop any NSAIDs or potential disease-modifying medications or 
supplements for SLE from Screening through Visit 6 (Day 113), unless a change is 
recommended by the site investigator or other treating physicians 
9. Willing not to use any legal or illegal cannabinoids, including FDA-approved 
cannabinoids or cannabinoid-mimic drugs, or any illegal substance of abuse from 
Screening through Visit 6 (Day 113) 
10. If a woman of child-bearing potential, willing to use one of the highly effective (failure 
rate < 1% per year) birth control method from Screening through Visit 6 (Day 113) or for 
28 ± 3 days after the last dose of study product (See Appendix A: Reproductive Potential 
and Effective Methods of Contraception) 
11. Willing to follow instructions, complete study procedures and attend study visits as 
required by this protocol 
4.2 Exclusion Criteria 
Individuals who meet ANY of the following criteria are not eligible for enrollment: 
1. Severe or unstable SLE, such as any one of the following: 
a. A BILAG A score in one or more BILAG domains at Screening 
b. Treatment with any intraarticular, intravenous, or intramuscular systemic 
corticosteroids within 14 days of Screening 
c. Treatment with oral prednisone  > 10 mg per day or > 20 mg every other day (or 
equivalent dose of another corticosteroid) within 14 days of Screening  
d. Increased dose of systemic corticosteroids in the 14 days prior to Screening 
e. Treatment with cyclophosphamide or anti-TNFα biologic agents within 3 months 
before Visit 1 (Day 1) 
f. Treatment with B cell-depleting monoclonal antibodies (rituximab, Ocrelizumab, 
anti-CD-22) within 6 months before Visit 1 (Day 1) 
g. Treatment with methotrexate, mycophenolate, azathioprine, leflunomide, 
cyclosporine, belimumab, tacrolimus, or any other immunosuppressive agent not 
included in 1b.-f. above, when the dose of that immunosuppressive agent has 
increased within 3 months before Visit 1 (Day 1). Concurrent treatment with any of 


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these medications is allowed as long as the doses have been stable for at least 3 
months before Visit 1 (Day 1) 
h. Actively listed on an organ transplantation list or have received an organ transplant 
other than a corneal transplant 
2. Significant diseases or conditions other than SLE that may influence response to the 
study product or safety, such as: 
a. Active bacterial or viral infection requiring systemic antibiotic or anti-viral treatment 
within 14 days before Visit 1 (Day 1) 
b. Acute or chronic hepatitis B or C infection   
c. Human immunodeficiency infection 
d. History of active tuberculosis or positive tuberculosis skin or blood test without: 1) 
completing a course of appropriate treatment; or 2) having received at least one 
month of appropriate treatment prior to Visit 1 (Day 1) and continuing to receive 
appropriate treatment during the study 
e. No elective surgery should be planned from Visit 1 (Day 1) through Visit 6 (Day 
113) 
f. A history of cancer. Except basal cell carcinoma or in situ carcinoma of the cervix 
treated with apparent success with curative therapy greater than one year before Visit 
1 (Day 1) 
g. Significant heart disease as defined by: 
i. Uncontrollable congestive heart failure, unstable angina, unstable atherosclerotic 
cardiovascular disease, significant arrhythmia requiring chronic therapy, 
pulmonary arterial hypertension with dyspnea, disability rated as New York heart 
Association Grade III or higher, severe systemic hypertension or severe peripheral 
vascular disease  
ii. Marked baseline prolongation of QT/QTc interval (i.e. repeated demonstration of 
a QTc interval ≥ 450 msec for males and ≥ 470 msec for females) 
iii. History of risk factors for torsade de pointes (e.g., heart failure, hypokalemia) 
iv. Clinically significant confirmed abnormality, as determined by the site 
investigator or qualified designee, on 12-lead ECG at Screening 
3. History of chronic pain requiring treatment with narcotic analgesia for more than 30 days 
total within 6 months (183 days) of baseline. This does not include self-limited pain 
associated with identifiable events such as surgery 
4. Current evidence of alcohol abuse (defined as 4 or more drinks per day on at least 4 days 
of the week) or history of abuse of illegal and/or legally prescribed drugs such as 
barbiturates, benzodiazepines, amphetamines, cocaine, or opioids during the 1 year prior 
to Screening 
5. Currently pregnant, breast-feeding, or lactating 


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6. Any investigational agent within 30 days or five therapeutic half-lives of that agent 
whichever is longer, before Visit 1 (Day 1) 
7. Any of the following values for laboratory tests at Screening: 
a. A positive pregnancy test (also at Visit 1 (Day 1)) 
b. A newly positive QuantiFERON® blood test for tuberculosis, without: 1) 
completing a course of appropriate treatment; or 2) having received at least one 
month of appropriate treatment prior to Visit 1 (Day 1) and continuing to receive 
appropriate treatment during the study. If the subject has a previous documented 
positive tuberculosis skin, then this testing does not need to be repeated. If the 
subject has a documented negative test result within the last year, testing does not 
need to be repeated, at the discretion of the site investigator 
c. Hemoglobin < 8 g/dL 
d. Neutrophils < 1.0 x 109/L 
e. Platelets < 75 x 109/L 
f. eGFR < 50 ml/min according to Cockcroft-Gault equation 
g. AST, ALT, or alkaline phosphatase > 2.0 x upper limit of normal 
8. Any other conditions that, in the opinion of the site investigator, are clinically significant 
and may put the subject at greater safety risk, influence response to study product, or 
interfere with study assessments. When in doubt, the site investigator or qualified 
designee should discuss the situation with the Protocol Chairs. 
4.3 Co-enrollment Guidelines 
Enrolled subjects are allowed to continue participation in observational research studies that 
do not dictate treatment. Co-enrollment in another research study that dictates treatment in 
any way is not allowed from Screening through Visit 6 (Day 113).  
4.4 Strategies for Recruitment and Retention 
The target enrollment is 100 eligible subjects. Most subjects will be recruited from 
specialized academic outpatient SLE clinics run by the site investigators or at which the site 
investigators participate. A need to advertise for subjects outside the sites is not anticipated, 
although it is acceptable. If it becomes necessary to advertise, DAIT/NIAID will review and 
approve such advertisements to make sure they meet FDA requirements. Children, pregnant 
females, prisoners and other vulnerable populations will not be recruited. The clinical trial 
will be listed on clinicaltrials.gov and possibly other relevant websites to make information 
about this trial easily accessible on the internet. 
To encourage retention in the study, every effort will be made to be respectful of the 
subject’s time. The total time required from the subject will vary with the visit and the 
efficiency of each site and is expected to be 11-15 hours across all visits plus travel time. 
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the study at each visit by study personnel and reminded of the date and time of their next 
visit.  
5 TREATMENT OF SUBJECTS 
5.1 Description of Study Product 
 
Product Description 
5.1.1
Active Product: JBT-101 is (6aR, 10aR)-3-(1,1-dimethylheptyl)- 8-tetrahydro-cannabinol-
9-carboxylic acid (see Figure 2), also known as Lenabasum, anabasum, resunab, ajulemic 
acid, CT-3, IP751 and CPL7075. It is a dimethylheptyl structural analogue of 
tetrahydrocannabinol-11-oic acid, designed and selected on the basis of cannabinoid 
structure-activity features associated with limited penetration of the blood-brain barrier, to 
reduce unwanted psychoactivity.  JBT-101 has preferential binding to CB2 versus CB1 and 
exhibits preferential cellular activation through CB2 (Tepper et al., 2014). Detailed study 
product information can be found in the IB for JBT-101. The structure of JBT-101 is shown 
in Figure 2. 
 
Figure 2. Structure of JBT-101 
Molecular Formula:  C25H36O4 
Molecular Weight:     400.55 
CAS Number:          137945-48-3 
Appearance:             White to tan powder 
 
JBT-101 is manufactured by Corbus Pharmaceuticals Holdings, Inc.  
Comparator Product: Placebo is microcrystalline cellulose (no active ingredient), 
formulated to have an appearance and weight similar to JBT-101. 
 
Packaging and Labeling of Study Product 
5.1.2
JBT-101 5 mg and 20 mg and placebo are powder-in-capsule preparations packaged in 
identical no. 2 gelatin capsules. JBT-101 and placebo will be packaged in coded bottles of 35 
capsules each that will be labeled in accordance with regulatory requirements. The bottles 
will be made of high density polyethylene with polypropylene child-resistant caps and an 
induction seal. Each bottle will contain a canister that absorbs oxygen.   
Study product will be supplied in kits of two bottles per kit. Each bottle will be numbered to 
match the kit.  Each kit will contain a 28-day supply of study product plus packaged overage 


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that is enough for another seven days of treatment, in case the next visit is delayed. In each 
kit, one bottle will be labeled for the morning dose and the other bottle will be labeled for 
evening dose, with written directions for morning or evening dosing and with visual clues 
about the time of dosing. Different kits will be manufactured to meet the needs of the study 
and will contain one of the following: 
 Cohort 1 Kit: One bottle of JBT-101 5 mg for a.m. dose and one bottle of 5 mg for 
p.m. dose 
 Cohort 2 Kit: One bottle of JBT-101 20 mg for a.m. dose and one bottle of placebo 
for p.m. dose 
 Cohort 3 Kit: One bottle of JBT-101 20 mg for a.m. dose and one bottle of JBT-101 
20 mg for p.m. dose 
 Cohort 4 Kit: One bottle of placebo for a.m. dose and one bottle of placebo for p.m. 
dose 
The bottles will be indistinguishable from each other in appearance, and the kits will be 
indistinguishable from each other in appearance. 
JBT-101 will be dispensed to study subjects in the original packaging with a label clearly 
indicating that the contents are for investigational purposes only. The label will include 
conditions for storage, a unique drug ID, and other pertinent information such as Sponsor and 
caution statement. Neither JBT-101 nor placebo should be used after the expiration date 
unless a written notification of an expiration date extension is provided by the manufacturer. 
If the packaging is damaged, or if there is anything unusual about the appearance or attributes 
of the pills or bottles, it should not be used. The study drug in question should be quarantined 
at the study site and the problem immediately reported to DAIT/NIAID or their 
representative.  
 
Storage and Handling of Study Product 
5.1.3
DAIT, NIAID will provide the investigational product for the conduct of this protocol and 
will be responsible for the disposal of unused product. 
The investigational product will be stored at the site pharmacy or in the site investigator’s 
locked storage cabinet/safe. Study product will to be stored at room temperature away from 
temperature and humidity extremes. Storage conditions must be appropriate for small 
quantities of Controlled Drugs Act Schedule 1 substances. The study product that is returned 
by the subjects to the site also will be stored under conditions appropriate for small quantities 
of Controlled Drugs Act Schedule 1, until disposal. 
The site pharmacist, site investigator or qualified designee is responsible for investigational 
product accountability, maintaining accurate logs of study product received, dispensed, 
returned or destroyed, and ensuring the appropriate amount of study drug is kept on site and 
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such as checking drug shipments against the shipping contents form, maintaining a log of the 
amount of study drug provided to individual subjects, and reconciling used and unused drug 
supply by subjects and the study unit.   
Upon completion of the study, any unused investigational product(s) at the study sites will be 
returned to the drug distributor, as requested by DAIT/NIAID. 
5.2 Dosage Regimen  
The JBT-101 doses selected for this study are 5 mg b.i.d., 20 mg q.d., and 20 mg b.i.d. for 
oral administration without regard for fed/fasted state. JBT-101 will be administered orally 
b.i.d. on Days 1-84, with at least 8 hours between doses. (See Section 3.1, Description of 
Study Design; Table 1.) 
5.3 Administration of Study Product 
JBT-101 will be self-administered orally b.i.d., with at least 8 hours between doses and 
without regard to fed state.  See Section 3.1, Description of Study Design; Table 1 for 
morning and evening dosing for the 4 cohorts.  The first dose of JBT-101 at Visit 1 (Day 1) 
will be taken in the clinic, and the subjects will be observed in the clinic for at least 30 
minutes after this dose or longer, until, in the opinion of the investigator, vital signs and 
clinical symptoms are acceptable for the subject to leave the clinic. After this observation 
period, subjects must still be available for additional assessments 2.5 to 3.5 hours after 
administration of the study product. 
JBT-101 should be taken in the following way: 
 JBT-101 and placebo capsules should be swallowed whole, with liquid as helpful, and 
should not be broken, chewed or opened. Morning and evening doses should be at 
least 8 hours apart. 
 If a dose of JBT-101 or placebo is missed, it should be taken as soon as possible on 
the same day, as long as the other dose that day can be timed to be at least 8 hours 
separate from the time of the missed dose. If it is missed for the entire day, it should 
not be made up. 
 Doses can be taken without regard to fed state.   
Subjects who take more than the prescribed dose of JBT-101 or placebo should be instructed 
to seek emergency medical care, if needed, and to contact the study staff as soon as possible. 
5.4 Management Plan for Potential Risks 
As of July 2017, no severe AEs have been found to be definitely related to JBT-101. As 
such, the plans detailed in the section are proposed as general precautions for potential risks.   
Expected AEs related to JBT-101 are via CB receptors. As of July 2017, a number of the 
AEs associated with CB1/CB2 agonists have been reported in subjects exposed to JBT-101, 
such as fatigue, dizziness, decreased concentration, feeling “weird”, lightheadedness, 


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asthenia, somnolence, nausea, vomiting, mild orthostatic hypotension, and dry mouth. 
Patients in the study will be monitored closely for all of these side effects as well as for 
potential toxicities including psychotropic, gastrointestinal and cardiovascular effects. They 
are scheduled to be seen frequently during the treatment period (on study Days 1, 15, 29, 57 
and 85) and on day 113 for safety follow-up. The ARCI-M scale will be used to assess 
psychotropic effects of the drug. The Lupus Activity Patient Global Assessment, PROMIS-
29 Short Form and PROMIS Item Bank v2.0 - Cognitive Function will be used to assess 
fatigue and quality of life. The IVRS e-diary for the NRS scale will be used to record pain on 
a daily basis. Disease activity will be evaluated using patient history, physical exams, 
hematologic, blood chemistries, urinalyses and serologies pertinent to the SLEDAI (C3, C4 
and anti-dsDNA antibodies).  
Prolongations of QTc interval to less than 500 msec total and up to 39 msec prolongation 
from pre-treatment baseline were observed in a previous Phase 1 study, and all of these 
prolongations were judged not clinically significant.  They were only observed in some 
subjects ≥ 65 years of age exposed to JBT-101 at a total daily dose of up to 180 mg for seven 
days.  For this reason, to ensure safety of subjects, the QT/QTc interval will be measured 
throughout the study, and maximum doses tested will not exceed 40 mg/day (given as 20 mg 
b.i.d.). 
If a subject develops a grade 3 or higher NCI-CTCAE (version 4.0) adverse event that is 
deemed by the blinded site investigator to be possibly related, probably related, or related to 
study drug, the subject will be discontinued from treatment but will continue to be monitored 
at the scheduled follow-up visits unless consent is withdrawn.  
There will be no dose modification in this study, other than temporary or permanent 
discontinuation of study drug and there is no rescue treatment. 
 
Prevention of Potential Risks to Study Product 
5.4.1
The Inclusion/Exclusion criteria have been designed to exclude subjects with significant 
other illnesses or conditions that would increase safety risks during the trial. Subjects with 
chronic pain requiring ongoing treatment with narcotic analgesia are also excluded. Subjects 
will additionally be reminded to call their study physician in the event that they develop any 
adverse event (whether or not they determine it to be related to the study) and may be 
evaluated for potential toxicity at an unscheduled visit. 
 
Management of Potential Risks to Study Product 
5.4.2
Severe symptoms related to the potential risks of JBT-101 may necessitate stopping study 
drug. Stopping study drug is not a reason for withdrawal from the study, but a subject may be 
withdrawn at the discretion of the PI if deemed it is in the subject’s best interest.  
For subjects who experience potential CB1/CB2 mediated AEs (fatigue, dizziness, decreased 
concentration, feeling “weird”, lightheadedness, asthenia, somnolence, GI disturbances such 
as nausea or vomiting, or dry mouth), treatment for symptoms should be prescribed as 
needed, and study treatment may be withheld at discretion of PI.  


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5.5 Concurrent Medications and Therapy 
The intent is that each subject is maintained on all his/her medications for SLE from 
Screening through Visit 6 (Day 113), unless the site investigator or other treating physicians 
judge that a change in therapy is needed to provide best medical care for the subject.  
Information about the concomitant medications and treatments will be collected at each Visit.  
All concomitant medications given to the subject during the study will be recorded on the 
eCRF.  
Concomitant therapies taken for the long term treatment of pre-existing conditions other than 
SLE may be continued during the study provided they are in accordance with the exclusion 
criteria.  It is preferred that these medications be stabilized before entry and continued 
wherever practical without variation of dose or regimen during the study. 
During the study, concomitant medications and new medications should be administered at 
the discretion of the site investigator or treating physician in order to provide the subject with 
the best possible medical care.  Because of the unavailability of toxicology data or clinical 
experience of JBT-101 in combination with many therapeutic agents, it is recommended that 
changes in ongoing treatments or introduction of new therapies are kept to a minimum.  The 
benefit: risk to the subject should be carefully assessed and consideration given to the timing 
of any necessary introductions of new medications. 
Permitted concomitant medications for SLE during the study include stable doses, including 
stable doses of as needed (prn) medication, of any of the following: 
 Anti-malarial medications 
 Systemic corticosteroids ≤ 10 mg q.d. or ≤ 20 mg every other day oral prednisone or 
equivalent corticosteroid 
 Methotrexate, mycophenolate, azathioprine, leflunomide, belimumab, cyclosporine, 
or tacrolimus 
 Topical therapies, such as topical corticosteroids, antibiotics, anti-viral agents, 
artificial tears, ophthalmic ointments 
 NSAIDS, dosing must be held within 12 hours of certain study Visits (see Table 2 
below) 
 Non-narcotic and narcotic analgesic, dosing of must be held within 6 or 12 hours, 
based on half-life of the analgesic, of certain study Visits (see Table 2). Narcotic 
analgesics are permitted only for prn use for acute events not related to SLE disease 
activity 
 Other medications not specifically included in this list of allowed concomitant 
medications for SLE are allowable, based on the judgment of the investigator and 
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5.6 Prohibited Medications 
A list of disallowed medications is provided in Table 2. 
 
Table 2.  Disallowed medications and conditions 
 
5.7 Procedures for Monitoring Subject Compliance 
The number of capsules of study product returned to the site will be counted and recorded on 
Visits 2 (Day 15), 3 (Day 29), 4 (Day 57), and 5 (Day 85). Note that at Visit 2, the study drug 
capsules will be counted to evaluate compliance, but the bottles will be returned to the 
subject for dosing until Visit 3. 
Drug Class 
Requirements 
Analgesics with half-life < 6 hours 
Prohibited for 6 hours prior to study 
assessments at Visits 1, 3, 4, 5, and 6 
NSAIDS and analgesics with half-life ≥ 6 
hours 
Prohibited for 12 hours prior to study 
assessments at Visits 1, 3, 4, 5, and 6 
Systemic corticosteroids > 10 mg per day 
or > 20 mg every other day oral prednisone 
or equivalent corticosteroid or increase in 
dose of systemic corticosteroid 
To accommodate the occasional use of extra 
corticosteroids by patients for reasons not 
associated with SLE flares, increases of up to 20 
mg/day that are decreased back to the baseline 
dose within 7 days are permitted, but not on 
more than 2 occasions during the study.  These 
short increases in dose may not be accompanied 
by a documented SLE disease flare. 
However, use is prohibited for 14 days prior to 
study visits for Screening.  
 
 
Intraarticular, intravenous, or 
intramuscular systemic corticosteroids 
Prohibited for 14 days prior to study visits for 
Screening and during the study 
Any cannabinoid, cannabinoid-mimic 
(except JBT-101), or illegal substance of 
abuse 
Prohibited from Screening through Visit 6 (Day 
113) 
Cyclophosphamide or anti-TNFα biologic 
agents 
Prohibited for 3 months before Visit 1 (Day 1) 
and during the study 
Rituximab, ocrelizumab, anti-CD22 
monoclonal antibody 
Prohibited for 6 months before Visit 1 (Day 1) 
and during the study 
Other investigational agents 
Prohibited for 30 days or 5 half-lives before 
Visit 1 (Day 1), whichever is longer and during 
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5.8 Treatment Discontinuation and Subject Withdrawal 
 
Interruption of Dosing and Study Treatment Discontinuation  
5.8.1
Interruption of continued dosing in individual subjects may occur for safety reasons and at 
the discretion of the site investigator, if it is felt that interruption of dosing is in the best 
interest of the subject. Other than in urgent situations, it is recommended that the site 
investigator discuss the reasons for interruption of dosing with the Protocol Chairs and 
DAIT/NIAID prior to interruption.  Multiple on-off periods of treatment with study drug are 
permitted, as necessary in the judgment of the investigator for safety purposes.  
Study treatment will be discontinued permanently for any individual subject under the 
following conditions: 
1. At any time during the study at the request of the subject or subject’s guardian 
2. If investigators or the DAIT/NIAID Medical Monitor determine(s) that the subject’s 
health, safety, and/or well-being are threatened 
3. Study treatment will be discontinued for any subject who experiences any of the 
following: 
 A severe flare by the SELENA SLEDAI Flare Index or a BILAG A in any 
domain except musculoskeletal  
 Starting a medication that is prohibited during the study (See Table 2 in Section 
5.6, Prohibited Medications) 
 Increases in doses of methotrexate, mycophenolate, azathioprine, leflunomide, 
belimumab, cyclosporine, or tacrolimus above stable baseline doses 
 Any Grade 3 or higher AE or SAE that, in the opinion of the blinded site 
investigator, is  at least “possibly related” to study product 
 Pregnancy. (See Section 7.6, Pregnancy Reporting) 
Abrupt discontinuation of treatment with JBT-101 is not known to cause any harmful effects; 
therefore, study product will be stopped without tapering or adding additional treatments. All 
remaining study product will be returned to the study staff.  
There will be no dose modification in this study, other than temporary or permanent 
discontinuation. 
 Procedures for Discontinuation of Protocol-Specified Treatment Requirements  
5.8.1.1
Whenever possible, subjects who have been discontinued from study treatment should 
complete all scheduled study visits including all exams, procedures, assessments, and tests 
for the duration of the study. Furthermore, if discontinuation is due to safety concerns, 
subjects will be given appropriate care under medical supervision beyond the last scheduled 
study visit, if necessary, until the symptoms of any AE resolve or the subject’s condition 
becomes stable. If the site Principal Investigator (PI) determines that completion of these 
visits is not clinically appropriate for the subject or if the subject or subject’s guardian elects 


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not to complete these visits, the subject will be withdrawn from the study per the guidelines 
in Section 5.8.2.1, Procedures for Subject Withdrawal from the Study.   
 
Subject Withdrawal from the Study 
5.8.2
When a subject is withdrawn from the study, protocol-specified treatment requirements are 
discontinued, and study-related visits, exams, procedures, assessments, tests and data 
collection are terminated. Individual subjects will be withdrawn from the study under the 
following conditions: 
 The subject or subject’s guardian withdraws consent 
 If the subject elects to participate in any other sort of study or clinical trial (excluding 
observational registries or cohorts), the subject may be withdrawn at the discretion of 
the DAIT/NIAID 
 Subject non-compliance with treatment regimens or failure to keep appointments 
 Procedures for Subject Withdrawal from the Study 
5.8.2.1
All withdrawn subjects will have a follow-up visit after study product is discontinued for 
final safety monitoring. The timing of the Early Withdrawal Visit in this study is 28 ± 3 days 
after study product is discontinued. Assessments will be the same for subjects who withdraw 
before completing all dosing and those who complete all dosing. Subjects who withdraw 
consent will be asked to complete the Early Withdrawal Visit; however, they will not be 
required to complete the visit.  
Subjects who are withdrawn due to pregnancy will be followed according to the procedures 
outlined in Section 6.1.9, Pregnancies. 
 
Safety Stopping Guidance 
5.8.3
In addition to the pre-scheduled data reviews and planned safety monitoring, the DSMB may 
be called upon for ad hoc reviews or emergency meetings. The DSMB will review any event 
that potentially impacts safety at the request of the protocol chair or DAIT/NIAID. The 
DSMB will have the discretion to recommend actions regarding study conduct and 
continuation as a consequence of any planned or unplanned monitoring activity.  
In addition to the planned safety reviews, the DSMB will be informed of the following events 
as they occur: 
 Any immediately life threatening event or death that occurs in the study that is at least 
possibly related to study intervention 
 Two or more subjects with QT-prolongations defined as QTc prolongation > 500 
msec total duration and > 60 msec from Visit 1 (Day 1) QTc interval prior to study 
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In addition, the following events will trigger both a comprehensive DSMB Emergency Safety 
Review and a temporary halt in enrollment: 
 After the first 20 subjects are randomized, the occurrence of a Grade 3 or higher 
unexpected SAE in 10%  or more of the study participants who have received study 
drug 
 Two grade 3 or above AEs with the same or similar preferred terms associated with 
CB1 agonists deemed at least possibly-related to study drug.  
 Determination of unexpected, significant, or unacceptable risks to subjects that 
contraindicate further dosing of additional subjects, in the opinion of the Protocol 
Chairs or DAIT 
 Any new safety information about JBT-101 from other clinical trials that would pose 
significant or unacceptable risk to subjects 
In the event of a temporary halt in enrollment, no new subjects will be consented or start on 
therapy with JBT-101 or placebo; and subjects already on JBT-101 or placebo will continue 
on therapy unless they are the focus of the DSMB review. Subjects in the screening phase of 
the study may continue to undergo minimal risk procedures (e.g., blood tests), but more than 
minimal risk procedures should be deferred. Randomization will not occur until the DSMB 
review is complete. The FDA will be notified of any halt in enrollment. After careful review 
of the data, the DSMB will make recommendations regarding study conduct and/or 
continuation. 
6 ASSESSMENT OF SAFETY AND EFFICACY 
6.1 Assessments of Eligibility and Safety 
The following laboratory safety tests will be done at regularly scheduled intervals: 
hematology (CBCs with cell differential and platelet count); chemistry (complete metabolic 
panel including electrolytes, renal function, and liver function tests); urinalysis with 
microscopic examination; and pregnancy testing in women with childbearing potential.  
Medical history, physical examination, and prior medications will be completed at Screening, 
for purposes of eligibility. Physical examination results, adverse events, and concomitant 
medications will be recorded as per Table 3, Schedule of Events.  
Psychoactivity of JBT-101 will be assessed using the ARCI-M questionnaire at Visit 1 (Day 
1) and follow-up visits per Table 3, Schedule of Events. Twelve-lead ECGs and QT/QTc 
intervals will be assessed at Screening and at Visit 1 (Day 1) and Visit 5 (Day 85). Both 
ARCI-M questionnaire and QT/QTc intervals will be assessed on Visit 1 (Day 1) prior to 
treatment and between 2.5 and 3.5 hours after the first dose of JBT-101, when plasma 
concentrations of JBT-101 should be about maximal. 


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Blood and urine laboratory safety tests, CRP, anti-DNA antibody tests, C3 levels, C4 levels, 
and urine protein/creatinine measurements will be done in central laboratories. A central 
reading center will be used to determine QT/QTc intervals.  
 
Medical History and Use of Contraception 
6.1.1
At Screening, a medical history will be performed and include subject demographics, history 
of SLE including current symptoms and past and present organ involvement, and current 
treatment for SLE. The medical history assessment will include concurrent illnesses, other 
current medications, past medical history, and review of systems. Child-bearing potential, 
last menstrual period and use of effective methods of contraception will be assessed for all 
women at Screening (See Appendix A: Reproductive Potential and Effective Methods of 
Contraception).  Date of last menstrual period will be assessed for all women of childbearing 
potential at Visits 1 (Day 1) and follow-up visits per Table 3, Schedule of Events. Concurrent 
illnesses, current medications, and review of body systems will occur at Visits 1 (Day 1) and 
follow-up visits per Table 3, Schedule of Events. Changes from Visit 1 (Day 1) that constitute 
adverse events should be reported (See Section 7.4, Grading and Attribution of Adverse 
Events).  
 
Concomitant Medication and Treatment History 
6.1.2
A list of current prescription and over-the-counter medications, supplements, and treatments 
for SLE will be obtained. Assessment of eligibility should include a review of permitted and 
prohibited medications. Concomitant medications will be recorded on the concomitant 
medication eCRF from Screening through Visit 6 (Day 113). The medication, dose, 
frequency, route, start date, stop date, and indication will be captured. 
 
Physical Examination 
6.1.3
At Screening, a physical examination is performed to assist in determining the subject’s 
eligibility for the study. Physical examinations also will be performed at Visits 1 (Day 1) and 
follow-up visits per Table 3, Schedule of Events. Physical examinations will include the 
following assessment: alertness and orientation, general appearance, skin, head, eyes, ears, 
nose, and throat, lungs, heart, peripheral pulses, abdomen, musculoskeletal examination 
including tender, swollen, and painful joints, reflexes and lymph nodes. Breast and 
genitourinary examinations are not required. The Visit 1 (Day 1) physical examination will 
be used as baseline. 
 
Vital Signs, Height and Weight Measurements 
6.1.4
Weight, systolic and diastolic BP, pulse (P), respiratory rate (R), and temperature will be 
recorded on Screening and all Visits. Weight will be measured with outerwear, such as coats 
and jackets, and footwear removed. The systolic and diastolic BP will be measured with the 
patient seated and will be recorded after at least 5 minutes of rest. The same arm will be used 
for the measurement throughout the study. Pulse will also be measured with the subject 
seated at rest for at least 5 minutes. Body temperature will be measured on the skin or in the 


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mouth. These vital sign measurements should be obtained prior to taking samples for the 
laboratory testing at the applicable study visits. Standing height is to be measured at Visit 1 
(Day 1) with footwear removed.  
 
