A Randomized Controlled Trial of Alternating Irrigation of Vancomycin Hydrochloride and Tobramycin Sulfate in Patients Undergoing Two-Stage Exchange Arthroplasty for Periprosthetic Joint Infection (PJI) of the Hip or Knee
Phase: PHASE2
Conditions: Prosthetic Joint Infection
Sponsor: Osteal Therapeutics, Inc.

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A Randomized Controlled Trial of Alternating Irrigation of Vancomycin HCl 
and Tobramycin Sulfate in Patients Undergoing Two-Stage Exchange 
Arthroplasty for Periprosthetic Joint Infection of the Hip or Knee 
 
 
 
 
 
Protocol Number: 
JPS-0301 
IND Number: 
132585 
Study Phase: 
2b 
Sponsor: 
Osteal Therapeutics, Inc.  
Address: 
750 N. Saint Paul St., Suite 250, PMB 72129 
Dallas, Texas 75201-3206 
Date: 
October 17, 2022 
 
 
The information provided in this document is confidential and is intended for the use of clinical 
investigators. The information in this document may not be disclosed unless federal or state law 
or regulations require such disclosure. Subject to the foregoing, this information may be 
disclosed only to those persons involved in the study who have a need to know it, with the 
obligation not to further disseminate this information. 
 
 
 

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Protocol Agreement 
 
I, the Investigator of Record, agree to conduct this study in full accordance with the provisions of 
this Protocol, the associated site agreement, and in accordance with applicable regulations and 
conditions required by the authorities overseeing this trial. I agree to maintain all study 
documentation for a minimum of two years after the study has been completed or for a longer 
period as required by law and regulations. Publication of the results of this study will be 
governed by the conditions stipulated in the Study Site Agreement. I agree to supervise the use 
of the Investigational Products at my institution and ensure that the informed consent form is 
obtained prior to subject enrollment. 
I have read and understand the information in this Protocol and will ensure that all associates, 
colleagues, and personnel assisting in the conduct of the study are informed of the obligations 
incurred by their participation. I will attest to the delegation of any obligation under this Protocol 
to my associates, colleagues, and personnel by signing such delegation in the Study Delegation 
Log. 
Protocol Number: JPS-0301 
Protocol Title: 
A Randomized Controlled Trial of Alternating Irrigation of 
Vancomycin HCl and Tobramycin Sulfate in Patients 
Undergoing Two-Stage Exchange Arthroplasty for 
Periprosthetic Joint Infection of the Hip or Knee 
Protocol Date: 
OCT 17, 2022 
Version:  
F.0 
 
 
Signature of Site Principal Investigator at Each Study Site 
Date 
 
 
Printed Name of Site Principal Investigator 
 
 
 

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Contents 
1 
Summary ..................................................................................................................................... 10 
2 
Background and Purpose of the Investigation ......................................................................... 17 
2.1 
Standard of Care Treatment for PJI ....................................................................................... 17 
2.1.1 Inefficacy of Systemic Route of Administration ................................................................... 17 
2.1.2 Inconsistent Local Therapy .................................................................................................... 18 
2.1.3 Failure to Complete Treatment .............................................................................................. 18 
2.1.4 Time to Reimplantation ......................................................................................................... 19 
2.1.5 Interstage Mortality ................................................................................................................ 19 
2.1.6 Cost-effectiveness .................................................................................................................. 19 
2.2 
Investigational Product .......................................................................................................... 20 
2.2.1 Investigational Drugs - tobramycin and vancomycin ............................................................ 20 
2.2.2 Investigational Device............................................................................................................ 20 
2.3 
Prior Investigations ................................................................................................................ 21 
2.3.1 Non-clinical Mechanical Performance Testing for VT-X7 Spacer Components................... 21 
2.3.2 Sterilization and Shelf Life for VT-X7 Spacer Components ................................................. 22 
2.3.3 Biocompatibility Evaluation for VT-X7 Spacer Components ............................................... 22 
2.3.4 Cadaver Lab Studies of VT-X7 ............................................................................................. 23 
2.3.5 Prior Clinical Experience ....................................................................................................... 23 
3 
Study Objectives ......................................................................................................................... 25 
4 
Study Design ................................................................................................................................ 25 
4.1 
Study Design .......................................................................................................................... 25 
4.2 
Subject Recruitment and Enrollment ..................................................................................... 26 
4.2.1 Randomization and Blinding ................................................................................................. 26 
4.2.2 Early Study Termination ........................................................................................................ 27 
4.2.3 Measures Taken to Avoid/Minimize Bias.............................................................................. 27 
5 
Study Endpoints .......................................................................................................................... 27 
5.1 
Efficacy Evaluations .............................................................................................................. 27 
5.1.1 Primary Efficacy Endpoint..................................................................................................... 27 
5.1.2 Secondary Efficacy Endpoints ............................................................................................... 27 
5.1.3 Exploratory Endpoints ........................................................................................................... 29 
5.1.4 Healthcare Service Costs ....................................................................................................... 30 
5.2 
Safety ..................................................................................................................................... 30 
6 
Subject Population and Selection .............................................................................................. 30 
6.1 
Inclusion Criteria .................................................................................................................... 30 
6.2 
Exclusion Criteria .................................................................................................................. 32 
6.3 
Subject Completion ................................................................................................................ 33 
6.4 
Subject Discontinuation ......................................................................................................... 33 
7 
Study Treatment Procedures ..................................................................................................... 34 
7.1 
Summary of Study Treatment ................................................................................................ 34 

