A Phase 1, Double-Blind, Randomized Clinical Trial to Evaluate the Safety, Tolerability, and Immunogenicity of the Single-Vial Lyophilized ID93 + GLA-SE Vaccine Administered Intramuscularly in Healthy Adult Subjects
Phase: PHASE1
Conditions: Pulmonary TB
Sponsor: Access to Advanced Health Institute (AAHI)

clinicaltrials.gov document upload cover page
NCT03722472
IDRI-TBVPX-120
Protocol
Version 2
05OCT2018

IDRI Protocol TBVPX-120, DMID 17-0104 
Final Version 2.0 
Single-vial Lyophilized ID93 + GLA-SE 
05 October 2018 
 
1 of 77 
This document is proprietary and is to be used only as authorized. No part is to be reproduced, disclosed to others, or quoted 
without prior written authorization from IDRI. 
A Phase 1, Double-Blind, Randomized Clinical Trial to 
Evaluate the Safety, Tolerability, and Immunogenicity of the 
Single-Vial Lyophilized ID93 + GLA-SE Vaccine Administered 
Intramuscularly in Healthy Adult Subjects 
 
IDRI Protocol Number: TBVPX-120 
DMID Protocol Number: 17-0104 
 
DMID Funding Mechanism: HHSN272201400041C 
IND Sponsor: Infectious Disease Research Institute (IDRI) 
Principal Investigator: Daniel Hoft, MD, PhD 
IDRI Medical Monitor: Stuart Kahn, MD 
DMID Medical Monitor: Mohamed Elsafy, MD, MSc 
DMID Medical Officer:  Mamodikoe Makhene, MD, MPH 
 
Version Number: 2.0 
05 October 2018 
 
 
 
 
 

IDRI Protocol TBVPX-120, DMID 17-0104 
Final Version 2.0 
Single-vial Lyophilized ID93 + GLA-SE 
05 October 2018 
 
2 of 77 
This document is proprietary and is to be used only as authorized. No part is to be reproduced, disclosed to others, or quoted 
without prior written authorization from IDRI. 
STATEMENT OF COMPLIANCE 
This trial will be conducted in compliance with the protocol, International Conference on 
Harmonisation (ICH) Guideline E6: Good Clinical Practice: Consolidated Guideline, (R2), the 
applicable regulatory requirements from US Code of Federal Regulations (CFR) (Title 45 CFR 
Part 46 and Title 21 CFR including Parts 50 and 56, 21 CFR Part 11, and 21 CFR Part 312) 
concerning informed consent and Institutional Review Board regulations, and the NIAID Clinical 
Terms of Award. 
All individuals responsible for the design and conduct of this study have completed Human 
Subjects Protection Training and are qualified to be conducting this research prior to the 
enrollment of any subjects. Curricula vitae for all investigators and sub-investigators participating 
in this trial are on file (21 CFR 312.23 [a] [6] [iii] [b] edition). 
 
 

IDRI Protocol TBVPX-120, DMID 17-0104 
Final Version 2.0 
Single-vial Lyophilized ID93 + GLA-SE 
05 October 2018 
 
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This document is proprietary and is to be used only as authorized. No part is to be reproduced, disclosed to others, or quoted 
without prior written authorization from IDRI. 
SIGNATURE PAGE 
The signature below constitutes the approval of this protocol and the attachments, and provides 
the necessary assurances that this trial will be conducted according to all stipulations of the 
protocol, including all statements regarding confidentiality, and according to local legal and 
regulatory requirements and applicable US federal regulations and ICH guidelines. 
 
Site Investigator Signature: 
 
 
Signed: 
 
Date: 
 
 
Daniel Hoft, MD, PhD 
Principal Investigator 
 
 
 
 
 
Sponsor Signature: 
 
 
Signed: 
 
Date: 
 
 
Corey Casper, MD, MPH 
Chief Scientific Officer 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

IDRI Protocol TBVPX-120, DMID 17-0104 
Final Version 2.0 
Single-vial Lyophilized ID93 + GLA-SE 
05 October 2018 
 
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This document is proprietary and is to be used only as authorized. No part is to be reproduced, disclosed to others, or quoted 
without prior written authorization from IDRI. 
TABLE OF CONTENTS 
 
 
Page 
1 
Key Roles .......................................................................................................................... 13 
2 
Background Information and Scientific Rationale ............................................................... 15 
2.1 
Background Information ............................................................................................... 15 
2.1.1 
GLA-SE ............................................................................................................... 16 
2.1.2 
Preclinical animal studies with ID93 ..................................................................... 16 
2.1.3 
Clinical Experience with ID93 + GLA-SE .............................................................. 16 
2.2 
Rationale ...................................................................................................................... 18 
2.3 
Potential Risks and Benefits ......................................................................................... 18 
2.3.1 
Potential Risks ..................................................................................................... 18 
2.3.2 
Known Potential Benefits ..................................................................................... 20 
3 
Objectives .......................................................................................................................... 21 
3.1 
Study Objectives .......................................................................................................... 21 
3.2 
Study Outcome Measures ............................................................................................ 21 
3.2.1 
Primary Outcome Measures ................................................................................ 21 
3.2.2 
Secondary Outcome Measures ............................................................................ 22 
3.2.3 
Exploratory Outcome Measures ........................................................................... 22 
4 
Study Design ...................................................................................................................... 23 
5 
Study Enrollment and Withdrawal ...................................................................................... 24 
5.1 
Subject Inclusion Criteria ............................................................................................. 24 
5.2 
Subject Exclusion Criteria ............................................................................................ 25 
5.3 
Eligibility Criteria for 2nd Injection .................................................................................. 27 
5.4 
Treatment Assignment Procedures .............................................................................. 27 
5.4.1 
Randomization Procedures .................................................................................. 27 
5.4.2 
Blinding Procedures ............................................................................................. 28 
5.4.3 
Reasons for Withdrawal ....................................................................................... 28 
5.4.4 
Handling of Withdrawals ...................................................................................... 29 
5.4.5 
Handling of Subjects Withdrawn from Further Study Injections ............................ 29 
5.4.6 
Termination of Study ............................................................................................ 30 
6 
Study Intervention/Investigational Product ......................................................................... 31 
6.1 
Study Product Description ............................................................................................ 31 
6.1.1 
Acquisition ........................................................................................................... 31 
6.1.2 
Formulation, Storage, Packaging, and Labeling ................................................... 31 
6.2 
Dosage, Preparation, and Administration of Study Intervention/Investigational 
Product ........................................................................................................................ 32 
6.3 
Modification of Study Intervention/Investigational Product for a Participant .................. 33 
6.4 
Accountability Procedures for the Study Intervention/Investigational Product(s)........... 33 
6.5 
Concomitant Medications/Treatments .......................................................................... 33 
7 
Study Schedule .................................................................................................................. 35 
7.1 
Screening Procedures (Day -30 to Day -1) ................................................................... 35 
7.2 
Day 0 Enrollment/Baseline Evaluations and First Study Injection ................................. 35 
7.3 
Day 7 (±1) Evaluations ................................................................................................. 36 
7.4 
Day 14 (±3) Evaluations ............................................................................................... 36 
7.5 
Day 56 (±3) Evaluations and Second Study Injection ................................................... 36 
7.6 
Day 63 (±1) Evaluations ............................................................................................... 37 
7.7 
Day 70 (±3) Evaluations ............................................................................................... 37 
7.8 
Day 84 (±5) Evaluation ................................................................................................. 38 
7.9 
Day 224 (±10) Evaluations ........................................................................................... 38 

IDRI Protocol TBVPX-120, DMID 17-0104 
Final Version 2.0 
Single-vial Lyophilized ID93 + GLA-SE 
05 October 2018 
 
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7.10 Day 421 (±14) Evaluations ........................................................................................... 38 
7.11 Early Termination Visit ................................................................................................. 38 
7.12 Unscheduled Visit ........................................................................................................ 39 
7.13 Visit Schedule to be followed if 2nd study injection is withheld ...................................... 39 
8 
Study Procedures AND Evaluations ................................................................................... 40 
8.1 
Clinical Evaluations ...................................................................................................... 40 
8.2 
Laboratory Evaluations ................................................................................................ 41 
8.2.1 
Clinical Laboratory Evaluations ............................................................................ 41 
8.2.2 
Special Assays or Procedures ............................................................................. 41 
8.2.3 
Specimen Shipment ............................................................................................. 42 
9 
Assessment of Safety ........................................................................................................ 43 
9.1 
Specification of Safety Parameters .............................................................................. 43 
9.2 
Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters ...... 43 
9.2.1 
Adverse Events.................................................................................................... 43 
9.2.2 
Assessment of Severity (Grading) ....................................................................... 45 
9.2.3 
Assessment of Causality (Relatedness to Study Injection) ................................... 46 
9.2.4 
Evaluation of Expectedness ................................................................................. 47 
9.2.5 
Reactogenicity ..................................................................................................... 48 
9.2.6 
Memory Aids ........................................................................................................ 48 
9.3 
Serious Adverse Events (SAE) .................................................................................... 49 
9.3.1 
Assessment of Seriousness ................................................................................. 49 
9.3.2 
Procedures to be Followed in the Event of Abnormal Laboratory Test Values 
or Abnormal Clinical Findings .............................................................................. 50 
9.4 
Reporting Procedures .................................................................................................. 50 
9.4.1 
Serious Adverse Events ....................................................................................... 50 
9.4.2 
Regulatory Reporting ........................................................................................... 52 
9.4.3 
Reporting Other Adverse Events (if applicable).................................................... 52 
9.4.4 
Reporting of Pregnancy ....................................................................................... 52 
9.5 
Type and Duration of Follow-up of Subjects after Adverse Events ............................... 52 
9.6 
Halting Rules ............................................................................................................... 53 
9.6.1 
Rules for Discontinuing Study injection in an Individual Subject ........................... 53 
9.6.2 
Rules for Suspension of the Entire Study ............................................................. 53 
9.7 
Safety Oversight (ISM plus SMC)................................................................................. 54 
9.7.1 
Independent Safety Monitor (ISM) ....................................................................... 54 
9.7.2 
Safety Monitoring Committee (SMC) .................................................................... 54 
10 Clinical Monitoring .............................................................................................................. 56 
10.1 Site Monitoring Plan ..................................................................................................... 56 
11 Statistical Considerations ................................................................................................... 57 
11.1 Introduction .................................................................................................................. 57 
11.2 Study Population .......................................................................................................... 57 
11.2.1 Intent to Treat Population ..................................................................................... 57 
11.2.2 Per Protocol Population ....................................................................................... 57 
11.2.3 Safety Population ................................................................................................. 57 
11.2.4 Immunogenicity Population .................................................................................. 57 
11.3 Sample Size Considerations ........................................................................................ 58 
11.4 Planned Interim Analyses (if applicable) ...................................................................... 58 
11.5 Final Analysis Plan ....................................................................................................... 58 
11.5.1 Analysis of Demographics and Disposition .......................................................... 58 
11.5.2 Analysis of Safety ................................................................................................ 59 
11.5.3 Immunology Analyses .......................................................................................... 60 
12 Source Documents and Access to Source Data/Documents .............................................. 61 

IDRI Protocol TBVPX-120, DMID 17-0104 
Final Version 2.0 
Single-vial Lyophilized ID93 + GLA-SE 
05 October 2018 
 
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13 Quality Control and Quality Assurance ............................................................................... 62 
14 Ethics/Protection of Human Subjects ................................................................................. 63 
14.1 Ethical Standard ........................................................................................................... 63 
14.2 Institutional Review Board ............................................................................................ 63 
14.3 Informed Consent Process ........................................................................................... 63 
14.4 Exclusion of Women, Minorities, and Children (Special Populations) ........................... 64 
14.5 Subject Confidentiality .................................................................................................. 64 
14.6 Study Discontinuation .................................................................................................. 65 
14.7 Future Use of Stored Specimens ................................................................................. 65 
14.8 Disclosure of Individual Research Information.............................................................. 66 
15 Data Handling and Record Keeping ................................................................................... 67 
15.1 Data Management Responsibilities .............................................................................. 67 
15.2 Data Capture Methods ................................................................................................. 67 
15.3 Types of Data .............................................................................................................. 67 
15.4 Timing/Reports............................................................................................................. 67 
15.5 Study Records Retention ............................................................................................. 68 
15.6 Protocol Deviations ...................................................................................................... 68 
16 Publication Policy ............................................................................................................... 69 
17 Literature References ......................................................................................................... 71 
Appendix 1: Schedule of Study Visits and Procedures .............................................................. 72 
Appendix 2: Schedule of Blood Draws and Volumes ................................................................. 73 
Appendix 3: Grading Scale for Clinical Laboratory Values ........................................................ 74 
Appendix 4: Grading Scale for Local Injection Site Reactions ................................................... 75 
Appendix 5: Grading Scale for Determining the Severity of Clinical AEs ................................... 76 
Appendix 6: List of PIMMCs ...................................................................................................... 77 
 

IDRI Protocol TBVPX-120, DMID 17-0104 
Final Version 2.0 
Single-vial Lyophilized ID93 + GLA-SE 
05 October 2018 
 
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without prior written authorization from IDRI. 
LIST OF ABBREVIATIONS 
AE 
Adverse Event/Adverse Experience 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
BCG 
Bacille Calmette-Guérin (Vaccine) 
BP 
Blood Pressure 
CBER 
Center for Biologics Evaluation and Research, FDA, DHHS 
CFR 
Code of Federal Regulations 
CROMS 
Clinical Research Operations and Management Support 
CRP 
C-Reactive Protein 
DHHS 
Department of Health and Human Services 
DMID 
Division of Microbiology and Infectious Diseases, NIAID, NIH, DHHS 
eCRF 
Electronic Case Report Form 
ELISA 
Enzyme linked immunosorbent assay 
ELISpot 
Enzyme linked immunospot assay 
ER 
Emergency room 
ET 
Early Termination 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GLA 
Glucopyranosyl Lipid A 
GLA-SE 
Glucopyranosyl Lipid A – Stable Emulsion 
GLP 
Good Laboratory Practice 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C Virus 
HEENT 
Head, Eyes, Ears, Nose, and Throat 
HGB 
Hemoglobin 
HIV 
Human Immunodeficiency Virus 
ICH 
International Conference on Harmonisation 
ICS 
Intracellular Cytokine Staining 
IDRI 
Infectious Diseases Research Institute 
IEC 
Independent or Institutional Ethics Committee 
IgG 
Immunoglobulin G 
IM 
Intramuscular 
IND 
Investigational New Drug Application 
IFNγ 
Interferon Gamma 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
IV 
Intravenous 
LLN 
Lower limit of normal 
Mtb 
Mycobacterium tuberculosis 
MPL 
Monophosphoryl Lipid A 
N 
Number (typically refers to subjects) 

IDRI Protocol TBVPX-120, DMID 17-0104 
Final Version 2.0 
Single-vial Lyophilized ID93 + GLA-SE 
05 October 2018 
 
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NIAID 
National Institute of Allergy and Infectious Diseases, NIH, DHHS 
NIH 
National Institutes of Health 
P 
Pulse 
PBMC 
Peripheral Blood Mononuclear Cell  
PE 
Physical exam 
PHI 
Protected Health Information 
PI 
Principal Investigator 
PID 
Participant identification number 
PIMMC 
Potential immune-mediated medical condition 
RBC 
Red Blood Cell 
RR 
Respiratory Rate 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SMC 
Safety Monitoring Committee 
SSP 
Study Specific Procedures 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TB 
Tuberculosis 
TLR 
Toll-like receptor 
TNF 
Tumor Necrosis Factor Alpha 
ULN 
Upper limit of normal 
US 
United States 
USP 
Unites States Pharmacopeia 
WBC 
White Blood Cell Count 
 
 

IDRI Protocol TBVPX-120, DMID 17-0104 
Final Version 2.0 
Single-vial Lyophilized ID93 + GLA-SE 
05 October 2018 
 
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without prior written authorization from IDRI. 
PROTOCOL SUMMARY 
Title: 
A Phase 1, Double-Blind, Randomized Clinical Trial to 
Evaluate the Safety, Tolerability, and Immunogenicity of 
the Single-Vial Lyophilized ID93 + GLA-SE Vaccine 
Administered Intramuscularly in Healthy Adult Subjects 
Phase: 
1 
Population: 
Healthy males and non-pregnant females, aged 18-55. A total of 
48 subjects will be enrolled. 
Number of Sites: 
One site: Saint Louis University 
Study Duration: 
~18 months 
Subject Participation 
Duration: 
~14 months 
Estimated Time to 
Complete Enrollment: 
Approximately 4 months 
Description of Agent or 
Intervention: 
• 
ID93 (2 µg, lyophilized) + GLA-SE (5 µg, liquid)  
[two-vial presentation] 
• 
ID93 + GLA-SE (2 µg ID93, 5 µg GLA)  
[lyophilized, single-vial] 
Study Objectives: 
Primary: 
• 
To evaluate the safety and tolerability of single-vial lyophilized 
ID93 + GLA-SE following two intramuscular (IM) injections 
administered on Days 0 and 56. 
• 
To compare the safety and tolerability of single-vial lyophilized 
ID93 + GLA-SE to the two-vial presentation consisting of 
lyophilized ID93 and liquid GLA-SE following two IM injections 
administered on Days 0 and 56. 
Secondary: 
• 
To assess the immunogenicity of single-vial lyophilized ID93 + 
GLA-SE following two IM injections administered on Days 0 
and 56 by quantifying cytokine production and IgG antibody 
responses to ID93 at specified time points. 
• 
To compare the immunogenicity of single-vial lyophilized ID93 
+ GLA-SE to the two-vial presentation consisting of lyophilized 

IDRI Protocol TBVPX-120, DMID 17-0104 
Final Version 2.0 
Single-vial Lyophilized ID93 + GLA-SE 
05 October 2018 
 
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ID93 and liquid GLA-SE following two IM injections 
administered on Days 0 and 56. 
Exploratory: 
• 
To further evaluate the immunogenicity of ID93 + GLA-SE 
following two IM injections administered on Days 0 and 56 by 
measuring mycobacterial growth inhibition, quantifying IgA 
levels in mucosal secretions, and measuring frequencies of 
circulating T follicular helper cells, antibody secreting cells, and 
memory B cells at specified time points. 
Study Outcome 
Measures: 
Primary: 
• 
The number of subjects experiencing solicited local injection 
site reactions within 7 days following each study injection. 
• 
The number of subjects experiencing solicited systemic 
reactions within 7 days following each study injection. 
• 
The number of subjects spontaneously reporting adverse 
events from Day 0 through Day 84.  
• 
The number of serious adverse events considered related to 
any of the study injections reported at any point during the 
study period. 
Secondary: 
• 
The proportion of subjects with at least a 4-fold increase in IgG 
antibody responses to ID93 on Days 14, 56, 70, 84, and 224 
relative to baseline (Day 0).  
• 
Mean fold change from baseline (Day 0) in IgG antibody 
responses to ID93 on Days 14, 56, 70, 84, and 224. 
• 
The number of IFN-γ and IL-10 cytokine-secreting cells in 
PBMC samples in response to the ID93 antigen relative to 
baseline (Day 0) at Days 14, 56, 70, 84, and 224, as assayed 
by ELISpot 
• 
Percentage of CD4 and CD8 T cells producing 1 or more 
cytokines (IFN-γ, TNF, and IL-2) simultaneously in response to 
stimulation with the ID93 antigen as measured by intracellular 
cytokine staining of PBMCs at Days 14, 56, 70, 84, and 224 
relative to baseline (Day 0). 
 