Disease Flares for Safety Assessment 
6.1.5
The original lupus instruments to assess disease flares included an evaluation of proteinuria 
based on the protein:creatinine ratio derived from a 24-hour urine.  For this study, the 
protein:creatinine ratio will typically be derived from the spot urine assessment although a 
24-hour urine may be used if the investigator believes it is indicated. 
 SELENA SLEDAI (28 day assessment) 
6.1.5.1
The SELENA SLEDAI is a validated measure of global disease activity in SLE and was 
modified from the original SLEDAI for the SELENA clinical trial in 1997. The original 
SLEDAI was developed in 1992; it includes both subjective reports from patients and 
objective findings from physicians and laboratory data [111]. The SELENA SLEDAI 
modification of the original SLEDAI changed some of the item definitions in order to clarify 
attribution and change in disease activity. These included changes to definitions of seizure 
activity, strokes, serositis, visual disturbances and proteinuria [109, 112]. 
The SELENA SLEDAI is a one page assessment that contains 24 items covering 9 organs 
systems and items are scored as either present or absent. Each item is assigned a weighted 
score. Two systems can score a maximum of 8 points each, 2 systems can score a maximum 
of 4 points each, 3 systems can score a maximum of 2 points each, and 2 systems can score a 
maximum of 1 point each. Scores range from 0–105 points. A score of 6 is considered 
clinically important and may affect the decision to treat. The original SLEDAI captured 
disease activity within the 10 days prior to assessment; however, this time period was 
extended to include the previous 30 days [113, 114]. 
The SLEDAI does not record improving or worsening, and does not include severity within 
an organ system. The sensitivity to change is less for the SLEDAI than other commonly used 
outcome measures in SLE [115]. 
 BILAG 2004 
6.1.5.2
The purpose of the BILAG is to assess organ-specific SLE activity based upon the “intent-to-
treat” premise. The updated version (BILAG 2004) was published in 2005 and is a validated 
measure of disease activity [110]. BILAG 2004 assesses 97 clinical signs, symptoms and 
laboratory parameters important in SLE across nine organ systems. Each symptom is scored 
with respect to severity over the previous 28 days (0 = not present, 1 = improving, 2 = same, 
3 = worse, and 4 = new). The BILAG provides a more sensitive measure of change than the 
SLEDAI [115].  
As above, each question is recorded as 0, 1, 2, 3, or 4. The BILAG 2004 scoring algorithm 
categorizes disease activity into 5 different levels from A–E. Grade A represents very active 
disease likely necessitating immunosuppressive drugs and/or a prednisolone (or equivalent) 


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dose of > 20 mg daily or high-dose anti-coagulation. Grade B represents moderate disease 
activity prompting consideration of a lower dose of corticosteroids, topical steroids, topical 
immunosuppressive drugs, anti-malarial drugs, or nonsteroidal anti-inflammatory drugs. 
Grade C indicates mild stable disease, while grade D implies no disease activity but the 
system had previously been affected. Grade E indicates no current or previous disease 
activity. 
 Flare Definitions 
6.1.5.3
Disease flares will be defined using SELENA SLEDAI Flare Index and BILAG 2004 
assessments. See Section 3.2.3, Safety Endpoints and Section 7.4.1, Grading Criteria for 
definitions and severity grading requirements.  
The SELENA SLEDAI Flare Index categorizes disease flares as mild/moderate or severe, 
based on the highest categories of clinical features recorded or by treatment 
recommendations by the physician.  
SELENA SLEDAI and BILAG 2004 disease flares will be identified centrally at the DAIT-
SACCC.  
 
Blood and Urine Laboratory Safety Tests 
6.1.6
Blood and urine laboratory safety tests will be performed throughout the study. The results of 
all tests will be reviewed by the investigator or qualified designee, who will make judgments 
on the medical significance of any new or worsening abnormal value. The results of clinical 
laboratory tests at Screening will assist in identifying subjects who are not suitable for the 
study due to some biochemical or hematological abnormalities. 
The results of clinical laboratory tests at Visit 1 (Day 1) prior to study drug administration 
will provide a baseline reference against which any fluctuations in these test results during 
the treatment phase of the trial can be compared. Abnormal tests will be reported as adverse 
events if they meet grading and reporting criteria (See Section 7.4, Grading and Attribution 
of Adverse Events). 
All laboratory safety tests will be performed in licensed clinical laboratories, according to the 
study schedule. The majority of the laboratory safety tests will be done centrally.  
 
Electrocardiograms and QT/QTc Intervals 
6.1.7
Twelve-lead ECGs are to be recorded in triplicate at Screening and Visits 1 (Day 1) and 5 
(Day 85). They will be evaluated for medically significant abnormalities and QT/QTc 
intervals. The QT/QTc intervals will be measured at Visit 1 (Day 1) before administration 
and between 2.5 and 3.5 hours after administration of study product in the clinic, at the time 
of maximum JBT-101 concentration in the blood. 
The triplet twelve-lead ECGs are to be recorded at least 5 minutes apart, with the subject in a 
rested supine position for at least 10 minutes. Food and drink should not be consumed by the 


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subject within the 30 minutes before the ECGs are to be recorded. A central reading center 
will be used to read all ECGs and determine QT/QTc intervals. 
Abnormal ECG findings will be reported as adverse events if they meet grading and 
reporting criteria (See Section 7.4, Grading and Attribution of Adverse Events).  
 
ARCI-M Questionnaire 
6.1.8
The ARCI-M questionnaire will be completed by subjects at Visits 1 (Day 1), 3 (Day 29), 
and 5 (Day 85). This is a 12-item yes-no questionnaire developed by the National Institute on 
Drug Abuse, designed to detect the full range of subjective responses experienced by 
marijuana users [106]. The ARCI-M questionnaire has been validated by subjects following 
marijuana smoking. The subject will be asked to fill out the ARCI-M questionnaire prior to 
other interactions with study staff except for Visit 1 (Day 1). At Visit 1 (Day 1), the ARCI-M 
questionnaire will be completed at the beginning of the visit, prior to interaction with study 
staff and between 2.5 and 3.5 hours after administration of study product in the clinic, at the 
time of maximum JBT-101 concentration in the blood. Evidence of psychotropic effects of 
the study drug in subjects will be identified by an increase of ≥ 1 in the ARCI-M score 
assessed longitudinally.  
 
Pregnancies 
6.1.9
The effect of JBT-101 in pregnancy is unknown in women who become pregnant while 
taking JBT-101 or in women who become pregnant by male partners who are taking JBT-
101. The effect of semen from men who are taking JBT-101 on pregnancies is unknown. 
Women subjects of childbearing potential will be instructed to inform the investigator if they 
become pregnant during the study and within 28 days after taking the final dose of study 
drug). If the pregnancy occurs during the treatment period, the investigator should 
discontinue the study drug and instruct the subject to return any unused portion of study drug 
to the study staff. Male subjects whose partner(s) becomes pregnant while the male subject is 
on JBT-101 or within 28 days after the male subject’s last dose of JBT-101 will be instructed 
to inform the investigator of the pregnancy. The investigator will counsel male and female 
subjects about the risks of the pregnancy and the possible effects on the fetus. 
See Section 7.6, Pregnancy Reporting for instructions on how to report pregnancies. 
 
Tuberculosis Screening 
6.1.10
To protect subject safety, subjects should not have untreated tuberculosis during the study 
with JBT-101. For that reason, tests for tuberculosis infection will be part of screening. 
Screening for tuberculosis will be consistent with Centers for Disease Control guidelines 
(http://www.cdc.gov/tb/publications/LTBI/pdf/TargetedLTBI.pdf). All subjects will be tested 
for tuberculosis using a central QuantiFERON® - TB Gold In-Tube Test (QuantiFERON®), 
unless they: 1) have a history of a positive tuberculosis screening test and have completed a 
course of appropriate treatment or have received at least one month of appropriate treatment 
prior to Visit 1 (Day 1) and will continue to receive appropriate treatment during the study; 


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or 2) have a documented negative test for tuberculosis within 12 months prior to Visit 1 (Day 
1).  
 The QuantiFERON® blood test will be run centrally, and that lab will set the cutoff 
for positive test. If the results of the blood test are indeterminate and the subject is 
low risk for tuberculosis in the opinion of the investigator, no further testing is needed 
for eligibility. Otherwise, if a blood test result is indeterminate, the site investigator 
can repeat a blood test and/or do a PPD skin test.  
All subjects with a positive test for tuberculosis are excluded from this study unless they 
have completed a course of appropriate treatment or have received at least one month of 
appropriate treatment prior to Visit 1 (Day 1) and will continue to receive appropriate 
treatment during the study (See Section 4.2, Exclusion Criteria).  
6.2 Assessments of Efficacy 
 
Primary Efficacy Variable: Maximum Daily Pain NRS Score 
6.2.1
Efficacy will be assessed using the maximum daily pain NRS score. The pain NRS is a 
single-item pain numerical rating scale for pain, which is a segmented numerical version of 
the visual analogue scale in which the respondent selects a whole number (0-10) that best 
reflects the intensity of their pain. The numerical rating score is anchored by two terms 
describing average pain severity extremes, one of “no pain” (score of 0) and one of “worst 
pain imaginable” (score of 10). The subjects will be instructed to rank their worst pain in the 
previous day, at about the same time each evening, so the recall period is about 24 hours of 
the most recent entry. The subjects will record their maximum daily pain NRS score each day 
using an IVRS (See Section 3.1, Description of Study Design.).  
Site personnel will receive daily notifications indicating if subjects have not completed their 
most recent pain scores and they will be responsible for contacting subjects to ensure pain 
scores are completed regularly. Sites will also receive monthly reports on overall compliance 
and data integrity. 
 
Secondary Efficacy Variables 
6.2.2
For any individual subject, the same physician should, if possible, assess the 66/68 joint 
count, physician-reported components of the SELENA SLEDAI and BILAG 2004 score, and 
the Physician’s Global Assessment. The SLE Responder Index, SELENA SLEDAI score, 
and BILAG 2004 domain scores will all be calculated centrally at the DAIT-SACCC. 
 Response Categories 
6.2.2.1
Improvement will be computed at the % change in the 7-day average of maximum daily pain 
NRS scores from Visits 1(Day 1) to Visits 3 (Day 29), 4 (Day 57), 5 (Day 85), and 6 (Day 
113).  Categories for 30%, 50%, 75% and 100% improvement will be evaluated. 


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 Pain Categories 
6.2.2.2
Change in pain category from baseline will be determined. Categories of pain, as defined by 
the 7-day average of maximum daily pain NRS, are: 
 No pain: 7-day average of maximum daily pain NRS ≤ 1 
 Mild pain: 7-day average of maximum daily pain NRS > 1 and ≤ 3 
 Moderate pain: 7-day average of maximum daily pain NRS > 3 and ≤ 7 
 Severe pain: 7-day average of maximum daily pain NRS > 7 
Changes in categories of pain, as defined by the 7-day average of maximum daily pain NRS 
are: 
 Major improvement: Improvement by at least two pain categories from baseline 
(Visit 1 (Day 1)) 
 Improvement: Improvement by one pain category from baseline (Visit 1 (Day 1)) 
 No change: No change in pain category from baseline (Visit 1 (Day 1)) 
 Worsening: Worsening by at least one pain category from baseline (Visit 1 (Day 1)) 
 66/68 Joint Count 
6.2.2.3
Determining the number of swollen joints and tender joints is a key component in the clinical 
assessment of active musculoskeletal disease in this study. This study will assess swelling 
and tenderness in 66 and tenderness in 68 joints, which includes joints in the feet. The 66/68 
joint count evaluates the following joints: upper—temporomandibular, sternoclavicular, 
acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal 
and distal interphalangeal; lower—hip, knee, ankle, tarsus, metatarsophalangeal and 
interphalangeal. 
Swelling and tenderness are measured separately. Joint swelling is soft tissue swelling that is 
detectable along the joint margins. When a synovial effusion is present, it invariably means 
the joint is swollen. Neither bony swelling nor deformity of the joints constitutes joint 
swelling. Fluctuation is a characteristic feature of swollen joints and it may influence the 
range of joint movement.  
Joint tenderness is the presence of pain in a joint at rest with pressure or on movement of the 
joint, e.g. on movement of the hip joints. Pressure to elicit tenderness should be exerted by 
the examiner's thumb and index finger sufficient to cause blanching of the examiner's nail 
bed.  
 Disease Activity 
6.2.2.4
See Section 6.1.5.1 and 6.1.5.2 for discussion of the SELENA SLEDAI and BILAG 2004.  
For each, longitudinal changes in total scores will be evaluated.[109-112, 114-116].  


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The Physician’s Global Assessment utilizes a 0 to 3 visual analogue scale that is anchored by 
verbal descriptors as follows; 0 = none, 1 = mild, 2 = moderate, 3 = severe. It is widely used 
in the assessment of disease activity in SLE and provides a simple, broad and accurate 
assessment from the examiner’s perspective [117]. The assessment should be completed as 
soon as possible after all information including laboratory test results for that visit is 
available to the physician. An increase of ≥ 0.3 points is considered worsening of the 
Physician’s Global Assessment [118, 119]. Both mean change from Visit 1 (Day 1) and 
proportion of subjects with worsening of the Physician’s Global Assessment will be tested. 
The SLE Responder Index is a composite index incorporating both the SELENA SLEDAI 
and BILAG indices and the Physician’s Global Assessment [119]. 
 
Patient-reported Outcomes 
6.2.3
All patient-reported outcome questionnaires should be completed by the subject prior to any 
other study-related procedures. 
 Lupus Activity Patient Global Assessment 
6.2.3.1
The Lupus Activity Patient Global Assessment is performed with a visual analogue scale (0 – 
100) in which the subject is asked to indicate how active she/he thinks her disease is. The 
visual analogue scale is anchored by two descriptors; “not active” (score of 0) and 
“extremely active” (score of 100). The recall period is one week.  
 PROMIS Forms 
6.2.3.2
The PROMIS-29 Short Form, Version 2.0, will be used to assess patient-reported state of 
health. The NIH established PROMIS (www.nihpromis.org) to create a standardized and 
uniformly scored set of patient-reported-outcomes instruments. The PROMIS network 
developed item (question) banks and short forms in more than 20 health domains, as well as, 
a set of global health items and 29-, 43-, and 57-item profile measures. The seven domains 
specifically relate to physical, mental and social health and cover the most relevant areas of 
self-reported health for the greatest majority of people with chronic illness: pain, fatigue, 
depression, anxiety, sleep and physical function. The PROMIS-29 includes four items each 
from these seven core PROMIS domains as well as one 10-point rating scale for pain 
intensity. Norm-based scores have been calculated for each domain, such that a score of 50 
represents the mean of the general population (standard deviation = 10). High scores 
represent more of the domain being measured. Thus, on symptom-oriented domains of 
PROMIS-29 (anxiety, depression, fatigue, sleep disturbance, and pain interference), higher 
scores represent worse symptomatology. On the function-oriented domains (physical 
functioning and social role), higher scores represent better functioning.  
The PROMIS-29 includes a single-item pain NRS, which is a segmented numerical version 
of the visual analogue scale in which the respondent selects a whole number (0-10 integers) 
that best reflects the intensity of their pain. The numerical rating score is anchored by two 


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terms describing average pain severity extremes, one of “no pain” (score of 0) and one of 
“worst pain imaginable” (score of 10). The recall period is 7 days.  
The PROMIS Item Bank v2.0 - Cognitive Function instrument is part of PROMIS. The 
PROMIS v2.0 Cognitive Function item bank contains 32 questions to assess adult patient-
perceived functional abilities with regard to cognitive tasks. 
 Fibromyalgia Symptom Scale 
6.2.3.3
The Fibromyalgia Symptom Scale is a modification of the ACR 2010 criteria (Modified 
2011) for fibromyalgia that allows use of the ACR 2010 criteria without the requirement for 
an examiner[107]. The criteria are simple to use and administer. The Widespread Pain Index 
and the Symptom Severity Scale comprised the ACR 2010 criteria. The Symptom Score was 
modified by eliminating the physician’s estimate of the extent of somatic symptoms and 
substituting the sum of 3 specific self-reported symptoms. Then, a 0–31 Fibromyalgia 
Symptom Scale was created by adding the Widespread Pain Index to the modified Symptom 
Severity Scale. The criteria properly identify diagnostic groups based on fibromyalgia 
severity variables. A Fibromyalgia Symptom Scale score = 13 best separates criteria positive 
and criteria negative patients, classifying 93.0% correctly, with a sensitivity of 96.6% and a 
specificity of 91.8%. 
 
Treatment Satisfaction Survey 
6.2.4
At the end of treatment, both the subject and physician will complete separately a survey 
asking what treatment assignment they think that subject received (JBT-101, placebo, or 
can’t tell), whether the subject received benefit from the assigned treatment (yes or no), and 
whether the subject or physician would chose to continue that treatment (yes or no). 
6.3 Mechanistic Studies 
 
Biomarkers of Inflammation 
6.3.1
Specimens for evaluation of biomarkers of active inflammation in SLE (detailed below) will 
be collected at Visits 1 (Day 1) and follow-up visits per Table 3, Schedule of Events. 
 C-reactive Protein 
6.3.1.1
C-reactive protein levels will be measured in peripheral blood. Elevated CRP levels have 
been reported in SLE, although levels do not always correlate with disease activity [120]. 
 Pro-Inflammatory Cytokines 
6.3.1.2
Production of pro-inflammatory cytokines, IFNα, IFNγ, IL-6, TNFα and IL-1β, in peripheral 
blood will be evaluated in vitro in unstimulated and stimulated cell cultures. Supernatants 
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 Type 1 IFN gene signature 
6.3.1.3
Type 1 IFN gene signature will be assessed from whole blood RNA.  Gene expression will 
be analyzed using published data for IFNα inducible genes [121] and second generation 
modular transcriptional repertoire analyses [122].  
 
Metabolipidomic Profile 
6.3.2
Metabolipidomic profiles will be assessed in plasma at Visit 1 (Day 1) and Visit 2 (Day 15). 
At Visit 1 (Day 1), metabolipidomic profiles will be assessed before and 2.5 to 3.5 hours 
after study product is administered. The metabolipidomic profiles will include measurement 
of certain SPMs, anti-inflammatory eicosanoids, and pro-inflammatory eicosanoids. As 
possible, the blood samples for metabolipidomic profile testing should be collected at least 2 
hours after the last solid meal.  
 
JBT-101 Plasma Concentrations and Metabolites 
6.3.3
Plasma concentrations of JBT-101 and its metabolites will be measured at Visit 1 (Day 1) 
and Visit 2 (Day 15). At Visit 1 (Day 1), plasma levels of JBT-101 and metabolites will be 
measured before and 2.5 to 3.5 hours after study product is administered. 
JBT-101 plasma concentrations and metabolites will be measured using validated assays 
[101]. Collection at 3 hours after dosing should provide concentrations near peak plasma 
concentrations and first pass metabolites.  
 
Optional Unspecified Future Studies 
6.3.4
If the subject provides written informed consent, extra serum and leftover specimens derived 
from blood samples, including serum, plasma, mRNA, whole blood cells, and whole blood 
cells culture supernatants, will be stored for future unspecified studies related to JBT-101, the 
immune system, or SLE.  
In addition, if appropriate consents are given, peripheral blood mononuclear cell (PBMC) 
samples for future, unspecified, IRB approved studies related to JBT-101, the immune 
system, or SLE will be collected at Visit 1 (Day 1) and follow-up visits per Table 3, Schedule 
of Events.  
 
Blood Draw Prioritization 
6.3.5
The volume of blood to be drawn at a given visit is limited under the following situations: 
 Should the subject have been experiencing severe anemia (hemoglobin < 8g/dL) or 
have poor venous access, the blood draw limit is 30 mL.   
 Should the subject have been experiencing moderate-severe anemia (hemoglobin 8-9 
g/dL), the blood draw limit is 50 mL. 


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 In any patient whose clinical condition might be adversely affected by removal of the 
volumes required for this protocol, for example, patients with significant anemia (as 
noted above) or compromised cardiac output, investigators should consider further 
limiting the volume of blood withdrawn for research purposes. 
The priority of samples to collect is as follows:  
NOTE: Whole blood for pro-inflammatory cytokines should always be drawn first in the 
TruCulture tubes. 
 Whole blood: TruCulture tubes, pro-inflammatory cytokines (3 mL) 
 Safety draws: chemistries, hematologies, anti-dsDNA, C3, C4, CRP (8-11 mL, 
depending on visit) 
 Blood/plasma: metabolipidomic profile, and JBT-101 plasma concentrations and 
metabolites (4 mL) (Note: For Visit 1 (Day 1), blood is collected twice; pre-dose and 
post-dose; the post-dose blood draw can be eliminated if indicated) 
 RNA: Type 1 IFN gene signature (2.5 mL) 
 Serum for future use (5 mL; limit to 2 mL if necessary)  
 PBMCs for future use (30 mL; omit totally for severe anemia or poor venous access) 
6.4 Evaluations by Study Visit 
Refer to Table 3, Schedule of Events (below) for a complete listing of evaluations by study 
visit. 
 
Screening Period 
6.4.1
This study will be explained in lay language to each potential participant. Each participant 
will sign an informed consent form before committing to study screening procedures. 
Unless otherwise specified, the screening evaluations must be performed within 42 days prior 
to Visit 1 (Day 1). Screening will take place over multiple days. The 7-day average of 
maximum daily pain NRS score will be calculated by the IVRS to assess eligibility.  
Screening laboratory tests, except HIV, hepatitis, and pregnancy testing, may be repeated to 
establish eligibility within the 42 day window prior to Visit 1 (Day 1), at the investigator’s 
discretion. Subjects who fail screening may be rescreened at a later date, if the investigator 
judges it likely that the reason for failing to meet eligibility criteria is no longer present. 
The following procedures will be performed during the Screening Period: 
 Consent presentation and consent signing 
 Consent for optional storage and future use of de-identified left-over blood-derived 
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 Demographics 
 Medical history 
 Confirm date of last menstrual period in all women and assess birth control status in 
women of childbearing potential 
 Record prior medications 
 Vital signs: weight, blood pressure, pulse, respiratory rate, and temperature 
 Physical examination 
 Physician assessments (all scores will be calculated centrally)  
o SELENA SLEDAI and Flare Index 
o BILAG 2004 
o Physician’s Global Assessment 
 Patient-reported outcomes 
o Fibromyalgia Symptom Scale 
o Complete the subject registration for the IVRS and give him/her the envelope that 
includes subject-specific username and password, instructions for daily entries, 
and information on system support. Each subject should be instructed on the use 
of the IVRS and competency evaluated before leaving the clinic. 
 Blood tests 
o Infectious disease screen including HIV antibody, hepatitis B surface antigen, 
hepatitis C virus (HCV) antibody with HCV RNA (PCR) if antibody positive 
(unless documented as negative within 12 weeks prior to the Screening visit) 
o QuantiFERON® blood test for tuberculosis, for subjects who do not have a 
history of prior positive tuberculosis screening test and optional for subjects 
who have a documented negative result within 12 months prior to Visit 1 (Day 
1) 
o Follicle stimulating hormone, for women > 45 and ≤ 55 years of age with no 
menses for < 2 years 
o Hematology: CBC with differential cell count and platelets 
o Chemistry: Complete metabolic panel, including electrolytes, renal function, 
and liver function tests 
o Anti-dsDNA antibody titers, C3, and C4 levels 
 Urine tests 
o Urinalysis: microscopic evaluation, and spot protein/creatinine  


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o Urine βHCG or blood drawn pregnancy test in women of childbearing 
potential 
 Triplet 12 lead ECGs for medically significant abnormalities and QT/QTc interval. 
 Evaluation of Eligibility and Randomization   
6.4.1.1
The subject’s average of 7-day maximum daily pain NRS score will be computed by the 
IVRS and reported to site personnel.   
If the average is ≥ 4, and the subject meets other eligibility criteria for enrollment, then 
proceed as follows:  
 Instruct the subject to continue to record maximum daily pain NRS score using the 
IVRS. Randomization will not be allowed, if compliance with reporting falls below 
67% during the Screening period. 
 Schedule Visit 1 (Day 1) (within 42 days of 1st Screening assessment)  
o Randomizations must occur at least 7 days prior to Visit 1 to ensure that drug 
will be available on site for Visit 1. 
o Instruct eligible subjects to hold short-acting analgesics for 6 hours and 
NSAIDs and long-acting analgesics for 12 hours prior to Visit 1 (Day 1). 
 Randomize the subject (ensure sufficient time for shipment of study drug prior to the 
scheduled Visit 1 (Day 1)) 
If the subject is not eligible, inform the subject and let them know IVRS will no longer 
accept daily entries. 
 
Treatment Period 
6.4.2
 Visit 1 (Day 1) 
6.4.2.1
The following procedures will be performed: 
 Verify eligibility criteria 
 Patient-reported outcomes, before other interactions with study staff 
o ARCI-M questionnaire (Pre-Dose) 
o Lupus Activity Patient Global Assessment 
o PROMIS-29 Short Form 
o PROMIS Item Bank v2.0 - Cognitive Function 
o Fibromyalgia Symptom Scale 
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 Record prior medications  
 Vital signs: Height, weight, blood pressure, pulse, respiratory rate, and temperature 
 Physical examination 
 Physician assessments (all scores will be calculated centrally) 
o 66/68 joint count 
o SELENA SLEDAI and Flare Index  
o BILAG 2004 
o Physician’s Global Assessment 
 AE monitoring 
 Before study product administration 
o Blood tests 
 Hematology: CBC with differential cell count and platelets 
 Chemistry: Complete metabolic panel, including electrolytes, renal 
function, and liver function tests 
 CRP 
 Anti-dsDNA antibody titers, C3, and C4 levels 
o Blood draws for mechanistic studies 
 Whole blood: TruCulture tubes; pro-inflammatory cytokines 
 Plasma: metabolipidomic profile, and JBT-101 plasma concentrations and 
metabolites; sampled ≥ 2 hours after last solid meal, if possible.  
 RNA: Type 1 IFN gene signature  
 Serum: future use  (if subject provided written consent)  
 PBMC: future use (if subject provided written consent) 
 Urine tests before study product administration  
o Urinalysis: microscopic evaluation, and spot protein/creatinine  
o Urine βHCG pregnancy test in women of childbearing potential 
 Triplet 12 lead ECGs for medically significant abnormalities and QT/QTc interval prior 
to study product administration 
 Dispense study product according to randomization schedule. Women of child bearing 
potential must have negative urine βHCG pregnancy test prior to dispensing study 
product 
 Administer study product in clinic and record time of dose 


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 Observe subject for at least 30 minutes in clinic, until stable in the judgment of the 
investigator 
 2.5 to 3.5 hours after study product administration 
o ARCI-M questionnaire (Post-Dose) 
o Triplet 12 lead ECGs for QT/QTc interval 
o Blood draws for mechanistic studies 
 Plasma: metabolipidomic profile, and JBT-101 plasma concentrations 
and metabolites; sampled ≥ 2 hours after last solid meal, if possible   
 Reminders: 
o Remind subjects to bring the bottles of study drug with them to their next visit. 
o Remind subject to refrain from taking morning dose before Visit 2.  Subjects with 
visits after 2 PM will be instructed to take their morning dose.  This is being done 
to measure trough plasma concentration of JBT-101 at specified visits. 
 Visit 2 (Day 15 ± 3 days) 
6.4.2.2
The following procedures will be performed: 
 Record concomitant medications  
 Vital signs: weight, blood pressure, pulse, respiratory rate, and temperature 
 AE monitoring 
 Blood tests 
o Hematology: CBC with differential cell count and platelets 
o Chemistry: Complete metabolic panel, including electrolytes, renal function, 
and liver function tests 
 Blood draws for mechanistic studies 
o Plasma: metabolipidomic profile, and JBT-101 plasma concentrations and 
metabolites; sampled ≥ 2 hours after last solid meal, if possible  
o PBMC: future use (if subject provided written consent) 
 
Count and record number of capsules the subject has remaining 
 Instruct subjects to hold short-acting analgesics for 6 hours and NSAIDs and long-
acting analgesics for 12 hours prior to the assessments at Visit 3 (Day 29) and remind 
them to bring the bottles of study drug with them to their next visit. 
 Visit 3 (Day 29 ± 3 days) 
6.4.2.3
The following procedures will be performed: 


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 Patient-reported outcomes, before other interactions with study staff 
o ARCI-M questionnaire 
o Lupus Activity Patient Global Assessment 
o PROMIS-29 Short Form 
o PROMIS Item Bank v2.0 - Cognitive Function 
 Confirm date of last menstrual period in women of childbearing potential 
 Record concomitant medications  
 Vital signs: weight, blood pressure, pulse, respiratory rate, and temperature 
 Physical examination 
 Physician assessments (all scores will be calculated centrally) 
o 66/68 joint count 
o SELENA SLEDAI and Flare Index  
o BILAG 2004 
o Physician’s Global Assessment 
 AE monitoring 
 Blood tests 
o Hematology: CBC with differential cell count and platelets 
o Chemistry: Complete metabolic panel, including electrolytes, renal function, 
and liver function tests 
o CRP 
o Anti-dsDNA antibody titers, C3, and C4 levels 
  Blood draws for mechanistic studies 
o Whole blood: TruCulture tubes; pro-inflammatory cytokines 
o RNA: Type 1 IFN gene signature  
o Serum: future use  (if subject provided written consent) 
 Urine tests 
o Urinalysis: microscopic evaluation, and spot protein/creatinine  
o Urine βHCG pregnancy test in women of childbearing potential 
 Collect returned study product and count and record number of returned capsules 
 Dispense study product according to randomization schedule. Women of child bearing 
potential must have negative urine βHCG pregnancy test prior to dispensing study 
product. 