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8 
Schedule of Visits ........................................................................................................................ 35 
8.1 
Treatment and Data Collection Table .................................................................................... 36 
8.2 
Unscheduled Visits ................................................................................................................ 39 
9 
Data and Safety Monitoring Board ........................................................................................... 39 
10 Statistical and Data Considerations .......................................................................................... 40 
10.1 
Overall Statistical Design....................................................................................................... 40 
10.2 
Efficacy Endpoints ................................................................................................................. 40 
10.2.1 Primary Efficacy Endpoint..................................................................................................... 40 
10.2.2 Secondary Endpoints ............................................................................................................. 40 
10.2.3 Exploratory endpoints ............................................................................................................ 41 
10.3 
Analysis Populations .............................................................................................................. 41 
10.4 
Type I Error ............................................................................................................................ 41 
10.5 
Sample Size and Power .......................................................................................................... 41 
10.6 
Missing Value Imputations .................................................................................................... 41 
10.7 
Sub-group Analyses ............................................................................................................... 41 
10.8 
Additional Analyses ............................................................................................................... 42 
10.8.1 Interim Analysis of Stage 2 Success ...................................................................................... 42 
10.8.2 Interim Safety Analysis .......................................................................................................... 42 
11 Risk-Benefit Analysis .................................................................................................................. 42 
11.1 
Potential Benefits ................................................................................................................... 42 
11.2 
Risks Associated with Investigational Product ...................................................................... 42 
11.3 
Risks Associated with Participation in the Clinical Investigation ......................................... 48 
11.4 
Minimization of Risks ............................................................................................................ 48 
12 Discontinuation of Study, Study Sites, or Subjects .................................................................. 49 
12.1 
Discontinuation of Study Sites ............................................................................................... 49 
12.2 
Treatment Discontinuation in the Experimental Arm ............................................................ 49 
12.3 
Treatment Discontinuation in the Control Arm ..................................................................... 50 
12.4 
Subject Lost to Follow-Up ..................................................................................................... 50 
12.5 
Study Discontinuation ............................................................................................................ 50 
13 Adverse Events ............................................................................................................................ 50 
13.1 
Basis of Adverse Event Management .................................................................................... 50 
13.2 
Definitions .............................................................................................................................. 51 
13.3 
Adverse Event Recording ...................................................................................................... 52 
13.4 
Adverse Event Assessment .................................................................................................... 52 
13.5 
Adverse Event Reporting ....................................................................................................... 53 
13.6 
Device Deficiency .................................................................................................................. 53 

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13.6.1 Definition of Device Deficiency ............................................................................................ 53 
13.6.2 Device Deficiency Report ...................................................................................................... 54 
13.6.3 Timing for Reportable Event ................................................................................................. 54 
14 Investigational Product Accountability .................................................................................... 54 
14.1 
Investigational Drug ............................................................................................................... 55 
14.2 
Investigational Device and Instruments ................................................................................. 55 
15 Selection of Study Sites and Principal Investigators ............................................................... 55 
15.1 
Training .................................................................................................................................. 56 
15.1.1 Site Training ........................................................................................................................... 56 
15.1.2 Monitor Training .................................................................................................................... 56 
15.2 
Study Monitoring ................................................................................................................... 56 
15.3 
Source Data Verification ........................................................................................................ 56 
15.4 
Direct Access to Source Data/Documents ............................................................................. 57 
15.5 
Protocol Deviations ................................................................................................................ 57 
16 Data Handling and Record Keeping ......................................................................................... 58 
16.1 
Subject Coding ....................................................................................................................... 58 
16.2 
Data Handling and Record Keeping ...................................................................................... 58 
16.3 
Electronic Case Report Form Completion ............................................................................. 58 
16.4 
Record Retention ................................................................................................................... 59 
17 Ethical Considerations ............................................................................................................... 59 
17.1 
Subject Compensation ........................................................................................................... 59 
17.2 
Informed Consent ................................................................................................................... 59 
17.3 
Institutional Review Boards ................................................................................................... 59 
17.4 
Confidentiality and Protection of Study Files ........................................................................ 60 
18 Sponsor and Principal Investigator Reports ............................................................................ 60 
18.1 
Principal Investigator Reports ................................................................................................ 60 
18.2 
Sponsor Safety Reports .......................................................................................................... 61 
19 Reporting and Publication of Results ....................................................................................... 61 
20 Literature Cited .......................................................................................................................... 62 
 
 
 
 
 
 
 

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List of Abbreviations 
 
Abbreviation 
Definition 
ADE 
Adverse device effect 
AE 
Adverse event 
API 
Application programming interface 
BA/BE 
Bioavailability/bioequivalence 
BMI 
Body mass index 
BUN 
Blood urea nitrogen 
CAPA 
Corrective and preventive action 
CBC 
Complete blood count 
CC 
Completed case 
CCI 
Charlson Comorbidity Index 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CKD 
Chronic kidney disease 
CMS 
Centers for Medicare and Medicaid Services 
CRA 
Clinical research associate 
CRO 
Contract research organization 
CRP 
C-reactive protein 
DSMB 
Data and Safety Monitoring Board 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EMC 
Electromagnetic compatibility 
EMR 
Electronic medical record 
EPS 
Extracellular polymeric substances 
EQ-5D-3L 
EQ-5D 3-level version 
ESR 
Erythrocyte sedimentation rate 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GFR 
Glomerular filtration rate  
HCl 
Hydrochloride 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
Human immunodeficiency virus 
HOOS 
Hip Disability and Osteoarthritis Outcome Score 
I&D 
Incision and drainage 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use 
ICMMI 
International Consensus Meeting of Musculoskeletal Infection 
IDSA 
Infectious Diseases Society of America 

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IFU 
Instructions for use 
IMSM 
Independent medical safety monitor 
IND 
Investigational new drug  
IRB 
Institutional review board 
ISO 
International Organization for Standardization  
ITT 
Intent-to-treat 
IV 
Intravenous 
KOOS 
Knee Injury and Osteoarthritis Outcome Score 
LAL 
Limulus amoebocyte lysate 
LE 
Leukocyte esterase 
MBEC 
Minimum biofilm eradication concentration 
MDR 
Multi-drug resistant 
MIC 
Minimum inhibitory concentration 
µg/mL 
Micrograms per milliliter 
mg/dL 
Milligrams per deciliter 
mg/mL 
Milligrams per milliliter 
MMRM 
Mixed models for repeated measures 
MSIS 
Musculoskeletal Infection Society 
ng/mL 
Nanograms per milliliter 
NPWT 
Negative pressure wound therapy 
PI 
Principal investigator at each study site 
PJI 
Periprosthetic joint infection 
PMN 
Polymorphonuclear leukocytes 
PP 
Per-protocol 
PSI 
Pounds per square inch 
Q48 
Every 48 hours 
QoL 
Quality of life 
RCT 
Randomized controlled trial 
SADE 
Serious adverse device effect 
SAE 
Serious adverse event 
SAL 
Sterility assurance level 
SAP 
Statistical analysis plan 
sCr 
Serum creatinine 
SDV 
Source data verification 
SIV 
Site initiation visit 
SNF 
Skilled nursing facility 
SOC 
Standard of care 
SW 
Source worksheet 
TTWB 
Toe touch weight bearing 
TXA 
Tranexamic acid 
UADE 
Unanticipated adverse device effect 
UAE 
Unanticipated adverse event 
USADE 
Unanticipated serious device effect 