IDRI Protocol TBVPX-120, DMID 17-0104 
Final Version 2.0 
Single-vial Lyophilized ID93 + GLA-SE 
05 October 2018 
 
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Exploratory: 
• 
Measurement of net intracellular growth inhibition of Mtb using 
whole blood on Days 0, 70, and 224. 
• 
Quantitate IgA titers in mucosal secretions (nasal swabs and tear 
collections) by ELISA on Days 0, 70, and 224. 
• 
Quantitate number of antibody-secreting cells in PBMC by short-
culture B cell ELISpot on Days 0, 7, and 63. 
• 
Quantitate number of antigen-specific memory B cells in PBMC 
by long-culture B cell ELISpot on Days 0, 56, 84, and 224. 
• 
Quantitate T follicular helper cells, memory B cells, and T cell 
homing markers in PBMC by immunophenotyping flow cytometry 
on Days 0, 7, 14, 63, 70, and 224. 
Description of Study 
Design: 
This is a phase 1, double-blind, randomized clinical trial to 
evaluate the safety, tolerability, and immunogenicity of single-vial 
lyophilized ID93 + GLA-SE compared to the two-vial presentation 
consisting of lyophilized ID93 and liquid GLA-SE administered as 
two IM injections in healthy adult subjects (aged 18 - 55). 
The two treatment groups are outlined in the table below. Subjects 
will receive a total of two doses administered IM on Days 0 and 56. 
Subjects will be monitored for approximately 421 days (one year 
following the last study injection), including safety laboratory 
analyses done just prior to and 7 days following each study 
injection. Tears and nasal swabs will be obtained for exploratory 
antibody analysis at Days 0, 70, and 224. Blood samples will be 
obtained for immunological assays (secondary and exploratory) at 
Days 0, 7, 14, 56, 63, 70, 84, and 224). 
Group N 
Study Injections 
Timing of Study 
Injections 
1 
24 
ID93 (2 µg, lyophilized) + 
GLA-SE (5 µg, liquid)  
[two-vial presentation] 
Days 0, 56 
2 
24 
ID93 + GLA-SE  
(2 µg ID93, 5 µg GLA)  
[lyophilized, single-vial] 
Days 0, 56 
 
 
 

IDRI Protocol TBVPX-120, DMID 17-0104 
Final Version 2.0 
Single-vial Lyophilized ID93 + GLA-SE 
05 October 2018 
 
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SCHEMATIC OF STUDY DESIGN 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomize 
Planned enrollment, N=48, healthy males and females 18-55 years of age with 
negative HIV, HBsAg, HCV, and no history of BCG vaccination 
Follow for safety, reactogenicity, and 
immunogenicity assessments 
through Day 421 
ID93 (2 µg, lyophilized) + GLA-SE (5 µg, liquid)  
[two-vial presentation]  
 
N=24 
Study injections on 
Days 0 and 56 
Consent, assess for eligibility, and 
perform screening laboratory tests 
ID93 + GLA-SE (2 µg ID93, 5 µg GLA)  
[lyophilized, single-vial]  
 
N=24 
Study injections on 
Days 0 and 56 

IDRI Protocol TBVPX-120, DMID 17-0104 
Final Version 2.0 
Single-vial Lyophilized ID93 + GLA-SE 
05 October 2018 
 
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without prior written authorization from IDRI. 
1 
KEY ROLES 
Principal Investigator: 
Daniel Hoft, MD, PhD 
Saint Louis University 
Center for Vaccine Development 
1100 S. Grand Blvd., 8th Floor 
St. Louis, MO  63104  
Phone: 314-977-9044 
Fax: 314-771-3816  
E-mail: Daniel.Hoft@health.slu.edu 
 
Sponsor: 
Infectious Disease Research Institute (IDRI) 
1616 Eastlake Avenue East, Suite 400 
Seattle, WA 98102 
Phone: 206-381-0883 
Fax: 206-858-6098 
 
NIAID Contract Principal Investigator: 
Chris Fox, PhD 
VP, Formulations 
Phone: 206-858-6027 
E-mail: Chris.Fox@idri.org 
 
Anna Marie Beckmann, PhD 
SVP, Product Development and Regulatory Affairs 
Phone: 206-858-6099 
E-mail: AnnaMarie.Beckmann@idri.org 
 
Corey Casper, MD, MPH 
Chief Scientific Officer 
Phone: 206-858-6054 
E-mail: Corey.Casper@idri.org 
 
Aude Frevol, RN, PMP 
Clinical Trial Director 
Phone: 206-858-6039 
E-mail: Aude.Frevol@idri.org 
 
Zachary Sagawa, MS 
Regulatory Manager 
Phone: 206-858-6040 
E-mail: Zachary.Sagawa@idri.org 
 
Rhea Coler, PhD 
SVP, Pre-Clinical and Translational Research 
Phone: 206-858-6065 
E-mail: Rhea.Coler@idri.org 

IDRI Protocol TBVPX-120, DMID 17-0104 
Final Version 2.0 
Single-vial Lyophilized ID93 + GLA-SE 
05 October 2018 
 
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without prior written authorization from IDRI. 
 
Tracey Day, PhD 
Clinical Immunologist 
Phone: 206-858-6044 
E-mail: Tracey.Day@idri.org 
 
IDRI Medical Monitor 
Stuart Kahn, MD 
Phone: 206-330-7604 
E-mail: stujkahn@outlook.com 
 
DMID Medical Monitor 
 
Mohamed Elsafy, MD, MSc 
OCRA/DMID/NIAID/NIH 
5601 Fishers Lane, 7E56 
Rockville, MD 20852 USA 
Tel: +1 (240) 292 4241 
Mobile: +1 (301) 204 3735 
Email: mo.elsafy@nih.gov 
 
DMID Medical Officer 
Mamodikoe Makhene, MD, MPH 
RDB/DMID/NIAID/NIH 
5601 Fishers Lane, 8E24 
Rockville, MD 20852 
Tel: 240-627-3309 
Email: mmakhene@niaid.nih.gov 
Statistics and Data 
Management 
DF/Net Research, Inc. 
Lisa Ondrejcek 
President 
140 Lakeside Avenue, Suite 310  
Seattle, WA  98122  
Phone: 206-322-5931 
Fax: 206-686-5119 
Email: lisa@dfnetresearch.com 
 
Clinical Site 
Saint Louis University 
Center for Vaccine Development 
1100 S. Grand Blvd., 8th Floor 
St. Louis, MO  63104 
 
Clinical Safety Laboratory 
Lab One, LLC Quest Diagnostic 
10101 Renner Blvd 
Lenexa, KS  66219-9752 
 
Immunology Laboratory 
IDRI 
1616 Eastlake Avenue East, Suite 400 
Seattle, WA  98102 
 
 

IDRI Protocol TBVPX-120, DMID 17-0104 
Final Version 2.0 
Single-vial Lyophilized ID93 + GLA-SE 
05 October 2018 
 
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without prior written authorization from IDRI. 
2 
BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE 
2.1 
Background Information 
Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis 
(Mtb). TB is one of the leading causes of morbidity and mortality around the world with an 
estimated 8 million cases of active TB each year and 1.3 million deaths annually 
(http://www.who.int/mediacentre/factsheets/fs104/en/). Though TB is often curable, treatment 
requires prolonged multidrug therapy (6 or more months). Compliance is difficult in all patient 
populations, but it is particularly difficult in resource-limited countries where the majority of 
cases of active TB are identified. Therapy has become more complex since it is increasingly 
common to find strains of Mtb that have developed resistance to many of the standard 
antimycobacterial drugs. Extensively drug resistant strains that are resistant to first and second 
line antitubercular agents have been identified around the world. 
Given the widespread prevalence of TB, the high rates of morbidity and mortality, and the 
complexities of treatment, effective TB vaccines could have profound impacts on global health. 
However, it is critical to realize that the nature of protective immunity for Mtb is complex and 
immune correlates of protection remain unknown [1]. Animal and human studies have 
demonstrated that a robust T cell-mediated immune response with active engagement of Th1 
CD4 and CD8 cells is critical for control of Mtb. In particular, interferon gamma (IFNγ) and tumor 
necrosis factor (TNF) producing CD4 T cells are critical [2-5]. 
The only licensed TB vaccine is Bacille Calmette-Guérin (BCG), a live attenuated strain of 
Mycobacterium bovis. BCG has been extensively studied around the world. It is effective in 
preventing TB meningitis and disseminated TB in children living in high prevalence areas of the 
world, but has had little effect on preventing reinfection and active pulmonary disease [6-8]. 
Today, BCG is often administered to infants and young children residing in many TB endemic 
countries, but as TB remains the leading infectious disease killer in the word, there is a clear need 
for more effective vaccines that better prevent infection, reactivation and reinfection. 
A number of Mtb vaccine candidates are under development and have entered clinical trials 
(Reviewed in [1, 9-11]). Vaccines can be grouped based on their target population as therapeutic 
or preventative and preventative vaccines can be used either pre-exposure or post-exposure. 
Post-exposure vaccines are intended to prevent development of active disease in already 
exposed and/or latently infected individuals. Though some of the vaccine candidates are being 
designed to replace BCG, others incorporate BCG into their proposed vaccine schema and would 
serve as a booster vaccine to be administered either soon after BCG administration in infants or 
later in life to boost waning BCG-responses [11]. ID93 is a recombinant subunit vaccine antigen 
that combines four antigens comprised of Mtb proteins that are associated with virulence and 
latency into a single recombinant protein [12]. The antigenicity of ID93 was tested by ex vivo 
stimulation of human leukocytes isolated from humans who were reactive to Mtb purified protein 
derivative (PPD+). ID93 stimulation elicited CD4 and CD8 T cells expressing one or more of the 
cytokines, IFNγ, TNF, or IL-2. Various adjuvants and adjuvant formulations were explored to 

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enhance the Th1 response [13]. Mice, guinea pigs, and cynomolgus monkeys immunized with 
ID93 + GLA-SE showed reduced pathology and/or fewer bacilli after challenge with virulent Mtb 
[12]. 
This trial will evaluate ID93 + GLA-SE lyophilized in a single vial to produce a thermostable 
candidate vaccine. Previous clinical trials have used a two-vial presentation, which in this trial 
serves as a comparator. 
2.1.1 GLA-SE  
Glucopyranosyl Lipid A (GLA) is a synthetic Toll-like Receptor 4 (TLR4) agonist and is an analog 
of the well-studied adjuvant Monophosphoryl Lipid A (MPL®; GlaxoSmithKline Biologicals). GLA 
is formulated in a stable oil-in-water emulsion (SE) to yield the adjuvant formulation GLA-SE. Due 
to the TLR4 activity of the GLA molecule, the combination of GLA-SE with a recombinant protein 
antigen (ID93) results in a Th1-type T cell response.  
2.1.2 Preclinical animal studies with ID93 
Multiple preclinical studies in human cells, mice, guinea pigs, non-human primates, and GLP 
toxicity studies in rabbits have demonstrated the safety and immunogenicity of ID93 + GLA-SE. 
Mice, guinea pigs, and non-human primates have shown that ID93 + GLA-SE is well-tolerated 
and immunogenic. Upon challenge with Mtb, animals showed significantly lower bacterial burdens 
in lungs and spleens compared with animals injected with saline, antigen alone, or adjuvant alone 
(see Investigator’s Brochure). Cells isolated from lung infiltrates showed that there was an 
increased proportion of ID93-specific CD4 T cells that expressed both IFNγ and TNF compared 
to controls. Primate studies showed that animals developed a mild acute phase response 
following each injection with mild-moderate increases in neutrophils, white blood cells, fibrinogen, 
and C-reactive protein (CRP). Increases in neutrophils and WBC were similar following repeated 
doses, though there was a mild increase in the magnitude of fibrinogen and CRP with each dose. 
Findings resolved within 2 weeks. 
Murine studies showed that ID93 + GLA-SE enhanced the Th1 response and elicited specific 
splenic CD4 T cells producing IFNγ, TNF, and IL-2. Similar reductions in bacterial burden were 
seen in the lungs of Mtb challenged mice. 
A repeated-dose toxicity study was performed in New Zealand white rabbits evaluating four 
weekly intramuscular doses of ID93 + GLA-SE. The vaccine candidate was well tolerated and 
immunogenic. As with the primate studies, mild increases in WBC, fibrinogen, and globulin were 
seen. 
2.1.3 Clinical Experience with ID93 + GLA-SE 
This trial will be the first in which the lyophilized, single-vial presentation of ID93 + GLA-SE is 
tested. ID93 + GLA-SE in the two-vial presentation has been evaluated in four completed Phase 
1 and 2 clinical trials.  

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The first trial, TBVPX-113, was a phase 1, dose-escalation study evaluating 60 healthy adults 
randomized into eight different groups that explored two different dose levels of ID93 antigen (2 
or 10 µg), two different dose levels of the GLA-SE adjuvant (2 or 5 µg), or ID93 antigen alone (2 
or 10 µg). Each subject received three IM injections on Days 0, 28, and 56. The vaccine was safe 
and well-tolerated at all dose levels. Adverse reactions included injection site reactions and mild-
moderate systemic symptoms. There were no clinically significant changes in clinical chemistry 
or hematology values related to the study product. The mild changes in sodium and potassium 
that are outlined in the Investigator’s Brochure were determined to be due to normal values for 
the particular laboratory that overlapped with the FDA toxicity tables and to delayed laboratory 
processing of blood samples. ID93 + GLA-SE elicited a robust ID93-specific antibody response 
and a polyfunctional CD4 T cell response, whereas responses to ID93 alone were significantly 
lower.  
The second study, TBVPX-114, was a phase 1b, randomized, double-blind, placebo-controlled, 
dose-escalation evaluation of two dose levels of the ID93 antigen (2 or 10 µg) administered in 
combination with two dose levels of the GLA-SE adjuvant (2 or 5 µg). Each subject received three 
IM injections on Days 0, 28, and 112. The study was conducted in South Africa and enrolled 66 
healthy adults previously vaccinated with BCG. Some groups included individuals with a positive 
QuantiFERON®-TB Gold test (i.e., with a history of exposure to TB). The vaccine was safe and 
well-tolerated in this endemic population with a similar safety profile to TBVPX-113. Adverse 
reactions mainly consisted of local and systemic reactogenicity, including mild to moderate 
injection site pain, injection site swelling, myalgia, headache, and chills. The vaccine elicited ID93-
specific CD4 T cell and antibody responses in all groups. Higher responses were observed in 
QuantiFERON-positive than in QuantiFERON-negative individuals. 
The third phase 1 trial, DMID 12-0109, was a randomized and double-blind clinical trial to evaluate 
the safety, tolerability, and immunogenicity of ID93 (10 µg) alone or in combination with AP10-
602 (5 or 10 µg) or GLA-SE (5 µg). AP 10-602 is another GLA-based adjuvant in a liposomal 
formulation with the saponin QS-21. Each subject received three IM injections on Days 0, 28, and 
56. A total of 70 participants were enrolled and the study is complete. The database was recently 
locked and the clinical study report is in preparation. Unblinded results are not yet available; 
however, no significant safety issues were identified. 
The phase 2a study, TBVPX-203, was a randomized, double-blind, placebo-controlled, dose-
escalation evaluation of two dose levels of the ID93 antigen (2 or 10 µg) administered IM in 
combination with two dose levels of the GLA-SE adjuvant (2 or 5 µg). The study also compared 
a two-dose regimen (Days 0, 56) with the three-dose regimen (Days 0, 28, 56) studied in the 
phase 1 trials. This study was conducted in 60 South African adults following successful 
completion of standard treatment and cure for Mtb culture-confirmed, drug-susceptible pulmonary 
TB. This trial was a lead-in to a future larger phase 2b trial intended to test efficacy for reducing 
the rate of disease relapse in people recently cured of TB. The vaccine was safe and well-
tolerated in this population.  
Numerous studies have evaluated GLA-SE in combination with a wide variety of other infectious 
disease antigens, with no significant safety issues identified. In addition, two studies evaluated 
the safety and tolerability of two dose levels of GLA-SE given alone without antigen by the IM or 

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SC route. GLA-SE was safe and well-tolerated. The most common adverse events (AEs) were 
injection site reactions and systemic reactions including headache, fatigue, myalgia, malaise, and 
dizziness. Most AEs were graded as mild. There were no clinically significant changes in clinical 
chemistry or hematology values. 
2.2 
Rationale 
TB causes significant morbidity and mortality throughout the world. Strains of Mtb are becoming 
increasingly resistant to antimycobacterial drugs and therapy is often associated with poor 
compliance, which increases the likelihood of antimicrobial resistance. The current licensed BCG 
vaccine does not prevent reactivation or reinfection in adults so there is a great need for a more 
effective vaccine. ID93 is a recombinant antigen that, when mixed with the adjuvant GLA-SE, 
shows great promise in eliciting what is thought to be an important Th1 T cell response and limits 
the bacterial burden in Mtb challenged animals. Thermostable vaccines facilitate greater 
distribution capacity in the developing world and reduce vaccine wastage. Development of a 
vaccine against Mtb that does not require cold-chain maintenance would significantly lower 
distribution cost and enable more effective delivery in low resource settings. 
This phase 1, double-blind, randomized clinical trial will evaluate the safety, tolerability, and 
immunogenicity of ID93 + GLA-SE in the lyophilized, single-vial presentation. The goal of this 
study is to evaluate the safety and tolerability of the new lyophilized single-vial presentation ID93 
+ GLA-SE and how immunological responses elicited by this product compare to ID93 + GLA-SE 
prepared from the two-vial presentation. One dose level of ID93 + GLA-SE will be tested (2 µg of 
ID93 and 5 µg of GLA-SE). This dose was selected because safety and immunogenicity results 
from previous clinical trials have indicated this may be the optimal dose. This trial is a bridging 
study that will allow the thermostable single-vial vaccine to move forward in clinical development.  
2.3 
Potential Risks and Benefits 
2.3.1 Potential Risks 
Safety data from the TBVPX-113, -114, and -203 trials of ID93 + GLA-SE are summarized here. 
The vaccine (combined ID93 + GLA-SE) was safe and well-tolerated: 
• 
The most common adverse events were injection site reactions (pain/tenderness, 
erythema, and induration) and certain injection-associated systemic reactions 
(headache, fatigue, myalgia, anorexia, chills, and arthralgia). The majority of adverse 
events were graded as mild (Grade 1). 
• 
There were no clinically significant changes in clinical chemistry or hematology values 
though there were subjects that experienced Grade 1 and Grade 2 fluctuations in 
clinical chemistry and hematology values (including decreased hemoglobin, 
neutrophils, lymphocytes, and WBC). 