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 Instruct subjects to hold short-acting analgesics for 6 hours and NSAIDs and long-acting 
analgesics for 12 hours prior to the assessments at Visit 4 (Day 57) and remind them to 
bring the bottles of study drug with them to their next visit. 
 Visit 4 (Day 57 ± 3 days) 
6.4.2.4
The following procedures will be performed: 
 Patient-reported outcomes, before other interactions with study staff 
o Lupus Activity Patient Global Assessment 
o PROMIS-29 Short Form 
o PROMIS Item Bank v2.0 - Cognitive Function 
 Confirm date of last menstrual period in women of childbearing potential 
 Record concomitant medications  
 Vital signs: weight, blood pressure, pulse, respiratory rate, and temperature 
 Physical examination 
 Physician assessments (all scores will be calculated centrally) 
o 66/68 joint count 
o SELENA SLEDAI and Flare Index  
o BILAG 2004 
o Physician’s Global Assessment 
 AE monitoring 
 Blood tests 
o Hematology: CBC with differential cell count and platelets 
o Chemistry: Complete metabolic panel, including electrolytes, renal function, 
and liver function tests 
o Anti-dsDNA antibody titers, C3, and C4 levels 
 Urine tests 
o Urinalysis: microscopic evaluation, and spot protein/creatinine  
o Urine βHCG pregnancy test in women of childbearing potential 
 Collect returned study product and count and record number of returned capsules 
 Dispense study product according to randomization schedule. Women of child 
bearing potential must have negative urine βHCG pregnancy test prior to dispensing 
study product. 


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 Instruct subjects to hold short-acting analgesics for 6 hours and NSAIDs and long-
acting analgesics for 12 prior to the assessments at Visit 5 (Day 85) and remind them 
to bring the bottles of study drug with them to their next visit. 
 Visit 5 (Day 85 ± 3 days) 
6.4.2.5
The following procedures will be performed: 
 Patient-reported outcomes, before other interactions with study staff 
o ARCI-M questionnaire 
o Lupus Activity Patient Global Assessment 
o PROMIS-29 Short Form 
o PROMIS Item Bank v2.0 - Cognitive Function 
o Fibromyalgia Symptom Scale 
o Treatment Satisfaction Survey 
 Confirm date of last menstrual period in women of childbearing potential 
 Record concomitant medications  
 Vital signs: weight, blood pressure, pulse, respiratory rate, and temperature 
 Physical examination 
 Physician assessments (all scores will be calculated centrally) 
o 66/68 joint count 
o SELENA SLEDAI and Flare Index  
o BILAG 2004 
o Physician’s Global Assessment 
o Treatment Satisfaction Survey 
 AE monitoring 
 Blood tests 
o Hematology: CBC with differential cell count and platelets 
o Chemistry: Complete metabolic panel, including electrolytes, renal function, 
and liver function tests 
o CRP 
o Anti-dsDNA antibody titers, C3, and C4 levels 
 Blood draws for mechanistic studies 
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o RNA: Type 1 IFN gene signature 
o Serum: future use  (if subject provided written consent) 
o PBMC: future use (if subject provided written consent) 
 Urine tests 
o Urinalysis: microscopic evaluation, and spot protein/creatinine  
o Urine βHCG pregnancy test in women of childbearing potential 
 Triplet 12 lead ECGs for medically significant abnormalities and QT/QTc interval 
 Collect returned study product and count and record number of returned capsules. If 
study product is not returned, subjects should be instructed not to take any additional 
study drug and arrangements should be made for the subject to return the study 
product as soon as possible. 
 Instruct subjects to hold short-acting analgesics for 6 hours and NSAIDs and long-
acting analgesics for 12 hours prior to the assessments at Visit 6 (Day 113). 
 Visit 6 (Day 113 ± 3 days) 
6.4.2.6
The following procedures will be performed: 
 Patient-reported outcomes, before other interactions with study staff 
o Lupus Activity Patient Global Assessment 
o PROMIS-29 Short Form 
o PROMIS Item Bank v2.0 - Cognitive Function 
o Fibromyalgia Symptom Scale 
 Confirm date of last menstrual period in women of childbearing potential 
 Record concomitant medications  
 Vital signs: weight, blood pressure, pulse, respiratory rate, and temperature 
 Physical examination 
 Physician assessments (all scores will be calculated centrally) 
o 66/68 joint count 
o SELENA SLEDAI and Flare Index 
o BILAG 2004 
o Physician’s Global Assessment 
 AE monitoring 
 Blood tests 
o Hematology: CBC with differential cell count and platelets 


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o Chemistry: Complete metabolic panel, including electrolytes, renal function, 
and liver function tests 
o CRP 
o Anti-dsDNA antibody titers, C3, and C4 levels 
 Blood draws for mechanistic studies 
o Whole blood: TruCulture tubes; pro-inflammatory cytokines 
o RNA: Type 1 IFN gene signature  
o Serum: future use  (if subject provided written consent) 
o PBMC: future use (if subject provided written consent) 
 Urine tests 
o Urinalysis: microscopic evaluation, and spot protein/creatinine  
o Urine βHCG pregnancy test in women of childbearing potential  
 Early Withdrawal Visit 
6.4.2.7
If a subject is withdrawn from the study or discontinues the study on or before Visit 1 (Day 
1), no additional procedures should be done. If withdrawal or discontinuation is after Visit 1 
(Day 1) and at the time of a scheduled visit, the procedures scheduled for that visit should be 
done and an Early Withdrawal Visit should be done 28 ± 3 days after the last dose of study 
product, unless consent is withdrawn. If withdrawal or discontinuation is after Visit 1 (Day 1) 
and not at the time of a scheduled visit, then an unscheduled visit should be done as soon as 
possible and include evaluations and laboratory safety testing as appropriate for the reasons 
for withdrawal or discontinuation, and an Early Withdrawal Visit should be done 28 ± 3 days 
after the last dose of study product, unless consent is withdrawn. 
The following procedures will be performed: 
 Patient-reported outcomes, before other interactions with study staff 
o ARCI-M questionnaire 
o Lupus Activity Patient Global Assessment 
o PROMIS-29 Short Form 
o PROMIS Item Bank v2.0 - Cognitive Function 
o Fibromyalgia Symptom Scale 
o Treatment Satisfaction Survey, if withdrawal is prior to Visit 5 (Day 85) 
 Confirm date of last menstrual period in women of childbearing potential 
 Record concomitant medications  
 Vital signs: weight, blood pressure, pulse, respiratory rate, and temperature 


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 Physical examination 
 Physician assessments (all scores will be calculated centrally) 
o 66/68 joint count 
o SELENA SLEDAI and Flare Index 
o BILAG 2004 
o Physician’s Global Assessment  
o Treatment Satisfaction Survey, if withdrawal is prior to Visit 5 (Day 85) 
 AE monitoring 
 Blood tests 
o Hematology: CBC with differential cell count and platelets 
o Chemistry: Complete metabolic panel, including electrolytes, renal function, 
and liver function tests 
o CRP 
o Anti-dsDNA antibody titers, C3, and C4 levels 
 Blood draws for mechanistic studies 
o Whole blood: TruCulture tubes; pro-inflammatory cytokines  
o RNA: Type 1 IFN gene signature 
o Serum: future use  (if subject provided written consent) 
o PBMC: future use (if subject provided written consent) 
 Urine tests 
o Urinalysis: microscopic evaluation, and spot protein/creatinine  
o Urine βHCG pregnancy test in women of childbearing potential  
 Collect any remaining study product and count and record number of returned 
capsules 
 
Visit Windows 
6.4.3
All study procedures should be performed within the designated visit window (i.e.,  3 days) 
for each scheduled visit (see Table 3, Schedule of Events (below)). Whenever possible, a 
rescheduled visit should remain within the designated visit window. The coordinating center 
should be notified if the study procedures for any scheduled visit cannot be performed within 
the designated window. 


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Unscheduled Visits 
6.4.4
Subjects will be instructed to call study personnel to report any abnormalities during the 
intervals between study visits and to come to the study site if medical evaluation is needed 
and the urgency of the situation permits. An unscheduled visit will be made, if necessary, for 
medical issues that arise between study visits. For emergency and other unscheduled visits to 
a medical facility other than the study site, medical records will be obtained by the site 
investigator or qualified designee. 
If an unscheduled visit is necessary to assess the subject for safety purposes, the following 
evaluations should be obtained, at a minimum: 
 Record concomitant medications  
 Vital signs: weight, blood pressure, pulse, respiratory rate, and temperature 
 Physical examination as relevant to the reason for the unscheduled visit 
 AE monitoring 
 Urine βHCG pregnancy test in women of childbearing potential  
 Laboratory tests as relevant to the reason for the unscheduled visit 
 


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Table 3: Schedule of Events (Screening through Post Treatment) 
 
 
 
 
Treatment 
Post Treatment 
Unscheduled 
Visit 
Time Point 
ScreeningA 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Early 
Withdrawal 
Visit (if 
needed) 
Visit Windows (Days) 
Up to -42 
Day 1 
Day 15 ± 3  
Day 29 ± 3 
Day 57 ± 3 
Day 85 ± 3 
Day 113 ± 3  
Clinical Blood Draw (mL) 
20-23 
11 
8 
11 
11 
11 
11 
11 
11 
Research Blood Draw (mL) 
NA 
48.5 
34 
10.5 
NA 
40.5 
40.5 
40.5 
NA 
Visit Draw Total (mL) 
20-23 
59.5 
42 
21.5 
11 
51.5 
51.5 
51.5 
11 
General Assessments 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Demographics  
X 
 
 
 
 
 
 
 
 
 Verify Eligibility Criteria 
 
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
Assess reproductive and birth control status 
X 
 
 
 
 
 
 
 
 
Last menstrual period 
X 
XB 
 
XB 
XB 
XB 
XB 
XB 
 
Prior/ Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination 
X 
X 
 
X 
X 
X 
X 
X 
X 
Register subject in IVRS system 
X 
 
 
 
 
 
 
 
 
Randomization, prior to Day 1 
X 
 
 
 
 
 
 
 
 
Vital signs: Weight, blood pressure and pulseC, 
respiratory rate, and temperature (& height at Visit 1)  
X             
X 
X 
X 
X 
X 
X 
X 
X 
Adverse event monitoring 
 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead electrocardiograms, QT/QTc analyses 
X 
XD 
 
 
 
X 
 
 
 
Patient Reports 
Maximum daily pain NRS scoreE 
Reported daily by subject via IVRS 
Review reported pain NRS scores 
Site personnel will review subject reported data each week 
Addiction Research Center Inventory-Marijuana 
(ARCI-M) 
 
XD 
 
X 
 
X 
 
XF 
 
Lupus Activity Patient Global Assessment 
 
X 
 
X 
X 
X 
X 
X 
 
PROMIS-29 Short Form 
 
X 
 
X 
X 
X 
X 
X 
 
PROMIS Item Bank v2.0 - Cognitive Function 
 
X 
 
X 
X 
X 
X 
X 
 
Fibromyalgia Symptom Scale 
X 
X 
 
 
 
X 
X 
X 
 
Treatment Satisfaction SurveyG 
 
 
 
 
 
X 
 
XG 
 
Physician Assessment 
66/68 Joint Count  
 
X 
 
X 
X 
X 
X 
X 
 
SELENA SLEDAI 
X 
X 
 
X 
X 
X 
X 
X 
 
BILAG 2004 
X 
X 
 
X 
X 
X 
X 
X 
 
Physician’s Global Assessment 
X 
X 
 
X 
X 
X 
X 
X 
 
Treatment Satisfaction Survey 
 
 
 
 
 
X 
 
XG 
 


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A. The screening period can be any duration between 7 and 42 days prior to Visit 1 (Day 1), provided the duration is adequate to ensure the subject meets all inclusion and 
exclusion criteria and drug can be shipped to the site on time for that subject. Screening can take place over more than one visit to the clinic. Screening laboratory tests, 
other than HIV, hepatitis, or pregnancy testing, can be repeated at the investigator’s discretion. 
B. 
For women of childbearing potential.  
C. 
Seated (> 5 minutes) blood pressure and pulse.  
D. Will be measured at Visit 1 (Day 1) both before and 2.5 to 3.5 hours after administration of study product in the clinic.  
E. 
Record within 24 hours after most recent diary entry to prevent reporting of the same data. 
F. 
ARCI-M will be assessed at the Early Withdrawal Visit if a subject is withdrawn from the study or discontinues the study prior to Visit 6 (Day 113). 
G. At the end of treatment, both the subject and physician will complete a Treatment Satisfaction Survey. If a subject withdrawals from treatment prior to Day 85, the 
Treatment Satisfaction Survey will be completed at the Early Withdrawal Visit.   
H. Infectious disease screen including HIV antibody, hepatitis B surface antigen, hepatitis C virus (HCV) antibody with HCV RNA (PCR) if antibody positive (unless 
documented as negative within 12 weeks prior to the Screening visit). 
 
 
Treatment 
Post Treatment 
Unscheduled 
Visit 
Time Point 
ScreeningA 
1 
2 
3 
4 
5 
6 
Early 
Withdrawal 
Visit (if 
needed) 
Visit Windows (Days) 
Up to -42 
Day 1 
Day 15 ± 3  
Day 29 ± 3 
Day 57 ± 3 
Day 85 ± 3 
Day 113 ± 3 
Clinical Laboratory Assessments 
Infectious Disease: Hepatitis B and C tests, human 
immunodeficiency virusH 
X 
 
 
 
 
 
 
 
 
Tuberculosis screening testI  
X 
 
 
 
 
 
 
 
 
Follicle stimulating hormoneJ 
X 
 
 
 
 
 
 
 
 
Hematology: CBC with differential cell count and 
platelets 
X 
XL 
X 
X 
X 
X 
X 
X 
XM 
Chemistry: Complete metabolic panelK 
X 
XL 
X 
X 
X 
X 
X 
X 
XM 
Anti-dsDNA antibodies, C3, C4 
X 
XL 
 
X 
X 
X 
X 
X 
XM 
C-reactive protein 
 
XL 
 
X 
 
X 
X 
X 
XM 
Urinalysis: Microscopic, & spot protein/creatinine 
X 
XL 
 
X 
X 
X 
X 
X 
XM 
Urine pregnancy testB 
XN 
XL 
 
X 
X 
X 
X 
X 
XM 
Blood Draws for Mechanistic Specimen Collection 
Whole blood Pro-Inflammatory Cytokine Studies 
(3mL) 
 
XL 
 
X 
 
X 
X 
X 
 
Plasma: Metabolipidomic profile/JBT-101 plasma 
concentrations and metabolites (4mL) 
 
XDL 
X 
 
 
 
 
 
 
RNA: IFN signature (2.5mL) 
 
XL 
 
X 
 
X 
X 
X 
 
Serum: Future UseO (5mL) 
 
XL 
 
X 
 
X 
X 
X 
 
PBMC: Future UseO (30mL) 
 
XL 
X 
 
 
X 
X 
X 
 
Study Product 
Dispense study productP 
 
X 
 
X 
X 
 
 
 
 
Administer study product in clinicQ 
 
X 
 
 
 
 
 
 
 
Study product pill count 
 
 
X 
X 
X 
X 
X  
(if needed) 
X  
(if needed) 
 


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I. 
TB testing will be done centrally using a QuantiFERON® blood test. Testing is optional if skin or blood testing was done within 12 months before Visit 1 (Day 1), with 
documented negative results. See section 6.1.10 Tuberculosis Screening for repeat testing options.   
J. 
For women > 45 and ≤ 55 years of age with no menses for < 2 years. 
K. Complete metabolic panel includes at least glucose, urea nitrogen, creatinine, sodium, potassium, chloride, carbon dioxide, calcium, total protein, albumin, total 
bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and calculated glomerular filtration rate. 
L. 
Blood and urine tests will be performed prior to study product administration. 
M. Laboratory tests as relevant to the reason for the unscheduled visit.  
N. Pregnancy test at screening can be done through a blood or urine test.   
O. If the subject provides written informed consent, blood samples, including serum, plasma, mRNA, and PBMC culture supernatants, will be stored for future unspecified 
studies related to JBT-101 or SLE. 
P. 
Study product will be dispensed in women of childbearing potential only if urine pregnancy test is negative. 
Q. The first dose of study product at Visit 1 (Day 1) will be taken in clinic from the dispensed study product. The subject will be observed for 30 minutes or until stable in 
the judgment of the investigator, whichever is longer. 
 
 
 


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7 SAFETY MONITORING AND REPORTING 
7.1 Overview 
This section defines the types of safety data that will be collected under this protocol and 
outlines the procedures for appropriately collecting, grading, recording, and reporting those 
data. Adverse events that are classified as serious according to the definition of health 
authorities must be reported promptly (per Section 7.5.4, Reporting of Adverse Events to 
IRBs) to the DAIT/NIAID.  Appropriate notifications will also be made to site principal 
investigators, Institutional Review Boards (IRBs), and health authorities.  
Information in this section complies with ICH Guideline E2A: Clinical Safety Data 
Management: Definitions and Standards for Expedited Reporting, ICH Guideline E-6: 
Guideline for Good Clinical Practice, 21CFR Parts 312 and 320, and applies the standards set 
forth in the National Cancer Institute (NCI), Common Terminology Criteria for Adverse 
Events (CTCAE), Version 4 : http://ctep.cancer.gov/reporting/ctc.html. 
7.2 Definitions 
 
Adverse Event (AE) 
7.2.1
Any untoward or unfavorable medical occurrence associated with the subject’s participation 
in the research, whether or not considered related to the subject’s participation in the research 
(modified from the definition of adverse events in the 1996 International Conference on 
Harmonization E-6 Guidelines for Good Clinical Practice) (from OHRP "Guidance on 
Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and 
Adverse Events (1/15/07)" http://www.hhs.gov/ohrp/policy/advevntguid.html#Q2 )  
 Suspected Adverse Reaction (SAR)  
7.2.1.1
Any adverse event for which there is a reasonable possibility that the investigational drug [or 
investigational study therapy regimen] caused the adverse event. For the purposes of safety 
reporting, ‘reasonable possibility’ means there is evidence to suggest a causal relationship 
between the drug and the adverse event. A suspected adverse reaction implies a lesser degree 
of certainty about causality than adverse reaction, which means any adverse event caused by 
a drug (21 CFR 312.32(a)). 
 
Unexpected Adverse Event  
7.2.2
An adverse event or suspected adverse reaction is considered “unexpected” if it is not listed 
in the Investigator Brochure or is not listed at the specificity, severity or rate of occurrence 
that has been observed; or is not consistent with the risk information described in the general 
investigational plan or elsewhere in the IND.  


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 “Unexpected” also refers to adverse events or suspected adverse reactions that are 
mentioned in the Investigator Brochure or package insert as occurring with a class of drugs 
or as anticipated from the pharmacological properties of the drug, but are not specifically 
mentioned as occurring with the particular drug under investigation (21 CFR 312.32(a)).  
 
Serious Adverse Event (SAE) 
7.2.3
An adverse event or suspected adverse reaction is considered “serious” if, in the view of 
either the investigator or Sponsor [DAIT/NIAID], it results in any of the following outcomes 
(21 CFR 312.32(a)): 
 Death. 
 A life-threatening event: An AE or SAR is considered “life-threatening” if, in the 
view of either the investigator or DAIT/NIAID, its occurrence places the subject at 
immediate risk of death. It does not include an AE or SAR that, had it occurred in a 
more severe form, might have caused death.  
 Inpatient hospitalization or prolongation of existing hospitalization. 
 Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions. 
 Congenital anomaly or birth defect.  
 Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed above. 
Elective hospitalizations or hospital admissions for the purpose of conduct of protocol 
mandated procedures are not to be reported as an SAE unless hospitalization is prolonged 
due to complications. 
 
Adverse Events of Special Interest (AESI) 
7.2.4
Adverse Events of Special Interest will be collected and reported to the IND sponsor 
(NIAID), the NIAID Autoimmune DSMB, and to the manufacturer (Corbus Pharmaceuticals 
Holdings, Inc.).  
 QTc prolongation > 500 msec total duration and > 60 msec from Visit 1 (Day 1) QTc 
interval prior to study drug administration 
 Severe disease flares by SELENA SLEDAI Flare Index and/or a new BILAG A score 
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 Aspartate aminotransferase or alanine aminotransferase ≥ 3 x upper limit of normal 
and total bilirubin > 1.5 x the upper limit of normal, present on repeat testing 
If an event meets any of the above AESI categories, regardless of the relationship of the 
event to the study drug or severity, the event must be reported to the IND sponsor 
(DAIT/NIAID) as described in Section 7.5.2, Reporting of AESIs to DAIT/NIAID and to 
Corbus Pharmaceuticals Holdings, Inc. as described in Section 7.5.5, Reporting of Safety 
Information (AEs, SAEs and AESIs) to Corbus. 
7.3 Collection and Recording of Adverse Events 
 
Collection Period 
7.3.1
AEs of Grade 2 and above will be collected from time of signing of informed consent until 
the subject completes study participation, or until 30 days after he/she prematurely withdraws 
(without withdrawing consent), or is withdrawn from the study. See Section 7.4, Grading 
and Attribution of Adverse Events for grading criteria. 
 
Collecting Adverse Events 
7.3.2
Adverse events (including SAEs) may be discovered through any of these methods: 
 Observing the subject. 
 Interviewing the subject [e.g., using a checklist, structured questioning, diary, etc.]. 
 Receiving an unsolicited complaint from the subject. 
 In addition, an abnormal value or result from a clinical or laboratory evaluation can 
also indicate an adverse event, as defined in Section 7.4, Grading and Attribution of 
Adverse Events. 
 
Recording Adverse Events 
7.3.3
Throughout the study, the investigator will record adverse events and serious adverse events 
as described previously (Section 7.2, Definitions) on the appropriate AE eCRF regardless of 
the relationship to study therapy regimen or study procedure. 
Once recorded, an AE/SAE will be followed until it resolves with or without sequelae, or 
until the end of study participation, whichever occurs first.  End of study participation is the 
final study visit, either at time of study completion or when a subject prematurely withdraws 
or is withdrawn. 


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7.4 Grading and Attribution of Adverse Events 
 
Grading Criteria 
7.4.1
The study site will grade the severity of adverse events experienced by the study subjects 
according to the criteria set forth in the National Cancer Institute’s Common Terminology 
Criteria for Adverse Events (CTCAE) version 4.   This document (referred to herein as the 
NCI-CTCAE manual) provides a common language to describe levels of severity, to analyze 
and interpret data, and to articulate the clinical significance of all adverse events. The NCI-
CTCAE has been reviewed by the Protocol Chairs and has been deemed appropriate for the 
subject population to be studied in this protocol.  
Adverse events will be graded on a scale from 1 to 5 according to the following standards in 
the NCI-CTCAE manual: 
 Grade 1 = mild adverse event. 
 Grade 2 = moderate adverse event. 
 Grade 3 = severe and undesirable adverse event. 
 Grade 4 = life-threatening or disabling adverse event. 
 Grade 5 = death. 
For grading an abnormal value or result of a clinical or laboratory evaluation (including, but 
not limited to, a radiograph, an ultrasound, an electrocardiogram etc.), a treatment-emergent 
adverse event is defined as an increase in grade from baseline or from the last post-baseline 
value that doesn’t meet grading criteria (i.e. Grade 0, normal). Similarly, changes from 
screening to baseline will also be recorded as adverse events, but these are not treatment-
emergent.  If a specific event or result from a given clinical or laboratory evaluation is not 
included in the NCI-CTCAE manual, then an abnormal result would be considered an 
adverse event if changes in therapy or monitoring are implemented as a result of the 
event/result. Grade 2 or higher AEs will be reported on the appropriate AE electronic case 
report (AE eCRF) for this study. 
In addition, for this study, BILAG 2004 disease flares will be graded as follows: 
 Mild SLE flare (Grade 1): New BILAG 2004 grade C in one or more organ systems 
 Moderate SLE flare (Grade 2): New BILAG 2004 grade B in one or more organ 
systems 
 Severe SLE flare (Grade 3): New BILAG 2004 grade A in one organ system 
 Life-threatening or disabling SLE flare (Grade 4): A life-threatening or disabling new 
BILAG 2004 grade A 


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New BILAG flares of Grade 2 or higher (i.e. B or A) will be reported as AEs. Mild/moderate 
SELENA SLEDAI flares should be reported as AEs if changes in therapy or monitoring are 
implemented. Severe SELENA SLEDAI flares should be reported as AEs. Signs, symptoms 
and laboratory test abnormalities reported as part of a SLE flare will not be reported as 
separate AEs. 
 
Attribution Definitions 
7.4.2
The relationship, or attribution, of an adverse event to the study therapy regimen or study 
procedure(s) will initially be determined by the site investigator and recorded on the 
appropriate AE eCRF.  Final determination of attribution for safety reporting will be 
determined by DAIT/NIAID.  The relationship of an adverse event to study therapy regimen 
or procedures will be determined using the descriptors and definitions provided in Table 4 
(below).  
       
Table 4. Attribution of Adverse Events 
Code 
Descriptor 
Relationship (to primary investigational 
product and/or other concurrent mandated 
study therapy or study procedure) 
Unrelated Categories 
1 
Not related 
The adverse event is clearly not related:  there is 
insufficient evidence to suggest a causal 
relationship. 
2 
Unlikely Related 
The adverse event is unlikely related 
 Related Categories 
3 
Possibly Related 
The adverse event has a reasonable possibility to 
be related; there is evidence to suggest a causal 
relationship. 
4 
Probably Related 
The adverse event is likely related 
5 
Related 
The adverse event is clearly related. 
7.5 Reporting of Serious Adverse Events and Adverse Events 
 
Reporting of Serious Adverse Events to DAIT/NIAID 
7.5.1
This section describes the responsibilities of the site investigator to report serious adverse 
events to the sponsor via the DAIT-SACCC.  Timely reporting of adverse events is required 
by 21 CFR and ICH E6 guidelines.  
Site investigators will report all serious adverse events (see Section 7.2.3, Serious Adverse 
Event), regardless of relationship or expectedness within 24 hours of discovering the event. 
For serious adverse events, all requested information on the AE/SAE eCRF will be provided.  
However, unavailable details of the event will not delay submission of the known 


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information.  As additional details become available, the AE/SAE eCRF will be updated and 
submitted. 
For additional information regarding SAE reporting, contact Rho Product Safety:  
Rho Product Safety  
6330 Quadrangle Drive, Suite 500  
Chapel Hill, NC 27517  
Toll-free: 1-888-746-7231  
SAE Fax Line: 1-888-746-3293  
Email: rho_productsafety@rhoworld.com 
 
Reporting AESIs to DAIT/NIAID 
7.5.2
After learning that a participant has experienced an AESI, the investigator or designee is 
responsible for reporting the AESI via an eCRF within 24 hours of becoming aware of the 
event. The initial eCRF should include as much information as possible, but at a minimum 
must include the following: 
 AESI term. 
 Relationship to study medications. 
 Whether or not the event meets serious criteria. 
 Supplementary eCRF pages that are current at the time of AESI reporting: medical 
history, concomitant medications, demographics, study drug administration, death.  
As additional details become available, the eCRF should be updated and submitted. Every 
time the eCRF is submitted, it should be electronically signed by the investigator or sub-
investigator.  
For additional information regarding reporting, contact the DAIT-SACCC. 
 
Reporting to Health Authority 
7.5.3
After an adverse event requiring 24 hour reporting (per Section 7.5.1, Reporting of Serious 
Adverse Events to DAIT/NIAID) is submitted by the site investigator and assessed by 
DAIT/NIAID, there are two options for DAIT/NIAID to report the adverse event to the 
appropriate health authorities: 
 Annual Reporting 
7.5.3.1
DAIT/NIAID will include in the annual study report to health authorities all adverse events 
classified as: 
 Serious, expected, suspected adverse reactions (see Section 7.2.1.1, Suspected 
Adverse Reaction, and Section 7.2.2, Unexpected Adverse Event). 


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 Serious and not a suspected adverse reaction (see Section 7.2.1.1, Suspected Adverse 
Reaction). 
 Pregnancies. 
Note that all adverse events (not just those requiring 24-hour reporting) will be reported in 
the Annual IND Report. 
 Expedited Safety Reporting 
7.5.3.2
This option, with 2 possible categories, applies if the adverse event is classified as one of the 
following: 
Category 1:  Serious and unexpected suspected adverse reaction [SUSAR] (see Section 
7.2.1.1, Suspected Adverse Reaction and Section 7.2.2, Unexpected Adverse Event and 21 
CFR 312.32(c)(1)i).  
The sponsor shall report any suspected adverse reaction that is both serious and unexpected.  
The sponsor shall report an adverse event as a suspected adverse reaction only if there is 
evidence to suggest a causal relationship between the study drug and the adverse event, such 
as: 
1. 
A single occurrence of an event that is uncommon and known to be strongly 
associated with drug exposure (e.g., angioedema, hepatic injury, or Stevens-
Johnson Syndrome) 
2. 
One or more occurrences of an event that is not commonly associated with drug 
exposure, but is otherwise uncommon in the population exposed to the drug (e.g., 
tendon rupture) 
3. 
An aggregate analysis of specific events observed in a clinical trial (such as 
known consequences of the underlying disease or condition under investigation or 
other events that commonly occur in the study population independent of drug 
therapy) that indicates those events occur more frequently in the drug treatment 
group than in a concurrent or historical control group 
Category 2: Any findings from studies that suggests a significant human risk  
The sponsor shall report any findings from other epidemiological studies, analyses of adverse 
events within the current study or pooled analysis across clinical studies or animal or in vitro 
testing (e.g. mutagenicity, teratogenicity, carcinogenicity) that suggest a significant risk in 
humans exposed to the drug that would result in a safety-related change in the protocol, 
informed consent, investigator brochure or package insert or other aspects of the overall 
conduct of the study.   


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DAIT/NIAID shall notify the FDA and all participating investigators of expedited Safety 
Reports within 15 calendar days; unexpected fatal or immediately life-threatening suspected 
adverse reaction(s) shall be reported as soon as possible or within 7 calendar days.  
 
Reporting of Adverse Events to IRBs 
7.5.4
All investigators shall report adverse events, including expedited reports, in a timely fashion 
to their respective IRBs in accordance with applicable regulations and guidelines. All Safety 
Reports to the FDA shall be distributed by DAIT/NIAID or designee to all participating 
institutions for site IRB submission. 
 