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USP 
U.S. Pharmacopeia 
WBC 
White blood cells 

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Control Arm: Two-stage exchange arthroplasty per SOC, consisting of Stage 1 
resection arthroplasty and debridement, insertion of a temporary antibiotic-
impregnated cement spacer and administration of 6 weeks systemic antibiotics 
followed by 2 weeks antibiotic holiday, and Stage 2 revision arthroplasty at a 
time deemed clinically appropriate by the investigator. 
Both Arms: All subjects receive 12 weeks of systemic antibiotics post-Stage 2. 
Objectives: 
The objective is to evaluate safety and determine preliminary efficacy of VT-
X7. Efficacy is evaluated as superiority of the Experimental Arm in a 
composite endpoint of Overall Success at 90 days, consisting of a revision 
prosthesis implanted at Stage 2, patient survival, absence of reoperation and 
absence of PJI.  Secondary objectives are to evaluate superiority at 180 days 
and 365 days in a composite endpoint of Overall Success, and in separate 
secondary endpoints for quality of life (QoL), rate of successful reimplantation 
and patient survival. The exploratory objective is to compare Experimental and 
Control Arms in exploratory endpoints. 
Study 
Endpoints(s): 
Primary Endpoint 
 
Composite endpoint of Overall Success at 90 days consisting of: 
• 
Stage 2 revision prosthesis implanted; 
• 
Absence of PJI* post-Stage 2; 
• 
Absence of reoperation*** of the affected joint pre- or post- Stage 2; 
and 
• 
Absence of mortality. 
 
*  If clinical evidence of infection is present post-Stage 2 surgery, use ICMMI 
2018 for definitive PJI confirmation.   
*** Reoperation includes only procedures to irrigate, debride, remove or replace 
the Stage 1 spacer or any Stage 2 implant component. 
 
Secondary Outcome Endpoints 
1. Composite endpoint of Overall Success at 180 days consisting of: 
• 
Stage 2 revision prosthesis implanted; 
• 
Absence of PJI* post-Stage 2; 
• 
Absence of continued antibiotic therapy for treatment or prophylaxis 
of PJI **; 
• 
Absence of reoperation*** of the affected joint pre- and post-Stage 2; 
and 
• 
Absence of mortality. 
 
*  If clinical evidence of infection is present post-Stage 2 surgery, use ICMMI 
2018 for definitive PJI confirmation.   
** Continued antibiotic therapy includes antibiotic therapy at 180 days or beyond 
12 weeks post-Stage 2 surgery, excluding antibiotics for documented pre-
procedural prophylaxis or infection other than PJI. 
*** Reoperation includes only procedures to irrigate, debride, remove or replace 
the Stage 1 spacer or any Stage 2 implant component. 

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2. Composite endpoint of Overall Success at 365 days consisting of: 
• 
Stage 2 revision prosthesis implanted; 
• 
Absence of PJI* post-Stage 2; 
• 
Absence of continued antibiotic therapy for treatment or prophylaxis 
of PJI **; 
• 
Absence of reoperation*** of the affected joint pre- and post-Stage 2; 
and 
• 
Absence of mortality. 
 
*  If clinical evidence of infection is present post-Stage 2 surgery, use ICMMI 
2018 for definitive PJI confirmation.   
** Continued antibiotic therapy includes antibiotic therapy at 365 days or beyond 
12 weeks post-Stage 2 surgery, excluding antibiotics for documented pre-
procedural prophylaxis or infection other than PJI. 
*** Reoperation includes only procedures to irrigate, debride, remove or replace 
the Stage 1 spacer or any Stage 2 implant component. 
 
3. Cumulative proportion of subjects with a revision prosthesis 
implanted at Stage 2 by time to implantation. 
4. Comparison of Quality Adjusted Life Years (QALY) at 365-day follow-
up between the treatment arms.  
5. Survival at 365 days post-Stage 1 surgery. 
 
Exploratory Endpoints: 
• 
Cumulative number of surgeries on the affected joint per subject; 
• 
Change in Knee Injury and Osteoarthritis Outcome Total Score 
(KOOS) (for patients with knee joint treatment) at 90-, 180-, and 365-
day follow-up compared to baseline; 
• 
Change in Hip Disability and Osteoarthritis Outcome Total Score 
(HOOS) (for patients with hip joint treatment) at 90-, 180-, and 365-
day follow-up compared to baseline; 
• 
Clinical lab data; 
• 
Bacterial culture data; 
• 
Serum levels of vancomycin HCl and tobramycin sulfate during the 
irrigation therapy to monitor for toxic systemic levels (Experimental 
Arm only); 
• 
Duration and cumulative Morphine Milligram Equivalents of 
prescribed opioids; 
• 
Duration of antibiotic administration; 
• 
Number of units of blood transfused in 1 week after Stage 1 and Stage 
2 surgery.  
 