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These findings were typically mild and transient, typical of vaccinations by the IM route, and 
indicative of the expected immunomodulatory effect of GLA-SE. There were no Grade 4 AEs, nor 
were there any serious AEs, AEs defined as a dose-limiting toxicity, or AEs of special interest 
(AEs of special interest were renamed Potential Immune-Mediated Medical Conditions 
(PIMMCs)). No subjects withdrew from the studies because of an AE. 
GLA-SE has been tested in numerous clinical trials in combination with a wide variety of antigens 
for infectious diseases including influenza, leishmaniasis, leprosy, schistosomiasis, and malaria. 
Several trials evaluated GLA-SE given alone or in combination with an antigen as a cancer 
immunotherapy. 
These clinical trials are evaluating GLA-SE at dose levels ranging from 0.5 to 20 µg. In these 
studies, over 1100 subjects have received at least one study injection containing GLA-SE. Safety 
data have not revealed any significant safety issues at any dose level tested. These studies have 
revealed an acceptable safety profile: 
• 
Study injections are generally well tolerated 
• 
There have been no serious adverse events related to study injection 
• 
Injection site reactions are common and may include pain, tenderness, erythema, and 
induration 
• 
Systemic reactions may include headache, fatigue, anorexia, fever, chills, myalgia, 
arthralgia, and anorexia 
• 
Transient elevations in CRP levels were noted in one study 
• 
Hematologic changes may occur (including decreases in hemoglobin, WBC, 
lymphocytes, and neutrophils). 
These reactions varied from study to study, were generally mild, resolved quickly, and are typical 
of vaccinations by the IM route. GLA-SE often increases the rate and severity of local and 
systemic reactogenicity compared to the antigen alone. This is in line with the nonclinical animal 
experience and is to be expected of a potent immunostimulant. 
Based on the evidence provided, we expect the risks for this study to include discomfort of having 
blood drawn and there may be pain, soreness, redness, warmth, swelling, firmness, and itching 
at the site of injection. Other reactions may include fever, chills, rash, myalgia, nausea, arthralgia, 
headache, fatigue, malaise. As with other vaccines, an allergic reaction including anaphylaxis is 
possible. We expect that there may be some mild to moderate transient fluctuations in serum 
chemistry and hematology values. 
There may be other side effects from the study injections, even serious ones that are not yet 
known. 
It is unknown if ID93 alone or in combination with GLA-SE poses any risks to an unborn or 
breastfeeding child. 

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Subjects will be asked to provide personal health information (PHI). All attempts will be made to 
keep this PHI confidential within the limits of the law. However, there is a chance that unauthorized 
persons will see the subjects’ PHI. All records will be kept in a locked file cabinet or maintained in 
a locked room at the clinical site. Electronic files will be password protected. Only people who are 
involved in the conduct, oversight, monitoring, or auditing of this study will be allowed access to 
the PHI that is collected. Any publications from this study will not use information that will identify 
subjects by name. Organizations that may inspect and/or copy research records maintained at 
the clinical site for quality assurance and data analysis include groups, such as the sponsor IDRI, 
the National Institute of Allergy and Infectious Diseases (NIAID), and the Food and Drug 
Administration (FDA). 
2.3.2 Known Potential Benefits 
There will be no direct benefit to subjects from the experimental vaccine. Subjects who participate 
will contribute to knowledge about the safety and immunogenicity of this investigational vaccine 
that may lead to better prevention and treatment of TB for those living in parts of the world where 
TB is endemic. Subjects will receive a complete physical exam and routine laboratory tests to 
assess their health status. 
Society may benefit from the potential development of a new vaccine against TB. 
 
 

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3 
OBJECTIVES 
3.1 
Study Objectives 
Primary: 
• 
To evaluate the safety and tolerability of single-vial lyophilized ID93 + GLA-SE following 
two intramuscular (IM) injections administered on Days 0 and 56. 
• 
To compare the safety and tolerability of single-vial lyophilized ID93 + GLA-SE to the two-
vial presentation consisting of lyophilized ID93 and liquid GLA-SE following two IM 
injections administered on Days 0 and 56. 
Secondary: 
• 
To assess the immunogenicity of single-vial lyophilized ID93 + GLA-SE following two IM 
injections administered on Days 0 and 56 by quantifying cytokine production and IgG 
antibody responses to ID93 at specified time points. 
• 
To compare the immunogenicity of single-vial lyophilized ID93 + GLA-SE to the two-vial 
presentation consisting of lyophilized ID93 and liquid GLA-SE following two IM injections 
administered on Days 0 and 56. 
Exploratory: 
• 
To further evaluate the immunogenicity of ID93 + GLA-SE following two IM injections 
administered on Days 0 and 56 by measuring mycobacterial growth inhibition, quantifying 
IgA levels in mucosal secretions, and measuring frequencies of circulating T follicular 
helper cells, antibody secreting cells, and memory B cells at specified time points. 
3.2 
Study Outcome Measures 
3.2.1 Primary Outcome Measures 
• 
The number of subjects experiencing solicited local injection site reactions within 7 
days following each study injection. 
• 
The number of subjects experiencing solicited systemic reactions within 7 days 
following each study injection. 
• 
The number of subjects spontaneously reporting adverse events from Day 0 through 
Day 84. 
• 
The number of serious adverse events considered related to any of the study injections 
reported at any point during the study period. 

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3.2.2 Secondary Outcome Measures 
• 
The proportion of subjects with at least a 4-fold increase in IgG antibody responses to 
ID93 on Days 14, 56, 70, 84, and 224 relative to baseline (Day 0). 
• 
Mean fold change from baseline (Day 0) in IgG antibody responses to ID93 on Days 
14, 56, 70, 84, and 224. 
• 
The number of IFN-γ and IL-10 cytokine-secreting cells in PBMC samples in response 
to the ID93 antigen relative to baseline (Day 0) at Days 14, 56, 70, 84, and 224, as 
assayed by ELISpot. 
• 
Percentage of CD4 and CD8 T cells producing 1 or more cytokines (IFN-γ, TNF, and 
IL-2) simultaneously in response to stimulation with the ID93 antigen as measured by 
intracellular cytokine staining of PBMCs at Days 14, 56, 70, 84, and 224 relative to 
baseline (Day 0). 
3.2.3 Exploratory Outcome Measures 
• 
Measurement of net intracellular growth inhibition of Mtb using whole blood on Days 
0, 70, and 224. 
• 
Quantitate IgA titers in mucosal secretions (nasal swabs and tear collections) by 
ELISA on Days 0, 70, and 224. 
• 
Quantitate number of antibody-secreting cells in PBMC by short-culture B cell ELISpot 
on Days 0, 7, and 63. 
• 
Quantitate number of antigen-specific memory B cells in PBMC by long-culture B cell 
ELISpot on Days 0, 56, 84, and 224. 
• 
Quantitate T follicular helper cells, memory B cells, and T cell homing markers in 
PBMC by immunophenotyping flow cytometry on Days 0, 7, 14, 63, 70, and 224. 
 

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4 
STUDY DESIGN 
This study is a phase 1, randomized, double-blind clinical trial designed to evaluate the safety, 
tolerability, and immunogenicity of single-vial lyophilized ID93 + GLA-SE compared to the two-
vial presentation consisting of lyophilized ID93 and liquid GLA-SE administered as two 
intramuscular injections in healthy adult subjects. 
This study will enroll 48 healthy subjects aged 18 to 55. Subjects will be counseled on the study 
and will then give an informed consent. Screening will be performed that will include evaluation 
of medical history, medication history, a physical examination, and safety laboratory evaluations. 
Subjects who meet all eligibility criteria will be randomized 1:1 into the two treatment groups. 
Study injections will be performed and subjects will be observed in clinic for 60 minutes. All 
subjects will complete a written subject memory aid that solicits local and systemic reactogenicity 
adverse events for 7 days following each study injection. Subjects will undergo a second study 
injection on Day 56. General safety will be evaluated on Days 0, 7, 56, 63, and 84 for each subject. 
All data will be recorded in the source document during the study period. 
Non-serious adverse events will be collected through Day 84 (28 days following the last study 
injection). The occurrence of serious adverse events (SAEs) and the new onset of any potential 
immune-mediated medical conditions (PIMMCs) will be collected throughout the study period 
(approximately 421 days). 
The details of all study visits are outlined in Section 7. Each subject’s duration of participation will 
be about 14 months. A detailed outline of the study visits and procedures is provided in the Study 
Visit Schedule (Appendix 1). Immunogenicity will be assessed on Day 0 (pre-dose) and on Days 
7, 14, 56, 63, 70, 84, and 224. Blood will be assessed for safety laboratories on the day of 
screening, and on Days 7 and 63. Urinalysis will be performed at screening. 
 
 

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5 
STUDY ENROLLMENT AND WITHDRAWAL 
Forty-eight (48) subjects between the ages of 18 and 55 years will be enrolled over an estimated 
4 month period. It is the intent of this study to enroll subjects who are considered healthy 
volunteers. Subjects with pre-existing clinically significant conditions are not considered normal, 
healthy volunteers. The target population will reflect the community at large in the Saint Louis 
area. Various methods of recruitment may be used such as letters, postcards, e-mails, brochures, 
posters, media boards, websites, social media, telephone contact, advertisements, and press 
releases. All forms and mechanisms of recruitment as well as the recruitment materials will be 
approved by the site’s IRB prior to use. Retention of participants is accomplished through study 
reminder telephone calls, texts, emails, and mailings as per the preferences of each individual 
volunteer. 
5.1 
Subject Inclusion Criteria 
Subjects must meet ALL of the following criteria to be eligible for inclusion in the study: 
1. Males and females 18 to 55 years of age. 
2. In good general health as confirmed by a medical history and physical exam, vital signs*, 
and screening laboratories conducted no more than 30 days prior to study injection 
administration. 
*Temperature <38°C, respiratory rate < 17 breaths pm, heart rate ≤100 bpm and >54 bpm, 
systolic blood pressure ≤140 mmHg and >89 mmHg, diastolic blood pressure ≤90 mmHg 
and ≥60 mmHg. 
NOTE: Athletically trained subjects with a pulse ≥40 may be enrolled at the discretion of the 
principal investigator or designated licensed clinical investigator. 
3. Screening laboratory values within normal limits: sodium, potassium, ALT, AST, total 
bilirubin, alkaline phosphatase, creatinine, random glucose, total WBC count, hemoglobin, 
and platelet count. 
4. Negative HIV 1/2 antibody, hepatitis B surface antigen (HBsAg), and hepatitis C virus 
(HCV) antibody. 
5. Urine dipstick for protein and glucose (negative to trace protein are acceptable). 
6. Women of childbearing potential* in sexual relationships with men must agree to practice 
acceptable contraception** for the 30-day period before Day 0 through 90 days after the 
last study injection. 
*Not sterilized via tubal ligation, bilateral oophorectomy, hysterectomy or successful Essure® placement 
(permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 
90 days after the procedure, and still menstruating or < 1 year of the last menses if menopausal). Post-
menopausal defined as at least 12 months spontaneous amenorrhea and confirmed with FSH > 40 mIU/ml. 

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**Includes, but is not limited to, sexual abstinence, monogamous relationship with vasectomized partner who 
has been vasectomized for 6 months or more prior to the subject receiving study product, barrier methods 
such as condoms or diaphragms with spermicide or foam, effective intrauterine devices, NuvaRing ®, and 
licensed hormonal methods such as implants, injectables or oral contraceptives (“the pill”).  
7. Able to understand and comply with planned study procedures and willing to be available 
for all study-required procedures, visits and calls for the duration of the study. 
8. Provide written informed consent before initiation of any study procedures. 
9. Willing to abstain from donating whole blood or blood derivatives until 90 days after the 
final study injection.  
5.2 
Subject Exclusion Criteria 
Subjects who meet any of the following criteria at screening/baseline will be excluded from study 
participation: 
1. Previous exposure to ID93 vaccines or experimental products containing GLA-SE. 
2. History of treatment for active or latent tuberculosis infection. 
3. History or evidence of active or documented latent tuberculosis, or positive 
QuantiFERON®-TB Gold test. 
4. Shared a residence within the last year prior to randomization with an individual on anti-
tuberculosis treatment or with culture or smear positive tuberculosis. 
5. Received a tuberculin skin test within 3 months (90 days) prior to randomization. 
6. History of autoimmune disease or immunosuppression. 
7. Used immunosuppressive medication (e.g., oral or injected steroids) within 3 months 
prior to randomization (inhaled and topical corticosteroids are permitted). 
8. Received any investigational drug therapy or investigational vaccine within past 6 months 
prior to randomization, or planned participation in any other investigational study during 
the study period. 
9. Received investigational TB vaccine at any time prior to randomization. 
10. Received any vaccine within 30 days prior to the first study vaccination and no planned 
immunizations between Day 0-84 or Day 210-224 due to the washout period prior to 
immunology blood draws. 
11. History or laboratory evidence of immunodeficiency state including but not limited to 
laboratory indication of HIV-1 infection at screening. 

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12. History of allergic disease or reactions, likely to be exacerbated by any component of the 
study vaccine. 
13. History of allergic reaction to kanamycin-related antibiotics. 
14. Subjects with a history of previous anaphylaxis or severe allergic reaction to vaccines or 
unknown allergens. 
15. Previous medical history that may compromise the safety of the subject in the study, 
including but not limited to: severe impairment of pulmonary function from tuberculosis 
infection or other pulmonary disease; chronic illness with signs of cardiac or renal failure; 
suspected progressive neurological disease; or uncontrolled epilepsy or infantile spasms. 
16. Known or suspected alcohol or drug abuse within the past 5 years. 
17. Smokes 1 pack or more of cigarettes per day. 
18. History of keloid formation or excessive scarring. 
19. History or evidence on physical examination of any systemic disease or any acute or 
chronic illness that, in the opinion of the investigator, may interfere with the evaluation of 
the safety or immunogenicity of the vaccine, including axillary lymphadenopathy. 
20. Received a blood transfusion or immunoglobulin within the past 3 months prior to 
randomization. 
21. Donated blood products (platelets, whole blood, plasma, etc.) within past 1 month prior to 
randomization. 
22. Presence of any febrile illness, oral temperature of >100.4 °F/38.0 °C within 24 hours of 
study injection administration. Such subjects may be re-evaluated for enrolment after 
resolution of illness. 
23. Positive serum (at screening visit only) or urine pregnancy test at screening or within 24 
hours prior to study injection for women of childbearing potential. 
24. Breastfeeding at any time throughout the study. 
25. Rash, tattoos, or any other dermatological condition on the upper anterolateral arm that 
could adversely affect the vaccine injection site or interfere with its evaluation. 
26. BMI <18 or >35 kg/m2. 
27. Any medical or neuropsychiatric condition which, in the Investigator’s opinion, would 
render the subject incompetent to provide informed consent or unable to provide valid 
safety observations and reporting. 

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28. Cancer or treatment for cancer within 3 years of study injection administration. Persons 
with a history of cancer who are disease-free without treatment for 3 years or more are 
eligible. Persons with treated and uncomplicated basal cell carcinoma of the skin are 
eligible. 
29. Subjects unlikely to cooperate with the requirements of the study protocol. 
Vital signs are performed after subjects have been in a seated position for five minutes, with no 
hot or cold beverages or smoking in the past five minutes. Vital signs may be performed up to 
three times to allow for transient conditions to resolve. Screening laboratory values that are 
abnormal, but are considered abnormal due to an acute illness or process may be repeated once. 
Creatinine, AST, ALT, bilirubin values that fall below the FDA standard toxicity tables (Appendix 
3 - Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventative Vaccine Clinical Trials; FDA/CBER; 2007) are not considered abnormal 
for the purposes of this study. Additionally, abnormalities in the RBC parameters other than 
hemoglobin and abnormalities in the WBC differential not specified in the inclusion criteria above 
(e.g. low lymphocytes, basophils, or eosinophils) will not be considered exclusionary for this study 
and will be followed with the standard safety laboratory follow ups outlined in the study. Laboratory 
values that are performed as a standard panel by the clinical laboratory, but are not requested for 
the study, will be reviewed by a licensed study clinician and the clinician will determine whether 
the laboratory value abnormality is clinically significant and should be considered exclusionary. If 
determined to be clinically insignificant, the study team is not required to follow the laboratory until 
resolution or the value is determined to be clinically stable. 
5.3 
Eligibility Criteria for 2nd Injection 
Subjects must meet all inclusion and exclusion criteria as outlined in Sections 5.1 and 5.2 with 
the exception of clinical safety lab values. Subjects with safety laboratory values that meet Grade 
2 or greater severity (according to the toxicity table, Appendix 3), that do not return to the protocol-
defined normal range prior to the second study injection will not be eligible to receive the second 
study injection. Repeat HIV, hepatitis B and hepatitis C serologies are not required prior to the 
second study injection. 
5.4 
Treatment Assignment Procedures 
5.4.1 Randomization Procedures 
Forty-eight (48) subjects will be randomly assigned to one of two groups, as shown in Table 1. 
Block randomization of appropriate size will accommodate balanced enrollment in a ratio of 1:1 
into each of the two groups for the planned 48 subjects. 
The list of randomized treatment assignments will be prepared by statisticians at DF/Net 
Research and included in the enrollment module of Interactive Web Randomization System 

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(IWRS). A designated individual at each site will be provided with a treatment key, which links the 
treatment code to the actual treatment assignment, which will be kept in a secure place. 
Instructions for use of IWRS will be included in the Study Specific Procedures (SSP) Manual. 
Manual back-up randomization procedures will be provided in the event that the site temporarily 
loses access to the Internet or the online enrollment system is unavailable. 
Table 1: Treatment Assignments 
Group 
N 
Study Injections 
Timing of Study Injections 
1 
24 
ID93 (2 µg, lyophilized) + GLA-SE (5 µg, liquid)  
[two-vial presentation] 
Days 0, 56 
2 
24 
ID93 + GLA-SE (2 µg ID93, 5 µg GLA)  
[lyophilized, single-vial] 
Days 0, 56 
 