Reporting of Safety Information (AEs, SAEs and AESIs) to Corbus 
7.5.5
DAIT/NIAID will report safety information (AEs, SAEs and AESI) to Corbus as follows:  
 For any safety report that meets all of the following criteria of, (i) serious (ii) 
unexpected and (iii) suspected adverse reaction, NIAID will provide to Corbus a 
completed copy of the initial safety report at the time the initial report is submitted to 
FDA. NIAID will provide follow up information to Corbus at the time the follow up 
safety report is submitted to FDA.  
 NIAID will provide monthly listing of safety information (AEs, SAEs, and AESI) to 
Corbus on a monthly basis.  
 NIAID will provide a copy of the IND annual reports at the same time as the 
transmission to the FDA. 
In addition, NIAID will forward the Clinical Study Report as well as any literature articles 
that are a result of the study to Corbus. 
7.6 Pregnancy Reporting 
The investigator shall be informed immediately of any pregnancy in a study subject or a 
partner of a study subject. Pregnancies in women occurring while the subject is on JBT-101 
or within 28 days after the subject’s last dose of JBT-101 are considered expedited reportable 
events.  A pregnant subject shall be instructed to stop taking study medication. The 
investigator shall counsel the subject and discuss the risks of continuing with the pregnancy 
and the possible effects on the fetus. Monitoring of the pregnant subject shall continue until 
the conclusion of the pregnancy. 
The investigator shall report all pregnancies to the DAIT-SACCC within 1 business day of 
becoming aware of the event using the Pregnancy eCRF. All pregnancies identified during 
the study shall be followed to conclusion and the outcome of each must be reported. The 
Pregnancy eCRF shall be updated and submitted to the DAIT-SACCC when details about the 
outcome are available. When possible, similar information shall be obtained for a pregnancy 
occurring in a partner of a study subject. 
Information requested about the delivery shall include: 


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 Gestational age at delivery 
 Birth weight, length, and head circumference 
 Gender 
 Appearance, pulse, grimace, activity, and respiration (APGAR) score at 1 minute, 5 
minutes, and 24 hours after birth, if available 
 Any abnormalities 
All pregnancy complications that result in a congenital abnormality, birth defect, miscarriage, 
and medically indicated abortion - an SAE shall be submitted to the DAIT-SACCC using the 
SAE reporting procedures described above.  
7.7 Reporting of Other Safety Information 
An investigator shall promptly notify the site IRB as well as the DAIT/NIAID when an 
“unanticipated problem involving risks to subjects or others” is identified, which is not 
otherwise reportable as an adverse event. 
7.8 Review of Safety Information 
 
Medical Monitor Review 
7.8.1
The DAIT/NIAID Medical Monitor shall receive monthly reports from the DAIT-SACCC 
compiling new and accumulating information on AEs, SAEs, AESI and pregnancies recorded 
by the study site(s) on appropriate eCRFs. 
In addition, the Medical Monitor shall review and make decisions on the disposition of the 
SAE and pregnancy reports received by the DAIT-SACCC (See Section 7.3, Collection and 
Recording of Adverse Events).   
 
DSMB Review  
7.8.2
 Planned DSMB Reviews  
7.8.2.1
The Data and Safety Monitoring Board (DSMB) shall review safety data at least yearly 
during planned DSMB Data Review Meetings. Data for the planned safety reviews will 
include, at a minimum, a listing of all reported AEs and SAEs.   
The DSMB will be informed of an Expedited Safety Report in a timely manner. 
 Ad hoc DSMB Reviews  
7.8.2.2
In addition to the pre-scheduled data reviews and planned safety monitoring, the DSMB may 
be called upon for ad hoc reviews or emergency meetings (see Section 5.8.3, Safety Stopping 


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Guidance). The DSMB will have the discretion to recommend actions regarding study 
conduct and continuation as a consequence of any planned or unplanned monitoring activity. 
8 STATISTICAL CONSIDERATIONS AND ANALYTICAL PLAN 
8.1 Sample Size and Power 
A total of approximately 100 eligible subjects (approximately 25 per treatment arm) will 
participate in the study.  
The primary hypothesis will be tested using the 3 degree of freedom (df) contrast comparing 
the difference in predicted means from Day 1 to Day 84 for each JBT-101 cohort versus 
placebo, where estimates will be derived from a random regression model (See Section 
8.3.2.1, Primary Efficacy Analysis). The method of Stroup (1999) [123] was used to estimate 
power and sample size. To apply the method, we made reasonable assumptions about (1) the 
covariance matrix for the random effects and the residual variance, and (2) mean changes 
over time for each treatment group.   
Subjects who complete the study will have approximately 84 NRS scores assessed daily. To 
derive the within-subject covariance matrix, we need the within-subject correlation matrix 
and the standard deviation.  We assume the daily assessments have an AR(1) within-subject 
correlation structure, which seems reasonable based on preliminary data on 24 subjects 
assessed on days 1, 14, and 28 [101]. Based on this preliminary data, the correlation 
coefficient for assessments 1 day apart is very high (estimated as 0.9775).   The standard 
deviation (SD) of the NRS is assumed to be the same for each day and likely to be on the 
range from 1.3 to 1.6.  The range is based on a study by Farrar (2001) [124] that examined 
data from 10 clinical trials including 2724 patients with a variety of conditions characterized 
by chronic pain who had baseline pain of ≥ 4 on the NRS.  The study suggests that patient’s 
perceptions of pain and improvement is similar and consistent across disease indications. 
Results of this study influenced the recommendations on clinical importance of treatment 
effects on pain in clinical trials authored by The Initiative on Methods, Measurement, and 
Pain Assessment in Clinical Trials (IMMPACT) group [125].  
The covariance matrix for the 84 repeated NRS measures can be derived assuming an AR(1) 
correlation matrix (r=0.9775 for a 1 day interval) and a choice of SD; we considered the two 
extremes in SD = 1.3 and 1.6, as well as the pooled estimate (1.43) across the 10 studies in 
[124]. The next step was to derive the covariance matrix for the random effects in the random 
regression model (i.e. the subject-level intercepts and slopes). To this end, we simulated day 
0 to 84 data for 10,000 subjects, fit the model with fixed and random subject-level intercepts 
and slopes, and used the output covariance estimates as parameters for power/ sample size 
computation.  Covariance parameters are displayed in Table 5.  
 


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Table 5: Covariance Parameters for the Random Regression Model 
 
Variance 
(intercept) 
Variance       
(1-day slope) 
Covariance 
(intercept, slope) 
Residual 
Pooled 
(daily NRS SD=1.43) 
2.35 
0.00063 
-0.027 
0.49 
Best case                 
(daily NRS SD=1.3) 
1.93 
0.00053 
-0.023 
0.41 
Worst Case                
(daily NRS SD=1.6) 
2.96 
0.00081 
-0.034 
0.62 
 
We considered several scenarios for mean changes over time.  The IMMPACT group 
suggests that on average decrease of 2 points (~30% improvement on average) on the NRS 
scale is consistent with clinically important improvement from the perspective of an 
individual patient, but they did not make a recommendation for clinically relevant mean 
decrease in NRS for a treatment group relative to placebo [125]. Although a mean decrease 
of 2 points on the NRS for a treatment group would certainly be important clinically, a 
decrease of a smaller magnitude might also include a substantial number of individual 
subjects who showed improvement of at least 2 points. As such, we considered mean 
decreases, d, ranging from 1.5 to 2.0 points over 84 days and assumed no change for placebo.  
For each value of d, we present power/sample size calculations for 2 scenarios.  In Scenario 
1, the mean decrease of d is achieved in 1 of the JBT-101 treatment groups.  The other 2 
JBT-101 groups show mean decreases of 0.5d and 0.25d.  In Scenario 2, two of the JBT-101 
treatment groups achieve a mean decrease of d, and the third shows a decrease of 0.25d.  
These scenarios are summarized in Table 6. We also considered a 3rd scenario where all 3 
treatment groups achieved a mean decrease of d, but power estimates were nearly identical to 
Scenario 2, and hence, results are not shown. 
Table 6: Treatment Effect Scenarios 
 
Scenario 1 
Scenario 2 
Placebo 
0 
0 
JBT-101 group 1 
-0.25d 
-0.25d 
JBT-101 group 2 
-0.5d 
-d 
JBT-101 group 3 
-d 
-d 
Using the covariance parameters for pooled, best and worst cases (Table 5) and treatment 
effects for Scenarios 1 and 2 (Table 6), we generated non-centrality parameters for the F 
statistic for evaluating the 3 df test, and computed power according to the method of Stroup 
(1999).  Power estimates for a Type 1 error rate = 0.05 and treatment group sizes of 22 and 
25 are displayed in Figure 3. The x axis ranges from 1.5 to 2.0 (i.e. values of d) and 
represents the maximum difference between treatment versus placebo for 1 JBT-101 treated 
group in Scenario 1 or 2 treated groups in Scenario 2. The y axis displays associated power. 


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When 2 JBT-101 treated groups achieve the target treatment effect (Scenario 2), power 
exceeds 80% for treatment effects of at least 1.6 using the pooled SD with 25 per group 
(Figure 3a).   These estimates assume complete data for each subject. Given that this study is 
of relatively short duration, subject retention is expected to be good with minimal data 
missing. However, if the sample size drops to 22 per group due to missing data or 
withdrawals, minimum power is still nearly 80%.  If only 1 JBT-101 treated group achieves 
the target treatment effect (Scenario 1), then a treatment effect of at least 1.9 would be 
needed for 80% power on the 3 df test. 
This analysis does not take into account that the random regression model will include the 
Screening 7-day average maximum daily pain NRS as a covariate as well as terms for 
quadratic trends in time, both of which will account for a fraction of the variance in the NRS 
scores and, hence, may reduce the residual variance and increase power.  Figure 3b shows the 
impact of a small reduction in residual variance from 0.49 to 0.41 (Table 5).    For Scenario 
2, power exceeds 80% for treatment effects of at least 1.5 with 22 or 25 per group. If only 1 
JBT-101 treated group achieves the target treatment effect (Scenario 1), then a treatment 
effect of at least 1.7 gives power of ~80% or better. 
Figure 3c presents a worst case scenario where the variability associated with the NRS scores 
is high (SD=1.6).  All power curves drop by about 10 percentage points compared to Figure 
3a.  Under this worst case scenario the study would be under-powered except for Scenario 2 
for treatment effects exceeding 1.8. However, since results from Farrar suggest that patient’s 
perceptions of pain and improvement is similar and consistent across disease indications, the 
estimated pooled SD based on over 2000 patients represents a reasonable expectation of the 
“truth” for our study population [124]. As such, power estimates in Figure 3a are appropriate 
for this study, and may in fact underestimate power given the enhancements planned for the 
random regression model as noted above.  
In general, power is better when at least 2 of the 3 JBT-101 treatment groups differ 
meaningfully from placebo. The study will likely be underpowered if only 1 of the JBT-101 
treatment groups differs meaningfully from placebo unless that difference is relatively large 
(1.9 or higher, Figure 3a), for the first Phase 2 study in this patient population, this risk is 
acceptable. Power is expected to be acceptable with ~22 subjects per arm, but if >12% of 
subjects who initiate treatment discontinue treatment prematurely, the total sample size may 
be augmented to ensure adequate power. 


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Figure 3. Power estimates for Scenarios 1 and 2 
 
a: Pooled SD of daily NRS = 1.43 
 
b: Best Case- SD of daily NRS = 1.3 
 
c: Worst Case – SD of daily NRS = 1.6 
 


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8.2 Analysis Populations 
 
Modified Intent-to-Treat Population  
8.2.1
The modified Intent-to-Treat population (mITT) will consist of all randomized subjects who 
have received at least one dose of study product. The mITT population will be used for all 
efficacy analyses and will include subjects under the treatment to which they were 
randomized, regardless of compliance with assigned treatment.  
 
Per Protocol Population 
8.2.2
The per protocol population (PP) will consist of mITT subjects who:  
 complete Visit 3 (Day 29), without missing more than 7 days of study product 
between Visit 1 (Day 1) through Visit 3 (Day 29).  
 have ≥ 80% compliance with study drug administration from Visits 1- 5 (Days 1-85), 
as assessed by numbers of capsules of study product returned to the site, excluding 
periods off study drug when directed per protocol by the site investigator or treating 
physician) 
 complete the study without protocol violations deemed likely to effect the efficacy 
outcomes of interest 
A masked data review panel will evaluate deviations from the protocol including, for 
example, violations of entry criteria, departures from assigned treatment regimen, 
modifications of concurrent therapy, failure to complete study visits, or administration of 
study procedures outside the specified visit windows to determine if occurrence of these 
deviations should exclude subjects from the PP population. 
The PP population will be used for secondary efficacy. 
 
Safety Population 
8.2.3
The safety population will include all subjects for whom study treatment is initiated. The 
safety population will be used for all safety analysis. Analysis performed on the safety 
population will be according to the treatment actually received. 
 
PK Population 
8.2.4
The PK population will consist of all subjects with at least one valid measure of JBT-101 
plasma concentration. Analysis performed on the PK population will be according to the 
treatment actually received. 
8.3 Description of the Analyses 
 All data will be provided in data listings sorted by treatment groups, subject number, 
and visit.  
 Summary data will be presented in tabular format by treatment groups.  


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 Categorical data will be summarized by the number and percentage of subjects in 
each category.  
 Continuous data will be summarized by descriptive statistics including N, mean, 
standard deviation, median, and range.  
 All percentages will be rounded to one decimal place.  
 Differences between groups will be calculated as active – placebo and change from 
baseline (ΔNRS) will be calculated as follow-up visit – baseline.  
 The baseline measure will be defined as the last non-missing measure prior to 
initiation of study product. It is expected that baseline values for efficacy assessments 
will be measured at Visit 1 (Day 1).  
 P-values will be assessed at a 2-sided alpha = 0.05 level for the primary efficacy 
analysis.   
 Secondary analyses are exploratory and intended to deepen our understanding of risks 
and benefits, to refine hypotheses, and to obtain information from which to design, 
select doses, and power future pivotal studies.  P-values will be presented for 
secondary efficacy analyses. No adjustments for multiple comparisons are planned 
for secondary analyses. 
 
Subject Disposition 
8.3.1
The disposition of all subjects over the course of the trial will be summarized by cohort and 
overall. The number and percent of subjects in each analysis population (mITT, PP, safety, 
and PK) will be displayed. In addition, the presentation will include the number of subjects 
who completed the study, the number who withdrew prematurely from the study, as well as 
the reason for withdrawal. In addition, the number of subjects who continued treatment to 
Visit 5 (Day 85) and who discontinued treatment early will also be summarized along with 
reasons for discontinuation. 
 
Efficacy Analysis 
8.3.2
 Primary Efficacy Analysis 
8.3.2.1
The primary hypothesis for this study is that JBT-101 treatment will result in improvement in 
the maximum daily pain NRS scores in SLE patients with active musculoskeletal disease.  
The null hypothesis to be tested is: 
H0: Linear trends from Day 1 to Day 84 are equivalent for each JBT-101 cohort and placebo. 
HA: Linear trends from Day 1 to Day 84 are not equivalent across groups. 
In addition, pairwise comparisons of each JBT-101 cohort versus placebo are of key interest. 
For the primary analysis, the maximum daily pain NRS scores from Day 1 through end of 
treatment (typically Day 84) will be modeled using a random regression approach.  The fixed 


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effects model will include treatment group, time, time2, time- and time2 by treatment group 
interactions, as well as the Screening 7-day average maximum daily pain NRS as a covariate. 
Within-subject random effects for intercept and slopes for time and time2 will be fit using an 
unstructured covariance matrix assuming the same structure for all treatment groups. In the 
event of convergence problems, the covariance structure will be simplified by dropping the 
random effect for time2.  The primary hypothesis will be tested using the 3 degrees of 
freedom contrast comparing the difference in predicted means (m̂) from Day 1 to Day 84 for 
each JBT-101 group versus placebo. That is, (m̂84 – m̂1)cohort i - (m̂84 – m̂1)placebo = 0 for i=1 to 3.   
NRS data up to the day of last dose of study treatment will be included in the analysis for all 
subjects in the mITT population. Any NRS data entered into the IVRS after discontinuation 
of study treatment or entered on days when narcotic analgesics were taken will be excluded.  
If the 3 df test is significant, Dunnett’s tests for 1 df pairwise comparisons with placebo are 
planned. If the 3 df test is not statistically significant, confidence intervals for the 1df pair-
wise comparisons with placebo will still be presented, but this information will be used for 
hypothesis generation and planning of future studies.   


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 Secondary Efficacy Analyses 
8.3.2.2
Secondary analyses of the longitudinally assessed maximum daily pain NRS scores will 
include: 
 A 1 df contrast to compare placebo versus the average across all treated groups  
 Analyses to modify the primary analysis model by replacing treatment group with 
JBT-101 dose, so that dose response may be evaluated  
 Modification of the primary random regression model to include interaction terms to 
evaluate the impact of the Screening 7-day average maximum daily pain NRS on 
trends over time 
 Analyses analogous to the primary analyses using % change in NRS from baseline 
(i.e. where baseline is the Screening 7-day average maximum daily pain NRS) as the 
outcome variable 
 Evaluation of persistence in trends after treatment is stopped by including data after 
day 84 in a new random regression model where slopes are allowed to change after 
this point 
The 7-day average of maximum daily pain NRS scores prior to Visits 1 (Day 1), 3 (Day 29), 
4 (Day 57), 5 (Day 85), and 6 (Day 113) will be used to identify responders whose averages 
improve by 30% (or 50%, 75% or 100%) over Visit 1 (Day 1) and to evaluate ordinal 
changes in pain categories (major improvement, improvement, no change, worsening) from 
Visit 1 (Day 1) to subsequent visits.  Relationships between treatment group and each 
categorical outcome will be evaluated using contingency table analyses. Generalized linear 
models that account for the correlation structure of the data may be used to further explore 
any trends that might be suggested by the stratified analyses.   
Analyses plans for other categorical secondary endpoints (e.g. presence/absence of arthritis 
on the SELENA SLEDAI or BILAG scores for the musculoskeletal domain) will be 
analogous to those noted in the previous paragraph. Generally, mixed models will be used to 
evaluate disease activity or patient-reported secondary endpoints that are indices or scores 
assessed at Visits 1 – 5 (Days 1 – 85). Models will be used to compare trajectories and 
changes in the secondary endpoints over time among the individual JBT-101 groups (Cohort 
1, Cohort 2, and Cohort 3) and placebo (Cohort 4). Data transformations will be considered, 
as appropriate.  Larger models may be constructed for these comparisons with consideration 
of additional covariates that are found to differ between the treatment groups. Covariates may 
include, but are not limited to: 7-day average of the maximum daily pain NRS score at Visit 
1 (Day 1), Fibromyalgia Symptom Score at Visit 1 (Day 1), gender, age, disease duration, 
and severity.  
 
Safety Analyses 
8.3.3
 Adverse events 
8.3.3.1


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Safety will be assessed primarily by summarizing TEAEs, including treatment-emergent 
SAEs, and the proportion of subjects with TEAEs and treatment-emergent SAEs in each 
individual JBT-101 cohort (Cohort 1, Cohort 2, and Cohort 3) to the placebo (Cohort 4). 
For placebo and each JBT-101 cohort, the frequency of AEs and SAEs from Screening 
through Visit 6 (Day 113) will be summarized by system organ class, preferred term, severity 
(grade), and relationship to study treatment.  
Safety endpoint identified in Section 3.2.3, Safety Endpoints, will be summarized and listed 
separately.  With the exception of the “psychotropic activity” endpoint, safety endpoints are 
“events”.  For each such endpoint, the number of events and numbers and percentages of 
subjects who experience these events will be summarized for placebo and each individual 
JBT-101 cohort. No formal statistical testing will be performed to compare safety in different 
cohorts. 
 Laboratory safety outcomes 
8.3.3.2
Results of blood and urine laboratory safety tests, including CBC with cell differential and 
platelets, metabolic panel, and urine tests will be summarized by visit and time point using 
descriptive statistics for continuous measures. Changes from Visit 1 (Day 1) will also be 
summarized. Shift tables will be presented summarizing the shift from Visit 1 (Day 1) to 
subsequent visits. Results will be presented for placebo and each individual JBT-101 cohort.  
 Electrocardiograms and QT/QTc intervals 
8.3.3.3
The QT/QTc intervals and change from Visit 1 (Day 1) to subsequent visits will be 
summarized by visit using continuous summary statistics for placebo and each individual 
JBT-101 cohort. 
 ARCI-M questionnaire 
8.3.3.4
ARCI-M questionnaire scores will be summarized by visit for Visits 1 (Day 1) (before and 
after first dose of study drug), 3 (Day 29), and 5 (Day 85), and for change from Visit 1 (Day 
1) prior to the first dose of study drug to the visit using continuous summary statistics. The 
number of subjects with an increase in score by ≥ 1 from Visit 1 (Day 1) prior to study 
product administration will be presented by visit for Visit 1 (Day 1) after study drug 
administration, Visits 3 (Day 29) and 5 (Day 85). 
 
Plasma Concentrations of JBT-101 and Metabolites 
8.3.4
Results of JBT-101 plasma concentrations and metabolites for Visits 1 (Day 1) and Visit 2 
(Day 15) will be described, using continuous summary statistics, by visit. 
In addition, plasma concentrations will be listed by subject and cohort in a blinded manner, 
using a mock identification number separate from the subject id, at several times during the 
trial to determine whether exposure to JBT-101 in the SLE subjects is within the expected 


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range for the doses administered. Complete analyses of the plasma concentrations and 
metabolites will be done at the end of the trial. 
 
Mechanistic Analyses 
8.3.5
Descriptive statistics and plots (including, but not limited to, those described subsequently) 
will be used to gain an understanding of the data prior to developing any statistical models. 
Means, medians, standard deviations, minimums, and maximums will be computed for each 
continuous mechanistic endpoint at each time point for treatment groups and separately for 
subjects who do/do not experience clinically significant disease reactivation. For 
dichotomous mechanistic endpoints, frequencies and percent’s will be computed at each time 
point for treatment. To gain a better understanding of trends over time, summary statistics 
(e.g., means, medians, or percents) will be plotted versus time at the relevant time points. 
Plots for individual subjects may also be useful. Complete analyses of the mechanistic 
endpoints will be done at the end of the trial and will be described in a statistical analysis 
plan for mechanistic studies. 
8.4 Interim Analysis 
Interim analyses of data will be reported to the DSMB at planned DSMB meetings and as 
requested by the DSMB. Planned interim analyses for the DSMB will focus on study conduct 
and subject safety and may include information on enrollment, randomization, site activation 
status, major protocol deviations, subject status and demographics, and safety analyses. In 
addition, the DSMB may review selected efficacy data. 
No other interim analyses are planned.  
8.5 Other Statistical Considerations 
8.6 Covariates 
No specific adjustments for covariates are planned for this study. 
8.7 Multi-center Studies 
No special consideration of site effects is planned. The number of subjects at some study 
sites is expected to be insufficient (< 5 subjects) for evaluation of site effects. In addition, 
because the maximum daily pain NRS is patient-reported rather than physician-assessed, site 
effects would be expected to have a minimal impact on primary endpoint analysis.  
8.8 Multiple Comparisons and Multiplicity 
The primary analysis for the efficacy of JBT-101 compares the individual trajectories of the 4 
cohorts over time. Section 8.3.2 describes the use of Dunnett’s test for multiple comparisons 
against the placebo group. The secondary efficacy analyses will evaluate trends for efficacy, 
with p-values and confidence intervals presented as descriptive measures of strength of 


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evidence rather than formal statistical inference. Therefore, no additional multiplicity 
adjustments are needed for this study.  
8.9 Examination of Subgroups 
Exploratory subgroup analyses of efficacy endpoints will be done based on subject Screening 
7-day average of the maximum daily pain NRS score ≤ 6 versus ≥ 7 and Fibromyalgia 
Symptom Scale score < 13 and ≥ 13 at Visit 1 (Day 1).  
8.10 Changes to the Statistical Analysis Plan 
A detailed description of the planned analyses will be provided in a Statistical Analysis Plan 
that will be completed and signed off prior to database lock. Major changes from this 
protocol will be noted in the Statistical Analysis Plan. Changes to the Statistical Analysis 
Plan that are made subsequent to database lock will be documented in the clinical study 
report. 
8.11 Missing Data 
For the primary analysis, a longitudinal mixed model is planned, which will include all 
available data from all subjects in the mITT population regardless of completeness. Because 
this is a short study, data is expected to be missing at random, but any obvious contradictions 
to this assumption will be noted and considered.  Standard procedures will be used to ensure 
that data are as complete and accurate as possible. Generally, missing data will not be 
imputed. Deviations from this approach will be specified in the Statistical Analysis Plan. 
9 ACCESS TO SOURCE DATA AND DOCUMENTS 
Each participating site will maintain the highest degree of confidentiality permitted for the 
clinical and research information obtained from subjects participating in this clinical trial. 
Medical and research records should be maintained at each site in the strictest confidence. 
However, as a part of the quality assurance and legal responsibilities of an investigation, each 
site must permit authorized representatives of the IND sponsor(s), the DAIT-SACCC, 
Corbus Pharmaceuticals Holdings, Inc., and health authorities to examine (and when required 
by applicable law, to copy) clinical records for the purposes of quality assurance reviews, 
audits, and evaluation of the study safety and progress. Unless required by the laws 
permitting copying of records, only the coded identity associated with documents or other 
subject data may be copied (obscuring any personally identifying information). Authorized 
representatives as noted above are bound to maintain the strict confidentiality of medical and 
research information that may be linked to identified individuals. Participating sites will 
normally be notified in advance of auditing visits. 
All subject records and study documentation will be kept after the protocol is completed. 
This will include all documentation of AEs, records of study drug receipt and dispensation, 
and all IRB correspondence. All study records will be kept for at least two years after the 
investigation is completed. 


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10 DATA COLLECTION, QUALITY CONTROL AND QUALITY 
ASSURANCE 
The investigator is required to keep accurate records to ensure the conduct of the study is 
fully documented. The period of record retention should be consistent with the record 
retention policies of the sponsoring agency or applicable regulatory agencies. However, in 
certain instances, documents should be retained for a longer period if required by the 
applicable regulatory agency or by the National Institutes of Health. 
The investigator will report all major protocol deviations to DAIT and the DAIT-SACCC per 
the instructions in the Autoimmunity Centers of Excellence (ACE) Manual of Procedures. 
The DAIT-SACCC will forward reports of protocol deviations to the responsible 
DAIT/NIAID medical officer for review as specified in the Manual of Procedures. 
The DAIT-SACCC is responsible for regular inspection of the conduct of the trial, for 
verifying adherence to the protocol, and for confirming the completeness, consistency, and 
accuracy of all documented data. 
Data will be obtained from a variety of sources including, but not limited to laboratory 
notebooks, automated instrument output files, and clinical subject charts. Data from these 
source materials will be transmitted to the DAIT-SACCC via one of two mechanisms. Data 
collected electronically at central laboratories will be transferred electronically directly from 
the laboratory to the DAIT-SACCC using standard secure data transfer procedures. Data 
collected at the clinical sites will be transmitted to the DAIT-SACCC using an internet-based 
remote data entry system. Clinical site personnel use an internet browser to key data into 
eCRFs; each CRF page is submitted to the clinical database electronically as the page is 
completed. Univariate data validation tests are performed as the data are keyed. The clinical 
database is backed up nightly; backup tapes are saved in a secure, off-site location. At any 
time, authorized site personnel may log in to the remote data entry system, review and 
correct previously entered data, or key additional data. The data will be further validated per 
the study data validation plan via a series of computerized and manual edit checks, and all 
relevant data queries will be raised and resolved on an ongoing basis. Complete, clean data 
will be frozen to prevent further inadvertent modifications. All discrepancies will be 
reviewed and any resulting queries will be resolved with the investigators and amended in the 
database. All elements of data entry (i.e., time, date, verbatim text, and the person performing 
the data entry) will be recorded in an electronic audit trail to allow all data changes in the 
database to be monitored and maintained in accordance with federal regulations. 
The DAIT-SACCC will periodically visit the participating clinical sites and audit the source 
documents in order to validate the data in the DAIT-SACCC central database. Data will be 
provided using the subject’s screening or enrollment number, the DAIT-SACCC will not 
collect personally identifying information such as the subject’s name or social security 
number. Subjects will provide demographic information such as race, ethnicity, and birth 
date. 
Data collected by the DAIT-SACCC will be held in the strictest confidence, and are 
protected from access that could reveal personally identifying information about any subject 
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11 ETHICAL CONSIDERATIONS AND COMPLIANCE WITH GOOD 
CLINICAL PRACTICE 
The study will be conducted according to GCP guidelines, U.S. 21 CFR Part 50 – Protection 
of Human Subjects, and Part 56 – Institutional Review Boards. 
11.1 Compliance with Good Clinical Practices 
This trial will be conducted in compliance with the protocol, current GCPs recommended by 
the ICH and the applicable regulatory requirements for participating institutions. These 
include the tenets of the Declaration of Helsinki and review and approval by the appropriate 
ethics review committee or IRBs of participating organizations. The DAIT-SACCC will 
assure compliance through a program of quality assurance audits performed both at 
participating sites and within the DAIT-SACCC for data quality and adherence to protocol 
requirements. The DAIT-SACCC is operated by Rho Federal Systems Division, Inc. 
(RhoFED), Chapel Hill, North Carolina under a cooperative agreement with NIAID. 
11.2 Institutional Review Board 
Each participating institution must provide for the review and approval of this protocol and 
associated informed consent documents by an appropriate ethics review committee or IRB. 
Any amendments to the protocol or consent materials must be approved by the IRB before 
they are placed into use. In both the United States and in other countries, only institutions 
holding a current Federal Wide Assurance issued by the Office of Human Research 
Protection (OHRP) at the Department of Health and Human Services (DHHS) may 
participate. 
The investigator will inform the IRB of serious or unexpected AEs that might occur during 
the study and are likely to affect the safety of the subjects, or the conduct of the study. The 
investigators will comply fully with all IRB requirements for both the reporting of AEs, 
protocol or consent form changes, as well as any new information pertaining to the use of the 
study medication that might affect the conduct of the study. 
11.3 Informed Consent 
 The principles of informed consent in the current edition of the Declaration of Helsinki, as 
well as compliance with all IRB requirements, will be implemented in the study, before any 
protocol-specified procedures are carried out. A standard consent form for subject 
participation will be provided with the protocol to each institution. Any modifications to the 
standard information in the template will require review and approval by DAIT/NIAID. 
Informed consent will be obtained in accordance with 21 CFR 50.52. Information may be 
given to subjects in oral, written, or video form by the investigator. All prospective subjects 
will be given ample time to read the consent form, and ask questions, before signing. 
If subjects are to be enrolled who do not speak and read English, the consent materials must 
be translated into the language appropriate for the enrolling subject. Translated documents 


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must be certified to contain the complete descriptions provided in the English version of the 
document. If an interpreter is used to provide or assist in describing the consent materials to 
an enrolling subject, the interpreter must also sign the consent materials certifying their 
involvement with the consent process. 
After completion, a copy of the signed consent form will be given to the subject. The original 
signed consent form will be kept on file in the subject’s study chart, available for inspection 
by regulatory authorities, both federal and institutional. 
11.4 Data and Safety Monitoring Board 
The responsibility for reviewing the ethical conduct of the study and for monitoring reports 
of evidence of adverse or beneficial effect is assigned to the DAIT Autoimmunity DSMB. 
The DSMB is an independent group composed of biomedical ethic experts, physicians, and 
other scientists who are responsible for continuing review of study information. The DSMB 
makes recommendations to DAIT/NIAID on issues affecting the course and conduct of this 
clinical study. 
11.5 Study Termination 
In the event that the study is discontinued, sites will immediately notify subjects to terminate 
study agent and return for a close-out visit to the site within 30 days. 
12 FINANCING AND INSURANCE 
Participating institutions must comply with their institution’s policies on compensation, 
insurance, and indemnity. Institutions must have adequate liability insurance coverage to 
satisfy their local and national requirements for study participation. 
13 PUBLICATION POLICY 
The Autoimmunity Centers of Excellence (ACE) policy on publication of study results will 
apply to this study. Authorized participants may find details regarding the policy statement 
on the ACE internet website at http://www.rhoworld.com. Study investigators are 
encouraged to communicate and publish study results with prior notification of DAIT, 
NIAID, and Corbus Pharmaceuticals Holdings, Inc. The following procedure is suggested: 
1. Manuscripts, abstracts, posters and other material for public distribution will be 
submitted to DAIT, NIAID, and Corbus Pharmaceuticals Holdings, Inc. at least 30 
days prior to submission for publication or public presentation. 
2. DAIT, NIAID, and Corbus Pharmaceuticals Holdings, Inc. will review and comment 
on the proposed material within 30 days. 
3. DAIT, NIAID, and/or Corbus Pharmaceuticals Holdings, Inc. may ask that 
confidential information be deleted or redacted in this case where a patent may be 
filed or where confidential information is involved. Publication or presentation may 
be delayed up to 60 additional days in order to file a patent application. 