 

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Cost Outcome 
• 
Overall treatment cost determined from Medicare Claims Data using 
BlueButtonPro™, a Centers for Medicare and Medicaid Services 
(CMS)-approved Blue Button® 2.0 Application Programming 
Interface (API). 
Safety: 
The safety profile will be characterized by assessing the incidence of adverse 
events (AEs), serious adverse events (SAEs), suspected adverse reactions, 
adverse reactions, unexpected adverse reactions, serious adverse device effects 
(SADEs), and unanticipated adverse device effects (UADEs). 
Inclusion 
Criteria: 
1. Scheduled two-stage exchange arthroplasty due to hip or knee 
PJI1; 
2. Signed informed consent; 
3. 22 to 84 years of age (inclusive); 
4. Medical clearance for surgery; 
5. Preoperative diagnosis of PJI of the hip or knee per the 
International Consensus Meeting of Musculoskeletal Infection 
(ICMMI) 2018 definition of Periprosthetic Hip and Knee 
Infection, which is one of the following 2 major criteria: 
a. The presence of a sinus tract communicating with the 
prosthesis;  
b. Two positive growths of the same organism from at least 2 
separate fluid or tissue samples from different areas of the 
affected joint using standard culture methods;  
OR 
- 
A pre-Stage 1 score ≥6 from all minor criteria for Periprosthetic 
Hip and Knee Infection listed in the table below, including 
intraoperative criteria from procedures performed prior to Stage 1. 
[2]  
 
Preoperative Diagnosis: Minor Criteria 
Score 
Serum 
Elevated CRP (>1 mg/dL) or D-dimer (>860 
ng/mL) 
2 
Elevated ESR (>30 mm/h) 
1 
Synovial 
Elevated synovial WBC (>3000 
cells/µL) or LE (++) 
3 
 
 
1 For this study, a scheduled two-stage exchange arthroplasty consists of two planned surgical procedures for 
treatment of PJI in which the first stage includes surgical removal of an implant from the infected joint, and the 
second stage includes implantation of a permanent replacement prosthesis. The implant removed in the first stage 
may be either i) a permanent implant or, ii) a temporary spacer implanted during the first stage of a prior two-stage 
exchange arthroplasty that has failed. 

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Positive alpha-defensin (signal-to-cutoff ratio 
>1) 
3 
Elevated synovial PMN (>80%) 
2 
Elevated synovial CRP (>6.9 mg/L) 
1 
Intraoperative Diagnosis: Inconclusive 
Pre-op Score or Dry Tap* 
Score 
Preoperative score 
- 
Positive histology** 
3 
Positive purulence 
3 
Single positive culture 
2 
Abbreviations: CRP = c-reactive protein; 
ESR = erythrocyte sedimentation rate; 
WBC = white blood cell; LE = leukocyte 
esterase; PMN = polymorphonuclear 
leukocytes 
* Patients with a score ≥6 from any preoperative or 
intraoperative minor criteria obtained prior to 
Stage 1 meet the ICMMI criteria. Patients with a 
score of <6 prior to Stage 1 surgery do not meet 
the inclusion criteria for this clinical study. 
** More than 5 neutrophils per high-power field in 5 
high-power fields observed from histologic 
analysis of periprosthetic tissue at 400X 
magnification. 
 
Exclusion 
Criteria: 
1. 
Patients with 2 or more prior one-stage or two-stage exchange 
arthroplasties of the infected joint; 
2. 
Patients who have been diagnosed with an acute PJI as a result 
of a total joint arthroplasty which took place within the last 4 
weeks; 
3. 
Patients with bacteremia or positive bacterial blood culture in the 
last 30 days; 
4. 
Patients with concurrent PJI of more than one joint; 
5. 
Patients with ongoing active infection of an intravenous (IV) site; 
6. 
Patients who require long-term anticoagulation or antiplatelet 
therapy, and for whom bridging or withholding therapy is not 
recommended based on the individual’s clinical condition; 
7. 
Patients with advanced renal insufficiency (chronic kidney disease 
(CKD) Stage 4 or greater or glomerular filtration rate (GFR) <30 
mL/min); 
8. 
Patients on chemotherapy for malignant disease; 
9. 
Patients on systemic glucocorticoid therapy (prednisone >10 mg/day 

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or equivalent); 
10. 
Patients with immunodeficiency (e.g., splenectomy, sickle cell 
anemia, Stage 3 human immunodeficiency virus (HIV) infection, 
primary immunodeficiency disease), except immunodeficiency due 
to immunosuppressive therapy; 
11. 
Patients who have an allergy to vancomycin HCl or tobramycin 
sulfate (Note: prior history of red man syndrome is not considered 
an allergy); 
12. 
Patients who have an allergy to titanium, titanium alloys, 
polymethylmethacrylate or polyurethane. 
13. 
Patients who are pregnant or planning to become pregnant in the 
next 12 months; 
14. 
Patients in whom NPWT is contraindicated; 
15. 
Patients with a fungal PJI as determined by one or more positive 
fluid and/or tissue cultures;  
16. 
Patients who have a skeletal defect greater than 150 mm in length in 
the tibia or femur of the infected joint; 
17. 
Patients who have a planned surgical procedure within 6 months of 
enrollment that can impact the conduct of the study; 
18. 
Patients who are breastfeeding at the screening visit; 
19. 
Patients who are incarcerated or are facing impending incarceration; 
20. 
Patients who have been in treatment or referred to treatment for 
substance abuse within the past year; 
21. 
Patients with any medical condition, including schizophrenia or 
another psychiatric disorder with hallucinations and/or delusions, 
that would interfere with the interpretation of the study results, the 
conduct of the study, or patient participation would not be in the best 
interest of the patient in the opinion of the Study Site PI;  
22. 
Patients who will participate in another clinical study of an 
investigational drug or investigational device or have participated in 
another clinical study of an investigational drug or investigational 
device within the past 30 days that would interfere with the 
interpretation of the study results or the conduct of the study;  
23. 
Patients who are judged by the Investigator to be unsuitable for the 
study. 
24. 
Patients receiving immunosuppressive drug therapy for bone 
marrow or another transplant. 
25. 
Patients currently or previously enrolled in this study. 
26. 
Patients who receive therapy including any of the following biologic 
agents, which will not be withheld for a period beginning at least 
one dosing cycle (minimum 7 days) prior to planned surgery and 

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ending at least 14 days following planned surgery: 
Adalimumab (Humira)                Tocilizumab (Actemra) 
Etenercept (Enbrel)                     Anakinra (Kineret) 
Golimumab (Simponi)                Secukinimab (Cosentyx) 
Infliximab (Remicade)                Ustekinumab (Stelara) 
Abatacept (Orencia)                    Rituximab (Rituxan) 
Certolizumab (Cimzia)                Tofacitinib (Xeljanz) 
 Belimumab (Benlysta) 
Follow-up 
Schedule: 
Patients will be evaluated at 90-, 180-, and 365-day follow-up visits. 
Safety 
Monitoring: 
Safety will be monitored throughout the study. The Investigators will assess 
the occurrence of AEs at each follow-up visit. The Independent Medical Safety 
Monitor (IMSM) will evaluate all SAEs, Suspected Adverse Reactions, 
Adverse Drug Reactions, Unexpected Adverse Reactions, and UADEs. The 
DSMB will monitor and evaluate the safety data throughout the study. 
 