5.4.2 Blinding Procedures 
This is a double-blind study. Subjects, investigators, study personnel performing any study-related 
assessments following study injection, and laboratory personnel performing immunology assays 
will be blinded to treatment assignment. 
The randomization scheme will be generated by DF/Net Research and provided to unblinded 
study personnel (i.e., pharmacists performing study product preparations and unblinded study 
product administrators). 
The unblinded study product administrator is a study personnel licensed to administer 
medications/vaccines, but will not be involved in study-related assessments or have subject 
contact for data collection following study injection. 
The Safety Monitoring Committee (SMC) may receive data in aggregate and by group 
assignment, or may be unblinded to individual study treatment assignments, as needed to assess 
safety issues. 
Refer to the Study Specific Procedures (SSP) Manual for unblinding procedures. 
5.4.3 Reasons for Withdrawal 
Any enrolled/vaccinated subject may withdraw or be withdrawn from the study for the following 
reasons: 
• 
The subject withdraws consent  
• 
The subject fails to comply with the scheduled study visits  
• 
The study is terminated  

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• 
For any reason that, in the opinion of the investigator, precludes the subject's 
participation in the study 
• 
Medical disease or condition, or any new clinical finding for which continued 
participation, in the opinion of the site PI or appropriate sub-investigator, would 
compromise the safety of the subject, or would interfere with the subject's successful 
completion of this trial, or would interfere with the evaluation of responses (for 
example, has significant laboratory abnormalities) 
• 
 Subject lost to follow-up 
• 
Subject no longer meets eligibility criteria 
Subjects may withdraw from participation in the study at any time. If a subject withdraws or is 
withdrawn prior to completion of the study, the reason for this decision must be recorded in the 
electronic case report forms (eCRFs). Refer to Section 7.11 for procedures to be followed if a 
subject withdraws from the study. 
5.4.4 Handling of Withdrawals 
In the case of subjects who fail to appear for a follow-up assessment, extensive efforts (i.e., 
documented phone calls and certified mail) should be made to locate or recall them, or at least to 
determine their health status. These efforts should be documented in the subjects' records and 
their health status documented in the appropriate eCRF. 
Subjects who withdraw from the study after randomization but prior to the first study injection may 
be replaced. Subjects who withdraw from the study after the first study injection will not be 
replaced. 
5.4.5 Handling of Subjects Withdrawn from Further Study Injections 
A volunteer may withdraw voluntarily from or be withdrawn from receiving further study injections, 
but will be encouraged to permit continued follow-up of AEs and to donate scheduled blood 
samples. If the volunteer agrees, other study procedures (e.g., blood sampling for safety and 
immunogenicity responses) may be continued. Refer to Section 7.13 for the visit schedule to be 
followed if second study injection is withheld.  
 Withdrawal from receiving further study injections will occur if: 
• 
Any rule for discontinuing study injection in an individual subject is met (Section 9.6.1) 
• 
The subject no longer meets inclusion/exclusion criteria  
• 
The subject develops a serious adverse event that warrants withdrawal 
• 
The subject becomes pregnant 

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• 
Other safety-related reasons at the discretion of the PI, IDRI Medical Monitor, DMID 
Medical Monitor, SMC, or the subject 
 
5.4.6 Termination of Study 
The sponsor IDRI, the IRB, or the FDA have the right to terminate this study at any time. Reasons 
for terminating the study may include, but are not limited to, the following: 
• 
Incidence or severity of AEs indicating a potential health hazard 
• 
Data recording is inaccurate or incomplete 
• 
The Investigator has not been adhering to the protocol or applicable regulatory 
guidelines in conducting the study 

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6 
STUDY INTERVENTION/INVESTIGATIONAL PRODUCT 
6.1 
Study Product Description 
ID93 for Injection 
Studies by investigators in the TB research program at IDRI have resulted in the identification of 
a recombinant subunit vaccine antigen (ID93) formulated as a fusion protein from four Mtb 
proteins associated with virulence and latency (Rv2608, Rv3619, Rv3620, and Rv1813). The final 
891 amino acid fusion protein has a predicted mass of 93KDa. 
GLA-SE Adjuvant (also known as AP 10-201) 
Glucopyranosyl Lipid A (GLA) is a synthetic Monophosphoryl Lipid A-like molecule (MPL®; GSK 
Biologicals) which is a Toll-like receptor 4 (TLR4) agonist. GLA is formulated in a stable oil-in-
water emulsion (SE) to produce GLA-SE. Due to the TLR4 activity of the GLA molecule, the 
combination of GLA-SE with a recombinant protein antigen (ID93) results in a Th1-type T cell 
response, which is important for protection from infection with Mtb. 
ID93 + GLA-SE for Injection 
The single-vial presentation of ID93 + GLA-SE contains the antigen and adjuvant components 
formulated together and lyophilized in the same vial. After reconstitution with water-for-injection, 
it is ready for administration to the study participant.  
6.1.1 Acquisition 
All investigational products will be supplied by IDRI and shipped to the clinical site at Saint Louis 
University. Water for Injection, USP diluent (WFI) will be supplied by the clinical site. 
6.1.2 Formulation, Storage, Packaging, and Labeling 
ID93 for Injection 
ID93 for Injection is formulated as a lyophilized solid and appears as a white to off-white cake. 
Each 2 mL glass vial contains 100 µg of ID93 antigen and must be stored at 2-8°C. Reconstitution 
of ID93 with WFI results in a clear solution. After reconstitution, vials may be held at ambient 
temperature while preparing doses for injection. Vials are for single-use only. For the two-vial 
presentation, ID93 is vialed separately and labeled “ID93 for Injection”. 

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GLA-SE Adjuvant (also known as AP 10-201) 
GLA-SE Adjuvant (labeled as “AP 10-201”) is formulated as 20 µg/mL GLA in 4% stable oil-in-
water emulsion and supplied as single use glass vials. GLA-SE appears as a milky-white liquid. 
Each 2 mL vial contains a fill volume of 0.4 mL and must be stored at 2-8°C. Do not freeze. For 
the two-vial presentation, GLA-SE is vialed separately and labeled “AP 10-201”. 
ID93 + GLA-SE for Injection  
ID93 + GLA-SE is formulated as a lyophilized solid, appears as a white to off-white cake, and 
must be stored at 2-8°C. Do not freeze. Each 3 mL glass vial, when reconstituted with 0.8 mL 
WFI, contains 4 µg/mL of ID93 antigen and 10 µg/mL GLA in 2% stable oil-in-water emulsion. 
Reconstitution of ID93 + GLA-SE for Injection with WFI results in a milky-white solution. For the 
single-vial presentation, that includes both ID93 and GLA-SE, each vial is labeled “ID93 + GLA-
SE for Injection”. 
Each of the study products containing ID93 antigen and/or GLA-SE adjuvant will be labeled 
according to manufacturer specifications and include the statement “Caution: New Drug – Limited 
by Federal Law to Investigational Use.” 
Sterile Water for Injection, USP 
The sterile WFI sourced by the clinical site should be nonpyrogenic and contain no bacteriostatic, 
antimicrobial agent, or added buffer. This product should be used to reconstitute the antigen ID93 
for Injection and for reconstituting the single-vial ID93 + GLA-SE, and will be supplied as single-
use containers. The sterile WFI vials are stored at 20 to 25ºC (68 to 77ºF) [See USP Controlled 
Room Temperature; excursions between 15 and 30°C (59 and 86°F) are permitted] 
6.2 
Dosage, Preparation, and Administration of Study 
Intervention/Investigational Product 
Study vaccine preparation, including vaccine dilutions and admixing for the various dosing groups, 
will be performed by the unblinded site pharmacist using aseptic technique under a biological 
safety cabinet (BSC) or laminar flow hood on the same day of study vaccine administration.  
 
Long-term stability of mixtures of ID93 and GLA-SE is unknown at this time. Therefore, all study 
injection preparations must be administered within 2 hours of preparation. The 2 hour window 
begins when the final formulated preparation is mixed and drawn into a syringe for administration 
to a study participant. The time of preparation and time of administration should be noted in the 
source documentation. 
 
Vials of antigen and adjuvant should be removed from the 2-8°C storage refrigerator at least 5 
minutes prior to study injection preparation to allow equilibration with room temperature. The vials 
and prepared syringes may be maintained at room temperature (below 37°C) during preparation 

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time and prior to administration. The designee assigned to administer the study injections will be 
supplied with a loaded syringe labeled with the participant identification number (PID#) and 
hospital required identification data. 
 
All vials are single-use only. 
 
All used and labeled vials for each subject per dosing day should be placed in a sealable bag. 
The bag should be labeled with PID#(s) and the date of injection. The used vials must be kept in 
a secured location. Used vials may be kept at room temperature or refrigerated until drug 
accountability is completed by the unblinded investigational product monitor. 
 
Refer to the SSP Manual for detailed information on the preparation, labeling, and storage of 
study product. 
6.3 
Modification of Study Intervention/Investigational Product for a Participant 
No modification of the study intervention or investigational product will occur for individual 
participants. 
6.4 
Accountability Procedures for the Study Intervention/Investigational 
Product(s) 
After receipt of the investigational products, the site PI is responsible for study product distribution 
and disposition, and has ultimate responsibility for study product accountability. The PI may 
delegate to the site Research Pharmacist the responsibility for study product accountability. The 
site Research Pharmacist will be responsible for maintaining complete records and 
documentation of product receipt, accountability, dispensation, temperature and storage 
conditions, and final disposition of study product. All study product, whether administered or not, 
must be documented on the appropriate study product accountability record or dispensing log. 
 
Used and unused vials of investigational product will be retained until monitored and released for 
disposition as applicable. Upon completion or termination of the study and after the final 
monitoring visit, final disposition of the unused study product will be determined by the sponsor 
and communicated to the participating site(s). For details regarding final disposition of study 
products, see the SSP Manual. 
6.5 
Concomitant Medications/Treatments 
Administration of any medications, therapies, or vaccines will be documented in the subject’s 
source documentation and reported on the subject’s electronic case report form (eCRF). 
Concomitant medications will include all medications, vitamins, and supplements taken within the 
30 days before enrollment and through 28 days after the last study injection (approximately Day 
84) or early termination, whichever occurs first. 

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Medications that might interfere with the evaluation of the investigational product should not be 
used unless necessary. Medications in this category include, but are not limited to, glucocorticoids 
(i.e., oral, parenteral, and high-dose inhaled steroids), and immunosuppressive or cytotoxic drugs. 
Analgesics and antipyretics should be avoided for the 24 hours following study injection, unless 
necessary. 

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7 
STUDY SCHEDULE 
7.1 
Screening Procedures (Day -30 to Day -1) 
More than one clinic visit may be required in order to complete all screening evaluations for an 
individual subject. The following procedures will be performed: 
• 
Obtain informed consent. This should be performed prior to conducting any of the 
assessments listed below.  
• 
Assign a Screening Identification number (SID #). 
• 
Review inclusion/exclusion criteria as specified for the initial study injection. 
• 
Obtain medical history, and concomitant medications (prescription and over-the counter 
drugs taken 30 days prior to enrollment will be reviewed and documented). 
• 
Perform a physical exam that assesses general appearance and the following 
areas/systems: skin, lymph nodes, HEENT, neck, pulmonary/respiratory, cardiovascular, 
abdomen, musculoskeletal, and neurological. 
• 
Obtain height and weight. Calculate BMI. 
• 
Obtain vital signs including blood pressure (BP), pulse (P), respiratory rate (RR), and 
oral temperature. 
• 
Assess visual acuity (Snellen test or other objective measure of visual acuity) 
• 
Obtain blood and urine sample for screening laboratories and QuantiFERON®-TB Gold 
test. 
• 
Perform serum pregnancy test for female subjects of childbearing potential or serum 
FSH for post-menopausal females. 
• 
Review of contraceptive methods (female subjects of childbearing potential only). 
• 
Counseling on avoidance of pregnancy (for all female subjects of childbearing potential). 
• 
All screening laboratory results must be available for review by the investigator prior to 
visit Day 0. 
7.2 
Day 0 Enrollment/Baseline Evaluations and First Study Injection 
Prior to Study Injection: 
• 
Review Inclusion/Exclusion criteria as specified for the initial study injection. 
• 
Review concomitant medications. 
• 
Obtain vital signs (BP, P, RR, oral temperature). 
• 
Perform a targeted physical exam if indicated based on symptoms. 
• 
Perform urine pregnancy test for females of childbearing potential within 24 hours prior 
to study injection. Test results must be confirmed as negative prior to study injection. 
• 
Review of acceptable contraceptive methods (female subjects only). 
• 
Counseling on avoidance of pregnancy (for all female subjects of childbearing potential). 
• 
Collect nasal swab 
• 
Collect tears 
• 
Collect blood prior to study injection for baseline immunologic evaluations for: 
o Serum for IgG ELISA 
o Serum to bank (baseline for auto-immune testing, if indicated) 
o Whole blood for MGIA 
o PBMC isolation 

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• 
Perform randomization procedures. 
 
Study Injection: 
• 
Administer study injection in the non-dominant deltoid unless there is a reason to inject in 
the alternate deltoid. Both injections are preferably administered in the same arm. 
• 
Dispense memory aid, measuring tool, and thermometer. 
 
Immediately Following Study Injection: 
 
All subjects will be observed for a minimum of 60 minutes following study injection. After 60 
minutes: 
• 
Obtain vital signs (BP, P, RR, oral temperature). 
• 
Examine the injection site and assess any AE/SAEs (including specific solicited systemic 
reactions: headache, arthralgia, chills, loss of appetite, fever, fatigue, and myalgia), prior 
to discharge from the clinic.  
• 
Request subject to bring their completed memory aid to the next clinic visit.  
 
All subjects will be asked to record, on a subject memory aid, daily maximum temperatures, 
symptoms for 7 days, measure erythema or induration if any, beginning with the day of study 
injection and report them to the clinic staff. Subjects will be asked to bring their completed 
memory aid to the Day 7 post-injection clinic visit. 
7.3 
Day 7 (±1) Evaluations 
• 
Obtain vital signs (BP, P, RR, oral temperature). 
• 
Evaluate site of injection.  
• 
Perform a targeted physical exam if indicated, based on symptoms. 
• 
Review memory aid.  
• 
Review adverse events, including SAEs and PIMMCs. 
• 
Review concomitant medications 
• 
Collect blood for: 
o Hematology: WBC with differential, HGB, platelets  
o Serum chemistry: includes sodium, potassium, ALT, AST, total bilirubin, alkaline 
phosphatase, and creatinine. 
o PBMC isolation 
7.4 
Day 14 (±3) Evaluations 
• 
Collect blood for: 
o Serum for IgG ELISA 
o PBMC isolation 
7.5 
Day 56 (±3) Evaluations and Second Study Injection 
Prior to Study Injection: 
• 
Review Inclusion/Exclusion criteria as specified for the second study injection. 
• 
Review adverse events, including SAEs and PIMMCs. 

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• 
Review concomitant medications. 
• 
Obtain vital signs (BP, P, RR, oral temperature). 
• 
Perform a targeted physical exam if indicated, based on symptoms. 
• 
Perform urine pregnancy test for females of childbearing potential within 24 hours prior to 
study injection. Test results must be confirmed as negative prior to study injection. 
• 
Review of acceptable contraceptive methods (female subjects only). 
• 
Counseling on avoidance of pregnancy (for all female subjects of childbearing potential). 
• 
Collect blood prior to study injection for baseline immunologic evaluations for:  
o Serum for IgG ELISA 
o PBMC isolation 
Study Injection: 
• 
Administer study injection in the non-dominant deltoid unless there is a reason to inject in 
the alternate deltoid. Both injections are preferably administered in the same arm. 
• 
Dispense memory aid, measuring tool, and thermometer. 
 
Immediately Following Study Injection: 
 
All subjects will be observed for a minimum of 60 minutes following study injection. After 60 
minutes: 
• 
Obtain vital signs (BP, P, RR, oral temperature). 
• 
Examine the injection site and assess any AE/SAEs (including specific solicited systemic 
reactions: headache, arthralgia, chills, loss of appetite, fever, fatigue, and myalgia), prior 
to discharge from the clinic.  
• 
Request subject to bring their completed memory aid to the next clinic visit.  
 
All subjects will be asked to record, on a subject memory aid, daily maximum temperatures, 
symptoms for 7 days, and measure erythema or induration if any beginning with the day of 
study injection and report them to the clinic staff. Subjects will be asked to bring their completed 
memory aid to the Day 7 post-injection clinic visit. 
7.6 
Day 63 (±1) Evaluations 
• 
Obtain vital signs (BP, P, RR, oral temperature). 
• 
Evaluate site of injection. 
• 
Perform a targeted physical exam if indicated, based on symptoms. 
• 
Review memory aid.  
• 
Review adverse events, including SAEs and PIMMCs. 
• 
Review concomitant medications. 
• 
Collect blood for: 
o Hematology: WBC with differential, HGB, platelets. 
o Serum chemistry: includes sodium, potassium, ALT, AST, total bilirubin, alkaline 
phosphatase, and creatinine. 
o PBMC isolation 
7.7 
Day 70 (±3) Evaluations 
• 
Collect nasal swab 
• 
Collect tears 

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• 
Collect blood for: 
o Serum for IgG ELISA 
o Whole blood for MGIA 
o PBMC isolation 
7.8 
Day 84 (±5) Evaluation 
• 
Obtain vital signs (BP, P, RR, oral temperature). 
• 
Perform a targeted physical exam if indicated, based on symptoms. 
• 
Review adverse events, including SAEs and PIMMCs. 
• 
Review concomitant medications. 
• 
Collect blood for: 
o Serum for IgG ELISA 
o PBMC isolation 
7.9 
Day 224 (±10) Evaluations  
• 
Perform a targeted physical exam if indicated, based on symptoms. 
• 
Review SAEs and PIMMCs. 
• 
Record concomitant medications used for treatment of SAEs or PIMMCs, if any. 
• 
Collect nasal swab 
• 
Collect tears 
• 
Collect blood for: 
o Serum for IgG ELISA 
o Whole blood for MGIA 
o PBMC isolation 
7.10 Day 421 (±14) Evaluations 
The follow-up at one year after the last study injection will be performed by telephone. 
• 
Review SAEs and PIMMCs. 
• 
Record concomitant medications used for treatment of SAEs or PIMMCs, if any.  
7.11 Early Termination Visit 
If a subject withdraws from the study early, the following procedures should be performed at the 
early termination visit, if possible. 
• 
Review current health status (interim medical history) and note any changes since the last 
visit. 
• 
Obtain vital signs (BP, P, RR, oral temperature). All concomitant medications will be 
recorded if before Day 84 visit. 
• 
Collect blood for (refer to Schedule of Blood Draws and Volumes): 
o Serum for IgG ELISA 
o PBMC isolation  
If prior to Day 63, for: 
o Hematology: WBC with differential, HGB, platelets 

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o Serum chemistry: includes sodium, potassium, ALT, AST, total bilirubin, alkaline 
phosphatase, and creatinine 
• 
A targeted physical examination may be performed, if indicated. 
• 
Information regarding AEs, SAEs, and new onset chronic medical conditions will be 
solicited (AEs will be solicited only if prior to Day 84). Any ongoing AEs or PIMMCs will be 
followed to resolution or until a stable chronic condition has been established. 
Subjects may withdraw voluntarily from participation in the study at any time. Subjects may also 
withdraw voluntarily from receiving the study intervention for any reason. An investigator may also 
withdraw a subject from receiving further study intervention. The subject may be withdrawn from 
the study if the sponsor terminates the study. 
Follow-up assessments will be completed according to the protocol schedule, if possible. 
7.12 Unscheduled Visit 
Unscheduled visits may occur at any time during the study. The procedures below are to be 
performed at any unscheduled visit. See the SSP Manual for instructions for documentation and 
data reporting. 
• 
Review concomitant medications. 
• 
Obtain vital signs, if clinically indicated. 
• 
Perform a targeted physical exam if indicated, based on symptoms. 
• 
Blood and/or urine samples will be collected for safety laboratory tests, if indicated 
• 
Evaluate injection site, if within 7 days of injection or if indicated. 
• 
Review memory aid and adverse events if within 7 days of injection or if ongoing local 
or systemic reactogenicity on day 7 post study injection.  
• 
Review adverse events, if within 84 days of first injection or if indicated.  
• 
Review SAEs and PIMMCs 
7.13 Visit Schedule to be followed if 2nd study injection is withheld 
Subjects who receive only the first study injection will continue to be followed for 28 days after the 
injection, and then a telephone visit will be performed on Day 421. The appropriate scheduled 
blood samples will be obtained for these visits as outlined in the study visit schedule. 
 