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14 APPENDICES 
14.1 Appendix A: Reproductive Potential and Effective Methods of Contraception 
Women are considered to have “no reproductive potential” if they meet any one of the following criteria:  
 
Hysterectomy 
 
Bilateral oophorectomy 
 
Bilateral salpingectomy, or 
 
Post-menopausal with no menses for 12 months without an alternative medical cause. A high 
follicle stimulating hormone in the postmenopausal range can be used to confirm a post-
menopausal state in women not using hormonal contraception or hormonal replacement therapy. 
In the absence of 12 months of amenorrhea, a single follicle stimulating hormone measurement is 
insufficient.  
Highly effective methods of birth control are those that result in a low failure rate (i.e., less than 1 percent 
per year) when used consistently and correctly. Examples of highly reliable method of birth control when 
used consistently and correctly are given: 
 
Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation  
o Oral 
o Intravaginal 
o Transdermal 
 
Progestogen-only hormonal contraception associated with inhibition of ovulation  
o Oral 
o Injectable  
o Implantable  
 
Intrauterine device  
 
Intrauterine hormone-releasing system  
 
Bilateral tubal occlusion  
 
Vasectomised partner  
Other acceptable method of birth control: 
 
Double barrier (male condom with or without spermicide used in combination with a diaphragm 
or cervical cap with spermicide)  
 
Sexual abstinence. Abstinence is only acceptable when this is the preferred and usual life style of 
the individual.  
Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus) 
and lactational amenorrhea method are not acceptable means of contraception. 


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14.2 Appendix B: Fibromyalgia Symptom Scale 


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14.3 Appendix C: Lupus Activity Patient’s Global Assessment 
 


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14.4 Appendix D: ARCI-M Questionnaire (Pre-Dose) 
 


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14.5 Appendix E: ARCI-M Questionnaire (Post-Dose) 


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14.6 Appendix F: PROMIS-29 Short Form 
 


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14.7 Appendix G: PROMIS Item Bank v2.0 - Cognitive Function 
 


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14.8 Appendix H: Treatment Satisfaction Survey (Participant) 


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14.9 Appendix I: Participant Drug Screening Materials 
 
Clinical Trial Participant Identification Card: 
Front: 
 
Back: 
 


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14.10 Appendix J: Participant Daily Pain NRS Materials 
 


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selectivity with reduced CB1 activity. Bioorg Med Chem, 2014. 22(13): p. 3245-51. 
95. 
Burstein, S.H., et al., Synthetic nonpsychotropic cannabinoids with potent 
antiinflammatory, analgesic, and leukocyte antiadhesion activities. J Med Chem, 1992. 
35(17): p. 3135-41. 


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96. 
Zurier, R.B., et al., Dimethylheptyl-THC-11 oic acid: a nonpsychoactive 
antiinflammatory agent with a cannabinoid template structure. Arthritis Rheum, 1998. 
41(1): p. 163-70. 
97. 
Zurier, R.B., et al., Suppression of human monocyte interleukin-1beta production by 
ajulemic acid, a nonpsychoactive cannabinoid. Biochem Pharmacol, 2003. 65(4): p. 649-
55. 
98. 
Zurier, R.B., et al., Ajulemic acid, a synthetic cannabinoid, increases formation of the 
endogenous proresolving and anti-inflammatory eicosanoid, lipoxin A4. FASEB J, 2009. 
23(5): p. 1503-9. 
99. 
Parker, J., et al., Suppression of human macrophage interleukin-6 by a nonpsychoactive 
cannabinoid acid. Rheumatol Int, 2008. 28(7): p. 631-5. 
100. 
Robinson ES, B.M., Alves P, Khan N, Tiao J, Okon L, Okama J, Feng R, Werth V., 
Ajulemic acid, a novel cannabinoid, suppresses the secretion of tumor necrosis factor 
alpha and interferon alpha from the peripheral blood mononuclear cells of 
dermatomyositis patients in vitro. Journal of Investigative Dermatology 2015. 
101. 
Corbus, Unpublished Data on File. Corbus Pharmaceuticals Holdings Inc., 100 River 
Ridge Dr. Norwood, MA 02062. 
102. 
Bonfield TL, T.M., Resunab benefits in the murine mode of CF lung infection and 
inflammation without jeopardizing resolution of Pseudomonas aeruginosa (PA) 
colonization in the lung. Cystic Fibrosis Foundation Research Conference: Pushing the 
Frontiers. , June 2015. 
103. 
Batista, C., et al., Determination of ajulemic acid and its glucuronide in human plasma 
by gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed 
Life Sci, 2005. 820(1): p. 77-82. 
104. 
Karst, M., et al., Analgesic effect of the synthetic cannabinoid CT-3 on chronic 
neuropathic pain: a randomized controlled trial. JAMA, 2003. 290(13): p. 1757-62. 
105. 
Pertwee, R.G., Emerging strategies for exploiting cannabinoid receptor agonists as 
medicines. Br J Pharmacol, 2009. 156(3): p. 397-411. 
106. 
Huestis, M.A., et al., Single and multiple doses of rimonabant antagonize acute effects of 
smoked cannabis in male cannabis users. Psychopharmacology (Berl), 2007. 194(4): p. 
505-15. 
107. 
Wolfe, F., et al., Fibromyalgia criteria and severity scales for clinical and 
epidemiological studies: a modification of the ACR Preliminary Diagnostic Criteria for 
Fibromyalgia. J Rheumatol, 2011. 38(6): p. 1113-22. 
108. 
Hochberg, M.C., Updating the American College of Rheumatology revised criteria for 
the classification of systemic lupus erythematosus. Arthritis Rheum, 1997. 40(9): p. 1725. 
109. 
Petri, M., J. Buyon, and M. Kim, Classification and definition of major flares in SLE 
clinical trials. Lupus, 1999. 8(8): p. 685-91. 
110. 
Isenberg, D.A., et al., BILAG 2004. Development and initial validation of an updated 
version of the British Isles Lupus Assessment Group's disease activity index for patients 
with systemic lupus erythematosus. Rheumatology (Oxford), 2005. 44(7): p. 902-6. 
111. 
Bombardier, C., et al., Derivation of the SLEDAI. A disease activity index for lupus 
patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum, 1992. 35(6): p. 
630-40. 
112. 
Petri, M.A., et al., Effects of prasterone on disease activity and symptoms in women with 
active systemic lupus erythematosus. Arthritis Rheum, 2004. 50(9): p. 2858-68. 


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113. 
Buyon, J.P., et al., The effect of combined estrogen and progesterone hormone 
replacement therapy on disease activity in systemic lupus erythematosus: a randomized 
trial. Annals of internal medicine, 2005. 142(12 Pt 1): p. 953-62. 
114. 
Touma, Z., M.B. Urowitz, and D.D. Gladman, SLEDAI-2K for a 30-day window. Lupus, 
2010. 19(1): p. 49-51. 
115. 
Ward, M.M., A.S. Marx, and N.N. Barry, Identification of clinically important changes in 
health status using receiver operating characteristic curves. J Clin Epidemiol, 2000. 
53(3): p. 279-84. 
116. 
Buyon, J.P., et al., The effect of combined estrogen and progesterone hormone 
replacement therapy on disease activity in systemic lupus erythematosus: a randomized 
trial. Ann Intern Med, 2005. 142(12 Pt 1): p. 953-62. 
117. 
Lam, G.K. and M. Petri, Assessment of systemic lupus erythematosus. Clin Exp 
Rheumatol, 2005. 23(5 Suppl 39): p. S120-32. 
118. 
Strand, V. and A.D. Chu, Measuring outcomes in systemic lupus erythematosus clinical 
trials. Expert Rev Pharmacoecon Outcomes Res, 2011. 11(4): p. 455-68. 
119. 
Furie, R.A., et al., Novel evidence-based systemic lupus erythematosus responder index. 
Arthritis Rheum, 2009. 61(9): p. 1143-51. 
120. 
Williams, R.C., Jr., et al., Studies of serum C-reactive protein in systemic lupus 
erythematosus. J Rheumatol, 2005. 32(3): p. 454-61. 
121. 
Baechler, E.C., et al., Interferon-inducible gene expression signature in peripheral blood 
cells of patients with severe lupus. Proc Natl Acad Sci U S A, 2003. 100(5): p. 2610-5. 
122. 
Chiche, L., et al., Modular transcriptional repertoire analyses of adults with systemic 
lupus erythematosus reveal distinct type I and type II interferon signatures. Arthritis 
Rheumatol, 2014. 66(6): p. 1583-95. 
123. 
Stroup, W.W., Mixed model procedures to assess power, precision, and sample size in 
the design of experiments. Biopharmaceutical Section. Am. Stat. Assoc., Baltimore, MD, 
1999: p. 15–24. 
124. 
Farrar, J.T., et al., Clinical importance of changes in chronic pain intensity measured on 
an 11-point numerical pain rating scale. Pain, 2001. 94(2): p. 149-58. 
125. 
Dworkin, Consensus statement: Interpreting the Clinical Importance of Treatment 
Outcomes in Chronic Pain Clinical Trials: IMMPACT Recommendations. The Journal of 
Pain, 2008. 9(2): p. 105-121. 
 
 

SAP_001.pdf: 
DAIT NIAID 
Statistical Analysis Plan 
Protocol No. ALE09  
28 April 2022
 
Version: 2.0  
Page 1 of 67
 
DAIT/Rho STATISTICAL ANALYSIS PLAN 
28 April 2022 
 
 
A Phase 2, Double-blind, Randomized, Placebo-controlled Multicenter 
Study to Evaluate Efficacy, Safety, and Tolerability of JBT-101 in Systemic 
Lupus Erythematosus 
VERSION: 
2.0 
DATE: 
28 April 2022  
SPONSOR: 
Division of Allergy, Immunology, and Transplantation 
National Institute of Allergy and Infectious Diseases – NIH 
5601 Fishers Lane 
Rockville, MD 20852 
Telephone: (301) 496-5717 
Fax: (301) 402-3573 
 
 
PREPARED BY: 
Rho 
Rho Building 
2635 E NC Hwy 54 
Durham, NC 27713 
Telephone: (919) 408-8000 
Fax: (919) 408-0999 
 
 
 


DAIT NIAID 
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Protocol No. ALE09  
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DAIT/Rho STATISTICAL ANALYSIS PLAN 
ACKNOWLEDGMENT AND SIGNATURE SHEET 
 
ALE09 
 
 
Approved: 
__________________________________ Date: 
_______________ 
 
Meggan Mackay, M.D. 
 
 
 
Protocol Chair 
 
 
 
 
 
Approved: 
__________________________________ Date: 
_______________ 
 
Linna Ding, MD, Ph.D. 
 
 
 
NIAID Medical Monitor 
 
 
 
 
 
Approved: 
__________________________________ Date: 
_______________ 
 
Lynette Keyes-Elstein, DrPH 
 
 
 
Rho Scientist 
 
 
 
 
 
Approved: 
__________________________________ Date: 
_______________ 
 
Kati Steinmiller, MS 
 
 
 
Rho Statistician 
 
 
 
 
 


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Document History 
 
Version 
 
Date 
 
Change(s) 
 
Author 
0.1 
28 October 2021 
Initial Draft 
Kati Steinmiller 
0.2 
26 November 2021 
Changes incorporated from team review 
Kati Steinmiller 
0.3 
30 December 2021 
Updates based on team comments 
Lynette Keyes-Elstein 
0.4 
06 January 2022 
Updates to BILAG arthritis analyses 
Lynette Keyes-Elstein 
0.5 
08 March 2022 
Updates based on Corbus and DAIT 
statistical review 
Lynette Keyes-Elstein 
0.6 
17 March 2022 
Minor updates and corrections 
Kati Steinmiller 
1.0 
29 March 2022 
Final  
Kati Steinmiller 
2.0 
28 April 2022 
Update primary analysis to include a 
covariate for the screening Fibromyalgia 
Symptom Scale Score 
Kati Steinmiller 


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Table of Contents 
 
1. 
PROTOCOL SYNOPSIS ............................................................................................. 9 
2. 
INTRODUCTION ....................................................................................................... 13 
3. 
GENERAL ANALYSIS AND REPORTING CONVENTIONS..................................... 13 
4. 
ANALYSIS SAMPLES .............................................................................................. 14 
4.1. 
Modified Intent-to-Treat Population ................................................................ 14 
4.2. 
Per Protocol Population ................................................................................. 14 
4.3. 
Safety Population ........................................................................................... 14 
5. 
STUDY SUBJECTS .................................................................................................. 15 
5.1. 
Disposition of Subjects ................................................................................... 15 
5.2. 
Demographic and Other Baseline Characteristics .......................................... 15 
5.2.1. Screening 7-day Average Maximum Daily Pain NRS ................................ 16 
6. 
STUDY OPERATIONS .............................................................................................. 17 
6.1. 
Protocol Deviations ........................................................................................ 17 
6.2. 
Treatment Adherence .................................................................................... 17 
6.2.1. Treatment Cohorts .................................................................................... 17 
7. 
EFFICACY EVALUATION ........................................................................................ 19 
7.1. 
Overview of Efficacy Analysis Methods .......................................................... 19 
7.1.1. Multicenter Studies .................................................................................... 19 
7.1.2. Assessment Time Windows....................................................................... 19 
7.2. 
Estimand for the Primary Analysis.................................................................. 19 
7.2.1. Primary Analysis Variable .......................................................................... 19 
7.2.2. Population ................................................................................................. 20 
7.2.3. Intercurrent Events and Strategies ............................................................ 20 
7.2.4. Primary Analysis and Population-Level Summary ..................................... 21 
7.2.5. Sensitivity Analyses Supporting the Primary Analysis................................ 22 
7.3. 
Secondary Estimands Supporting the Primary Objective ............................... 22 
7.3.1. Secondary Estimands based on the Primary Analysis Variable ................. 22 
7.3.2. Pain and Improvement Categories ............................................................ 24 
7.3.3. Percent Improvement Responder Status ................................................... 25 
7.4. 
Estimands Supporting Secondary Objectives ................................................. 26 
7.4.1. Evaluation of Active Musculoskeletal Disease Activity ............................... 26 
7.4.1.1. Physician Tender Joint Count .............................................................. 26 
7.4.1.2. Physician Swollen Joint Count ............................................................. 27 
7.4.1.3. Physician Tender and Swollen Joint Count .......................................... 27 
7.4.1.4. SELENA SLEDAI Score ....................................................................... 27 
7.4.1.5. BILAG 2004 Total Score ...................................................................... 28 
7.4.1.6. Arthritis on the SELENA-SLEDAI ......................................................... 29 
7.4.1.7. BILAG-based Arthritis Severity Assessment......................................... 29 
7.4.1.8. Physician’s Global Assessment ............................................................ 30 
7.4.1.9. SLE Responder Index .......................................................................... 31 
7.4.2. Evaluation of Patient-reported Outcomes .................................................. 31 
7.4.2.1. Lupus Activity Patient Global Assessment ........................................... 31 
7.4.2.2. PROMIS-29 Short Form ....................................................................... 31 


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7.4.2.3. PROMIS v2.0 – Cognitive Function Short Form 8a .............................. 32 
7.4.2.4. Treatment Satisfaction Survey ............................................................. 32 
8. 
SAFETY EVALUATION ............................................................................................ 32 
8.1. 
Overview of Safety Analysis Methods ............................................................ 32 
8.2. 
Extent of Exposure ......................................................................................... 32 
8.3. 
Adverse Events .............................................................................................. 33 
8.4. 
Deaths and Serious Adverse Events .............................................................. 34 
8.5. 
Clinical Laboratory Evaluation ........................................................................ 34 
8.6. 
Other Observations Related to Safety ............................................................ 35 
8.6.1. Disease Flares .......................................................................................... 35 
8.6.2. ARCI-M ..................................................................................................... 35 
8.6.3. New or Increased SLE Medications ........................................................... 36 
9. 
OTHER ANALYSES ................................................................................................. 36 
9.1. 
Use of Medications ........................................................................................ 36 
10. 
INTERIM ANALYSES AND DATA MONITORING .................................................... 36 
11. 
CHANGES TO THE ANALYSES PLANNED IN THE PROTOCOL ........................... 37 
12. 
REFERENCES .......................................................................................................... 38 
13. 
APPENDICES ........................................................................................................... 39 
13.1. 
Schedule of Events ........................................................................................ 39 
13.2. 
Study Flow Chart ........................................................................................... 41 
13.3. 
SELENA SLEDAI and Flare Index.................................................................. 42 
13.4 
BILAG-2004 Index Scoring ............................................................................ 45 
13.5 
Fibromyalgia Symptom Scale ......................................................................... 56 
13.6 
Lupus Activity Patient’s Global Assessment ................................................... 57 
13.7 
ARCI-M Questionnaire ................................................................................... 58 
13.8 
PROMIS-29 Short Form ................................................................................. 59 
13.9 
PROMIS Item Bank v2.0 - Cognitive Function Short Form 8a ........................ 62 
13.10 Treatment Satisfaction Survey (Participant) ................................................... 63 
13.11   Email Documentation of Decision to Add Screening FSS as a Covariate ....... 64 
14. 
ATTACHMENTS ....................................................................................................... 66 
 


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1. 
PROTOCOL SYNOPSIS ........................................................................................... 10 
2. 
INTRODUCTION ....................................................................................................... 14 
3. 
GENERAL ANALYSIS AND REPORTING CONVENTIONS..................................... 14 
4. 
ANALYSIS SAMPLES .............................................................................................. 15 
5. 
STUDY SUBJECTS .................................................................................................. 16 
6. 
STUDY OPERATIONS .............................................................................................. 18 
7. 
EFFICACY EVALUATION ........................................................................................ 20 
8. 
SAFETY EVALUATION ............................................................................................ 33 
9. 
OTHER ANALYSES ................................................................................................. 37 
10. 
INTERIM ANALYSES AND DATA MONITORING .................................................... 37 
11. 
CHANGES TO THE ANALYSES PLANNED IN THE PROTOCOL ........................... 38 
12. 
REFERENCES .......................................................................................................... 39 
13. 
APPENDICES ........................................................................................................... 40 
14. 
ATTACHMENTS ....................................................................................................... 67 
 
 


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LIST OF ABBREVIATIONS 
 
Abbreviation 
Meaning 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
AIC 
Akaike Information Criterion 
ALT 
Alanine Aminotransferase 
ARCI-M 
Addiction Research Center Inventory – Marijuana 
AST 
Aspartate Aminotransferase 
BILAG 
British Isles Lupus Assessment Group 
BMI 
Body Mass Index 
C3 
Complement component 3 
C4 
Complement component 4 
CB1 
Cannabinoid receptor type 1 
CH50 
Total complement 
CI 
Confidence Interval 
CNS 
Central Nervous System 
CRF  
Case Report Form 
CTCAE 
Common Toxicity Criteria for Adverse Events 
DAIT 
Division of Allergy, Immunology, and 
Transplantation 
DMARD 
Disease Modifying Anti-Rheumatic Drugs 
df 
degrees of freedom 
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
EDC 
Electronic Data Capture 


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FSS 
Fibromyalgia Symptom Scale 
GFR 
Glomerular Filtration Rate 
HCV 
Hepatitis C Virus 
ID 
Identifier 
IFNα 
Interferon alpha 
IFNγ 
Interferon gamma 
IL-1β 
Interleukin – 1 beta  
IL-6 
Interleukin - 6 
IRB 
Institutional Review Board 
IVRS 
Interactive Voice-Response E-diary System 
MAR 
Missing at Random 
max 
maximum 
MCAR 
Missing Completely at Random 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
min 
minimum 
mITT 
modified Intent-to-Treat 
mm 
millimeter 
MMF 
Mycophenolate mofetil 
NCI 
National Cancer Institute 
NIAID 
National Institute of Allergies and Infectious 
Diseases 
NIH 
National Institute of Health 
NRS 
Numerical Ratings Scale 
NSAID 
Non-steroidal Anti-inflammatory Drugs 


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PGA 
Physician’s Global Assessment 
PK 
Pharmacokinetic 
PP 
Per Protocol 
PROMIS 
Patient-Reported Outcomes Measurement 
Information System 
q 
Every 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SE 
Standard Error 
SELENA SLEDAI 
Systemic Lupus Erythematosus Disease Activity 
Index 
SLE 
Systemic Lupus Erythematosus 
SOC 
System Organ Class 
SPM 
Specialized Pro-resolving Lipid Mediator 
SRI 
SLE Responder Index 
TB 
Tuberculosis 
TEAE 
Treatment Emergent Adverse Event 
TNFα 
Tumor Necrosis Factor alpha 
VAS 
Visual Analog Scale 
WHO 
World Health Organization 
 


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1. 
PROTOCOL SYNOPSIS 
Title of the Protocol: A Phase 2, Double-blind, Randomized, Placebo-controlled Multicenter 
Study to Evaluate Efficacy, Safety, and Tolerability of JBT-101 in Systemic Lupus 
Erythematosus 
ACE Protocol Number: ALE09 
Protocol Chair(s): Meggan Mackay, M.D.  
IND Holder: DAIT/NIAID, NIH  
Objectives: To evaluate the efficacy, safety, tolerability, and biologic effects of JBT-101. The 
primary objective is to evaluate effect on inflammatory pain related to active musculoskeletal disease 
in SLE. 
Hypotheses/Estimates: The hypothesis is that JBT-101 will provide clinical efficacy in SLE patients 
with at least moderate musculoskeletal disease activity by activation of pathways that resolve 
ongoing, adverse immune responses and inhibit inflammatory cytokine production associated with 
SLE.  
Study Arms: four cohorts:  
JBT-101 5 mg q a.m. and JBT-101 5 mg q p.m. 
JBT-101 20 mg q a.m. and placebo q p.m. 
JBT-101 20 mg q a.m. and JBT-101 20 mg q p.m. 
Placebo q a.m. and placebo q p.m. 
Study Design: One hundred eligible subjects will be randomized in a 1:1:1:1 ratio to one of four 
cohorts to receive either JBT-101 (three groups: 5 mg q a.m. and 5 mg q p.m., 20 mg q a.m. and 
placebo q p.m., 20 mg q a.m. and 20 mg q p.m.) or placebo for 84 days, then 28 days of follow-up. 
Subject visits to assess endpoints occur at six times: Days 1, 15 ± 3, 29 ± 3, 57 ± 3, 85 ± 3 and 113 
± 3. 
Endpoints: 
PRIMARY EFFICACY ENDPOINT: 
The primary endpoint for evaluation of the primary objective will be improvement in maximum daily 
pain NRS scores in the treated groups relative to the control after 12 weeks of treatment. 
Longitudinal trends over the course of the treatment period will be modeled and used to estimate 
differences between means at baseline and Day 84 for each treatment group. 
SECONDARY EFFICACY ENDPOINTS: 
1. The 7-day average of maximum daily pain NRS scores prior to Visits 1 (Day 1), 3 (Day 29), 4 
(Day 57), 5 (Day 85), and 6 (Day 113) will be used to evaluate the number (%) of subjects 
with: 
• 
Changes in pain categories from Visit 1 (Day 1) to Visits 3 (Day 29), 4 (Day 57), 5 
(Day 85) and 6 (Day 113) (See Section 6.2.2.2 Pain Categories) 


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Title of the Protocol: A Phase 2, Double-blind, Randomized, Placebo-controlled Multicenter 
Study to Evaluate Efficacy, Safety, and Tolerability of JBT-101 in Systemic Lupus 
Erythematosus 
• 
Improvement of 30% from Visit 1 (Day 1) to Visits 3 (Day 29), 4 (Day 57), 5 (Day 85) 
and 6 (Day 113) 
• 
Improvement of 50% from Visit 1 (Day 1) to Visits 3 (Day 29), 4 (Day 57), 5 (Day 85) 
and 6 (Day 113)  
• 
Improvement of 75% from Visit 1 (Day 1) to Visits 3 (Day 29), 4 (Day 57), 5 (Day 85) 
and 6 (Day 113)  
• 
Improvement of 100% from Visit 1 (Day 1) to Visits 3 (Day 29), 4 (Day 57), 5 (Day 
85) and 6 (Day 113)  
2. Trends in active musculoskeletal disease activity over the duration of the treatment period 
(i.e. Visit 1 (Day 1) through Visit 5 (Day 85)) will be evaluated longitudinally using multiple 
indices: 
• 
Physician assessed tender joint count  
• 
Physician assessed swollen joint count  
• 
Presence or absence of arthritis on the SELENA SLEDAI  
• 
Musculoskeletal domain of the BILAG 2004  
3. Persistence of trends in musculoskeletal disease activity after stopping treatment will be 
evaluated at Visit 6 (Day 113) 
4. Trends in overall SLE disease activity over the duration of the treatment period (i.e. Visit 1 
(Day 1) through Visit 5 (Day 85)) will be evaluated longitudinally using multiple indices:  
• 
SLE Responder Index , where a responder is defined as having all of the following:  
o ≥4 point reduction in SELENA-SLEDAI score,  
o no new BILAG A or no more than 1 new BILAG B domain score, and  
o no deterioration from baseline in the Physician's Global Assessment defined 
as an increase of ≥0.3 points.  
• 
SELENA SLEDAI score 
• 
BILAG 2004 score 
• 
Physician’s Global Assessment 
5. Persistence of trends in overall SLE disease activity after stopping treatment will be 
evaluated at Visit 6 (Day 113) 
6. Trends in patient-reported outcomes over the duration of the treatment period (i.e. Visit 1 
(Day 1) through Visit 5 (Day 85)) will be evaluated longitudinally using multiple indices: 
• 
Lupus Activity Patient Global Assessment  
• 
PROMIS-29 Short Form  
• 
PROMIS Item Bank v2.0 - Cognitive Function 
7. Treatment Satisfaction Survey 
8. Persistence of trends in patient-reported outcomes after stopping treatment will be evaluated 
at Visit 6 (Day 113) 
SAFETY ENDPOINTS: 
Safety will be evaluated by describing incidence of treatment emergent adverse events (TEAEs) 
from Visit 1 (Day 1) through Visit 6 (Day 113). The TEAEs will be identified by monitoring subject-
reported AEs, Adverse Events of Special Interest, vital signs, medical history, physical examination, 
blood and urine laboratory safety tests, 12-lead electrocardiograms, including QT/QTc 
measurements, and Addiction Research Center Inventory-Marijuana scale. Analyses on the following 
specific events are planned. 
1. Any Grade 3 or higher AE or SAE that, in the opinion of the blinded site investigator, is at 
least “possibly related to study product. Unless noted otherwise, grading is defined by the 
National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE) 
system version 4.0  


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Title of the Protocol: A Phase 2, Double-blind, Randomized, Placebo-controlled Multicenter 
Study to Evaluate Efficacy, Safety, and Tolerability of JBT-101 in Systemic Lupus 
Erythematosus 
2. QTc prolongation > 500 msec total duration and > 60 msec from Visit 1 (Day 1) QTc interval 
prior to study drug administration 
3. Mild/moderate and severe disease flares by SELENA SLEDAI Flare Index  
4. BILAG 2004 disease flares, defined as one new BILAG A or two new BILAG B scores 
5. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3 x upper limit of 
normal and total bilirubin > 1.5 x the upper limit of normal (confirmed on repeat testing) 
6. Tolerability, assessed by incidence of discontinuation of study product due to TEAEs at least 
“possibly” related to study product from Visits 1 (Day 1) through 5 (Day 85) 
7. Psychotropic activity, assessed using the ARCI-M 
MECHANISTIC ENDPOINTS: 
1. Trends in C-reactive protein levels in the blood over the duration of the treatment period (i.e. 
Visit 1 (Day 1) through Visit 5 (Day 85)) will be evaluated longitudinally 
2.  Persistence of trends in C-reactive protein levels after stopping treatment will be evaluated 
at Visit 6 (Day 113) 
3. Trends in pro-inflammatory cytokine levels over the duration of the treatment period (i.e. 
Visits 1 (Day 1), 3 (Day 29) and 5 (Day 85)) will be evaluated longitudinally using multiple 
indices: 
• 
Pro-inflammatory cytokines in serum 
i. IFNα, IFNγ, IL-6, TNFα, and IL-1β  
ii. Expression of other cytokines will be explored  
• 
Pro-inflammatory cytokines in whole blood with and without in vitro TLR stimulation  
i.  IFNα, IFNγ, IL-6, TNFα, and IL-1β in supernatant of stimulated and 
unstimulated whole blood cells 
• 
Type 1 IFN gene signature in whole blood mRNA.   
4. Persistence of trends in biomarkers of inflammation after stopping treatment will be 
evaluated at Visit 6 (Day 113) 
5. Changes in bioactive lipids in plasma from Visit 1 (Day 1) (pre and post dose) to Visit 2 (Day 
15) will be evaluated longitudinally using multiple indices: 
• 
Specialized Pro-resolving lipid Mediators (SPMs), including lipoxin A4  
• 
Anti-inflammatory eicosanoids 
• 
Pro-inflammatory eicosanoids 
6. Changes in plasma concentrations of JBT-101 and its metabolites from Visit 1 (Day 1) (pre 
and post dose) to Visit 2 (Day 15)  
 
EXPLORATORY ENDPOINTS: 
1. Fibromyalgia Symptom Scale score, from Visit 1 (Day 1) to Visits 5 (Day 85) and 6 (Day 113) 
Sample Size: 100 eligible subjects will be randomized within 24 months and followed for 112 days; 
the study duration is estimated to be 33 months. 
Safety Stopping Guidance: The following events will trigger both a comprehensive DSMB 
Emergency Safety Review and a temporary halt in enrollment: 
• 
After the first 20 subjects are randomized, the occurrence of a Grade 3 or higher unexpected 
SAE in 10% or more of the study participants who have received study drug 
• 
Two grade 3 or above AEs with the same or similar preferred terms associated with CB1 
agonists deemed at least possibly-related to study drug.  