 
 
Phase: 
Phase 2b. 
Number of Sites 
Enrolling 
Participants: 
Up to 20 Study Sites will enroll 76 Randomized subjects. 
Participant 
Duration: 
Subjects will be followed up from the time when they sign the informed 
consent form (ICF) to 365 days after the Stage 1 surgery.  
Statistical 
Planning: 
The efficacy will be confirmed by establishing superiority of Overall Success 
at 90 days (Primary Endpoint) in the Experimental Arm as compared to the 
Control Arm. A sample size of 76 subjects in a ratio of 1:1 will have 90% 
power to reject the superiority constructed statistical null hypothesis of no 
difference between the groups under the assumption of an Overall Success 
proportion of 80% in the Experimental Arm and 45% in the Control Arm, and 
a one-sided alpha of 0.025.   
A pre-planned analysis of the secondary endpoints will be performed testing 
the superiority of the Experimental Arm compared to the Control Arm. The 
multiplicity and Type 1 Error within the secondary endpoints family will be 
controlled using the fixed sequence approach and one-sided alpha value of 
0.025.  
 
Exploratory endpoints will be analyzed using t-test, McNemar’s test, chi-
square test, and Fisher’s exact test, as appropriate. Longitudinal changes will 
be analyzed using mixed models for repeated measures (MMRM). 
AEs will be tabulated by body system, preferred term, severity, relationship to 
the investigational product, relationship to the procedure, and time to 
occurrence.  
 
 
 
 

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2 Background and Purpose of the Investigation 
A periprosthetic joint infection (PJI) is a rare complication of joint replacement surgery, also 
known as arthroplasty. Arthroplasty is done to relieve pain and restore function in a severely 
diseased joint. Approximately 0.5% to 1% of people with replacement joints develop a PJI. [3] 
Infections can occur early in the course of recovery from joint replacement surgery or much 
later. Signs and symptoms of PJI include fever, chills, drainage from the surgical site, and 
increasing redness, tenderness, swelling, and pain in the affected joint [4]. PJIs are often hard to 
treat because of the development of a structure called a biofilm within the joint [5, 6, 7]. Biofilms 
are multicellular aggregates of microbes encased in extracellular polymeric substances (EPS), 
which form a physical barrier against antibiotics and acts as a shield between the microbes and 
the patient’s immune system. [5, 7]. 
2.1 Standard of Care Treatment for PJI 
A number of surgical interventions are used to treat PJI. The SOC for treatment of chronic PJI in 
the U.S. is a two-stage exchange arthroplasty. Stage 1 of the procedure includes removal of the 
infected implant, radical debridement and insertion of a temporary antibiotic-impregnated 
cement spacer followed by administration of systemic antibiotic therapy as needed, typically for 
a period of 6 weeks. Stage 2 of the procedure is performed when patients are considered 
infection-free and includes removal of the temporary spacer and implantation of a new 
permanent prosthesis. Cochran et al., in their review of 16,622 Medicare patients treated for PJI 
from October 2005 through December 2011, reported that 80.3% of reinfections occurred in the 
first postoperative year. Looking at both acute and chronic cases in their review, two-stage 
revision had the lowest reinfection rate (19%) of all first-line treatment options for PJI other than 
amputation, as shown in Table 1 [8]. 
Table 1 Reinfection Rate at 12 Months for Various Treatments for PJI 
First-Line Treatment for PJI 
Reinfection Rate at 12 Months 
Incision and Drainage (I&D) 
28.2% 
I&D with Polyethylene Exchange 
25.7% 
One-stage Exchange Arthroplasty 
24.6% 
Two-stage Exchange Arthroplasty 
19.0% 
2.1.1 Inefficacy of Systemic Route of Administration  
The IV administration of systemic antibiotics for PJI does not result in adequate therapeutic 
concentrations for eradication of biofilm at the site of infection. Bone concentrations of 
vancomycin HCl range from 10% to 60% of serum and those of tobramycin sulfate range from 
9% to 13% [9]. Achievement of locally therapeutic levels is crucial for clinical success; however, 
this is difficult or impossible because most PJI pathogens are biofilm-forming. Biofilm-
encapsulated bacteria require minimum biofilm eradication concentrations (MBEC) of 
antibiotics that are several orders of magnitude (100 to 1000X) above the minimum inhibitory 