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8 
STUDY PROCEDURES AND EVALUATIONS 
8.1 
Clinical Evaluations 
The schedule of study visits and procedures is specified in Appendix 1. 
Medical History: Will be obtained by interview of the subjects. Subjects will be queried regarding 
a history of significant medical disorders of the head, eyes, ears, nose, throat, mouth, 
cardiovascular system, lungs, gastrointestinal tract, liver, pancreas, kidney, nervous system, 
blood, lymph glands, endocrine system, musculoskeletal system, skin, and genital/reproductive 
tract. A history of any allergies, cancer, immunodeficiency, psychiatric illness, substance abuse, 
and autoimmune disease will be solicited. The collection of medical history information will include 
a review of TB vaccine history and plans for vaccinations. 
Concomitant Medications: All current medications and medications taken in the 30 days before 
enrollment (prescription and over-the-counter drugs) will be included, as well as vitamins and 
supplements, through 28 days after the last study injection, unless if used for treatment of an SAE 
or PIMMC. In the latter case, it will be included through the end of the study. Assessment of 
eligibility also will include a review of prohibited medications (per the exclusion criteria). 
Physical Examination: This examination will be conducted at Screening and will assess general 
appearance including height and weight (at Screening only), vital signs (blood pressure, oral 
temperature, pulse), and the following areas/symptoms: skin, lymph nodes, head, eyes, ears, 
nose, 
throat, 
neck, 
respiratory, 
cardiovascular, 
pulmonary, 
abdomen, 
extremities, 
musculoskeletal, and neurological. 
Targeted Physical Examination: This may be conducted at any study visit based on indicated 
symptoms. No examination is necessary if no symptoms are present. 
Local and systemic reactogenicity assessments: This will include a brief review for assessment 
of AEs, which includes an assessment of pain, erythema, and induration at the injection site; and 
systemic reactions including headache, arthralgia, chills, loss of appetite, fever, fatigue, and 
myalgia. 
Memory Aids: All subjects will complete a subject memory aid for 7 days following each study 
injection. Subject memory aids will be reviewed with the subject for AEs at the clinic visit following 
each study injection. If a subject noted ongoing local or systemic reactogenicity on day 7 post 
study injection, the memory aid will continue to be used until resolved. The memory aids will be 
retained in the subject source document binder after review. A measuring tool and thermometer 
are included with the memory aid. 

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8.2 
Laboratory Evaluations 
Schedules and volumes of blood to be collected for clinical laboratory tests and immunogenicity 
assays are specified in Appendix 2. 
8.2.1 Clinical Laboratory Evaluations 
Clinical safety laboratory evaluations will be obtained at Screening and on Days 0, 7, 56, and 63. 
Specific tests to be performed are described below: 
Screening Visit:  
• 
Hematology: WBC with differential, HGB, platelets  
• 
Chemistry: sodium, potassium, ALT, AST, total bilirubin, alkaline phosphatase, creatinine, 
random glucose. 
• 
Serology tests: HIV 1/2 antibody, hepatitis B surface antigen (HBsAg), and hepatitis C 
virus (HCV) antibody. 
• 
Urinalysis: will be performed by dipstick testing (includes protein and glucose).  
• 
Pregnancy test: urine pregnancy test in females of childbearing potential or serum FSH 
for post-menopausal females.  
Days 7 and 63:  
• 
Hematology: WBC with differential, HGB, platelets.  
• 
Chemistry: sodium, potassium, ALT, AST, total bilirubin, alkaline phosphatase, and 
creatinine. 
 
Days 0 and 56: 
• 
Pregnancy test: urine pregnancy tests on Days 0 and 56 in females of childbearing 
potential.  
One or more of the laboratory parameters may be repeated at any time during the study as 
determined by the PI or licensed clinical study physician, if indicated by an AE. Screening 
laboratory values that are abnormal, but are considered abnormal due to an acute illness or 
process may be repeated once. A clinically significant abnormal value should be repeated within 
10 days if possible and followed up as clinically relevant. 
8.2.2 Special Assays or Procedures 
Screening Visit: 
• 
Prior exposure to TB antigens (prior infection with Mtb or vaccination with BCG) will be 
assessed using QuantiFERON®-TB Gold tests at the screening visit. Positive results will 
result in exclusion from the study and referral to medical treatment. 
Days 0, 14, 56, 70, 84, 224: 
• 
IgG antibody response in serum (secondary outcome measure) 

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o ID93-specific antibody responses will be measured by IgG binding to the ID93 
protein using ELISA. Studies will be performed at IDRI. 
• 
ELISpot and ICS assays in PBMC (secondary outcome measures) 
o T cell immune responses will be assessed by enumerating antigen-specific, 
cytokine-secreting T cells using IFN-γ enzyme-linked immunosorbent spot assays 
(ELISpot) and flow cytometry-based intracellular cytokine staining (ICS) from 
PBMC samples. Both assays will be performed at IDRI. 
 
Days 0, 70, 224: 
• 
IgA antibody response in mucosal secretions (exploratory outcome measure) 
o Antibody responses will be measured in nasal swab and tear specimens by IgA 
binding to the ID93 protein using ELISA. Assay will be performed by Dan Hoft’s 
laboratory at Saint Louis University. 
Days 0, 70, 224: 
• 
Mtb growth inhibition in whole blood (exploratory outcome measure) 
o Functionality of the immune response will be assessed by measuring the capacity 
of whole blood to inhibit the growth of mycobacteria. Assay will be performed by 
Dan Hoft’s laboratory at Saint Louis University. 
Days 0, 7, 14, 63, 70, 224: 
• 
Exploratory cellular immune responses (exploratory outcome measures) 
o PBMC samples will be used to quantitate the number of antibody-secreting cells 
in PBMC by short-culture B cell ELISpot, the number of antigen-specific memory 
B cells in PBMC by long-culture B cell ELISpot, and the frequencies of T follicular 
helper cells, memory B cells, and T cell homing markers in PBMC by 
immunophenotyping flow cytometry. Studies will be performed at IDRI. 
8.2.3 Specimen Shipment 
All participant samples (except for whole blood specimens) will be processed and stored through 
Study Day 224. Whole blood specimens are used fresh by the site and therefore not stored. 
Mucosal specimens will remain at the site for analysis (tears, nasal swabs). PBMC and serum 
specimens will be shipped to IDRI for analysis after the last Day 224 specimens are stored. PBMC 
and serum specimens from a single participant will be divided into separate boxes for storage and 
shipment. Shipment of PBMC and serum samples from the same individual and time point will 
take place on separate dates in case of specimen loss due to temperature excursions/deviation 
in cold chain. 

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9 
ASSESSMENT OF SAFETY 
9.1 
Specification of Safety Parameters 
Safety will be assessed by the frequency and severity of: 
1. Serious adverse events occurring from the time of the first study injection through the 
entire study period. 
2. Solicited adverse events – reactogenicity events occurring on the day of each study 
injection through 7 days after each study injection. This time period may be extended if a 
subject notes ongoing local or systemic reactogenicity on day 7 post study injection: 
a) Injection site reactions including pain, induration (hardening/swelling), and 
erythema (redness). 
b) Systemic reactions including headache, arthralgia (generalized joint pain), chills, 
loss of appetite, fever, fatigue, and myalgia (generalized muscle pain). 
3. Unsolicited adverse events – non-serious adverse events occurring from the time of the 
first study injection through Day 84, including vital sign and safety laboratory 
abnormalities. 
4. New-onset potential immune-mediated medical conditions (PIMMCs) occurring from the 
time of the first study injection through the entire study period.  
9.2 
Methods and Timing for Assessing, Recording, and Analyzing 
Safety Parameters 
9.2.1 Adverse Events 
Adverse Event: Adverse event means any untoward medical occurrence associated with the use 
of a drug in humans, whether or not considered drug or study injection related. An adverse event 
(also referred to as an adverse experience) can be any unfavorable and unintended sign (e.g., an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, 
and does not imply any judgment about causality. An adverse event can arise with any use of the 
drug (e.g., off-label use, use in combination with another drug) and with any route of 
administration, formulation, or dose, including an overdose. 
All conditions that exist prior to administration of the study injection (pre-existing conditions) will 
be recorded in the participant’s medical history to establish baseline. Day-to-day fluctuations in 
pre-existing conditions that do not represent a clinically significant change in the participant’s 
status will not necessarily be reported as adverse events. 

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Any adverse change from the participant’s baseline condition (determined from screening 
evaluations conducted to confirm study eligibility) that occurs following the administration of the 
study injection will be considered an adverse event. This includes the occurrence of a new 
adverse event or the worsening of a baseline condition, whether or not considered related to the 
study injection. Intermittent conditions such as headaches may be present on Study Day 0, but 
may represent an adverse event if the frequency, intensity, or duration of the event is worse than 
usual following receipt of study injection. Adverse events include but are not limited to: adverse 
changes from baseline that represent increases in toxicity grade, adverse changes in the general 
condition of the participant, signs and symptoms noted by the participant, concomitant disease 
with onset or increased severity after study injection administration, and changes in laboratory 
safety parameters occurring after study injection administration. 
A suspected adverse reaction is any adverse event for which there is a reasonable possibility 
that the study injection caused the event. Suspected adverse reactions are a subset of all adverse 
events. For example, headache or fever following study injection. 
An adverse reaction is any adverse event definitely caused by the study injection. Adverse 
reactions are a subset of all suspected adverse reactions. For example, local site of injection 
erythema or pain at the site of injection. 
Unexpected Adverse Event: An adverse event is considered “unexpected” if it is not listed in 
the Investigator’s Brochure or is not listed at the specificity or severity that has been observed. 
Serious Adverse Event: An adverse event is considered a serious adverse event (SAE) if, in the 
view of either the investigator or sponsor, it results in any of the following outcomes:  
• 
death, 
• 
a life-threatening adverse event, 
• 
inpatient hospitalization or prolongation of existing hospitalization, 
• 
persistent or significant disability/incapacity or substantial disruption of the ability to 
conduct normal life functions,  
• 
a congenital anomaly/birth defect in the offspring of a study subject. 
Important medical events that may not result in death, are not life-threatening, or do not require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, they 
may jeopardize the subject and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition. Examples of such medical events include allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions 
that do not result in inpatient hospitalization, or the development of drug dependency or drug 
abuse. 
NOTE: A distinction should be drawn between serious and severe events. A severe event is a 
major experience of its type. A severe event does not necessarily need to be serious. For 
example, nausea, which persists for several hours, may be considered severe nausea but not a 
serious adverse event. On the other hand, a stroke that results in only a limited degree of disability 
may be considered a mild stroke but would be a serious adverse event. 

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Life-threatening Event: An adverse event is considered “life-threatening” if, in the view of either 
the investigator or sponsor, its occurrence places the patient or subject at immediate risk of death. 
It does not include an adverse event that, had it occurred in a more severe form, might have 
caused death. 
Potential immune-mediated medical conditions (PIMMCs): FDA requires monitoring for 
specified known or suspected autoimmune disorders when testing novel adjuvants. PIMMCs will 
be recorded on the AE form and reported to IDRI Pharmacovigilance regardless of their attributed 
relationship to study injections. PIMMCs consist of any of the diagnoses listed in Appendix 6 
reported in study injection recipients at any time during the study period or after completion of the 
study.  
 
All adverse events (including PIMMCs) will be reported on the Adverse Event eCRF using a 
recognized medical term or diagnosis that accurately reflects the event. Adverse event 
evaluations will be reviewed by the PI or by a designated medically qualified practitioner. Adverse 
event eCRF pages are to be completed by members of the study team designated in writing by 
the PI. The onset and resolution dates of the event and action taken in response to the event will 
be documented. All adverse events must be followed until resolution or stabilization is 
demonstrated. The resolution date will be recorded on the eCRF as the last date on which the 
participant experienced the adverse event. If the subject cannot recall the date of resolution, then 
the resolution date will be the visit date on which the study staff determines the AE to be resolved.  
Adverse events that are still present at the end of the trial should be recorded as ongoing and be 
followed until resolved or considered stable. Information recorded on the eCRF must be 
substantiated in the source documents. If an adverse event evolves into a condition that becomes 
“serious,” it will be designated as serious on the Adverse Event eCRF and an SAE Report will be 
completed. 
 
9.2.2 Assessment of Severity (Grading) 
The safety concepts of “severity” and “seriousness” are distinct concepts. Severity refers to a 
degree of clinical manifestation. “Seriousness” refers to defined outcomes from an adverse event. 
A severe adverse event is not always serious and a serious adverse event is not always severe. 
For all adverse events, the investigator is responsible for assessing the severity of the event and 
the causal relationship of the event to the study injection. 
The severity of all adverse events, including clinical findings and abnormal laboratory values, will 
be classified as one of the following grades: 
• 
Grade 1: Mild 
• 
Grade 2: Moderate 
• 
Grade 3: Severe 

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Toxicity tables are provided in the protocol appendices for the assessment of severity of specified 
adverse events. The toxicity table adverse event grades do not correlate directly with the classical 
severity grades of mild, moderate, and severe. For the purposes of recording events on the eCRF, 
Grade 1 events will be considered mild in severity, Grade 2 events will be considered moderate 
in severity, and Grade 3 events will be considered as severe. In the grading scale for local 
reactions (Appendix 4), certain local reactions such as erythema and induration are graded 
according to size. Laboratory values are graded according to level of deviation from the normal 
range. 
For adverse events not listed in the toxicity tables, determination of severity requires some level 
of interpretation as outlined below. The degree of incapacity caused by the adverse event and 
the level of medical intervention required for treatment may be helpful in assessing the overall 
severity of the adverse event. 
For example: 
• 
“Mild” events are generally regarded as noticeable but have no impact on normal activities; 
they may or may not require over-the-counter treatment managed by the participant. 
• 
“Moderate” events generally have some impact on an individual’s normal daily activities 
and may require general symptomatic medical intervention by a healthcare professional 
or by the participant. 
• 
“Severe” adverse events may be incapacitating, leading to suspension of normal daily 
activities, and would generally require more immediate medical evaluation and 
intervention by a healthcare professional. 
A change in severity of an adverse event will not be recorded as a new adverse event. Only the 
highest severity level that occurs during the entire period of the adverse event will be recorded on 
the eCRF with the onset and resolution dates encompassing the entire duration of the event. 
9.2.3 Assessment of Causality (Relatedness to Study Injection) 
For all adverse events, the investigator will determine a causal relationship to the study injection. 
A number of factors will be considered in making this assessment, including: 1) the temporal 
relationship of the event to the administration of the study injection, 2) whether an alternative 
etiology has been identified including the toxicity profile of any concomitant medication, and 3) 
biological plausibility.  
The investigator will use the following guidelines to assess the causal relationship of an adverse 
event to study injection: 
• 
Not Related to study injection (i.e., there is not a reasonable possibility that the 
administration of the study product caused the adverse event). 
• 
Possibly Related to study injection (i.e., there is a reasonable possibility that the adverse 
event was caused by study injection. There must be a plausible mechanism for the event 

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to be related to study injection. The evidence is inadequate to accept or reject, or favors 
rejection of, a causal relationship; an association exists between the event and the study 
injection but there may also be an alternative etiology, such as characteristics of the 
participant’s clinical status or underlying condition). 
• 
Probably Related to study injection (i.e., it is likely that the adverse event was caused by 
administration of the study injection. The evidence favors acceptance of a causal 
relationship; an association exists between the event and receipt of the study injection and 
there is a plausible mechanism for the event to be related to the study injection, and an 
alternative etiology is not apparent). 
• 
Definitely Related to study injection (i.e., the study injection is known to be the cause of 
the adverse event. The evidence establishes a causal relationship; an association exists 
between the event and receipt of the study injection and there is a plausible mechanism 
for the event to be related to the study injection, and causes other than the study injection 
have been ruled out). 
For reporting purposes, consistent with NIAID guidelines, definitely, probably, and possibly related 
adverse events are considered related to study injection. Not related adverse events are 
considered unrelated. 
For adverse events requiring immediate reporting, the PI and the Sponsor Medical Monitor both 
determine causality. It is expected that communication and consultation may occur in the 
assessment of the causality of adverse events. The greatest degree of causal relationship 
(definite > probable > possible > not related) determined by either the investigator or Medical 
Monitor after their discussions will determine the ultimate classification of the adverse event. 
Adverse events where the causality is not assessable will be considered related to the study 
injection. 
Every effort should be made by the investigator to determine the existence of any pre-existing 
conditions that must be taken into consideration when assessing causal relationship of an adverse 
event. Pre-existing conditions should be recorded in the eCRF as baseline history and 
substantiated by appropriate source documentation. Intermittent conditions such as headaches 
in adults may not be present on Study Day 0 but may represent an adverse event if the frequency, 
intensity, or duration of the event is worse than usual following study injection. 
9.2.4 Evaluation of Expectedness 
Expected adverse events are adverse events consistent with the applicable product information 
provided by the sponsor (the Investigator’s Brochure for an investigational product). The sponsor, 
in the person of the Sponsor Medical Monitor, determines expectedness. If the assessment is that 
the adverse event is expected, no further action is required. If the Sponsor Medical Monitor’s 
assessment is that the adverse event is unexpected, then the event may represent a suspected 
unexpected serious adverse reaction (SUSAR) or expedited SAE.  