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Title of the Protocol: A Phase 2, Double-blind, Randomized, Placebo-controlled Multicenter 
Study to Evaluate Efficacy, Safety, and Tolerability of JBT-101 in Systemic Lupus 
Erythematosus 
• 
Determination of unexpected, significant, or unacceptable risks to subjects that 
contraindicate further dosing of additional subjects, in the opinion of the Protocol Chairs or 
DAIT 
• 
Any new safety information about JBT-101 from other clinical trials that would pose 
significant or unacceptable risk to subjects 
 
 


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2. 
INTRODUCTION 
This statistical analysis plan includes pre-planned analyses related to the study objectives outlined in 
the protocol. 
 
3. 
GENERAL ANALYSIS AND REPORTING CONVENTIONS 
The following analyses and reporting conventions will be used: 
• 
Categorical variables will be summarized using counts (n) and percentages (%) and will be 
presented in the form “n (%).” Percentages will be rounded to one decimal place. 
• 
Numeric variables will be summarized using n, mean, standard deviation (SD), median, 
minimum (min), maximum (max). The min/max will be reported at the same level of significance 
as original data. The mean and median will be reported at one more significant digit than the 
precision of the data, and SD will be reported at two more significant digits than the precision of 
the data. 
• 
The median will be reported as the average of the two middle numbers if the dataset contains 
an even number of observations. 
• 
Test statistics including t and z test statistics will be reported to two decimal places.  
• 
P-values will be reported to four decimal places if greater than or equal to 0.0001. If less than 
0.0001, the value will be reported as “<0.0001.” A p-value can be reported as “1.0000” only if it 
is exactly 1.0000 without rounding. A p-value can be reported as “0.0000” only if it is exactly 
0.0000 without rounding. 
If departures from these general conventions are present in the specific evaluations section of this 
SAP, then those conventions will take precedence over these general conventions.  
 


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4. 
ANALYSIS SAMPLES 
These definitions are intended to identify participants for inclusion in each population but handling of 
observations with respect to intercurrent events is discussed below for each estimand (Sections 7.2-
7.4). 
4.1. 
Modified Intent-to-Treat Population  
The modified Intent-to-Treat population (mITT) will consist of all randomized subjects who have 
received at least one dose of study product. The mITT population will be used for all efficacy analyses 
and will include subjects under the treatment to which they were randomized, regardless of compliance 
with assigned treatment.  
4.2. 
Per Protocol Population 
The per protocol population (PP) will consist of mITT subjects who:  
• 
complete Visit 3 (Day 29), without missing more than 7 days of study product between Visit 1 
(Day 1) through Visit 3 (Day 29).  
• 
have ≥ 80% compliance with study drug administration from Visits 1- 5 (Days 1-85), as 
assessed by numbers of capsules of study product returned to the site, excluding periods off 
study drug when directed per protocol by the site investigator or treating physician) 
• 
complete the study without protocol violations deemed likely to affect the efficacy outcomes of 
interest 
A masked data review panel will evaluate deviations from the protocol including, for example, violations 
of entry criteria, departures from assigned treatment regimen, modifications of concurrent therapy, 
failure to complete study visits, or administration of study procedures outside the specified visit 
windows to determine if occurrence of these deviations should exclude subjects from the PP 
population. 
The PP population will be used for secondary efficacy. 
4.3. 
Safety Population 
The safety population will include all subjects for whom study treatment is initiated. The safety 
population will be used for all safety analysis. Analysis performed on the safety population will be 
according to the treatment actually received. 
 
 


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5. 
STUDY SUBJECTS 
5.1. Disposition of Subjects  
The disposition of all enrolled subjects will be summarized in tables and listed by treatment group. 
The numbers and percentages of subjects randomized, in each analysis sample, as well as reasons 
for early termination from the study will be presented. For subjects discontinuing study treatment early, 
the reasons for discontinuing study treatment early will also be presented.  
5.2. Demographic and Other Baseline Characteristics  
Summary descriptive statistics for baseline and demographic characteristics will be reported for the 
mITT and PP samples by treatment group. Characteristics to be summarized include: 
• 
Age at Screening 
• 
Race 
• 
Ethnicity 
• 
Sex 
• 
Disease duration at Screening 
• 
Screening Fibromyalgia Symptom Scale Score (FSS) 
• 
FSS summarized categorically as <13 versus >= 13 
• 
Screening 7-day average maximum daily pain NRS (see Section 5.2.1)  
• 
Screening 7-day average maximum daily pain NRS score summarized categorically as <= 6 vs 
>6 
• 
Baseline 7-day average maximum daily pain NRS 
• 
Number with baseline 7-day average maximum daily pain NRS < 4 
• 
Patient global assessment 
• 
Physician global assessment 
• 
BILAG arthritis severity category, where the mutually exclusive categories are defined in a 
hierarchical fashion as follows: 
i. 
Severe arthritis scored as improving, same, new, or worse;   
If not (i), then 
ii. 
Moderate arthritis scored as improving, same, new, or worse; 
If not (ii), then 
iii. 
Mild arthritis scored as improving, same, new, or worse; 
If not (iii), then 
iv. 
Arthritis is not present. 
• 
Arthritis present on SLEDAI 
• 
Number of swollen joints  
• 
Number of tender joints  
• 
Number of tender and swollen joints 
• 
Number on depression/anxiety medication 
• 
Physical Function total score per the PROMIS 29 


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• 
Depression total score per the PROMIS 29 
• 
Anxiety total score per the PROMIS 29 
• 
Fatigue total score per the PROMIS 29 
• 
Sleep Disturbance total score per the PROMIS 29 
• 
Ability to Participate in Social Roles and Activities total score per the PROMIS 29 
• 
Pain Interference total score per the PROMIS 29 
• 
Pain Intensity score per the PROMIS 29 
• 
SLEDAI score  
• 
GFR by MDRD 
• 
Number with C3 lower the limit of normal 
• 
Number with C4 lower than the limit of normal 
• 
Number with any DMARD use 
• 
Number using each of the following DMARDs for treatment of SLE: abatacept, secukinemab, 
mycophenolate, azathioprine, methotrexate, leflunomide, tacrolimus and cyclosporine 
• 
Number using hydroxychloroquine 
• 
Number with Benlysta use 
• 
Number with steroid use 
• 
Oral steroid dose 
 
Depression or anxiety medications will include the following: alprazolam, amitriptyline, armodafinil, 
buspirone, bupropion, citalopram, clonazepam, dexmethylphenidate, diazepam, duloxetine, 
escitalopram, fluoxetine, lorazepam, milnacipran, nortriptyline, paroxetine, quetiapine, sertraline, 
trazodone, venlafaxine. 
 
Depression, anxiety, and fatigue total scores will be derived by summing the results of the 4 questions 
associated with each category on the PROMIS 29. 
 
All oral steroid doses will be calculated in terms of prednisone equivalents. Methylprednisolone will be 
converted to prednisone dosage by multiplying by 1.25. 
 
A listing of demographic and baseline characteristics for all randomized participants will be provided. 
No hypothesis testing will be used to compare treatment arms with respect to demographic or baseline 
characteristics.  
 
5.2.1. 
Screening 7-day Average Maximum Daily Pain NRS 
Subjects will report maximum daily pain NRS scores using an interactive voice-response e-diary 
system (IVRS), which can be accessed by any phone that supports tone dialing. At the Screening visit, 
subjects will be registered and provided with credentials allowing access to the IVRS. Subjects will be 
instructed on how to record the maximum daily pain NRS score, including directions for recording 
scores at approximately the same time every day, preferably before bedtime.  


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To be eligible for the study, a subject must have a 7-day average of maximum daily pain NRS scores of 
at least 4. Once a subject enters 7 consecutive days of maximum daily pain NRS scores, the 7-day 
average will be calculated. If the average is 4 or greater, the subject’s eligibility is permanently 
established, and the average will be saved for the NRS stratification value. If the subject’s average is 
less than 4 based on the first 7 consecutive days, they will continue to enter data. After each daily data 
entry, a new consecutive 7-day average will be calculated. If the subject qualifies at any point during 
the screening period, eligibility is secured, and the average is stored for the NRS stratification value. 
6. 
STUDY OPERATIONS 
6.1. Protocol Deviations 
Major protocol deviations will be listed by site with information such as type of deviation, date of 
occurrence, whether notification to IRB was required, and the reason for the deviation. Protocol 
deviations will be summarized in tabular format by type of deviation.  
6.2. Treatment Adherence 
Subjects are instructed to take 2 pills of study product (JBT-101 or matching placebo) by mouth daily, 
with at least 8 hours between doses and without regard to fed state, from Day 1 to Day 84. The first 
dose of study medication is administered in the clinic at the Day 1 visit.  
6.2.1. 
Treatment Cohorts 
Cohort 
Approximate 
n 
  
Days 1-84 
A.M. Study Product 
P.M. Study Product 
1 
25 
JBT-101 5 mg 
JBT-101 5 mg 
2 
25 
JBT-101 20 mg 
Placebo 
3 
25 
JBT-101 20 mg 
JBT-101 20 mg 
4 
25 
Placebo 
Placebo 
 
Study drug will be dispensed at Days 1, 29, and 57. Subjects will receive A.M. and P.M. bottles of study 
drug, each containing 35 pills. Subjects are instructed to take one pill from the A.M. bottle and one pill 
from the P.M. bottle daily and are counseled not to combine study drug into a single bottle. Both A.M. 
and P.M. bottles containing unused study drug will be returned to the site at Days 29, 57 and 85. At 
these visits, site staff will count the number of pills returned and collected information from the subject 
on the number of pills that were lost. In addition, study drug is also counted and returned to the subject 
at the Day 15 visit to ensure compliance and appropriately counseling if any doses were lost or missed.  
Due to the COVID-19 pandemic, it was allowable for study visits for Day 15 through Day 113 to be 
conducted remotely, which disrupted the return of study drug bottles to sites. When a remote visit was 
conducted for a drug dispensing or return visit, the site was instructed to collect additional information 
from the subject on the dates the first and last dose was taken from each bottle. Study drug was either 
shipped back to the study site or returned at a subsequent in clinic visit. 
Interruption of continued dosing in individual subjects was allowed for safety reasons and at the 
discretion of the site investigator, if it was felt that interruption of dosing is in the best interest of the 


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subject. Other than in urgent situations, it was recommended that the site investigator discuss the 
reasons for interruption of dosing with the Protocol Chairs and DAIT/NIAID prior to interruption. Multiple 
on-off periods of treatment with study drug were permitted, as necessary in the judgment of the 
investigator for safety purposes. There was no dose modification in this study, other than temporary or 
permanent discontinuation. 
The number of pills taken from each bottle will be computed as the number of pills in the bottle (i.e., 35) 
minus any pills lost or returned. Compliance will be calculated as the number of pills taken divided by 
the expected number of pills taken multiplied by 100. Compliance will be calculated overall for AM, PM 
and total daily doses. If a bottle is not returned, we will compute compliance under 2 scenarios: 
• 
Case 1 (best): the number of pills taken is assumed to equal the number expected,  
• 
Case 2: the number of pills taken is assumed to equal 35. 
Compliance for individuals who failed to return bottles will be reviewed by the masked data review 
committee for exclusion from the PP population. 
 
In-person Dispense or Return Visits 
For each bottle, the expected number of pills taken will be derived as the difference between the 
return date and dispense date, minus any days that the drug was temporarily suspended at the 
discretion of the investigator. If the treatment discontinuation date is prior to the return date, the 
treatment discontinuation date is used. If the expected number of pills exceeds the number of 
pills dispensed, the expected number of pills is capped at 35. It will be assumed that 2 doses 
(one A.M. and one P.M.) were taken when study drug is dispensed on Day 1 and that 1 dose 
(one P.M.) was taken from the new bottle when study drug is dispensed on Days 29 and 57. It 
will be assumed that the A.M. dose was taken on the return visit prior to returning the bottle 
(Days 29, 57 and 85).  
Remote Dispense or Return Visits 
If a remote visit was conducted at a visit where drug was expected to be dispensed and/or 
returned, the expected number of pills taken will be derived as the difference between the 
reported first and/or last dose date for the bottle if the dispense and/or return date is missing, 
minus any days that the study drug was temporarily suspended at the discretion of the 
investigator. If the treatment discontinuation date is prior to the return date, the treatment 
discontinuation date is used. It will be assumed that 2 doses (one A.M. and one P.M.) were 
taken when study drug is dispensed in-person on Day 1 and that 1 dose (one P.M.) was taken 
from the new bottle when study drug is dispensed in-person on Days 29 and 57. It will be 
assumed that the A.M. dose was taken on the in-person return visit prior to returning the bottle 
(Days 29, 57 and 85). When a bottle is not dispensed and/or returned at an in-person visit, it will 
be assumed that 2 doses (one A.M. and one P.M.) were taken on the reported start and/or stop 
date. 
In addition to determining compliance to the study drug while on treatment, the percent of the target 84 
dosing days will also be computed. The % of target 84 dosing days will be calculated as the (treatment 
stop date – the treatment start date + 1 – number of days drug was temporarily withheld per the 
investigator) divided by 84 x 100. The number of days drug was temporarily withheld per the 
investigator will be calculated as the start date of study drug hold – date the study drug was resumed. 


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Study drug dosing will be listed by subject, visit and bottle. Information will include the date of dispense 
and return, number of pills returned, and number of pills lost.  
7. 
EFFICACY EVALUATION 
7.1. Overview of Efficacy Analysis Methods 
7.1.1. 
Multicenter Studies 
Study subjects will be recruited from 16 study sites. Since the number of subjects at some study sites is 
expected to be insufficient (<5 subjects) for evaluating site effects, study data will be analyzed as a 
whole, and no formal accommodation for site-to-site variation will be made.  
 
7.1.2. 
Assessment Time Windows 
Visit 
Window (Days) 
Screening 
Up to -42* 
Day 1 (Baseline) 
N/A 
Day 15 
+/- 3 
Day 29 
+/- 3 
Day 57 
+/- 3 
Day 85 
+/- 3 
Day 113 
+/- 3 
* Note: For subjects who consented prior to Version 4.0 of the ALE09 protocol, the screening window 
was shorter and was required to occur within 21 days of Day 1 (Baseline), rather than 42.  
 
Allowable visit windows for all scheduled visits are provided in Table 7-1. 
 
7.2. Estimand for the Primary Analysis 
The estimand for the primary analysis will serve as the first step in assessing the study’s primary 
objective, “to evaluate efficacy of JBT-101 for treatment of inflammatory pain related to active 
musculoskeletal disease in SLE”. The estimand components are detailed below. 
7.2.1. 
Primary Analysis Variable  
The pain numerical ratings scale (NRS) is a single-item pain numerical rating scale for pain, which is a 
segmented numerical version of the visual analogue scale in which the respondent selects a whole 
number (0-10) that best reflects the intensity of their pain. The NRS is anchored by two terms 
describing average pain severity extremes, one of “no pain” (score of 0) and one of “worst pain 
imaginable” (score of 10). The subjects rank their worst pain in the previous day, at about the same 


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time each evening, so the recall period is about 24 hours of the most recent entry. The subjects record 
their maximum daily pain NRS score each day using an IVRS. 
7.2.2. 
Population 
The analysis will use the mITT population (Section 4.1). 
7.2.3. 
Intercurrent Events and Strategies 
Per protocol, individuals should take study treatment twice daily and take no narcotic analgesics for 84 
days. Pain NRS should be recorded daily. Intercurrent events to consider for this study include: 
1. Missed doses of study treatment 
• 
Chance missed doses due to participant error 
• 
Temporary interruption of dosing for safety or investigator discretion 
• 
Early discontinuation of study treatment for reasons detailed in Protocol Section 5.8.1, 
including participant request, investigator discretion, safety concerns, new or increases 
doses of concurrent therapies, or starting prohibited meds. 
• 
Premature study withdrawal 
2. Missed NRS data 
• 
Unplanned missed reports due to participant failure to report 
• 
Premature study withdrawal 
For the primary estimand, NRS data from the first through the last dose of study treatment will be 
included in the analysis. We assume that NRS data missing either by chance or monotonically after 
some point in time are “missing at random” such that unobserved trajectories are presumed to be 
consistent with observed trends. NRS data for days where doses were missed due to chance or 
temporary interruptions will be included in the analysis. However, NRS data will be excluded if entered 
into the IVRS: 
• 
after discontinuation of study treatment,  
• 
on days when narcotic analgesics were taken,  
• 
after DMARDs were started, 
• 
after any increase in dose of systemic corticosteroids for treatment of SLE, including increases 
from baseline dosing and initiation of new treatment, 
• 
after violation of rules for allowed corticosteroid use for reasons not associated with SLE flares. 
o Specifically, per Protocol Section 5.6, Prohibited Medications, Table 2, increases of up to 
20 mg/day that are decreased back to the baseline dose within 7 days are permitted, but 
not on more than 2 occasions during the study. 
Days that narcotic analgesics were taken will be identified using the concomitant medication log. All 
medications with a WHO Drug ATC Code beginning with N02A will be considered a narcotic analgesic.  


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7.2.4. 
Primary Analysis and Population-Level Summary 
The primary hypothesis for this study is that JBT-101 treatment will result in improvement in the 
maximum daily pain NRS scores in SLE patients with active musculoskeletal disease. The null and 
alternative hypotheses to be tested are: 
 
H0: Linear trends from Day 1 to Day 84 are equivalent for each JBT-101 cohort and  
      placebo.  
HA: Linear trends from Day 1 to Day 84 are not equivalent across groups. 
 
For the primary analysis, the maximum daily pain NRS scores from Day 1 through end of treatment 
(typically Day 84) will be modeled using a mixed-effects model. NRS data up to the day of last dose of 
study treatment will be included according to Section 7.2.3. The fixed effects will include treatment 
group, time, time2, time- and time2 by treatment group interactions, as well as the Screening 7-day 
average maximum daily pain NRS and Screening FSS score as covariates. In order to avoid 
convergence issues due to numerical scaling, time for this model will be defined as the fraction the 
planned treatment period ranging from 0 to 1, and equal to (assessment date – treatment start 
date)/83. Within-subject random effects for intercept and slopes for time and time2 will be fit using an 
unstructured covariance matrix assuming a different structure for placebo and pooled active treatment 
groups. With the proposed scaling of the time variable, convergence problems are not anticipated. 
However, in the event of convergence problems, we will consider alternative covariance structures for 
random effects including: unstructured (2); compound symmetric with heterogeneous variances, and 
independent matrices with and without the assumption of different structures for placebo and pooled 
active treatment groups. The model with the lowest Akaike Information Criterion (AIC) will be selected.  
 
The primary hypothesis will be tested using the 3 degrees of freedom contrast comparing the 
difference in predicted means (µො) from Day 1 to Day 84 for each JBT-101 group versus placebo. That 
is, 
 (µො84 – µො1)𝑐𝑐𝑐𝑐ℎ𝑜𝑜𝑜𝑜𝑜𝑜 𝑖𝑖 -  (µො84 – µො1)𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃𝑃 = 0 for i=1 to 3. 
 
Denominator degrees of freedom will be estimated using the Kenward-Rogers approach. If the 3 df test 
is significant (α=0.05, two-sided), Bonferroni-corrected tests for three 1 df pairwise comparisons with 
placebo will be performed (i.e., uncorrected p-values will be multiplied by 3).  If the 3 df test is not 
statistically significant, confidence intervals for the 1df pair-wise comparisons with placebo will still be 
presented, but this information will be used for hypothesis generation and planning of future studies. 
Setting the Screening 7-day average maximum daily pain NRS and Screening FSS score at their 
means for the analysis population, model-based estimates for means at Days 1 and 84, slopes, mean 
change from Day 1 to Day 84 along with standard errors and 95% confidence intervals will be 
presented for each treatment group. In addition, each active treatment arm will be compared to placebo 
by presenting the differences in mean change from Day 1 to Day 84 along with standard errors and 
95% confidence intervals. 


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7.2.5. 
Sensitivity Analyses Supporting the Primary Analysis 
Sensitivity analyses analogous to the primary analysis will be performed separately for each of the 
following modifications to the estimand framework. 
• 
Population modifications:  
o PP population (Section 4.2) 
• 
Intercurrent Event Strategy modifications: 
o NRS data entered into the IVRS after discontinuation of study treatment and on days 
where DMARDs or narcotics were taken will be included in the analysis. This constitutes 
a conservative evaluation of the treatment effect. 
• 
Analysis modifications: 
o Test equivalence of the fixed effects longitudinal trends among treatment groups; a 9df 
test comparing intercepts, time slopes, and time2 slopes for placebo versus each active 
treatment, simultaneously. 
7.3. 
Secondary Estimands Supporting the Primary Objective 
The secondary analyses will support the primary analysis by providing a deeper understanding of 
events. P-values for all inferential analyses will be presented as a description of strength of evidence 
of relationships rather than tests of hypotheses. As such, no corrections for multiplicity are planned. 
Unless otherwise noted, all secondary analyses will be conducted using the mITT population. 
Additional analyses may be repeated on the PP population to further explore findings. 
7.3.1. 
Secondary Estimands based on the Primary Analysis Variable 
Unless otherwise noted, the following secondary analyses will be performed using the intercurrent 
event strategy detailed in Section 7.2.3 and the primary analysis model described in Section 7.2.4. 
• 
Model-based estimates for means at Days 1, 28, and 56, adjusted for “Screening 7-day average 
maximum daily pain NRS” and “Screening FSS Score” at their baseline means, and for mean 
change from Day 1 to Days 28 and 56 along with standard errors and 95% confidence intervals 
will be presented for each treatment group. In addition, each active treatment arm will be 
compared to placebo by presenting the differences in mean change from Day 1 to Days 28 and 
56 along with standard errors and 95% confidence intervals. 
• 
Model-based estimates for mean changes (with SEs and 95% CIs) from Day 1 to Days 28, 56, 
and 84 for placebo and for all JBT-101 dose groups pooled will be presented along with 
estimates for the mean difference between placebo and pooled active treatments at each 
specified time point. The difference between placebo and pooled active treatments will be 
evaluated at Day 84; the p-value from the appropriate contrast statement will be presented (1df 
t-test).   
• 
To evaluate the dose response for the change from Day 1 to Day 84, linear and quadratic 
orthogonal contrasts derived from the dose vector, {0,10,20,40} will be evaluated. Coefficients 
for the linear and quadratic dose-effect contrasts are shown in the table below.  
 
 
Coefficients for orthogonal contrasts 
 
0 
a 
10 
b 
20 
c 
40 
d 
linear 
-0.591608  
-0.253546  
0.0845154  
0.7606388 
quadratic 
0.5640761  
-0.322329 
-0.644658 
0.4029115 


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• 
To evaluate the impact of the Screening 7-day average maximum daily pain NRS on trends over 
time, the primary analysis model will be modified to include its interactions with time and time2. 
• 
Analyses analogous to the primary analyses using % change in NRS from baseline as the 
outcome variable, where baseline is defined as the average maximum daily NRS in the 7 days 
prior to dosing. 
• 
To evaluate the persistence of trends after treatment is stopped, the primary analysis model will 
be modified to include a variable for “time post-treatment” and its interaction with treatment 
group, where  
 
Time post-treatment  = 0, if participant is on treatment; 
 = (assessment date – last treatment date)/83, if participant has stopped 
treatment. 
 
For this analysis, observations beyond Day 84 will be included. 
 
• 
The primary analysis model will be modified to control for possible baseline imbalances of any 
of the following covariates: 
o Depression/Anxiety Medication Status: a dichotomous indicator variable will be created 
to indicate if a was taking a medication for anxiety or depression at baseline 
o Depression per PROMIS 29: a baseline depression score will be derived using the 4 
depression questions on the PROMIS 29 at baseline. The total depression score will 
range from 4 to 20 (see Appendix 13.8).  
o Anxiety per PROMIS 29: a baseline depression score will be derived using the 4 
depression questions on the PROMIS 29 at baseline. The total anxiety score will range 
from 4 to 20 (see Appendix 13.8).   
o Fatigue per PROMIS 29: a baseline fatigue score will be derived using the 4 fatigue 
questions the PROMIS 29 at baseline. The total fatigue score will range from 4 to 20 
(see Appendix 13.8).   
o Musculoskeletal BILAG score: an ordinal variable characterizing the musculoskeletal 
score at baseline defined as A=3, B=2, C=1, D/E=0 
o Total number of baseline tender joints 
o Total number of baseline swollen joints 
o Total number of baseline tender and swollen joints 
o Baseline DMARD and/or immunobiologic use 
o Baseline MMF use 
o Baseline Steroid use 
Only covariates with p-values ≤0.05 after backwards selection from the full model will be 
included.  
Model-based estimates for means at Days 1, 28, 56, and 84, adjusted for all covariates at their 
baseline means, and for mean change from Day 1 to Days 28, 56, and 84 along with standard 
errors and 95% confidence intervals will be presented for each treatment group. In addition, 
each active treatment arm will be compared to placebo by presenting the differences in mean 
change from Day 1 to Days 28, 56, and 84 along with standard errors and 95% confidence 
intervals.  


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7.3.2. 
Pain and Improvement Categories 
Variables: The pain category for Visit x is defined using the average of maximum daily pain NRS 
score recorded during the 7 days preceding Visit x. For example, a Visit 3 occurring on Day 29 will use 
NRS scores over the 7-day interval from Day 22 to Day 28. For the 7-day average for Visit x, all 
available values reported in the 7-days interval will be used, but no imputation will be done for missing 
pain NRS scores. If no pain scores are available for the 7 days prior to Visit x, the 7-day average for 
Visit x will remain missing. Pain categories will be derived at Visits 1, 3, 4, 5 and 6 as follows: 
 
No Pain 
7-day average of maximum daily pain NRS ≤ 1 
Mild Pain 
7-day average of maximum daily pain NRS > 1 and ≤ 3 
Moderate Pain 
7-day average of maximum daily pain NRS > 3 and ≤ 7 
Severe Pain 
7-day average of maximum daily pain NRS > 7 
 
In addition, the improvement category for Visit x is defined using the observed change in pain 
categories from the Visit 1 to Visits 3, 4, 5, and 6 as follows:  
Major 
Improvement 
Improvement by at least 2 pain categories from Visit 1 
Improvement 
Improvement by 1 pain category from Visit 1 
No change 
No change in pain category from Visit 1 
Worsening 
Worsening by at least 1 pain category from Visit 1 
 
Population: For analyses on change from baseline variables, only individuals from the mITT 
population with an available post-baseline assessment are included. 
 
Intercurrent Events: The intercurrent event strategy is as detailed in Section 7.2.3. 
 
Analyses: The number and percent of subjects in each pain and improvement category will be 
presented by treatment group for each visit. For each post-baseline visit and treatment group, this 
table will also include the p-value for a test of symmetry to help identify notable shifts (e.g., towards 
improvement or worsening) from baseline (Visit 1).  
 
Unless missing data are missing-completely-at-random (MCAR), suggesting subject loss is consistent 
across treatment groups and unrelated to treatment or disease, these estimates may be biased 
especially at later time points where more missing data are expected due to participant attrition. As 
such, treatment groups will be compared under the MAR assumption using estimates and tests 
derived from logistic regression models fit using the generalized estimating equation (GEE) approach. 
For these analyses, the pain categories will be dichotomized to “no pain or mild pain” and “moderate 
or severe pain”. The improvement categories will be dichotomized to “improvement” or “no 


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improvement”. Proportional odds models may be explored if there are sufficient numbers across 
ordinal categories.   
 