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concentrations (MIC) sufficient to eradicate planktonic bacteria [10, 11]. Therapeutic target 
attainment at levels greater than the MBEC is impossible via systemic routes of administration 
without significant risk of toxicity to other organ systems. 
2.1.2 Inconsistent Local Therapy  
The multiple variables influencing the release of antimicrobials in cement spacers and other 
carriers present both efficacy limitations and toxicity concerns. For example, antimicrobials 
contained within the center of the spacer matrix are essentially isolated from the joint 
environment, with only the surface cement releasing significant amounts of drug. Mixing 
techniques, antimicrobial concentrations, type of cement, surface area, and movement make for a 
high degree of variability in elution. The amount of antibiotic released from the cement in one 
study ranged from 1.3% to 14.8% [12]. Most of the elution from bone cements occurs in the first 
48 to 72 hours, and, by day 5, the concentrations are often sub-therapeutic even for MIC targets 
for planktonic bacteria [13]. The sub-therapeutic antimicrobial concentrations can lead to the 
formation and colonization of multi-drug resistant (MDR) organisms as evidenced by multiple 
studies. One study showed the formation of pseudomonas biofilms with increasing slime layers 
in gentamicin-impregnated cement versus control, while another study isolated coagulase-
negative Staphylococci in 88% of cases that used gentamicin-loaded cement [14, 15]. The 
inability to control local elution rate also presents risk of systemic toxicity, without means of 
cessation outside of a repeat surgical procedure.  
2.1.3 Failure to Complete Treatment  
Gomez et al. [16] authored one of the first retrospective reviews to fundamentally reexamine the 
definition of successful treatment of PJI. They reported 81.4% treatment success among 329 
knee and hip patients who completed the Stage 2 treatment and had reached one-year follow-up; 
however, they reported that of the 504 PJI patients in their review, 60 (11.9%) were re-operated 
on during the interstage phase to place at least one more spacer (range of one to 6 additional 
spacers), and 87 (17.3%) retained their spacer (failed to complete Stage 2). After a minimum 
one-year follow-up, just 285/416 (68.5%) of all patients in the retrospective study of the two-
stage SOC were considered a treatment success. The authors recommended that the success of 
two-stage arthroplasty be considered from the starting point of initial spacer insertion rather than 
from Stage 2 reimplantation. 
Of those 87 cases in the Gomez study who did not undergo second-stage reimplantation, 15 
underwent amputation, arthrodesis, or Girdlestone procedures, and there were 72 (82.8%) cases 
of retained spacers. Of the 72 cases of retained spacers, 19 (26.4%) were lost to follow-up. When 
excluding these cases, treatment success was 32.1% (17 cases). In 36 (50.0%) of the 72 cases, 
the patients died before the second stage. [16]. 
In 2019, the Workgroup of the MSIS published guidelines for reporting of outcomes after 
surgical treatment of PJI. The need for reoperation, including: septic or aseptic revision, 
amputation, resection arthroplasty or arthrodesis, as well as a retained temporary spacer are all 

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reported as Tier 3 failure of the intended treatment [56]. Based upon this guidance, all patients 
who have failed a prior attempt at two-stage exchange arthroplasty due to the need for septic or 
aseptic revision of the stage 1 spacer or retention of such spacer beyond 12 weeks of concomitant 
systemic antibiotic therapy may be considered for a new two-stage exchange arthroplasty. 
2.1.4 Time to Reimplantation  
The interstage interval between Stage 1 insertion of the temporary spacer and Stage 2 
implantation of a revision prosthesis is critical for the patient. During the interstage period, the 
patient has only limited mobility and partial weight bearing on the affected limb. The risk of 
significant morbidity and permanent disability is high, as are the risks of systemic antibiotic-
related toxicity and development of resistance to antibiotics [17]. Treatment during this period 
may include inpatient rehabilitation (extended care facility/SNF) for part or all of the interstage 
phase, in-home nursing care for infusion services, extended physical therapy, long-term 
antibiotic use, extended opioid use, and ongoing monitoring for systemic toxicity. Andersson et 
al. interviewed 14 PJI patients and reported that those with deep surgical site infections suffer 
significantly from pain, isolation, and insecurity, and that it changes physical, emotional, social, 
and economic aspects of life in extremely negative ways, often persistently [18]. 
Gomez et al. reported an average interstage interval of 4.2 months (range 0.7 to 131.7 months) 
and median interval of 2.7 months in 504 patients who received Stage 1 temporary spacers at a 
single institution. Only slightly more than half of all patients completed the critical Stage 2 
surgical procedure by the typical 12-week postoperative follow-up [16]. 
Cancienne et al. reported on 18,533 knee PJI cases and 7,146 hip PJI cases with the ITT as two-
stage exchange arthroplasty, of which only 61.6% of knee PJI patients and 60.2% of hip PJI 
patients completed the Stage 2 revision within 12 months [19, 20]. 
2.1.5 Interstage Mortality  
Gomez et al. were also among the first to detail the underreported mortality of PJI patients prior 
to Stage 2 reimplantation. Historically, reports of two-stage exchange arthroplasty reported only 
the clinical results for patients who completed the Stage 2 revision procedure, and they were 
completely silent on the results of patients who did not complete the procedure. Gomez et al. 
reported 1.2% mortality (5 of 6 related to infection) in the first 30 days, 2.6% mortality within 90 
days, and 6.5% mortality in the first year, compared to a national mortality rate of 2.0% for the 
general population of the same age [16]. Recent evidence demonstrates that patients with PJI 
have a mortality rate of 25.9% at 5 years, which is 4-fold higher than the mortality of age- and 
comorbidity-matched patients undergoing revision arthroplasty for a non-infected cause [21]. 
2.1.6 Cost-effectiveness  
The burden of PJI for patients and society is substantial [22]. As described in Section 2.1.4, 
treatment burden, limited weight-bearing and mobility, pain management, and antibiotic-related 
complications are some of the challenges that patients face, resulting in critical negative impacts 
on physical, emotional, social, and financial aspects of life. Risk of amputation and death are 

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higher for patients with PJI. From hospital, insurer, and societal perspectives, in-hospital and 
direct costs for patients with PJI are high. Recent studies estimated that costs were 3 to 5 times 
higher than for those without infection [23-27]. The combination of morbidity and mortality and 
personal financial costs for patients, and costs for providers and society, necessitates that 
research into solutions for this devastating problem include estimates of health effects and costs.   
2.2 Investigational Product 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 

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2.3.5 Prior Clinical Experience 
2.3.5.1 Retrospective Clinical Study (JPS-R01) 
A matched retrospective cohort study was conducted to determine whether two-stage 
arthroplasty treatment of hip or knee PJI with local irrigation using vancomycin HCl and 
tobramycin sulfate by a single PI safely reduced the risk of delay or failure to implant a 
permanent hip or knee joint with effective infection control relative to SOC two-stage exchange 
arthroplasty. After matching for various covariates (age-adjusted Charlson Comorbidity Index 