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9.2.5 Reactogenicity  
Local site of injection reactions (pain, erythema, and induration) will be graded according to 
Appendix 4. Specific solicited systemic reactions (headache, arthralgia, chills, loss of appetite, 
fever, fatigue, and myalgia) will be graded according to Appendix 5. 
9.2.6 Memory Aids 
Memory aid booklets will be distributed to each subject to collect local and systemic adverse event 
information covering the 7-day period following the first and second study injections. All subjects 
will be instructed to record local and general signs and symptoms on individual memory aids on 
the evening of the day of injection and at approximately the same time daily for each of the six 
days following injection. Erythema and induration at the injection site will be measured in 
centimeters, using the measuring tool provided for that purpose. Subjects will also be asked to 
record any medications taken. The memory aid will be brought to the clinic on the scheduled visit 
7 days after each injection for review and will be collected by the study research staff on Days 7 
and 63. The memory aid is a tool to help aid the PI and/or designee to engage in a conversation 
with the subject about any AEs that may have occurred between visits. Memory aids not brought 
to the scheduled visit should be obtained before complete adverse event assessment can be 
performed and events discussed with the PI and/or designee. Adverse events obtained from the 
memory aid, as determined by the PI or designee, will not be directly recorded onto eCRFs. Any 
entry recorded by the subject on the memory aid that differs from the opinion of the investigator’s 
evaluation of the event (e.g., the severity level of an event is changed after interviewing the 
subject) must be explained by notation in source documentation.  
Subject-assessed symptoms related to the injection site in the memory aid will include injection 
site pain, redness (erythema), and hardening/swelling (induration).  
Grading of local pain at the injection site will be according to the following definitions: 
• 
None 
• 
Mild (does not interfere with normal* daily activities)  
• 
Moderate (repeated use of non-narcotic pain reliever > 24 hours or interferes with 
normal* daily activities) 
• 
Severe (any use of narcotic pain reliever or prevents normal* daily activities) 
Grading of redness and hardening/swelling at the injection site will be made according to the 
following (note: measurements are at the widest diameter): 
• 
None (0 to < 2.5 cm in diameter) 
• 
Mild (2.5 to 5 cm in diameter) 
• 
Moderate (5.1 to 10 cm in diameter) 
• 
Severe (>10 cm in diameter or necrosis or exfoliative dermatitis for redness) 
 
     (>10 cm in diameter or necrosis for induration) 

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Oral temperature will be measured daily and recorded in the memory aid. General signs and 
symptoms will be limited to headache, joint pain (arthralgia), chills, anorexia (loss of appetite), 
fever, tiredness (fatigue), and generalized muscle pain (myalgia). Grading of none, mild, 
moderate, and severe will be used according to the following definitions: 
• 
None 
• 
Mild (no interference with daily activity) 
• 
Moderate (some interference with daily activity) 
• 
Severe (Significant interference, prevents daily activity) 
‘Normal’ daily activities include those performed by most able people, such as dressing, bathing, 
walking, driving, housekeeping; they do not include unusually strenuous activities that may be 
‘normal’ for certain individuals such as lifting heavy weights. 
During the 60-minute observation period following the first study injection, subjects will be trained 
by the research staff on the proper completion of the memory aid and the schedule for completion. 
Subjects will also be trained in the proper procedure for taking oral temperature and will be asked 
to record their oral temperature each evening in the memory aid. Digital oral thermometers will be 
provided to all subjects for oral temperature readings. Subjects will also be provided with a 
measuring tool and trained on how to measure local redness (erythema) and hardening/swelling 
(induration). 
Explicit choices for mild, moderate, and severe reactions will be indicated in the memory aid by 
the subjects, as defined above. 
9.3 
Serious Adverse Events (SAE) 
9.3.1 Assessment of Seriousness 
Seriousness refers to the outcome of an adverse event. Seriousness is determined by both the 
PI and the Sponsor Medical Monitor. If either PI or Sponsor Medical Monitor determines an event 
to be serious, it will be classified as such. If any of the following outcomes are present then the 
adverse event is serious: 
• 
It results in death (i.e., the AE caused or led to the fatality). Serious does not describe an 
event that hypothetically might have caused death if it were more severe. 
• 
It was immediately life-threatening (i.e., the AE placed the subject at immediate risk of 
dying). It does not refer to an event that hypothetically may have led to death if it were more 
severe. 
• 
It required inpatient hospitalization or prolonged hospitalization beyond the expected 
length of stay. Hospitalizations for scheduled treatments and elective medical/surgical 
procedures related to a pre-existing condition that did not increase in severity or frequency 
following receipt of study injection, are not serious by this criterion. Hospitalization is defined 
as either a hospital admission or an emergency room visit for a period greater than 24 hours. 

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• 
It resulted in a persistent or significant disability/incapacity (i.e., substantial reduction of 
the subject’s ability to carry out activities of daily living). 
• 
It resulted in a congenital anomaly or birth defect (i.e., an adverse finding in a child or 
fetus of a subject exposed to the study vaccine prior to conception or during pregnancy). 
• 
Other medically important conditions that may not result in death, threaten life, or require 
hospitalization (i.e., the AE does not meet any of the above serious criteria) may be 
considered a serious adverse event when, based on appropriate medical judgment, they may 
jeopardize the subject and require medical or surgical intervention to prevent one of the 
serious outcomes listed in these criteria (e.g., allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias or convulsions that do not 
result in hospitalization, or the development of drug dependency or drug abuse).  
A serious adverse event is an adverse event meeting the outcome criteria for seriousness 
regardless of relationship to the study injection. 
When an adverse event is judged related to an investigational product and is serious and 
unexpected, it is a SUSAR and subject to expedited reporting. 
9.3.2 Procedures to be Followed in the Event of Abnormal Laboratory Test Values 
or Abnormal Clinical Findings 
Investigation, treatment, follow-up, and medical referral of all adverse events will be determined 
by the investigator using his/her best medical judgment and according to local clinical practice 
guidelines. 
Laboratory values that are abnormal based on the toxicity tables will be reported as an AE. In the 
event a subject experiences an AE or injection site reaction that is still present at the end of the 
subject’s participation in the study, the subject must be followed until resolution of the event or 
until the event or abnormality resolves or stabilizes to the investigator’s and/or sponsor’s 
satisfaction. Follow-up procedures, evaluations, and outcomes will be recorded on the subject’s 
eCRFs. 
9.4 
Reporting Procedures 
The PI (or designee) must report immediately (within 24 hours) any occurrence of SAEs or other 
reportable events described in this section to IDRI Pharmacovigilance. 
9.4.1 Serious Adverse Events 
Serious AEs will be collected from the time of the first study drug administration until the final 
study visit. Serious AEs that are related to the investigational drug and continue beyond the 
normal collection period (i.e., are ongoing at the time a subject exits the study) will be followed 
until resolution or until stabilized with sequelae. Serious AEs that begin after the subject’s 

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participation in the study is complete, but that the Investigator considers to be related to study 
drug, may be reported at any time.  
The Investigator or clinical site personnel should notify IDRI Pharmacovigilance of all SAEs, 
regardless of relationship to the investigational drug, within 24 hours of clinical site personnel 
becoming aware of the event. The Investigator will provide the initial notification by sending a 
completed “RAE Report Form,” which must include the Investigator’s assessment of the 
relationship of the event to investigational drug, and must be signed by the Investigator. 
In addition, notification is sent by the clinical site to the IRB as required. 
Follow-up information, or new information regarding an ongoing SAE, must be provided promptly 
to IDRI Pharmacovigilance. 
All SAE reports should be sent to the following contacts: 
In case of a serious adverse event, the Principal Investigator will send a report within 24 hours of 
notification to: 
IDRI Pharmacovigilance 
1616 Eastlake Ave. E, Suite 400 
Seattle, WA 98102 
E-mail: pvg@idri.org  
Fax: 206-858-6098 
Phone: 206-858-6039/6054 
IDRI will ensure notification of all serious adverse events as soon as possible, but no later than 
24 hours after learning of an event to DMID PVG below: 
DMID Pharmacovigilance Group 
Clinical Research Operations and Management Support (CROMS) 
6500 Rock Spring Drive, Suite 650 
Bethesda, MD 20817 
SAE Hot Line: (800) 537-9979 (U.S.) or (301) 897-1709 (outside U.S.) 
SAE FAX Phone Number: (800) 275-7619 (U.S.) or (301) 897-1710 (outside U.S.) 
SAE Email Address: pvg@dmidcroms.com 
IDRI is responsible for submitting the SAE to DMID as soon as possible, but no later than 24 
hours after learning of an SAE. 
The DMID Medical Monitor and the DMID Clinical Project Manager will be notified of the SAE by 
the DMID Pharmacovigilance Group. The DMID Medical Monitor will review and assess the SAE 
for potential impact on study subject safety and protocol conduct. 
The Independent Safety Monitor will receive copies of all correspondence between the Sponsor 
and FDA for SAEs. 
The sponsor is responsible for determining regulatory reporting requirements for SAEs. 

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9.4.2 Regulatory Reporting  
The sponsor will report all suspected unexpected serious adverse reactions (SUSARs) to the FDA 
within 7 or 15 days of receipt of the report of the event, depending on the nature of the SUSAR. 
In addition, all other SAEs and PIMMCs will be reported annually to the FDA in a dedicated 
tabulation by MedDRA coding term and relationship to study vaccine. 
9.4.3 Reporting Other Adverse Events (if applicable) 
The investigator must report the following events by scanning and emailing, or faxing, the 
appropriate form to the Sponsor Medical Monitor or designee within one business day of 
becoming aware of the event: 
• 
Protocol violation affecting the safety of a participant or involving the study injection 
process (Reportable Adverse Event Form) 
• 
Any event that, according to the protocol or in the opinion of the investigator, precludes 
further administration of the study injections (Reportable Adverse Event Form) 
• 
Pregnancy (Pregnancy Alert Report Form) 
9.4.4 Reporting of Pregnancy 
If a participant becomes pregnant during the study, she will not receive any further study injections 
but should be encouraged to continue in the study for safety follow-up. Follow-up should continue 
for pregnancy outcome including premature terminations, and data are to be included in the safety 
reports. 
The health status of the mother and child, the date of delivery, and the child’s sex, birth weight, 
and parity should be reported to the Sponsor. Pregnancy will not be recorded as an adverse 
event. However, if the pregnancy results in a miscarriage or a planned termination, the event 
(spontaneous abortion or elective abortion) will be reported as an adverse event or serious 
adverse event per the investigator's judgment (e.g., if it was a medically important or life-
threatening event that meets the definition of a serious adverse event). 
A congenital anomaly or birth defect (i.e., an adverse finding in a child or fetus of a participant 
exposed to the study vaccine before conception or during pregnancy) must be reported as a 
serious adverse event. 
9.5 
Type and Duration of Follow-up of Subjects after Adverse 
Events 
Adverse events will be considered resolved when the condition returns to normal or returns to the 
participant’s baseline status as established on Study Day 0, or when the condition has stabilized 
with the expectation that it will remain chronic. 

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The investigator will continue follow-up on adverse events, including laboratory abnormalities and 
solicited adverse events, until the event has resolved, is otherwise satisfactorily explained, or the 
participant completes the study. 
Follow-up for serious adverse events must continue until resolution and the outcome reported, 
even if this extends beyond the serious adverse event reporting period (i.e., after the final study 
visit). For analysis purposes, the outcome for serious adverse events will be determined on the 
final study visit. 
Outcome of all adverse events will be classified as one of the following: 
• 
Resolved 
• 
Resolved with sequelae 
• 
Death 
9.6 
Halting Rules 
9.6.1 Rules for Discontinuing Study injection in an Individual Subject 
Administration of additional study injections will be discontinued for an individual if he/she has any 
of the following reactions: 
• 
Changes in laboratory parameters that meet Grade 3 severity. 
• 
High fever (oral temperature ≥ 102.2°F/39°C) within 1 week following study injection 
associated with constitutional symptoms and not attributable to another cause. 
• 
Severe injection site reactogenicity that involves Grade 3 local pain, induration, or 
erythema. 
9.6.2 Rules for Suspension of the Entire Study 
The study will be immediately suspended (paused) and no additional study injections 
administered, pending review and discussion of all appropriate safety data by the SMC, if one or 
more subjects in any treatment group experience any of the following adverse events: 
• 
Anaphylaxis or bronchospasm within 4 hours of study injection indicative of an immediate 
hypersensitivity reaction to the vaccine and not attributable to another cause. 
• 
Any systemic rash, including but not limited to urticaria, generalized petechiae, or 
erythema multiforme, not attributable to another cause. 
• 
Tissue necrosis at the study injection site. 
• 
Any other serious adverse event deemed to be possibly, probably, or definitely relatable 
to the study injection by the PI or Sponsor Medical Monitor, based on close temporal 
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The study will also be immediately suspended (paused) and no additional study injections 
administered pending review and discussion of all appropriate safety data by the SMC if three or 
more subjects experience the following AEs determined to be related to study injection:  
• 
Changes in laboratory parameters that meet Grade 3 severity. 
• 
High fever (oral temperature ≥ 102.2°F/39°C) within 1 week following study injection 
associated with constitutional symptoms and not attributable to another cause. 
• 
Severe injection site reactogenicity that involves Grade 3 local pain, induration, or 
erythema. 
Study suspension or termination will only apply to additional study injections. Subjects for whom 
their study injections are discontinued will remain in limited visit follow-up for safety evaluations 
and immunology blood draws. 
9.7 
Safety Oversight (ISM plus SMC) 
9.7.1 Independent Safety Monitor (ISM) 
The ISM is a physician with relevant expertise whose primary responsibility is to provide 
independent safety monitoring in a timely fashion. The ISM will review SAEs and other AEs as 
needed and provide an independent assessment to DMID. Saint Louis University will have an 
ISM with experience in infectious diseases or internal medicine. 
9.7.2 Safety Monitoring Committee (SMC)  
This clinical trial will utilize an SMC, which will be comprised of an independent group of experts 
with experience with early phase clinical research studies. The primary responsibility of the SMC 
is to monitor subject safety. The SMC is external to DMID and composed of at least three voting 
members. The SMC will consist of members with appropriate expertise to contribute to the 
interpretation of the data from this trial. Committee activities will be delineated in an SMC charter 
that will delineate membership, responsibilities, and the scope and frequency of data reviews. 
The SMC will operate on a conflict-free basis independently of the study team. 
Subsequent to the Organizational Meeting, the SMC will review and discuss safety data at the 
following milestones: 
• 
Ad hoc meeting will be conducted: 
o If study halting criteria are met as described in Section 9.6 
o At the request of DMID to review a potential safety concern identified by the PI, 
the Sponsor’s Medical Monitor, DMID MM or ISM 
• 
Final review meeting: 6 to 8 months after clinical database lock to review the cumulative 
unblinded safety data for the study. The data will be provided in a standard summary 
format. The SMC may be asked to provide recommendations in response to questions 
posed by DMID. 

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The SMC will have access to unblinded data during its closed session, if applicable. After its 
assessment, the SMC will recommend continuation, modification, or termination of the clinical 
trial. Additionally, data management alerts will be implemented and monitored to determine if any 
of the halting rules described in Section 9.6 are met. 
If any of the halting rules are met following the first study injection, the study will not proceed with 
the remaining enrollment or study injections without a review by and recommendation from the 
SMC to proceed. 
The DMID Medical Monitor and Clinical Project Manager will review the SMC recommendations 
and will document what actions DMID recommends be implemented by the study team. The 
Sponsor will receive the recommendations and will be responsible for responding to the SMC and 
DMID regarding any actions that were recommended and will not be implemented. 
 

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10 
CLINICAL MONITORING 
10.1 Site Monitoring Plan 
Site monitoring will be conducted to ensure that human subject protection, study procedures, 
laboratory procedures, study intervention administration, and data collection processes are of 
high quality and meet sponsor, ICH/GCP guidelines, and applicable regulatory requirements, and 
that the study is conducted in accordance with the protocol and sponsor’s standard operating 
procedures. The sponsor or its designee will conduct site-monitoring visits as specified in the 
monitoring plan. 
Monitoring visits will include, but are not limited to, review of regulatory files, accountability 
records, eCRFs, informed consent forms, medical and laboratory reports, and protocol 
compliance. Study monitors will meet with investigators to discuss any problems and actions to 
be taken and document visit findings and discussions. 
 