For each dichotomous outcome, the model will include fixed effects for visit, treatment, and the 
visit*treatment interaction and be fit using the GEE approach under the binomial distribution with the 
logit link. The model will be fit with an unstructured within-subject correlation structure across visits 
unless convergence problems arise, in which case an exchangeable correlation structure will be 
assumed.  
 
The focus of the analysis will be on estimation of treatment effects. For each visit, estimated odds-
ratios (with 95% CI) for pairwise comparisons with placebo and probabilities (with 95% CI) for each 
treatment group will be presented. The p-values for the 3 degree-of-freedom tests comparing each 
active treatment versus placebo at each visit will be presented. Since the difference between active 
treatment groups and placebo at Visit 5 (i.e., Day 84, end of treatment period) is of key interest, p-
values for pairwise comparisons of each active group versus placebo will be presented. P-values are 
uncorrected for multiple comparison and will be interpreted with caution. 
 
7.3.3. 
Percent Improvement Responder Status 
At each visit, dichotomous responder status variables will be defined to indicate 30%, 50%, 75% or 
100% improvement. The responder status for various percentage thresholds will be derived using the 
% change in pain, defined as follows: 
 
% 𝑐𝑐ℎ𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎 𝑖𝑖𝑖𝑖 𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝= 𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉 17𝐴𝐴𝐴𝐴𝐴𝐴−𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉 𝑥𝑥7𝐴𝐴𝐴𝐴𝐴𝐴
𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉 17𝐴𝐴𝐴𝐴𝐴𝐴
 ×  100 
 
Where x is Visit 3 (Day 29), Visit 4 (Day 57), Visit 5 (Day 85) and Visit 6 (Day 113). The subscript 7AVG 
denotes the 7-day average maximum daily pain NRS score calculated using the 7 days prior to the 


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associated visit, as described for pain categories in Section 7.3.2. Positive values represent 
improvement. 
 
If the % change in pain is greater than or equal to the percentage threshold, a subject will be 
considered a responder for that threshold at the associated visit. For example, 
responder_30  
= 1, %change in pain is ≥ 30%; 
= 0, % change in pain < 30%; 
= missing, if % change in pain is missing. 
 
 
The population, intercurrent event strategy, and analyses for the response status variables will be 
analogous to those outlined in Section 7.3.2, Pain and Improvement Categories.   
 
7.4. 
Estimands Supporting Secondary Objectives 
 P-values for all inferential analyses will be presented as a description of strength of evidence of 
relationships rather than tests of hypotheses. As such, no corrections for multiplicity are planned. 
Unless otherwise noted, all secondary analyses will be conducted using the mITT population. 
7.4.1. 
Evaluation of Active Musculoskeletal Disease Activity 
7.4.1.1. Physician Tender Joint Count 
Variable: The Physician tender joint count will be assessed at Visit 1 and Visits 3 through 6. 
This assessment must be conducted in-person by a physician. Tenderness will be assessed in 
68 joints, which include: upper—temporomandibular, sternoclavicular, acromioclavicular, 
shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal 
interphalangeal; lower—hip, knee, ankle, tarsus, metatarsophalangeal and interphalangeal. The 
change in the total number of tender joints from Visit 1 to each post-baseline visit will be 
computed.  
Population: Analyses will use the mITT population. Inferential analysis will use the subset of 
the mITT subjects with at least one post-baseline assessment (Section 4.1).  
Intercurrent Event Strategy: Physician tender joint count data, the intercurrent event strategy 
is as detailed in Section 7.2.3. 
Population-level summary: Descriptive statistics on the physician tender joint count will be 
presented for each visit. The change in physician tender joint count from Visit 1 (Day 1) to Visits 
3 (Day 26), 4 (Day 57), 5 (Day 85), and 6 (Day 113) will be evaluated using a repeated 
measures mixed model. The fixed effect model will be fit with no intercept and include 
interaction terms for the baseline tender joint count (centered at the baseline mean for the mITT 
population)-by-visit (categorical) and treatment group*visit.  Parameter estimates for the 
treatment group*visit effects will be the estimated treatment means at each visit adjusted for 
differences at baseline. The random effects will include subject-level intercepts and slopes for 
time and time squared (as defined in Section 7.2.4) using separate unstructured covariance 
structures for placebo and pooled active treatments. This model is analogous to fitting separate 
analysis of covariance models for each visit but takes advantage of the multiple measures within 
subject to generate unbiased estimate in the presence of missing data under the missing-at-


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random assumption. Model-based estimates and 95% CI for mean change from baseline will be 
presented for each treatment group at each post-baseline time-point.  Estimated treatment 
group differences in mean change from baseline versus placebo with 95% CI will also be 
presented at each post-baseline time-point. The p-value for the test of overall treatment group 
effect will be presented at Day 85. If this p-value is <0.05, then p-values for pairwise 
comparisons of active groups versus placebo will be presented. Denominator degrees of 
freedom will be estimated using the Kenward-Rogers approach. 
The post-treatment time point, Visit 6 (Day 113), is not included in this model. To explain, in 
order to account for missing data under the missing-at-random assumption, the estimated 
subject-level trajectories over time (i.e., random effects) are used to estimate fixed-effect for 
treatment at each visit. If active treatment is effective in reducing joint counts, then that effect 
could wane after treatment is stopped. Hence, including this post-treatment time point in the 
random effect model that estimates subject-level trajectories over time could bias the fixed 
effects treatment estimates. Should model results show interesting treatment effects during the 
treatment period, the persistence of trends after treatment is stopped may be explored by 
modifying the model to include Visit 6 (Day 113) as a fixed effect and exploring different random 
effect models to appropriately account for a possible post-treatment change in subject-level 
trajectories. 
7.4.1.2. Physician Swollen Joint Count 
Variable: The Physician swollen joint count will be assessed at Visit 1 and Visits 3 through 6. 
This assessment must be conducted in-person by a physician. Swollenness will be assessed in 
66 joints, which include: upper—temporomandibular, sternoclavicular, acromioclavicular, 
shoulder, elbow, wrist, metacarpophalangeal, proximal interphalangeal and distal 
interphalangeal; lower—hip, knee, ankle, tarsus, metatarsophalangeal and interphalangeal. The 
change in the total number of swollen joints from Visit 1 to each post-baseline visit will be 
computed. 
The population, intercurrent event strategy, and analyses will be analogous to those specified in 
Section 7.4.1.1, Physician Tender Joint Count. 
7.4.1.3. Physician Tender and Swollen Joint Count 
Variable: The number of joints that are both tender and swollen will be calculated at Visit 1 and 
Visits 3 through 6 using the Physician Tender Joint Count (as described in Section 7.4.1.1) and 
Physician Swollen Joint Count (as described in Section 7.4.1.2). The change in the total number 
of joints that are both tender and swollen from Visit 1 to each post-baseline visit will be 
computed. 
The population, intercurrent event strategy, and analyses will be analogous to those specified in 
Section 7.4.1.1, Physician Tender Joint Count. 
 
7.4.1.4. SELENA SLEDAI Score 
Variable: At Visit 1 and Visits 3 through 6, study investigators complete the SLEDAI scale by 
indicating of presence of 24 SLE disease manifestations during the preceding 30 days. The 
original SLEDAI instrument includes an evaluation of proteinuria based on the protein: 


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creatinine ratio derived from a 24-hour urine. For this study, the protein: creatinine ratio will 
typically be derived from the spot urine assessment, although a 24-hour urine may be used if 
the spot urine assessment is not available. Each of the 24 disease manifestations has an 
assigned weight (see Appendix 13.3). Two systems can score a maximum of 8 points each, 2 
systems can score a maximum of 4 points each, 3 systems can score a maximum of 2 points 
each, and 2 systems can score a maximum of 1 point each. The SLEDAI total score will be 
computed as the sum of the weights for the items indicated as present and can range from 0 to 
105 points. If a component of the SLEDAI that is assessed using laboratory results (Questions 
11-14, 20-21 or 23-24) was missed at a visit, then the missing data will be imputed by using the 
last observation carried forward approach. If a component of the SLEDAI is missed over 
consecutive visits, then the subsequent components will not be imputed. If any other component 
was missed, the score will not be computed. 
 
The change in the SLEDAI total score from Visit 1 to each post-baseline visit will be computed. 
The population, intercurrent event strategy, and analyses will be analogous to those specified in 
Section 7.4.1.1, Physician Tender Joint Count. 
7.4.1.5. BILAG 2004 Total Score 
Variable: The British Isles Lupus Assessment Group (BILAG) 2004 (2009 Revision) instrument 
will be completed at Screening, Visit 1, and Visits 3 through 6 for all subjects.  
The rules for scoring the BILAG 2004 are in Appendix 13.4 BILAG 2004 Index Scoring. In each 
of the nine body system categories (constitutional, mucocutaneous, neuropsychiatric, 
musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal, and hematological) 
subjects are assessed on a variety of disease activity criteria. Each category is then scored as 
an A, B, C, or D/E, where A indicates most severe disease activity and D/E indicates inactive/no 
disease activity. For this study the following additional scoring rules are applied: 
1. According to the scoring algorithm, D means "Inactive disease but previously 
affected", and E means "System never involved". Since we may not know whether 
the subject has ever experienced involvement in a particular system prior to starting 
the study, we will not attempt to distinguish between D and E. Subjects will be 
assigned the score “D/E” if they did not meet the criteria for A, B, or C at the 
particular visit. 
2. In the Renal category, some of the scoring rules require looking at previous 
measurements to assess change (e.g., GFR < 80 ml/min per 1.73 m2 and having 
fallen to < 67% of previous value). BILAG is collected at Screening and may require 
further information (e.g., a pre-screening GFR) in order to ascertain a score. Under 
the following circumstances, sites will be asked to report recent (within 3 months of 
Screening) results in an attempt to fully score the renal category at Screening: 
• 
Urine protein: creatinine ratio ≥ 50 mg/mmol 
• 
Serum creatinine > 1.47 mg/dL (or 130 µmol/L) 
• 
GFR < 80 ml/min per 1.73 m2 
However, if these data are not available and it can be confirmed that that the Renal 
category would not score to an A, the subject may proceed in the study. Since it is 
not possible to determine if the score is a B, C or D/E in these cases, the subject will 
be missing a Renal score at Screening. 


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3. In the Renal category, the original instrument includes an evaluation of proteinuria 
based on the protein: creatinine ratio derived from a 24-hour urine. For this study, the 
protein: creatinine ratio will typically be derived from the spot urine assessment 
although a 24-hour urine may be used if the spot urine assessment is not available. 
 
A numerical BILAG total score will be computed using the coding scheme proposed by Yee et 
al. For each of the nine domains, a numerical score will be assigned based on the BILAG score 
as follows: A=12, B=8, C=1 and D/E=0. A single numerical BILAG total score will be calculated 
for each participant visit as the summation of the numerical scores for each of the nine domains. 
The change in the BILAG total score from Visit 1 to each post-baseline visit will be computed. 
The population, intercurrent event strategy, and analyses will be analogous to those specified in 
Section 7.4.1.1, Physician Tender Joint Count. 
 
7.4.1.6. Arthritis on the SELENA-SLEDAI 
Variable: The SELENA SLEDAI score is assessed as described in Section 7.4.1.4, SELENA 
SLEDAI Score. Question 9 on this instrument (see Appendix 13.3) assesses arthritis (present or 
absent), defined as more than 2 joints with pain and signs of inflammation (i.e., tenderness, 
swelling, or effusion).  
The change (improved, no change, worsened) from Visit 1 to each post-baseline visit will be 
computed. In addition, for evaluating longitudinal trends, a dichotomous response status 
variable at each follow-up visit will be defined as follows: 
o Improvement: Change from baseline score of “Improved” (e.g., present to not present) 
o No Improvement: Change from baseline score of “No Change” or “Worsened” 
The population and intercurrent event strategy will be analogous to those outlined in Section 
7.3.2, Pain and Improvement Categories. 
Analyses: Descriptive statistics summarizing the number and percentage of subjects with 
arthritis marked as present or absent will be summarized by treatment group and visit. The 
change (improved, no change, worsened) from Visit 1 to each post-baseline visit will also be 
summarized descriptively by treatment group and visit. To help identify notable shifts from 
baseline, either improvement or worsening, the p-value for McNemar’s test for symmetry will 
also be presented for each post-treatment visit and treatment group. 
The longitudinal GEE models for the presence/absence of arthritis and the dichotomous 
response status variables will be analogous to those outlined in Section 7.3.2, Pain and 
Improvement Categories. 
7.4.1.7. BILAG-based Arthritis Severity Assessment 
Variable: At Visit 1 (baseline), the ordinal BILAG-based arthritis severity category is defined as 
per Section 5.2.  The definition of “Improvement” during the treatment period (i.e., Visits 3 (Day 
29), 4 (Day 57) and 5 (Day 85)) depends on baseline severity category, as follows: 


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i. 
If the BILAG-based arthritis severity category is Severe at baseline, then improvement is 
demonstrated if 
• 
The Arthritis Severe item is scored as Improved or Not Present at least once on 
Days 29, 57 or 85, AND the Arthritis Severe item is not scored as Worse or New on 
any of those days, AND the Arthritis Moderate item is not scored as Worse or New 
on any of those days, or if 
• 
The Arthritis Severe item is scored as Not Present on Day 85. 
 
ii. 
If the BILAG-based arthritis severity category is Moderate at baseline, then improvement 
is demonstrated if 
• 
The Arthritis Moderate item is scored as Improved or Not Present at least once on 
Days 29, 57 or 85, AND the Arthritis Severe item is not scored as Worse or New on 
any of those days, AND the Arthritis Moderate item is not scored as Worse or New 
on any of those days, or if 
• 
The Arthritis Moderate item is scored as Not Present on Day 85. 
 
iii. 
If the BILAG-based arthritis severity category is Mild at baseline, then improvement is 
demonstrated if 
• 
The Arthritis Mild item is scored as Improved or Not Present at least once on Days 
29, 57 or 85, AND the Arthritis Severe item is not scored as Worse or New on any of 
those days, AND the Arthritis Moderate item is not scored as Worse or New on any 
of those days, AND the Arthritis Mild item is not scored as Worse or New on any of 
those days, or if 
• 
The Arthritis Mild item is scored as Not Present on Day 85. 
 
The population for these analyses is limited to the subset of individuals who have arthritis at 
Visit 1 and who have data available for Visits 3-5. The intercurrent event strategy requires 
complete data. 
Analyses: Descriptive statistics summarizing the number and percentage of subjects who 
improved during the treatment period will be presented by treatment group for each baseline 
BILAG-based arthritis severity category and overall. The help identify notable differences among 
treatment arms in the proportion who improved, the p-value for the Mantel-Haenszel chi-
squared test after adjusting for baseline BILAG-based arthritis severity category. If this p-value 
is <0.05, pair-wise comparisons for each active arm versus placebo will also be presented. 
 
7.4.1.8. Physician’s Global Assessment 
Variable: The Physician’s Global Assessment (PGA) will be completed at Screening, Visit 1, 
and Visits 3 through 6. The PGA utilizes a 0 to 3 visual analogue scale that is anchored by the 
following descriptors: 
• 
0 = none 
• 
1 = mild 
• 
2 = moderate 
• 
3 = severe 


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The change in the PGA from Visit 1 to each post-baseline visit will be computed. 
 
The population, intercurrent event strategy, and analyses will be analogous to those specified in 
Section 7.4.1.1, Physician Tender Joint Count. 
7.4.1.9. SLE Responder Index 
Variable: The SLE Responder Index (SRI) will define a responder as having met all of the 
following conditions: 
• 
≥ 4 point reduction in the SELENA SLEDAI score from Visit 1 (Day 1) 
• 
No new BILAG A or no more than 1 new BILAG B domain score from Visit 1 (Day 1) 
• 
No deterioration from baseline in the PGA, defined as an increase of ≥ 0.3 points from 
Visit 1 (Day 1) 
The population, intercurrent event strategy, and analyses for the response status variables will be 
analogous to those outlined in Section 7.3.2, Pain and Improvement Categories. 
7.4.2. 
Evaluation of Patient-reported Outcomes 
7.4.2.1. Lupus Activity Patient Global Assessment 
Variable: The Lupus Activity Patient Global Assessment will be completed at Screening, Visit 1, 
and Visits 3 through 6. The Lupus Activity Patient Global Assessment utilizes a 0 to 100 mm 
visual analogue scale that is anchored by the two descriptors: not active (score of 0) and 
extremely active (score of 100). The recall period for this assessment is one week. 
The change in the Lupus Activity Patient Global Assessment from Visit 1 to each post-baseline 
visit will be computed. 
 
The population, intercurrent event strategy, and analyses will be analogous to those specified in 
Section 7.4.1.1, Physician Tender Joint Count. 
 
7.4.2.2. PROMIS-29 Short Form 
Variable: The PROMIS-29 will be completed at Screening, Visit 1, and Visits 3 through 6. 
The PROMIS-29 contains 29 items which include 4 items each from the following domains 
known to impact activities of daily living: physical function, sleep disturbance, depression, 
anxiety, fatigue, pain interference, pain intensity, and social role satisfaction. The final item 
is an 11-point pain intensity numerical rating scale (NRS) by which the subject rates their 
average pain over the past 7 days from 0 (no pain) to 10 (worst pain imaginable). With the 
exception of physical function, which does not include a time frame, all item banks 
reference the past 7 days. Two scores are available for each PROMIS domain: the total raw 
score and transformed score (T-score). To find the total raw score for a domain, all items 
must be answered. The total raw score will be derived as the sum of the values associated 
with the response to each question (see Appendix 13.8). The total raw summed score can 
range from 4 to 20 for each domain. The total raw summed score will then be translated into 
a T-score for each participant using the associated table in the scoring guide found in 


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Attachment 14.1. The T-score will be analyzed in this study. The change in the T-score from 
Visit 1 to each post-baseline visit will be computed for each domain. 
Analysis: The population, intercurrent event strategy, and analyses will be analogous to those 
specified in Section 7.4.1.1, Physician Tender Joint Count. 
7.4.2.3. PROMIS v2.0 – Cognitive Function Short Form 8a 
Variable: The PROMIS v2.0 Cognitive Function will be completed at Screening, Visit 1, and 
Visits 3 through 6. The PROMIS Cognitive Function will be scored using the 8-question short 
form. Two scores are available for the PROMIS Cognitive function scoring: the total raw score 
and transformed score (T-score). To find the total row score, all items must be answered. The 
total raw score will be derived as the sum of the values associated with the response to each 
question (see Appendix 13.9). The total raw score can range from 8 to 40. The total raw 
summed score will then be translated into a T-score for each participant using the associated 
scoring table in the scoring guide found in Attachment 14.1. The T-score will be analyzed in this 
study. The change in the T-score from Visit 1 to each post-baseline visit will be computed. 
Analysis: The population, intercurrent event strategy, and analyses will be analogous to those 
specified in Section 7.4.1.1, Physician Tender Joint Count. 
7.4.2.4. Treatment Satisfaction Survey 
At the end of treatment, both the subject and the physician will complete separately a survey 
asking what treatment assignment they think that the subject received (JBT-101, placebo, can’t 
tell), whether the subject received benefit from the assigned treatment (yes or no), and whether 
the subject or physician would choose to continue that treatment (yes or no). 
Analysis: The number and percentage of subjects will be presented for each question and 
answer by treatment group.  
8. 
SAFETY EVALUATION 
8.1. 
Overview of Safety Analysis Methods 
All safety analyses will be carried out using the safety sample defined in Section 4.3 unless otherwise 
noted. Missing safety information will not be imputed. These analyses will not be stratified by site.  
Safety will be analyzed in each dose group through the reporting of adverse events (AEs), vital signs, 
physical examination findings, ECG findings, and changes in routine laboratory values. 
Listings will be prepared for all safety measurements. All listings will be sorted in order of treatment, 
subject identifier (ID), and time of assessment (e.g., visit, time, and/or event).} 
8.2. 
Extent of Exposure 
Duration of exposure will be defined as the last dose date – first dose date + 1. Descriptive statistics will 
be presented by treatment arm.  


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8.3. 
Adverse Events 
All AEs will be classified by system organ class (SOC) and preferred term, according to a standardized 
thesaurus (Medical Dictionary for Regulatory Activities [MedDRA] version 23.0). The severity of AEs will 
be classified using the National Cancer Institute’s (NCI’s) Common Toxicity Criteria for Adverse Events 
(CTCAE) version 4.0. Each AE is entered on the electronic case report form (eCRF) once at the highest 
severity. As such, no additional data manipulation is needed to identify events. 
AEs will be collected from screening through study termination. Treatment-emergent AEs will be 
identified as those with an onset date on or after the first dose of study medication. If the start of the AE 
in relation to the start of study medication cannot be established (e.g., the start date for the AE is 
missing), then the AE will be considered treatment-emergent. If an abnormal laboratory finding or an 
abnormal pre-dose ECG is reported as an AE on the first day of study drug (Day 1), these events will 
not be considered treatment emergent since these assessments occur prior to treatment initiation. All 
data tabulations will be of only treatment-emergent events while non-treatment-emergent AEs will be 
listed separately.  
 
An overall summary table will be developed to report the number of events and the number and 
percentage of subjects having at least one event in the following categories:  
• 
AEs 
• 
AEs indicated as serious 
• 
Adverse Events of Special Interest (AESIs) 
• 
AESIs by the following AESI criteria:  
• 
QTc prolongation > 500 msec total duration and > 60 msec from Visit 1 (Day 1) QTc interval prior 
to study drug administration 
• 
Severe disease flares by SELENA SLEDAI Flare Index and/or a new BILAG A score except in 
musculoskeletal domain 
• 
Aspartate aminotransferase or alanine aminotransferase ≥ 3 x upper limit of normal and total 
bilirubin > 1.5 x the upper limit of normal, present on repeat testing  
• 
AEs that lead to study drug discontinuation 
• 
AEs deemed at least possibly related to study drug that led to study drug discontinuation 
• 
AEs with an outcome of death 
• 
AEs that were reported as being related to a study drug 
• 
AEs reported by severity 
• 
Grade 3 or higher AE deemed at least possibly related to study drug 
 
In addition, AEs classified by MedDRA SOC, and preferred term will be summarized for each 
treatment group and overall, for each of the following: 
• 
All AEs 
• 
All SAEs 
 


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Summary tables will present the total number of events, the number and percentage of subjects 
experiencing the events, and the incidence density for each treatment arm and overall. If a subject 
experiences the same AE on multiple occasions, the event will be counted once for each occurrence 
when reporting the number of AEs. When reporting the number of subjects experiencing the events, a 
subject will only be counted once if they experience an event within the particular SOC or preferred 
term. Percentages will be based on the number of subjects in the safety population. To account for 
differential follow-up time between treatment arms, incidence density will be presented and calculated 
for each treatment arm as the number of AEs divided by the time of exposure aggregated across 
participants (person-weeks). 
 
For the pre-specified safety endpoints, including Grade 3 or higher related AEs, QTc prolongation 
AESIs, elevated liver function test AESIs, and all related AEs, Poisson regression models will be fit. 
Point estimates for incidence densities with 95% CIs will be presented for each arm. In addition, for 
each active arm, the incidence density ratio compared with placebo will be presented with the 95% 
CIs.  
 
Separate data listings will be provided for treatment-related AEs and AEs leading to study drug 
discontinuation. 
8.4. 
Deaths and Serious Adverse Events 
Serious adverse events (SAEs) will be listed and summarized in the same manner described in Section 
8.3. Separate displays listing and summarizing death, including time to death and cause of death, will 
also be created. 
8.5. 
Clinical Laboratory Evaluation 
Clinical laboratory measurements include serum chemistry, hematology, urinalysis (microscopic and 
spot protein: creatinine), anti-dsDNA antibodies, C3, C4, and C-reactive protein. Laboratory results will 
be reported from a central lab. However, sites can additionally report unscheduled results performed 
locally in the EDC. Local results will be converted to standardized units where possible. Changes in 
laboratory parameters that represent increases NCI-CTCAE severity grade over time are captured as 
AEs and summarized as described in Section 8.3. 
 
For numeric laboratory results, descriptive statistics of laboratory values and the change from baseline 
of laboratory values will be presented for each treatment group and overall. For categorical laboratory 
results, the number and percentage of subjects reporting each result will be presented for each 
treatment group and overall.  
 
Laboratory data will be plotted to show patterns over time. Summary statistics including 25th percentile, 
median, and 75th percentile will be plotted for each visit by treatment group. Lines connecting 
individual subject results from subjects with grade 2 or higher values will be overlaid on each figure. 
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normal or 0.5*lower limit of normal will be overlaid. Tests with qualitative results (such as “present” or 
“positive”) will not be plotted. 
 
8.6. 
Other Observations Related to Safety 
8.6.1. 
Disease Flares 
Disease flares will be assessed using BILAG and SLEDAI scoring criteria. BILAG 2004 disease flares 
will be defined as one new BILAG A or two new BILAG B scores from the previous visit. A BILAG flare 
will not be considered resolved until the score returns to a score of D/E. For example, a BILAG score of 
C at Visit 1 that increases to a B at Visit 2, decreases to a score of C at Visit 3, and increases to a 
score of B at Visit 4, will only be considered as new BILAG B score at Visit 2. 
The SELENA SLEDAI flare instrument assesses SLE flares based on changes in the SLEDAI score, 
the PGA, medication use, other disease activity criteria and hospitalization due to SLE. See Appendix 
13.3 for more information on scoring of the SELENA SLEDAI flare instrument. For each subject, yes/no 
variables will be created to indicate whether a subject had a mild/moderate flare or whether a subject 
had a severe flare at each visit. A subject will only be counted as the flare type of maximum severity. 
E.g., if a subject has a severe flare, they will not be counted as also having a mild/moderate flare. 
The number and percent of subjects experiencing any flare overall during the study and the number 
and percentage of subjects experiencing each of the following flare types will be summarized 
descriptively: 
• 
One new BILAG A score 
• 
Two new BILAG B scores 
• 
Mild/moderate SELENA SLEDAI flare 
• 
Severe SELENA SLEDAI flare 
• 
Severe SELENA SLEDAI flare, excluding those trigged only by the new prescription of major 
immunosuppressive for SLE activity criterion 
In addition, the number and percent of subjects experiencing at least one flare by each visit will be 
summarized descriptively overall and by flare type.  
In addition, the total number of flares and incidence density defined as the number of flares divided by 
the person-time of exposure aggregated in each treatment arm will be presented overall and for each 
flare type. A Poisson regression model will be fit and incidence density ratios with 95% CI for each 
active arm will be presented compared to placebo. Timeline plots indicating flares over time for each 
subject will be presented by treatment arm. 
8.6.2. 
ARCI-M 
The ARCI-M questionnaire will be completed by subjects at Visit1 (Day 1) pre- and post-dosing, Visit 3 
(Day 29) and Visit 5 (Day 85). This is a 12-item true/false questionnaire developed by the National 
Institutes of Drug Abuse, designed to detect the full range of subjective responses experienced by 
marijuana users. An answer of true has an assigned value of 1 and an answer of false has an assigned 
value of 0. The ARCI-M score will be computed as the sum of the assigned values for all 12 questions 
and can range from 0 to 12. If a question is missed, the score will not be calculated.  


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The number and percentage of subjects experiencing an increase of ≥ 1 from the Visit 1 (Day 1) pre-
dose assessment will be presented at Visit 1 (Day 1) post-dose, Visit 3 (Day 29) and Visit 5 (Day 85). 
 
8.6.3. 
New or Increased SLE Medications 
Medications will be collected in an ongoing log throughout the study. The following medications for SLE 
are either expected to remain stable or are disallowed during the course of the study: 
• 
Systemic corticosteroids (including oral, intra-articular, intravenous and intramuscular) 
• 
Cyclophosphamide or anti-TNFalpha biologic agents 
• 
Rituximab, ocrelizumab, anti-CD22 monoclonal antibody 
• 
Methotrexate, mycophenolate, azathioprine, leflunomide, belimumab, cyclosporine, or 
tacrolimus 
• 
Narcotic analgesics for SLE activity 
The above medications will be identified using the coded medication data. Any of these medications 
that are newly prescribed or increased in dose following treatment initiation will be flagged and the 
study day of the new or increase will be recorded.  
A time to event analysis will be performed on the time from treatment initiation until first new or 
increase in medication for SLE. Participants who prematurely terminate from the study will be 
censored at the time of last follow-up. The probability of event will be presented graphically using 
Kaplan-Meier curves by treatment group. Kaplan-Meier estimates of event-free survival and 
confidence intervals using Greenwood’s formula for standard error will be reported by treatment group 
at Day 85. A log rank test (2-sided α=0.05) will be performed to test the hypothesis that there is no 
difference between the survival curves by treatment arm.  
9. 
OTHER ANALYSES 
9.1. Use of Medications 
Medications will be coded according to the World Health Organization (WHO) Drug Dictionary (version 
2017.03). Medications reported on the CRF will be categorized for analysis as prior, concomitant, or 
after study treatment by comparing the medication start and stop dates with the first and last dose of 
study medication dates. Prior medications will have both the medication start and stop dates prior to 
the first dose of study medication date. After medications will have both the medication start and stop 
dates after the last dose of study medication date. All other medications will be classified as 
concomitant, indicating that use of the medication overlapped with use of the study medication by at 
least one day.  
 
Medications received prior to, concomitant with, and after study medications will be listed.   
 