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(CCI), body mass index (BMI), operative joint, and gender), a larger proportion of patients who 
received the experimental local irrigation therapy had a permanent prosthesis implanted by 84 
days post-Stage 1 surgery and retained the same functioning prosthesis 365 days post-Stage 1 
surgery with no signs of infection and no additional surgery for infection compared to the 
matched SOC group (control arm), 91.7% vs 55.6%.[46] 
The median interstage period between Stage 1 resection arthroplasty and Stage 2 reimplantation 
was 7 days in the experimental arm and 74 days in the control arm, a difference of 67 days (95% 
confidence interval [CI], 61 to 74 days). In the experimental arm, 36 of 36 patients (100%) 
received the Stage 2 implant within 9 days. In the control arm, 22 of 36 patients (61.1%) 
received the Stage 2 implant within 84 days. 
2.3.5.2 Feasibility Clinical Study (JPS-001) 
The Phase 2 Feasibility Study to determine the safety profile of local antibiotic irrigation for the 
treatment of PJI (“Safety and Efficacy in Patients Treated for Hip or Knee PJI with Vancomycin 
and Tobramycin Joint Irrigation”, ClinicalTrials.gov Identifier: NCT03721328) was completed 
in August 2020 as per IND 132585. The study was a prospective, single-arm, open-label, 
multicenter (4 sites), interventional trial that enrolled 15 patients (14 with knee PJI and 1 with 
hip PJI). The study employed the same 7-day local antibiotic irrigation protocol to be used in 
VT-X7 but without the use of the VT-X7 Spacer. Instead, the instillation line from the NPWT 
system manufacturer was placed in the joint space to irrigate the joint during the interstage 
period.  
Fourteen (14) of 15 Feasibility Study subjects had no clinically significant changes in CRE and 
blood urea nitrogen (BUN) measurements or SAEs due to renal impairment during the interstage 
or post-Stage 2. One of 15 subjects had an SAE of renal impairment in the post-Stage 2 period 
and had a higher-than-expected BUN value at screening; thus, this subject may have had some 
renal impairment prior to study enrollment [47]. A clinically significant BUN value at screening 
was not an exclusion criterion of this study. 
The serum antibiotic levels from JPS-001 show that with a high antibiotic concentration applied 
locally, subjects maintain serum levels within safe therapeutic ranges and less than that of similar 
doses given via the IV route, thus reducing the risks of nephrotoxicity. 
There were no observations of purulence at Stage 2, compared to 12/15 such cases at Stage 1 (p 
<0.0015). Eradication of infection at 84 days was achieved in all 15 subjects.  
Using a composite efficacy endpoint, 12 out of 15 subjects (80%) were classified as Overall 
Success at their 12-month follow-up visit. One subject was a failure due to a trauma-related 
fracture of both the tibia and fibula which resulted in exchange of the permanent tibial prosthesis 
component. One subject was a failure due to subsequent surgery for aseptic loosening which 
resulted in replacement of the permanent femoral component. One subject did not satisfy 
eradication of infection during the 12-month follow-up.  

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3 
 Study Objectives  
The objective is to evaluate safety and determine preliminary efficacy of VT-X7.  Specific 
objectives are to: 
1. Evaluate superiority of the investigational product (Experimental Arm) compared to SOC 
(Control Arm) in a composite endpoint of overall success at 90 days consisting of 
successful Stage 2 surgery by 90 days post-Stage 1, patient survival, absence of 
reoperation, and absence of PJI.   
2. Evaluate superiority of the investigational product (Experimental Arm) compared to SOC 
(Control Arm) in a composite endpoint of overall success at 180 days consisting of 
successful Stage 2 surgery, patient survival, absence of reoperation, absence of PJI, and 
absence of continued antibiotics. 
3. Evaluate superiority of the investigational product (Experimental Arm) compared to SOC 
(Control Arm) in a composite endpoint of overall success at 365 days consisting of 
successful Stage 2 surgery, patient survival, absence of reoperation, absence of PJI, and 
absence of continued antibiotics. 
4. Evaluate superiority of the investigational product (Experimental Arm) compared to SOC 
(Control Arm) in cumulative proportion of subjects with a revision prosthesis implanted at 
Stage 2 by time to implantation. 
5. Evaluate superiority of the investigational product (Experimental Arm) compared to SOC 
(Control Arm) in Quality Adjusted Life Years outcomes as estimated by EQ-5D-3L. 
6. Evaluate superiority of the investigational product (Experimental Arm) compared to SOC 
(Control Arm) in patient survival.   
7. Compare the investigational product (Experimental Arm) and SOC (Control Arm) in 
exploratory endpoints. 
8. Perform a cost-effectiveness analysis of the investigational product. 
 
4 
Study Design 
4.1 Study Design 
This study is a multi-site, parallel group randomized trial. A total of up to 76 subjects will be 
randomized in a 1:1 allocation to the Experimental Arm or the Control Arm with a minimum 
enrollment of 24 knee and 24 hip subjects.  
The Experimental Arm subjects will receive the investigational product 
 
 
 

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The Control Arm subjects will receive a two-stage exchange procedure per SOC, consisting of 
Stage 1 resection arthroplasty and debridement, insertion of a temporary antibiotic-impregnated 
cement spacer and administration of six (6) weeks systemic antibiotics followed by 2 weeks 
antibiotic holiday, and Stage 2 revision arthroplasty at a time deemed clinically appropriate by 
the treating physician.  
Subjects in Both Arms will receive twelve (12) weeks administration of systemic antibiotics 
post-Stage 2. 
All subjects will receive postoperative rehabilitation per SOC at the participating Study Sites. 
Subjects will be followed up from when they sign the ICF to their 365-day follow-up visit after 
Stage 1 surgery, with follow-up visits scheduled at regular time intervals beginning with the 
Stage 1 surgery. Depending on the timing of the Stage 2 surgery, one or more study follow-up 
visits for subjects in the Control Arm may occur prior to the Stage 2 surgery. 
4.2 Subject Recruitment and Enrollment  
Subjects will be recruited by Investigators at each Study Site. Candidates who are potentially 
eligible for the study will be scheduled for a screening visit. After giving written informed 
consent, subjects will undergo screening assessments. Screening data will be reviewed to 
determine subjects’ eligibility. Subjects who meet all inclusion criteria and none of the exclusion 
criteria will be enrolled into the study.  
A subject is considered enrolled in the study when the subject has given written informed 
consent and the Stage 1 surgery has been initiated.  
4.2.1 Randomization and Blinding 
Subjects will be randomized to either the Experimental Arm receiving the investigational product 
or the Control Arm in a 1:1 ratio stratified according to the affected joint (hip or knee). The exact 
approach will be described in the Randomization Plan.  
Randomization occurs upon successful completion of subject screening.  
Subjects will be blinded to their Randomized Arm assignment until the completion of Stage 1 
surgery. Blinding of subjects after Stage 1 surgery, and blinding of Investigators during the entire 
study, is not possible. 
Microbiology labs at each investigational site will be blinded to the therapy received by each 
subject. 