 

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11 
STATISTICAL CONSIDERATIONS 
11.1 Introduction 
This study is a phase 1, randomized, double-blind clinical trial designed to evaluate the safety, 
tolerability, and immunogenicity of the single-vial and two-vial presentations of ID93 + GLA-SE. 
As such, the sample size of n=48 was determined by what is reasonable for a phase 1 trial and 
not based on statistical considerations of power, and will allow only preliminary safety and 
immunogenicity information relevant to progression to larger trials.  
11.2 Study Population 
The study population for this protocol is healthy males and non-pregnant females, ages 18-55 
inclusive. The subjects must not have a history of infection with TB, must consent to all protocol 
requirements, and meet additional inclusion and exclusion criteria specified in Section 5. 
11.2.1 Intent to Treat Population 
The Intent-to-Treat (ITT) Population will include all subjects randomized to one of the treatment 
groups, classified according to the randomization assignment. 
11.2.2 Per Protocol Population 
The Per Protocol Population will include all eligible subjects randomized to one of the treatment 
groups and who received both assigned study injections. Subjects will be classified according to 
the treatment received. Analysis of immunogenicity endpoints occurring after the second study 
injection will be performed on this population. 
11.2.3 Safety Population 
The Safety Population will consist of all subjects who have received at least one dose of study 
injection and for whom any data on safety are available. Subjects will be classified according to 
the treatment received. The primary safety analysis will be done on this population. 
11.2.4 Immunogenicity Population 
The Immunogenicity Population will include all eligible subjects who have received at least one 
study injection, for whom data concerning post-baseline immunogenicity endpoint measures are 
available, and major protocol deviations are absent. The post-baseline immunogenicity 
endpoints may include humoral or cellular responses measured at the protocol-specified time 
points, or at the time of early termination. Subjects will be classified according to the treatment 

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received. Immunogenicity analysis will be done using this population or the Per Protocol 
Population, as appropriate. 
11.3 Sample Size Considerations 
Sample size for this study will allow only preliminary safety information relevant to progression to 
larger trials. The study is not designed to test a formal hypothesis. 
Sample Size Calculations for Safety: The goal of the safety evaluation for this trial is to identify 
safety concerns associated with the study injections. The probability of detecting at least one 
event for a number of true underlying event rates for three potential sample sizes is listed in Table 
2. 
Table 2: Probability of observing at least one event for several true event rates and the 
event rates which cannot be ruled out if no events are observed. 
True Event 
Rate 
Probability of observing 1 or more events 
N=10 
N=20 
N=30 
0.05 
40% 
64% 
79% 
0.10 
65% 
88% 
96% 
0.15 
80% 
96% 
99% 
0.25 
94% 
100% 
100% 
11.4 Planned Interim Analyses (if applicable) 
There is no planned interim analysis. Safety data will be reviewed by the SMC during the study if 
necessary as outlined in Section 9.7. 
11.5 Final Analysis Plan 
The final analysis will be used to evaluate the safety, tolerability, and immunogenicity of two IM 
doses of ID93 + GLA-SE in the single-vial or two-vial presentations at study Days 0 and 56. 
A detailed Statistical Analysis Plan will be developed prior to study completion and database lock. 
The analysis will consist of baseline and demographic data, safety data, immunogenicity data, 
and laboratory data. Data will be summarized with standard descriptive statistics and provided in 
tables, listings, and figures as appropriate. 
11.5.1 Analysis of Demographics and Disposition 
Summaries and descriptive statistics of demographic and baseline characteristics will be provided 
for the safety population. 
The following subject disposition information will be summarized for each treatment group: 

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• 
Number of subjects enrolled 
• 
Stratified by enrollment group: 
o Number (%) of subjects receiving one or two study injections 
o Number (%) of subjects who discontinued the study and reasons for 
discontinuation 
o Number (%) of subjects in the per-protocol population and reasons for those 
excluded 
o Number (%) of subjects with at least one protocol violation 
Protocol violations will be identified by the Medical Monitor (or designee) for the trial. 
11.5.2 Analysis of Safety 
Summaries of the safety endpoints will be completed for the safety population. Safety endpoints 
include solicited adverse events, unsolicited adverse events, changes in laboratory values, and 
changes in vital signs. All solicited and unsolicited adverse events will be recorded by the 
Investigator in the AE eCRF and all adverse event terms will be coded using MedDRA preferred 
term and system organ class. 
11.5.2.1 
Solicited Adverse Events 
The severity rating (Grade 1 to 3) assigned to each solicited adverse event that is reported based 
on in-clinic diagnosis and on review of the subject memory aids will be summarized by the 7-day 
injection interval following each injection and by treatment group. The worst value (i.e., the 
maximum severity) for each sign/symptom will also be summarized by injection interval and 
treatment group. 
11.5.2.2 
Unsolicited Adverse Events 
All unsolicited adverse event terms will be coded using MedDRA. Summaries of the number (%) 
of subjects in each treatment group with at least one adverse event, classified according to 
MedDRA preferred term and system organ class, will be provided for: 
• 
All adverse events 
• 
Related adverse events 
• 
Serious adverse events 
• 
PIMMCs 
Related adverse events are defined as adverse events that are possibly, probably, or definitely 
related to study injection, as assessed by the study PI.  
The following additional summaries of unsolicited adverse events will also be provided: 
• 
Incidence of adverse events after the first and second injections 
• 
Incidence of adverse events by severity of event 

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• 
Incidence of adverse events by relationship to study injection  
The adverse event summaries described in the previous paragraphs will also be provided based 
on all (i.e., unsolicited and solicited) adverse events.  
11.5.2.3 
Laboratory Data 
Summaries of the actual value and change from baseline for all laboratory tests will be provided 
for each study visit. A tabulated summary of laboratory abnormalities by toxicity grade will also be 
provided. 
11.5.2.4 
Vital Signs 
Summaries of the actual value and change from baseline for all vital signs will be provided for 
each study visit. 
11.5.2.5 
Missing Data 
Missing data will be recorded as they are, and there will be no imputation of missing values. 
11.5.3 Immunology Analyses 
Immunogenicity will be assessed from blood samples obtained on Days 0, 7, 14, 56, 63, 70, 84, 
and 224. Secondary immunogenicity evaluations will include quantification of T cell cytokine 
responses from stimulated PBMCs and serum IgG antibody responses to ID93. Exploratory 
analyses will include measurement of functionality of immune responses through the whole blood 
mycobacterial growth inhibition assay (MGIA), measurement of humoral responses in mucosal 
secretions (nasal swabs and tears), quantitation of IgA and IgG secreting B cells and memory B 
cells, and measurement of the frequencies of peripheral T follicular helper cells, memory B cells, 
and T cell homing markers. 
Immune responses for each treatment group will be evaluated by calculating the response rate 
and magnitude of response to ID93 at all timepoints for each immunologic endpoint. Comparisons 
of response rates for IgG and cytokine responses across treatment groups will be made using n 
x m Fisher’s exact tests. Pairwise comparisons will be done using 2 x 2 Fisher’s exact tests with 
multiplicity adjustment to control the family-wise error rate (FWER). 
The magnitude of IgG and cytokine responses will be compared across treatment groups using 
ANOVA when the distribution is Gaussian and Kruskal-Wallis when the distribution is non-
Gaussian. When ANOVA is used and a difference is observed across the treatment groups, 
pairwise comparisons will be made using t-tests with adjustment to control the FWER. If Kruskal-
Wallis is used, Wilcoxon rank-sum tests will be used. 
Percentages of CD4 and CD8 T cells producing selected cytokines will be summarized by time 
point and compared across and between treatment groups. 
 

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12 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS 
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported. 
The Investigator will allow representatives of IDRI (or their designee) to periodically audit, at 
mutually convenient times during and after the study, all eCRFs and corresponding source 
documents for each subject. It is important that the Investigator and/or other staff are available at 
these visits. The monitoring visits provide IDRI with the opportunity to evaluate the progress of 
the study, to verify the accuracy and completeness of eCRFs, to resolve any inconsistencies in 
the study records, as well as assuring that all protocol requirements, applicable regulations, and 
Investigator's obligations are being fulfilled. The Investigator must maintain source documents 
such as laboratory and consultation reports, history and physical examination reports, etc., for 
possible review. 
Telephone contact will be made as necessary during the data collection period and during the 
data and report writing periods. Data reported in the eCRF derived from the data collection forms 
should be consistent with the source documents or the discrepancies should be explained. 
The sponsor will provide guidance to investigators on making corrections to the data collection 
forms and eCRFs. 
 
 

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13 
QUALITY CONTROL AND QUALITY ASSURANCE 
Following a written sponsor and DMID-accepted site quality management plan, the investigational 
site is responsible for conducting routine quality assurance and quality control activities to 
internally monitor study progress and protocol compliance. The PI will provide direct access to all 
trial-related site source data/documents, and reports for the purpose of monitoring and auditing 
by the sponsor, and inspection by local and regulatory authorities. The PI will ensure all study 
personnel are appropriately trained and applicable documentation is maintained on site. 
Sponsor-designated clinical monitors will verify that the clinical trial is conducted and data are 
generated, documented (recorded), and reported in compliance with the protocol, ICH/GCP 
guidelines, and the applicable regulatory requirements. Clinical monitoring reports will be 
submitted to DMID. 
DF/Net Research will implement quality control procedures beginning with the data entry system 
and generate data quality control checks that will be run on the database. Any missing data or 
data anomalies will be communicated to the site for clarification and resolution. 
 
 

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14 
ETHICS/PROTECTION OF HUMAN SUBJECTS 
14.1 Ethical Standard 
The experimental protocol for this study has been designed in accordance with the E6 Good 
Clinical Practice: Consolidated Guidance (ICH), and the U.S. Code of Federal Regulations 
governing the protection of human subjects (21 CFR 50). The review of this protocol by the 
Institutional Review Board (IRB) and the performance of all aspects of the study, including the 
methods used for obtaining informed consent, must also be in accordance with the regulations 
described in Title 21 Code of Federal Regulations (CFR) Part 50 Protection of Human Subjects 
and Part 56 Institutional Review Boards. The sponsor and the investigator’s institution will hold a 
current Federal Wide Assurance issued by Office for Human Research Protections for federally 
funded research. 
14.2 Institutional Review Board 
Prior to enrollment of subjects into this trial, the approved protocol and the informed consent form 
will be reviewed and approved by the appropriate IRB. The Investigator will be responsible for 
preparing documents for submission to the relevant IRB and obtaining written approval for this 
study. The responsible official for the IRB will sign the IRB letter of approval of the protocol prior 
to the start of this trial and a copy will be provided to the sponsor and DMID. Notification of the 
IRB's composition, or the IRB’s Federal Wide Assurance number, will be provided to DMID. 
Should amendments to the protocol be required, the amendments will be written by the sponsor 
and provided to the investigator for submission to the IRB.  
14.3 Informed Consent Process 
All subjects must sign an informed consent form that complies with the requirements of both 21 
CFR 50 and 45 CFR 46. 
Prior to participation in the trial, subjects will receive a comprehensive explanation of the proposed 
vaccine, including the nature and risks of the trial, alternate therapies, any known AEs, the 
investigational status of the components, and the other elements that are part of obtaining proper 
informed consent. Subjects will also receive a detailed explanation of the proposed use and 
disclosure of their protected health information, including specifically their serum samples. 
Subjects will be allowed sufficient time to consider participation in the trial, after having the nature 
and risks of the trial explained to them. The consent form must not include any exculpatory 
statements. 
The sponsor will provide the investigator, in writing, any new information that significantly affects 
risk related to a subject’s receipt of the investigational product. This new information will be 
communicated by the investigator to subjects who consent to participate in the trial in accordance 

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with IRB requirements. The informed consent document will be updated and subjects will be re-
consented, if necessary. 
Site staff may utilize IRB-approved recruitment methods prior to the subject consenting; however, 
before any protocol-specific procedures are performed to determine protocol eligibility an 
informed consent form must be signed. Subjects will be given a copy of all consent forms that 
they sign. 
By signing the informed consent form, the subject agrees to complete all evaluations required by 
the trial, unless the subject withdraws voluntarily or is terminated from the trial for any reason. 
14.4 Exclusion of Women, Minorities, and Children (Special Populations) 
This study will be inclusive of all healthy adults who meet the inclusion/exclusion criteria, 
regardless of religion, sex, or ethnic background. Only individuals who are 18 to 55 years old, 
inclusive, will be included at this time. Children are excluded for safety reasons.  
14.5 Subject Confidentiality 
Subjects will have code numbers and will not be identified by name. Subject confidentiality is 
strictly held in trust by the participating investigators, their staff, the sponsor(s), and their agents. 
This confidentiality extends to genetic and biological sample tests, in addition to the clinical 
information relating to participating subjects. 
The study protocol, documentation, data, and all other information generated will be held in strict 
confidence. Documented evidence that shows that a potential investigator is aware of and agrees 
to the confidential nature of the information related to the study must be obtained by means of a 
confidentiality agreement. 
All information provided by the sponsor and all data and information generated by the site as part 
of the study (other than a subject’s medical records) will be kept confidential by the investigator 
and other site staff. This information and data will not be used by the investigator or other site 
personnel for any purpose other than conducting the study. These restrictions do not apply to: (1) 
information that becomes publicly available through no fault of the investigator or site staff; (2) 
information that it is necessary to disclose in confidence to an IRB solely for the evaluation of the 
study; (3) information that it is necessary to disclose in order to provide appropriate medical care 
to a study subject; or (4) study results that may be published as described in Section 16. If a 
written contract for the conduct of the study that includes confidentiality provisions inconsistent 
with this statement is executed, that contract’s confidentiality provisions shall apply rather than 
this statement. 
The study monitor or other authorized representatives of the sponsor and/or the FDA may inspect 
all documents and records required to be maintained by the investigator. This includes, but is not 
limited to, medical records (office, clinic, or hospital) and pharmacy records for the subjects in this 
study. Clinical study sites will permit access to such records. 

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To protect privacy, we have received a Certificate of Confidentiality.  With this Certificate, the 
researchers cannot be forced to release information that may identify the research subject, even 
by a court subpoena, in any federal, state, or local civil, criminal, administrative, legislative, or 
other proceedings.  The researchers will use the Certificate to resist any demands for information 
that would identify the subject, except as explained below. 
The Certificate cannot be used to resist a demand for information from personnel of the United 
States Government that is used for auditing or evaluation of federally funded projects, like this 
study, or for information that must be released in order to meet the requirements of the Federal 
Food and Drug Administration (FDA). 
A Certificate of Confidentiality does not prevent the subject from voluntarily releasing information 
about themselves or their involvement in this research.  If any person or agency obtains a written 
consent to receive research information, then the researchers may not use the Certificate to 
withhold that information.   
The Certificate of Confidentiality does not prevent the researchers from reporting without the 
subject’s consent, information that would identify the subject as a participant in the research 
project regarding matters that must be legally reported including: child and elder abuse, sexual 
abuse, or wanting to harm themselves or others.   
14.6 Study Discontinuation 
If the study is discontinued, enrolled subjects will continue to be followed for safety assessments. 
No further study injections will be administered. 
14.7 Future Use of Stored Specimens 
Subjects will be asked for permission to keep any remaining specimens for possible use in future 
research studies, such as testing for antibodies against viruses or bacteria. Samples will be stored 
at IDRI for up to 10 years. Samples may be shared with other investigators at other institutions. 
The samples will not be sold or used directly for production of any commercial product. Each 
sample will be encoded (labeled) only with a barcode and a unique tracking number to protect 
subject’s confidentiality. 
Additional samples will be taken for the sole purpose of banking serum for auto-immune testing, 
if indicated (i.e., if a participant has a PIMMC). These samples will not be used for other purposes 
and will be discarded after 10 years. 
There are no benefits to subjects in the collection, storage, and subsequent research use of 
specimens. Reports about future research done with a subject’s samples will NOT be kept in their 
health records. Subjects can decide if they want their samples to be used for future research or 
have their samples destroyed at the end of the study. A subject’s decision can be changed at any 
time prior to the end of the study by notifying the study doctors or nurses in writing. However, if a 

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subject consents to future use and some of their blood has already been used for research 
purposes, the information from that research may still be used.  
14.8 Disclosure of Individual Research Information 
IDRI does not intend to provide each participant with a summary of study results or their treatment 
assignment. 
 

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15 
DATA HANDLING AND RECORD KEEPING 
The investigator is responsible to ensure the accuracy, completeness, legibility, and timeliness of 
the data reported. Data reported in the eCRF derived from source documents should be 
consistent with the source documents or the discrepancies should be explained. IDRI and/or it 
designee will provide guidance to investigators on making corrections to the source documents 
and eCRF. 
15.1 Data Management Responsibilities 
All source documents and laboratory reports must be reviewed by the clinical team and data entry 
staff, who will ensure that they are accurate and complete. Adverse events must be graded, 
assessed for severity and causality, and reviewed by the site PI or designee. 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the 
site PI. During the study, the investigator must maintain complete and accurate documentation 
for the study. 
DF/Net Research will be responsible for data management, quality review, analysis, and reporting 
of the study data. 
15.2 Data Capture Methods 
Clinical data (including AEs, concomitant medications, and reactogenicity data) and clinical 
laboratory data will be entered into a 21 CFR Part 11-compliant data entry system provided by 
DF/Net Research. The data system includes password protection and internal quality checks, 
such as automatic range checks, to identify data that appear inconsistent, incomplete, or 
inaccurate. Clinical data will be entered directly from the source documents. 
15.3 Types of Data 
Data for this study will include safety, immunologic laboratory, and outcome measures (e.g., 
reactogenicity, immunogenicity). 
15.4 Timing/Reports 
Safety data will be reviewed by the SMC per the SMC charter for this study. The SMC will make 
a recommendation at that time as to the advisability of proceeding with study injections. Interim 
statistical reports may be generated as deemed necessary and appropriate by the sponsor and 
DMID. 

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15.5 Study Records Retention 
Each participating site will maintain appropriate medical and research records for this trial, in 
compliance with ICH E6, Section 4.9 and regulatory and institutional requirements for the 
protection of confidentiality of subjects. Each site will permit authorized representatives of IDRI, 
its designees, DMID, and appropriate regulatory agencies to examine (and when required by 
applicable law, to copy) clinical records for the purposes of quality assurance reviews, audits, 
monitoring, and evaluation of the study safety and progress. These representatives will be 
permitted access to all source data, which include, but are not limited to, hospital records, clinical 
and office charts, laboratory notes, memoranda, evaluation checklists, pharmacy dispensing 
records, recorded data from automated instruments, copies or transcriptions certified after 
verification as being accurate and complete, microfiches, photographic negatives, microfilm or 
magnetic media, x-rays, and subject files and records kept at the pharmacy, at the laboratories, 
and medico-technical departments involved in the clinical trial. Data collection forms used as 
source documents will be derived from the eCRFs and be provided by DF/Net Research. 
Records and documents pertaining to the conduct of this study, including eCRFs, data collection 
forms, other source documents, consent forms, laboratory test results, and medication inventory 
records, must be retained by the investigator for at least 2 years following submission of a 
Biologics License Application or until IDRI authorizes transfer or destruction of study records. No 
study records will be destroyed without prior authorization from IDRI. 
15.6 Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, Good Clinical Practice 
(GCP), or SSP Manual requirements. The noncompliance may be on the part of either the subject, 
the investigator, or the study site staff. As a result of deviations, corrective actions are to be 
developed by the site and implemented promptly. All deviations must be promptly reported. All 
deviations from the protocol must be addressed in study subject source documents. Protocol 
deviations must be sent to the local IRB per their guidelines. The site PI/study staff is responsible 
for knowing and adhering to their IRB requirements. 
 

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16 
PUBLICATION POLICY 
All information contained in this clinical study protocol and accompanying documents is 
confidential. All data collected during the course of this study are confidential and considered the 
property of IDRI. The Investigators agree to use this information and data only in accomplishing 
this study and will not use it for other purposes without the written permission of IDRI. IDRI 
encourages publication in peer-reviewed medical journals and will not unduly withhold permission 
to publish. However, all proposed publications, papers, abstracts, or written materials related to 
the study, or an outline or poster of any oral presentation, shall be submitted to and coordinated 
by IDRI for review at least thirty (30) days in advance of the submission to assure that no 
proprietary information is presented and that authorship is fairly represented. 
Within thirty (30) days after receipt of such materials, IDRI may request in writing that the 
proposed publication or presentation be delayed or modified, specifying in reasonable detail the 
reasons for the request. If IDRI objects to a proposed publication or presentation on the basis that 
it would disclose confidential information, the Investigator shall remove the objectionable 
information from such proposed publication or presentation. If the parties disagree concerning 
whether certain information should be deleted or modified, the parties agree to meet for the 
purpose of making good faith efforts to discuss and resolve any such issues or disagreements. 
IDRI will work with the Institution in a collaborative manner to make certain that the clinical study 
results contained within such presentation or publication (whether positive or negative) are 
accurate. 
Following completion of the study, the investigator or sponsor is expected to publish the results 
of this research in a scientific journal. The International Committee of Medical Journal Editors 
(ICMJE) member journals have adopted a trials-registration policy as a condition for publication. 
This policy requires that all clinical trials be registered in a public trials registry such as 
ClinicalTrials.gov, which is sponsored by the National Library of Medicine. Other biomedical 
journals are considering adopting similar policies. It is the responsibility of the Sponsor to register 
this trial in an acceptable registry. Any clinical trial starting enrollment after 01 July 2005 must be 
registered on or before patient enrollment. For trials that began enrollment prior to this date, the 
ICMJE member journals will require registration by 13 September 2005, before considering the 
results of the trial for publication. 
The ICMJE defines a clinical trial as any research project that prospectively assigns human 
subjects to intervention or comparison groups to study the cause-and-effect relationship between 
a medical intervention and a health outcome. Studies designed for other purposes, such as to 
study pharmacokinetics or major toxicity (e.g., Phase I trials), would be exempt from this policy. 
By signing the study protocol, the PI agrees that the results of the study may be used for national 
and international registration, publication, and information for medical and pharmaceutical 
professionals by the Sponsor. If necessary, the authorities will be notified of the PI's name, 
address, qualifications, and extent of involvement.  