10. 
INTERIM ANALYSES AND DATA MONITORING 
The progress of the study will be monitored by the Data and Safety Monitoring Board (DSMB). The 
Autoimmune DSMB will be chartered to review safety data and to make recommendations regarding 


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continuation, termination, or modification of the study. The DSMB will formally review the safety data 
at least yearly. The discontinuation of study treatment will also be periodically reported to the DSMB.  
In addition, safety data will be reviewed by the DSMB when an event occurs that is of sufficient 
concern to the National Institute of Allergy and Infectious Diseases (NIAID) medical monitor or protocol 
chair to warrant review, or when an event occurs that could contribute to a predefined stopping rule 
specified in the protocol.  
Findings will be reported to Institutional Review Boards (IRBs) and health authorities. 
11. 
CHANGES TO THE ANALYSES PLANNED IN THE PROTOCOL 
Section 8.3.2.1 of the protocol states, “In the event of convergence problems using an unstructured 
covariance matrix with within-subject random effects for intercept and slopes for time and time^2, that 
the covariance structure will be simplified by dropping the random effect for time^2.” Upon exploration 
of masked data, convergence problems can be avoided by rescaling the time variable as detailed in 
Section 7.2.4. However, we have also included the option to explore alternative covariance structures. 
In addition, the Dunnett’s correction for multiple comparisons was planned for the pairwise step-down 
test.  However, the operational characteristic of this correction when using Kenward-Rogers degrees of 
freedom are unknown. Hence, we have opted to use a simple Bonferroni-correction, which should not 
be overly conservative for 3 comparisons. 
Section 8.3.2.1 of the protocol states, “The fixed effects model will include treatment group, time, time2, 
time- and time2 by treatment group interactions, as well as the Screening 7-day average maximum daily 
pain NRS as a covariate.” An additional covariate for the Screening FSS Score will be added to the 
model. Including both the Screening 7-day average maximum daily pain NRS and Screening FSS 
Score as covariates should adequately control for random imbalances of baseline pain between the 
treatment arms. The decision to add Screening FSS Score as a covariate was agreed upon prior to 
finalization of Version 1.0 of the SAP, however due to an oversight was not included in Version 1.0. 
This issue was identified after database lock and unblinding, but prior to conducting the unblinded 
analyses. Since there was email documentation (see Appendix 13.11) that this edit was intended to be 
made prior to finalizing Version 1.0 of the SAP, the study team revised the SAP to Version 2.0 to 
include this covariate. 
 


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12. 
REFERENCES 
1. Yee CS, Cresswell L, Farewell V et al. Numerical scoring for the BILAG-2004 index. 
Rheumatology 2010;49:1665_9. 
 


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13. 
APPENDICES  
13.1. Schedule of Events 
 
 
 
 
 
Treatment 
Post Treatment 
Unsched
uled Visit 
Time Point 
Screeni
A
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Early 
Withdraw
al Visit (if 
needed)
Visit Windows (Days) 
Up to -
42 
Day 1 
Day 15 
± 3  
Day 29 
± 3 
Day 57 
± 3 
Day 85 
± 3 
Day 113 
± 3  
Clinical Blood Draw (mL) 
20-23 
11 
8 
11 
11 
11 
11 
11 
11 
Research Blood Draw (mL) 
NA 
48.5 
34 
10.5 
NA 
40.5 
40.5 
40.5 
NA 
Visit Draw Total (mL) 
20-23 
59.5 
42 
21.5 
11 
51.5 
51.5 
51.5 
11 
General Assessments 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Demographics  
X 
 
 
 
 
 
 
 
 
 Verify Eligibility Criteria 
 
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
Assess reproductive and birth control 
t t
X 
 
 
 
 
 
 
 
 
Last menstrual period 
X 
XB 
 
XB 
XB 
XB 
XB 
XB 
 
Prior/ Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination 
X 
X 
 
X 
X 
X 
X 
X 
X 
Register subject in IVRS system 
X 
 
 
 
 
 
 
 
 
Randomization, prior to Day 1 
X 
 
 
 
 
 
 
 
 
Vital signs: Weight, blood pressure and 
pulseC, respiratory rate, and temperature 
(& height at Visit 1)
X         
X 
X 
X 
X 
X 
X 
X 
X 
Adverse event monitoring 
 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead electrocardiograms, QT/QTc 
analyses 
X 
XD 
 
 
 
X 
 
 
 
Patient Reports 
Maximum daily pain NRS scoreE 
Reported daily by subject via IVRS 
Review reported pain NRS scores 
Site personnel will review subject reported data each week 
Addiction Research Center Inventory-
M
ij
(ARCI M)
 
XD 
 
X 
 
X 
 
XF 
 
Lupus Activity Patient Global Assessment 
 
X 
 
X 
X 
X 
X 
X 
 
PROMIS-29 Short Form 
 
X 
 
X 
X 
X 
X 
X 
 
PROMIS Item Bank v2.0 - Cognitive 
F
ti
 
X 
 
X 
X 
X 
X 
X 
 
Fibromyalgia Symptom Scale 
X 
X 
 
 
 
X 
X 
X 
 
Treatment Satisfaction SurveyG 
 
 
 
 
 
X 
 
XG 
 
Physician Assessment 
66/68 Joint Count  
 
X 
 
X 
X 
X 
X 
X 
 
SELENA SLEDAI 
X 
X 
 
X 
X 
X 
X 
X 
 
BILAG 2004 
X 
X 
 
X 
X 
X 
X 
X 
 
Physician’s Global Assessment 
X 
X 
 
X 
X 
X 
X 
X 
 
Treatment Satisfaction Survey 
 
 
 
 
 
X 
 
XG 
 
 


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A. The screening period can be any duration between 7 and 42 days prior to Visit 1 (Day 1), provided the duration is 
adequate to ensure the subject meets all inclusion and exclusion criteria and drug can be shipped to the site on time for 
that subject. Screening can take place over more than one visit to the clinic. Screening laboratory tests, other than HIV, 
hepatitis, or pregnancy testing, can be repeated at the investigator’s discretion. 
B. For women of childbearing potential.  
C. Seated (> 5 minutes) blood pressure and pulse.  
D. Will be measured at Visit 1 (Day 1) both before and 2.5 to 3.5 hours after administration of study product in the clinic.  
E. Record within 24 hours after most recent diary entry to prevent reporting of the same data. 
F. 
ARCI-M will be assessed at the Early Withdrawal Visit if a subject is withdrawn from the study or discontinues the study 
prior to Visit 6 (Day 113). 
G. At the end of treatment, both the subject and physician will complete a Treatment Satisfaction Survey. If a subject 
withdrawals from treatment prior to Day 85, the Treatment Satisfaction Survey will be completed at the Early Withdrawal 
Visit.   
H. Infectious disease screen including HIV antibody, hepatitis B surface antigen, hepatitis C virus (HCV) antibody with 
HCV RNA (PCR) if antibody positive (unless documented as negative within 12 weeks prior to the Screening visit). 
I. 
TB testing will be done centrally using a QuantiFERON® blood test. Testing is optional if skin or blood testing was done 
within 12 months before Visit 1 (Day 1), with documented negative results. See section 6.1.10 Tuberculosis Screening 
for repeat testing options.   
J. 
For women > 45 and ≤ 55 years of age with no menses for < 2 years. 
K. Complete metabolic panel includes at least glucose, urea nitrogen, creatinine, sodium, potassium, chloride, carbon 
dioxide, calcium, total protein, albumin, total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine 
aminotransferase, and calculated glomerular filtration rate. 
L. 
Blood and urine tests will be performed prior to study product administration. 
M. Laboratory tests as relevant to the reason for the unscheduled visit.  
N. Pregnancy test at screening can be done through a blood or urine test.   
O. If the subject provides written informed consent, blood samples, including serum, plasma, mRNA, and PBMC culture 
supernatants, will be stored for future unspecified studies related to JBT-101 or SLE. 
P. Study product will be dispensed in women of childbearing potential only if urine pregnancy test is negative. 
Q. The first dose of study product at Visit 1 (Day 1) will be taken in clinic from the dispensed study product. The subject will 
be observed for 30 minutes or until stable in the judgment of the investigator, whichever is longer. 
 
 
 
 
Treatment 
Post Treatment 
Unsche
duled 
Visit 
Time Point 
Screeni
A
1 
2 
3 
4 
5 
6 
Early 
Withdra
wal Visit
Visit Windows (Days) 
Up to -
42
Day 1 
Day 15 
3
Day 29 
3
Day 57 
3
Day 85 
3
Day 
113
3
Clinical Laboratory Assessments 
Infectious Disease: Hepatitis B and C 
h
i
d fi i
i
H
X 
 
 
 
 
 
 
 
 
Tuberculosis screening testI  
X 
 
 
 
 
 
 
 
 
Follicle stimulating hormoneJ 
X 
 
 
 
 
 
 
 
 
Hematology: CBC with differential cell 
d
l
l
X 
XL 
X 
X 
X 
X 
X 
X 
XM 
Chemistry: Complete metabolic panelK 
X 
XL 
X 
X 
X 
X 
X 
X 
XM 
Anti-dsDNA antibodies, C3, C4 
X 
XL 
 
X 
X 
X 
X 
X 
XM 
C-reactive protein 
 
XL 
 
X 
 
X 
X 
X 
XM 
Urinalysis: Microscopic, & spot 
i /
i i
X 
XL 
 
X 
X 
X 
X 
X 
XM 
Urine pregnancy testB 
XN 
XL 
 
X 
X 
X 
X 
X 
XM 
Blood Draws for Mechanistic Specimen Collection 
Whole blood Pro-Inflammatory 
C
ki
S
di
(3
L)
 
XL 
 
X 
 
X 
X 
X 
 
Plasma: Metabolipidomic profile/JBT-
101
l
i
d
 
XDL 
X 
 
 
 
 
 
 
RNA: IFNα signature (2.5mL) 
 
XL 
 
X 
 
X 
X 
X 
 
Serum: Future UseO (5mL) 
 
XL 
 
X 
 
X 
X 
X 
 
PBMC: Future UseO (30mL) 
 
XL 
X 
 
 
X 
X 
X 
 
Study Product 
Dispense study productP 
 
X 
 
X 
X 
 
 
 
 
Administer study product in clinicQ 
 
X 
 
 
 
 
 
 
 
Study product pill count 
 
 
X 
X 
X 
X 
X  
X  
 


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13.2. Study Flow Chart 
 


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13.3. SELENA SLEDAI and Flare Index 
*Note: The Physician’s Global Assessment must be completed AFTER lab results have been received and 
the 24 descriptors included in the SELENA-SLEDAI above have been assessed. 
PHYSICIAN’S GLOBAL 
ASSESSMENT: 
(3in) 
0
None
1
Mild
2
Moderate
3
Severe
Length of line (measure from 0 to vertical 
assessment by tenths using markings 
provided) 
 
Date of PGA Assessment (dd/mon/yyyy): 
  
 
SELENA-SLEDAI 
Check “Present” if descriptor is present at the time of visit or in the preceding 30 days. 
# 
Descriptor 
Definition 
Presen
t 
Absent Weight 
1 
Seizure 
Recent onset. Exclude metabolic, infectious, or drug 
cause, or seizure due to past irreversible CNS 
damage. 
 
 
8 
2 
Psychosis 
Altered ability to function in normal activity due to 
severe disturbance in the perception of reality. 
Include hallucinations, incoherence, marked loose 
associations, impoverished thought content, marked 
illogical thinking, bizarre, disorganized, or catatonic 
behavior. Exclude uremia and drug causes. 
 
 
8 
3 
Organic brain 
syndrome 
Altered mental function with impaired orientation, 
memory, or other intellectual function, with rapid 
onset and fluctuating clinical features. Include 
clouding of consciousness with reduced capacity to 
focus, and inability to sustain attention to 
environment, plus at least 2 of the following: 
perceptual disturbance, incoherent speech, 
insomnia or daytime drowsiness, or increased or 
decreased psychomotor activity. Exclude metabolic, 
infectious, or drug causes. 
 
 
8 
4 
Visual 
disturbance 
Retinal and eye changes of SLE. Include cytoid 
bodies, retinal hemorrhages, serous exudates, or 
hemorrhages in the choroid, optic neuritis, scleritis, 
or episcleritis.  Exclude hypertension, infection, or 
drug causes. 
 
 
8 
5 
Cranial nerve 
disorder 
New onset of sensory or motor neuropathy involving 
cranial nerves. Include vertigo due to lupus. 
 
 
8 
6 
Lupus headache Severe, persistent headache: may be migrainous, 
but nonresponsive to narcotic analgesia. 
 
 
8 


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SELENA-SLEDAI 
Check “Present” if descriptor is present at the time of visit or in the preceding 30 days. 
# 
Descriptor 
Definition 
Presen
t 
Absent Weight 
7 
CVA 
New onset of cerebrovascular accident(s). Exclude 
arteriosclerosis or hypertensive causes. 
 
 
8 
8 
Vasculitis 
Ulceration, gangrene, tender finger nodules, 
periungual, infarction, splinter hemorrhages, or 
biopsy or angiogram proof of vasculitis. 
 
 
8 
9 
Arthritis 
More than 2 joints with pain and signs of 
inflammation (i.e., tenderness, swelling, or effusion). 
 
 
4 
10 
Myositis 
Proximal muscle aching/weakness, associated with 
elevated creatine phosphokinase/aldolase or 
electromyogram changes or a biopsy showing 
myositis. 
 
 
4 
11 
Urinary casts 
Heme-granular or red blood cell casts. 
 
 
4 
12 
Hematuria 
> 5 red blood cells per high power field. Exclude 
stone, infection, or other causes. 
 
 
4 
13 
Proteinuria 
> 0.5 protein:creatinine ratio. New onset or recent 
increase of more than 0.5 on the protein:creatinine 
ratio. 
Note: ALE09 will typically use a spot urine 
protein:creatinine ratio. If only the 24-hour urine is 
available, then proteinuria is defined as: “>0.5 
gm/24 hours. New onset or recent increase of more 
than 0.5 gm/24 hours.” 
 
 
4 
14 
Pyuria 
> 5 white blood cells per high power field.  
Exclude infection. 
 
 
4 
15 
Rash 
Ongoing inflammatory lupus rash. 
 
 
2 
16 
Alopecia 
Ongoing abnormal, patchy, or diffuse loss of hair 
due to active lupus. 
 
 
2 
17 
Mucosal ulcers Ongoing, oral or nasal ulcerations due to active 
lupus. 
 
 
2 
18 
Pleurisy 
Classic and severe pleuritic chest pain, or pleural 
rub, or effusion, or new pleural thickening due to 
lupus. 
 
 
2 
19 
Pericarditis 
Classic and severe pericardial pain, or rub, or 
effusion, or electrocardiogram confirmation. 
 
 
2 
20 Low complement Decrease in CH50, C3, or C4 below the lower limit 
of normal for testing laboratory. 
 
 
2 
21 
Increased DNA 
Binding 
> 25% binding by Farr assay or above normal range 
for testing laboratory. 
 
 
2 
22 
Fever 
> 38°C. Exclude infectious cause. 
 
 
1 


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SELENA-SLEDAI 
Check “Present” if descriptor is present at the time of visit or in the preceding 30 days. 
# 
Descriptor 
Definition 
Presen
t 
Absent Weight 
23 Thrombocytopeni
a 
< 100,000 platelets/mm3 [equivalent to 100 x109/L] 
 
 
1 
24 
Leukopenia 
< 3,000 white blood cells/mm3 [equivalent to 3 
x109/L] 
Exclude drug causes. 
 
 
1 
Total Score (sum of weights next to descriptors marked present):  ________             
 
SELENA SLEDAI FLARE COMPOSITE 
Mild or Moderate Flare 
Severe Flare 
Change in SLEDAI instrument score of >=3 
points from previous visit with a total score 
<= 12 
Change in SLEDAI instrument score >= 1 from 
previous visit with a total score > 12 
New or worse: 
• 
Discoid, photosensitive, 
profundus, cutaneous 
vasculitis, bullous lupus 
• 
Nasopharyngeal ulcers 
• 
Pleuritis 
• 
Pericarditis 
• 
Arthritis 
• 
Fever (SLE) 
 New or worse: 
• 
CNS-SLE 
• 
Vasculitis 
• 
Nephritis 
• 
Myositis 
• 
Platelets < 60,000 
• 
Hemolytic anemia: Hemoglobin <70g/L 
or decrease in Hemoglobin >30 g/L 
 
Requiring: double prednisone, or 
prednisone increase to >0.5 mg/kg/day, or 
hospitalization 
Increase in prednisone, but not to 
>0.5mg/kg/day 
Increase in prednisone to >0.5 mg/kg/day  
Added NSAID or new prescription of 
hydroxychloroquine for SLE activiy 
New prescription of  cyclophosphamide, 
azathioprine, methotrexate, MMF or 
any other major immunosuppressive for 
SLE activity 
Increase in PGA of >=1.0 from previous visit 
with a total PGA <= 2.5 
Hospitalization for SLE Activity 
Increase in PGA of > 0 from previous visit 
with a total PGA>2.5 


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13.4 BILAG-2004 Index Scoring 
    
• scoring based on the principle of physician’s intention to treat 
Category 
Definition 
 
A 
 
Severe disease activity requiring any of the following treatment: 
 
1. systemic high dose oral glucocorticoids (equivalent to prednisolone > 20  
    mg/day) 
 
2. intravenous pulse glucocorticoids (equivalent to pulse methylprednisolone  
    ≥ 500 mg) 
 
3. systemic immunomodulators (include biologicals, immunoglobulins and  
    plasmapheresis) 
 
4. therapeutic high dose anticoagulation in the presence of high dose steroids  
    or immunomodulators 
      eg: warfarin with target INR 3 - 4 
 
 
B 
 
 
Moderate disease activity requiring any of the following treatment: 
 
1. systemic low dose oral glucocorticoids (equivalent to prednisolone ≤ 20  
    mg/day) 
 
2. intramuscular or intra-articular or soft tissue glucocorticoids injection  
    (equivalent to methylprednisolone < 500mg) 
 
3. topical glucocorticoids 
4. topical immunomodulators 
5. antimalarials or thalidomide or prasterone or acitretin 
6. symptomatic therapy 
      eg: NSAIDs for inflammatory arthritis 
 
 
C 
 
 
Mild disease 
 
 
D 
 
 
Inactive disease but previously affected 
 
 
E 
 
System never involved 
 
 
 


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CONSTITUTIONAL 
 
Category A: 
Pyrexia recorded as 2 (same), 3 (worse) or 4 (new)  AND  
 
Any 2 or more of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
 
 
Weight loss 
 
 
Lymphadenopathy/splenomegaly 
 
 
Anorexia 
 
Category B: 
Pyrexia recorded as 2 (same), 3 (worse) or 4 (new)  OR  
 
Any 2 or more of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
 
 
Weight loss 
 
 
Lymphadenopathy/splenomegaly 
 
 
Anorexia 
 
BUT do not fulfil criteria for Category A 
 
Category C 
Pyrexia recorded as 1 (improving)  OR 
 
One or more of the following recorded as > 0:  
 
Weight loss 
 
 
Lymphadenopathy/Splenomegaly 
 
 
Anorexia 
 
BUT does not fulfil criteria for category A or B 
 
Category D 
Previous involvement 
 
Category E 
No previous involvement 
 
 
 
 
 
 
 
 


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MUCOCUTANEOUS 
 
Category A   
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
 
 
Skin eruption - severe  
Angio-oedema - severe 
 
 
Mucosal ulceration - severe 
 
 
Panniculitis/Bullous lupus - severe 
Major cutaneous vasculitis/thrombosis 
 
Category B 
 
Any Category A features recorded as 1 (improving) OR  
 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
Skin eruption - mild 
Panniculitis/Bullous lupus - mild 
 
 
Digital infarcts or nodular vasculitis 
 
 
Alopecia - severe 
 
 
 
Category C   
Any Category B features recorded as 1 (improving) OR 
 
Any of the following recorded as > 0: 
 
 
 
Angio-oedema - mild 
 
 
Mucosal ulceration - mild 
 
 
Alopecia - mild 
Periungual erythema/chilblains 
Splinter haemorrhages 
 
Category D 
 
Previous involvement 
 
Category E 
 
No previous involvement 
 
 
 


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NEUROPSYCHIATRIC 
 
Category A 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
Aseptic meningitis 
Cerebral vasculitis 
Demyelinating syndrome 
Myelopathy 
Acute confusional state 
Psychosis 
Acute inflammatory demyelinating polyradiculoneuropathy 
Mononeuropathy (single/multiplex) 
Cranial neuropathy 
Plexopathy 
Polyneuropathy 
Status epilepticus 
Cerebellar ataxia 
 
Category B 
Any Category A features recorded as 1 (improving) OR 
 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
Seizure disorder  
Cerebrovascular disease (not due to vasculitis) 
Cognitive dysfunction 
Movement disorder 
Autonomic disorder  
Lupus headache - severe unremitting 
Headache due to raised intracranial hypertension 
 
Category C 
Any Category B features recorded as 1 (improving) 
 
Category D  
Previous involvement 
 
Category E  
No previous involvement 
 
 
 
 
 
 


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MUSCULOSKELETAL 
 
Category A 
Any of the following recorded  as 2 (same), 3 (worse) or 4 (new): 
 
 
Severe Myositis 
Severe Arthritis 
 
Category B 
Any Category A features recorded as 1 (improving)  OR 
 
Any of the following recorded  as 2 (same), 3 (worse) or 4 (new): 
 
 
Mild Myositis 
Moderate Arthritis/Tendonitis/Tenosynovitis 
 
Category C 
Any Category B features recorded as 1 (improving) OR  
 
Any of the following recorded as > 0: 
 
 
Mild Arthritis/Arthralgia/Myalgia 
 
 
 
Category D 
Previous involvement 
 
Category E 
No previous involvement 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


DAIT NIAID 
Statistical Analysis Plan 
Protocol No. ALE09  
28 April 2022
 
Version: 2.0  
Page 51 of 67
 
CARDIORESPIRATORY 
 
Category A 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
Myocarditis/Endocarditis + Cardiac failure 
 
 
Arrhythmia 
 
 
New valvular dysfunction 
Cardiac tamponade 
 
 
Pleural effusion with dyspnoea 
 
 
Pulmonary haemorrhage/vasculitis 
 
Interstitial alveolitis/pneumonitis  
Shrinking lung syndrome 
Aortitis 
Coronary vasculitis 
 
Category B 
Any Category A features recorded as 1 (improving) OR  
 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
Pleurisy/Pericarditis 
Myocarditis - mild 
 
Category C 
Any Category B features recorded as 1 (improving) 
 
Category D 
Previous involvement 
 
Category E 
No previous involvement 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


DAIT NIAID 
Statistical Analysis Plan 
Protocol No. ALE09  
28 April 2022
 
Version: 2.0  
Page 52 of 67
 
GASTROINTESTINAL 
 
Category A 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
Peritonitis 
Lupus enteritis/colitis 
Intestinal pseudo-obstruction  
Acute lupus cholecystitis 
Acute lupus pancreatitis 
 
Category B 
Any Category A feature recorded as 1 (improving) OR 
 
Any of the following recorded  as 2 (same), 3 (worse) or 4 (new): 
 
Abdominal serositis and/or ascites  
Malabsorption 
Protein losing enteropathy 
Lupus hepatitis 
 
Category C 
Any Category B features recorded as 1 (improving)  
 
Category D  
Previous involvement 
 
Category E   
No previous involvement 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


DAIT NIAID 
Statistical Analysis Plan 
Protocol No. ALE09  
28 April 2022
 
Version: 2.0  
Page 53 of 67
 
OPHTHALMIC 
 
Category A 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
Orbital inflammation/myositis/proptosis 
Keratitis - severe 
Posterior uveitis/retinal vasculitis - severe 
Scleritis - severe 
Retinal/choroidal vaso-occlusive disease 
Optic neuritis 
Anterior ischaemic optic neuropathy  
 
Category B 
Any Category A features recorded as 1 (improving) OR  
 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
 
 
Keratitis - mild 
Anterior uveitis 
Posterior uveitis/retinal vasculitis - mild 
Scleritis – mild 
 
Category C 
Any Category B features recorded as 1 (improving) OR  
 
Any of the following recorded as > 0: 
 
Episcleritis 
Isolated cotton-wool spots (cytoid bodies) 
 
Category D 
Previous involvement 
 
Category E 
No previous involvement 
 
 
 
 
 
 
 
 
 
 


DAIT NIAID 
Statistical Analysis Plan 
Protocol No. ALE09  
28 April 2022
 
Version: 2.0  
Page 54 of 67
 
RENAL 
 
Category A 
Two or more of the following providing 1, 4 or 5 is included: 
 
1. Deteriorating proteinuria (severe) defined as   
 
      (a) urine dipstick increased by ≥ 2 levels (used only if other methods of urine protein estimation not   
             available); or  
 
      (b) 24 hour urine protein > 1 g that has not decreased (improved) by ≥ 25%; or 
      (c) urine protein-creatinine ratio > 100 mg/mmol that has not decreased (improved) by ≥ 25%; or 
      (d) urine albumin-creatinine ratio > 100 mg/mmol that has not decreased (improved) by ≥ 25% 
 
2. Accelerated hypertension  
3. Deteriorating renal function (severe) defined as  
 
      (a) plasma creatinine > 130 µmol/l and having risen to > 130% of previous value; or  
      (b) GFR < 80 ml/min per 1.73 m2 and having fallen to < 67% of previous value; or  
      (c) GFR < 50 ml/min per 1.73 m2, and last time was > 50 ml/min per 1.73 m2 or was not measured. 
 
4. Active urinary sediment 
5. Histological evidence of active nephritis within last 3 months  
6. Nephrotic syndrome 
 
Category B 
One of the following: 
 
1. One of the Category A feature 
 
2. Proteinuria (that has not fulfilled Category A criteria) 
      (a) urine dipstick which has risen by 1 level to at least 2+ (used only if other methods of urine  
             protein estimation not available); or 
 
      (b) 24 hour urine protein ≥ 0.5 g that has not decreased (improved) by ≥ 25%; or 
      (c) urine protein-creatinine ratio ≥ 50 mg/mmol that has not decreased (improved) by ≥ 25%; or 
      (d) urine albumin-creatinine ratio ≥ 50 mg/mmol that has not decreased (improved) by ≥ 25% 
 
3. Plasma creatinine > 130 µmol/l and having risen to ≥ 115% but ≤ 130% of previous value 
 
Category C 
One of the following: 
 
1. Mild/Stable proteinuria defined as 
 
(a) urine dipstick ≥ 1+ but has not fulfilled criteria for Category A & B (used only if other methods  


DAIT NIAID 
Statistical Analysis Plan 
Protocol No. ALE09  
28 April 2022
 
Version: 2.0  
Page 55 of 67
 
 of urine protein estimation not available); or 
      (b) 24 hour urine protein > 0.25 g but has not fulfilled criteria for Category A & B ; or 
      (c) urine protein-creatinine ratio > 25 mg/mmol but has not fulfilled criteria for Category A & B; or  
      (d) urine albumin-creatinine ratio > 25 mg/mmol but has not fulfilled criteria for Category A & B 
 
 
2. Rising blood pressure (providing the recorded values are > 140/90 mm Hg) which has not fulfilled 
criteria for Category A & B, defined as 
  
(a) systolic rise of ≥ 30 mm Hg; and  
(b) diastolic rise of ≥ 15mm Hg  
 
Category D 
Previous involvement 
 
Category E 
No previous involvement 
 
 
Note: although albumin-creatinine ratio and protein-creatinine ratio are different, we use the same cut- 
          off values for this index 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


DAIT NIAID 
Statistical Analysis Plan 
Protocol No. ALE09  
28 April 2022
 
Version: 2.0  
Page 56 of 67
 
HAEMATOLOGICAL  
 
Category A 
TTP recorded as 2 (same), 3 (worse) or 4 (new)   OR 
 
Any of the following: 
 
 
 
Evidence of haemolysis and Haemoglobin < 8 g/dl 
Platelet count   
< 25 x 109/l 
 
Category B 
TTP recorded as 1 (improving)   OR 
 
Any of the following:  
 
 
 
Evidence of haemolysis and Haemoglobin 8 - 9.9 g/dl 
Haemoglobin   
< 8 g/dl (without haemolysis) 
White cell count  
< 1.0 x 109/l 
Neutrophil count  
< 0.5 x 109/l 
Platelet count   
25 - 49 x 109/l 
 
Category C 
Any of the following: 
 
Evidence of haemolysis and Haemoglobin ≥ 10g/dl 
Haemoglobin   
8 - 10.9 g/dl (without haemolysis) 
White cell count  
1 - 3.9 x 109/l 
Neutrophil count  
0.5 - 1.9 x 109/l 
Lymphocyte count  
< 1.0 x 109/L 
Platelet count  
50 - 149 x 109/l 
Isolated Coombs’ test positive  
 
Category D 
Previous involvement 
 
Category E 
No previous involvement 
 
 
 


DAIT NIAID 
Statistical Analysis Plan 
Protocol No. ALE09  
28 April 2022
 
Version: 2.0  
Page 57 of 67
 
13.5 Fibromyalgia Symptom Scale 


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Statistical Analysis Plan 
Protocol No. ALE09  
28 April 2022
 
Version: 2.0  
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13.6 Lupus Activity Patient’s Global Assessment 
 


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Statistical Analysis Plan 
Protocol No. ALE09  
28 April 2022
 
Version: 2.0  
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13.7 ARCI-M Questionnaire  
 


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Statistical Analysis Plan 
Protocol No. ALE09  
28 April 2022
 
Version: 2.0  
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13.8 PROMIS-29 Short Form 
 


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Protocol No. ALE09  
28 April 2022
 
Version: 2.0  
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Statistical Analysis Plan 
Protocol No. ALE09  
28 April 2022
 
Version: 2.0  
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Statistical Analysis Plan 
Protocol No. ALE09  
28 April 2022
 
Version: 2.0  
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13.9 PROMIS Item Bank v2.0 - Cognitive Function Short Form 8a 


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Statistical Analysis Plan 
Protocol No. ALE09  
28 April 2022
 
Version: 2.0  
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13.10 
Treatment Satisfaction Survey (Participant) 
 
 
 
 


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Statistical Analysis Plan 
Protocol No. ALE09  
28 April 2022
 
Version: 2.0  
Page 65 of 67
 
13.11   Email Documentation of Decision to Add Screening FSS as a Covariate 
 


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Statistical Analysis Plan 
Protocol No. ALE09  
28 April 2022
 
Version: 2.0  
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DAIT NIAID 
Statistical Analysis Plan 
Protocol No. ALE09  
28 April 2022
 
Version: 2.0  
Page 67 of 67
 
14. 
ATTACHMENTS 
14.1 PROMIS Adult Profile Instruments