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This document is proprietary and is to be used only as authorized. No part is to be reproduced, disclosed to others, or quoted 
without prior written authorization from IDRI. 
If the PI or site is to be included as an author of a publication manuscript prepared by the Sponsor, 
the Sponsor will allow the PI or site 60 days for full review of the manuscript before publication. 
As of January 2018, all clinical trials supported by the NIH must be registered on 
ClinicalTrials.gov, no later than 21 days after the enrollment of the first subject. Results of all 
clinical trials supported by the NIH, generally, need to be submitted no later than 12 months 
following the primary completion date. A delay of up to 2 years is available for trials that meet 
certain criteria and have applied for certification of delayed posting. 
As part of the result posting a copy of this protocol (and its amendments) and a copy of the 
Statistical Analysis Plan will be posted on ClincialTrials.gov. 
For this trial the responsible party is IDRI, which will register the trial and post results.   
The responsible party does not plan to request certification of delayed posting. 
Refer to: 
• 
Public Law 110-85, Section 801, Clinical Trial Databases 
• 
42CFR11 
• 
NIH NOT-OD-16-149 
 
 

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without prior written authorization from IDRI. 
17 
LITERATURE REFERENCES 
1. Ottenhoff TH, Kaufmann SH. Vaccines against tuberculosis: where are we and where do we 
need to go? PLoS pathogens 2012; 8:e1002607. 
2. Flynn JL, Goldstein MM, Chan J, et al. Tumor necrosis factor-alpha is required in the 
protective immune response against Mycobacterium tuberculosis in mice. Immunity 1995; 
2:561-72. 
3. Flynn JL, Chan J. Immunology of tuberculosis. Annu Rev Immunol 2001; 19:93-129. 
4. Gardam MA, Keystone EC, Menzies R, et al. Anti-tumour necrosis factor agents and 
tuberculosis risk: mechanisms of action and clinical management. Lancet Infect Dis 2003; 
3:148-55. 
5. Hoft DF. Tuberculosis vaccine development: goals, immunological design, and evaluation. 
Lancet 2008; 372:164-75. 
6. Colditz GA, Brewer TF, Berkey CS, et al. Efficacy of BCG vaccine in the prevention of 
tuberculosis. Meta-analysis of the published literature. JAMA 1994; 271:698-702. 
7. Rodrigues LC, Diwan VK, Wheeler JG. Protective effect of BCG against tuberculous 
meningitis and miliary tuberculosis: a meta-analysis. Int J Epidemiol 1993; 22:1154-8. 
8. Trunz BB, Fine P, Dye C. Effect of BCG vaccination on childhood tuberculous meningitis and 
miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness. 
Lancet 2006; 367:1173-80. 
9. Kaufmann SH, Hussey G, Lambert PH. New vaccines for tuberculosis. Lancet 2010; 
375:2110-9. 
10. McShane H. Tuberculosis vaccines: beyond bacille Calmette-Guerin. Philos Trans R Soc 
Lond B Biol Sci 2011; 366:2782-9. 
11. Weiner J, 3rd, Kaufmann SH. Recent advances towards tuberculosis control: vaccines and 
biomarkers. Journal of internal medicine 2014; 275:467-80. 
12. Bertholet S, Ireton GC, Ordway DJ, et al. A defined tuberculosis vaccine candidate boosts 
BCG and protects against multidrug-resistant Mycobacterium tuberculosis. Science 
translational medicine 2010; 2:53ra74. 
13. Baldwin SL, Bertholet S, Reese VA, Ching LK, Reed SG, Coler RN. The importance of 
adjuvant formulation in the development of a tuberculosis vaccine. J Immunol 2012; 
188:2189-97. 
 
 

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written authorization from IDRI. 
Appendix 1: Schedule of Study Visits and Procedures 
 
Screen 
Schedule for Study Injection Phase  
(Days with allowable visit window) 
Follow-Up  
visit      visit    phone 
ET1 
visit 
 
Day -30 
to Day 
0 
 
0 
7  
(±1) 
14  
(±3) 
56  
(±3) 
63  
(±1) 
70  
(±3) 
84  
(±5) 
224 
(±10) 
421 
(±14) 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
X 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
Concomitant medications 
X 
X 
X 
 
X 
X 
 
X 
(X)6 
(X)6 
X 
Physical exam 
X 
 
 
 
 
 
 
 
 
 
 
Targeted physical exam5 
 
X 
X 
 
X 
X 
 
X 
X 
 
X 
Vital signs 
X 
X2 
X 
 
X2 
X 
 
X 
 
 
X 
Safety labs 
X 
 
X 
 
 
X 
 
 
 
 
 
HIV, HCV, HBsAg 
X 
 
 
 
 
 
 
 
 
 
 
Urinalysis (protein, glucose) 
X 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test or 
FSH3 
X 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test  
 
X 
 
 
X 
 
 
 
 
 
 
Visual acuity 
X 
 
 
 
 
 
 
 
 
 
 
QuantiFERON®-TB Gold  
X 
 
 
 
 
 
 
 
 
 
 
Nasal swab and tear 
collection 
 
X 
 
 
 
 
X 
 
X 
 
(X)7 
Immunology blood4 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
(X)7 
Study injection 
 
X 
 
 
X 
 
 
 
 
 
 
Injection site checks 
 
X 
X 
 
X 
X 
 
 
 
 
 
Dispense memory aid 
 
X 
 
 
X 
 
 
 
 
 
 
Review memory aid 
 
 
X 
 
 
X 
 
 
 
 
 
Adverse events 
X 
X 
X 
 
X 
X 
 
X 
 
 
X 
SAE/PIMMC 
X 
X 
X 
 
X 
X 
 
X 
X 
X 
X 
1 ET = Early termination  
2 Vital signs are performed prior to and at 60 minutes post study injection.  
3 Serum pregnancy test for females of childbearing potential; FSH for post-menopausal females 
4 See Appendix 2 for volumes of immunology blood.  
5 If indicated, based on review of symptoms  
6 Concomitant meds to be collected only if used for treatment of an SAE or PIMMC. 
7 If indicated 
 
 
 

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Appendix 2: Schedule of Blood Draws and Volumes 
 
Screen 
Day  
0 
Day 
7 
(±1) 
Day 
14 
(±3) 
Day 
56 
(±3) 
Day 
63 
(±1) 
Day 
70 
(±3) 
Day 
84 
(±5) 
Day 
224 
(±10) 
Serum chemistry and 
hematology 
12.5 
 
12.5 
 
 
12.5 
 
 
 
HIV 1/2, HBsAg, HCV 
12 
 
 
 
 
 
 
 
 
QuantiFERON®-TB 
Gold  
3 
 
 
 
 
 
 
 
 
Serum IgG 
 
6* 
 
4 
4 
 
4 
4 
4 
MGIA 
 
4 
 
 
 
 
4 
  
4 
PBMC** 
 
64 
24 
64 
64 
24 
64 
64 
64 
Blood volume per 
visit 
27.5 
74 
36.5 
68 
68 
36.5 
72 
68 
72 
Cumulative total 
volume 
27.5 
101.5 138 
206 
274 
310.5 382.5 450.5 522.5 
Note: blood volumes are approximate and may be adjusted for clinical site requirements 
* Includes 2 mL for serum to be banked for autoimmune testing, if indicated 
** PBMC utilized in ICS and ELISpot will be left unstimulated or stimulated with ID93 protein or overlapping 
peptides pools encompassing the individual vaccine antigens (Rv1813, Rv2608, Rv3619, Rv3620), or a 
positive control (SEB). PBMC used in B cell ELISpot will be left unstimulated or stimulated with ID93 protein, 
SEB, or polyclonal stimulation reagents. 
 
 

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written authorization from IDRI. 
 
Appendix 3: Grading Scale for Clinical Laboratory Values 
Parameter 
Grade for Abnormal Results (Value or Change from Reference) 1, 2 
Mild  
(Grade 1) 
Moderate  
(Grade 2) 
Severe  
(Grade 3) 
Sodium (mmol/L) 2 
< LLN - 130  
> ULN - 150  
125 - 129  
151 - 154  
< 125  
> 154  
Potassium (mmol/L) 2 
< LLN - 3.0  
> ULN - 6.0  
2.5 - 2.9  
6.1 - 6.5  
< 2.5  
> 6.5  
Creatinine (mg/dL) 
> ULN - 1.7  
1.8 - 2.0  
> 2.0  
Total bilirubin (mg/dL) 
> ULN - 1.5 x ULN* 
> ULN - 1.25 x ULN** 
> 1.5 - 2.0 x ULN* 
> 1.25 - 1.5 x ULN** 
> 2.0 x ULN* 
> 1.5 x ULN** 
ALT (SGPT) (U/L) 
> ULN - 2.5 x ULN 
> 2.5 - 5.0 x ULN  
> 5.0 ULN  
AST (SGOT) (U/L) 
> ULN - 2.5 x ULN 
> 2.5 - 5.0 x ULN  
> 5.0 ULN  
Alkaline phosphatase (U/L) 
> ULN - 2.0 x ULN 
> 2.0 - 3.0 x ULN  
> 3.0 ULN  
Random glucose (mg/dL) 
Not followed after baseline screening 
WBC  
(K/µL, K/mm3 or 109/L) 
> ULN - 15.0  
2.5 - < LLN  
> 15.0 - 20.0  
≥ 1.5 - < 2.5  
> 20.0  
< 1.5  
Hemoglobin (g/dL) 
M: 12.5 - < LLN  
F: 11 - < LLN  
M: 10.5 - 12.4  
F: 9.5 - 10.9  
M: < 10.5  
F: < 9.5  
Platelet count  
(K/µL, K/mm3 or 109/L) 
100 - < LLN  
50 - 99  
< 50  
 
ULN=upper limit of normal; LLN=lower limit of normal.  
1 FDA Guidance for Industry Toxicity Grading Scale for Healthy Adults Enrolled in Preventive Vaccine Clinical Trials, 2007.  
2 DAIDS Toxicity Grading scale for electrolytes. 
* Tox grading for total bilirubin when liver transaminases are normal.  
** Tox grading for total bilirubin when accompanied by increased transaminases. 
 
 

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Appendix 4: Grading Scale for Local Injection Site Reactions 
Local Finding 
Grade 0 
(None) 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Pain 
None 
Does not 
interfere with 
activity 
Repeated use of non-
narcotic pain reliever 
> 24 hours or 
interferes with activity 
Any use of narcotic pain 
reliever or prevents daily 
activity 
Erythema/Redness 
< 2.5 cm 
2.5 – 5.0 cm 
5.1 – 10 cm 
> 10 cm or necrosis or 
exfoliative dermatitis 
Induration/Swelling 
< 2.5 cm 
2.5 – 5.0 cm 
5.1 – 10 cm 
> 10 cm or necrosis 
 
Note: Local injection site reaction grading should not be confused with general AE grading. 

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Appendix 5: Grading Scale for Determining the Severity of Clinical AEs  
VITAL SIGNS* 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Fever: oral (˚C)** 
                  (˚F)** 
38.0 - 38.4  
100.4 - 101.2 
38.5 - 38.9  
101.3 - 102.1 
≥ 39.0  
≥ 102.2  
Tachycardia - bpm 
101 - 115 
116 - 130 
> 130 
Bradycardia – bpm* 
50 – 54 
or >10 bpm less than 
baseline, if baseline < 50 
45 – 49 
or >15 bpm less than 
baseline, if baseline < 
50 
< 45 
or > 20 bpm less than 
baseline, if baseline < 
50 
Hypertension (systolic) mm Hg 
141 - 150 
151 - 155 
> 155 
Hypertension (diastolic) mm Hg 91 - 95 
96 - 100 
> 100 
Hypotension (systolic) mm Hg 
85 - 89 
80 - 84 
< 80 
Hypotension (diastolic) mm Hg 
50 - 54  
45 - 49 
< 45 
Respiratory Rate – breath per 
minute 
17 - 20 
21 - 25 
> 25 
* Subjects should be at rest for at least 5 minutes prior to vital sign measurements 
** Oral temperature; no recent hot or cold beverages or smoking. Note: A fever can be considered not related to the study product if 
an alternative etiology can be documented and it is confirmed to be not related to the study product by the Independent Safety 
Monitor at the site.  
*** When resting heart rate is between 60-100 beats per minute. Use clinical judgment when characterizing bradycardia among 
some healthy subject populations, for example conditioned athletes.  
 
Systemic (General) 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3)  
Headache 
Does not interfere with 
activity 
Repeated use of non-
narcotic pain reliever >24 
hours or interferes with 
activity 
Significant; any use of 
narcotic pain reliever or 
prevents daily activity 
Fatigue 
Does not interfere with 
activity 
Interferes with activity 
Significant; prevents daily 
activity 
Myalgia (generalized 
muscle pain) 
Does not interfere with 
activity 
Interferes with activity 
Significant; prevents daily 
activity 
Arthralgia (joint pain) 
Does not interfere with 
activity 
Interferes with activity 
Prevents daily activity 
Chills 
Does not interfere with 
activity 
Interferes with activity 
Prevents daily activity 
Anorexia (loss of 
appetite) 
Does not interfere with 
activity 
Interferes with activity 
Prevents daily activity 
Nausea/Vomiting 
Does not interfere with 
activity or 1 - 2 episode in 
24 hours 
Interferes with activity or 
>2 episodes in 24 hours 
Prevents daily activity or 
requires outpatient IV 
hydration 
Diarrhea 
2-3 loose stools or < 400 
gms/24 h  
4-5 stools or 400-800 
gms/24 hours 
6 or more watery stools or 
>800 gms/24 hours or 
requires outpatient IV 
hydration 
Illness or clinical 
adverse event (as 
defined according to 
applicable 
regulations) 
Does not interfere with 
activity.  
Interferes with activity not 
requiring medical 
intervention 
Prevents daily activity and 
requires medical 
intervention 
 
 
 

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Appendix 6: List of PIMMCs 
This list is current as of November 2017. It is provided by FDA/CBER and is subject to periodic update. Any 
updates will be implemented via a Note to File. 
Gastrointestinal disorders 
Liver disorders 
Metabolic diseases 
• Celiac disease 
• Crohn’s disease 
• Ulcerative colitis 
• Ulcerative proctitis 
• Autoimmune cholangitis 
• Autoimmune hepatitis 
• Primary biliary cirrhosis 
• Primary sclerosing cholangitis 
• Addison’s disease 
• Autoimmune thyroiditis 
(including Hashimoto 
thyroiditis) 
• Diabetes mellitus type I 
• Grave’s or Basedow’s 
disease 
Neuroinflammatory disorders 
Musculoskeletal disorders 
Skin disorders 
• Acute disseminated encephalomyelitis, 
including site specific variants (eg, non-
infectious encephalitis, encephalomyelitis, 
myelitis, radiculomyelitis) 
• Cranial nerve disorders, included 
paralyses/paresis (eg, Bell’s palsy) 
• Guillain-Barré syndrome, including Miller 
Fisher syndrome and other variants 
• Immune-mediated peripheral neuropathies 
and plexopathies, including chronic 
inflammatory demyelinating 
polyneuropathy, multifocal motor 
neuropathy and polyneuropathies 
associated with monoclonal gammopathy 
• Multiple sclerosis 
• Myasthenia gravis, including Eaton-
Lambert syndrome 
• Narcolepsy 
• Optic neuritis 
• Transverse myelitis 
• Antisynthetase syndrome 
• Dermatomyositis 
• Juvenile chronic arthritis 
(including Still’s disease) 
• Mixed connective tissue disorder 
• Polymyalgia rheumatic 
• Polymyositis 
• Psoriatic arthropathy 
• Relapsing polychondritis 
• Rheumatoid arthritis 
• Scleroderma, including diffuse 
systemic form and CREST 
syndrome 
• Spondyloarthritis, including 
ankylosing spondylitis, reactive 
arthritis (Reiter’s Syndrome) and 
undifferentiated spondyloarthritis 
• Systemic lupus erythematosus 
• Systemic sclerosis 
• Alopecia areata 
• Autoimmune bullous skin 
diseases, including 
pemphigus, pemphigoid 
and dermatitis 
herpetiformis 
• Cutaneous lupus 
erythematosus 
• Erythema nodosum 
• Morphoea 
• Lichen planus 
• Psoriasis 
• Sweet’s syndrome 
• Vitiligo 
Vasculitides 
Others 
• Large vessels vasculitis including: giant 
cell arteritis such as Takayasu’s arteritis 
and temporal arteritis 
• Medium sized and/or small vessels 
vasculitis including: polyarteritis nodosa, 
Kawasaki’s disease, microscopic 
polyangiitis, Wegener’s granulomatosis, 
Churg-Strauss syndrome (allergic 
granulomatous angiitis), Buerger’s disease 
thromboangiitis obliterans, necrotizing 
vasculitis and anti-neutrophil cytoplasmic 
antibody (ANCA) positive vasculitis (type 
unspecified), Henoch-Schonlein purpura, 
Behcet’s syndrome, leukocytoclastic 
vasculitis 
• Antiphospholipid syndrome 
• Autoimmune hemolytic anemia 
• Autoimmune glomerulonephritis (including IgA nephropathy, 
glomerulonephritis rapidly progressive, membranous 
glomerulonephritis, membranoproliferative glomerulonephritis, 
and mesangioproliferative glomerulonephritis) 
• Autoimmune myocarditis/cardiomyopathy 
• Autoimmune thrombocytopenia 
• Goodpasture syndrome 
• Idiopathic pulmonary fibrosis 
• Pernicious anemia 
• Raynaud’s phenomenon 
• Sarcoidosis 
• Sjögren’s syndrome 
• Stevens-Johnson syndrome 
• Uveitis