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4.2.2 Early Study Termination 
The Sponsor reserves the right to discontinue the study at any stage for any reason at any time. 
Possible reasons for early termination may include, but are not limited to, unexpected adverse 
reactions or UADEs that may present unreasonable subject risk.  
If the study is terminated early, the sponsor will provide a written explanation describing why 
premature termination has occurred, and notify the PI, the Institutional Review Board (IRB), and 
the regulatory authority. All applicable clinical study documents will be subject to the same 
retention policy as detailed in the applicable section of this Protocol.  
4.2.3 Measures Taken to Avoid/Minimize Bias  
Measures to avoid or minimize bias include the use of a randomized controlled study design. 
Randomization minimizes the effect of confounding. Subjects will be blinded to the 
randomization of treatment until they complete the Stage 1 surgery to further minimize bias. 
Subjects in both Arms will receive the same minimum duration of post-Stage 2 systemic 
antibiotics and will receive the same post-Stage 2 surgery rehabilitation per SOC at the Study 
Site.  
 
5 
Study Endpoints 
5.1 Efficacy Evaluations 
5.1.1 Primary Efficacy Endpoint 
The primary efficacy endpoint is a composite endpoint of Overall Success at 90 days consisting 
of: 
• Stage 2 revision prosthesis implanted; 
• Absence of PJI* post-Stage 2; 
• Absence of reoperation** of the affected joint pre- and post-Stage 2; and 
• Absence of mortality. 
 
*  If clinical evidence of infection is present post-Stage 2 surgery, use ICMMI 2018 for definitive PJI 
confirmation.   
** Reoperation includes only procedures to debride, remove, or replace the Stage 1 spacer or any Stage 2 
implant component. 
 
5.1.2 Secondary Efficacy Endpoints 
5.1.2.1 Composite Endpoint of Overall Success at 180 days Consisting of: 
• Stage 2 revision prosthesis implanted; 
• Absence of PJI* post-Stage 2; 
• Absence of continued antibiotic therapy for treatment or prophylaxis of PJI **; 

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• Absence of reoperation*** of the affected joint pre- and post-Stage 2; and 
• Absence of mortality. 
 
*  If clinical evidence of infection is present post-Stage 2 surgery, use ICMMI 2018 for definitive PJI 
confirmation.   
** Continued antibiotic therapy at 180 days or beyond 12 weeks post-Stage 2 surgery, excluding antibiotics for 
documented pre-procedural prophylaxis or infection other than PJI. 
*** Reoperation includes only procedures to debride, remove, or replace the Stage 1 spacer or any Stage 2 
implant component. 
 
This endpoint of Overall Success at 180 days is a Key Secondary Endpoint. 
 
5.1.2.2 Composite Endpoint of Overall Success at 365 days Consisting of: 
• Stage 2 revision prosthesis implanted; 
• Absence of PJI* post-Stage 2; 
• Absence of continued antibiotic therapy for treatment or prophylaxis of PJI **; 
• Absence of reoperation*** of the affected joint pre- and post-Stage 2; and 
• Absence of mortality. 
 
*  If clinical evidence of infection is present post-Stage 2 surgery, use ICMMI 2018 for definitive PJI 
confirmation.   
** Continued antibiotic therapy at 365 days or beyond 12 weeks post-Stage 2 surgery, excluding antibiotics for 
documented pre-procedural prophylaxis or infection other than PJI. 
*** Reoperation includes only procedures to debride, remove, or replace the Stage 1 spacer or any Stage 2 
implant component. 
 
This endpoint of Overall Success at 365 days is a Key Secondary Endpoint. 
 
5.1.2.3 Cumulative Proportion of Reimplantation of a Permanent Prosthesis at Stage 2 
Completion of the Stage 2 surgery including implantation of a permanent prosthesis will be 
recorded, and the cumulative proportion of subjects with a revision prothesis implanted at Stage 
2 from time of Stage 1 surgery to 365 days post-Stage 1 surgery will be calculated, by time to 
implantation. 
5.1.2.4 Quality Adjusted Life Years by 365-day follow-up visit.  
Quality Adjusted Life Years (QUALY) will be estimated utilizing EQ-5D-3L. The EQ-5D-3L is 
a widely used health status and health utility measure that consists of 5 questions representing 5 
dimensions of health status including mobility, self-care, usual activities, pain/discomfort, and 
anxiety/depression. The measure provides a health status profile and a single index/utility value 
that can be used for health economic evaluation and cost-effectiveness analysis [48-51]. A utility 
is a measure of preference for a health state that is anchored at 0 = death and 1 = perfect health. 
Individual EQ-5D profiles (responses to each of the 5 questions) are transformed into a utility 
using an algorithm based on U.S utilities. U.S. norm EQ-5D utilities were estimated from a U.S. 

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sample, eliciting time trade off preferences for a wide range of health states.  
5.1.2.5 Survival at 365 Days Post-Stage 1 Surgery 
Mortality for any cause will be recorded through safety monitoring, and the survival from Stage 
1 surgery to 365 days post-Stage 1 surgery will be calculated.  
5.1.3 Exploratory Endpoints 
5.1.3.1 Number of Surgeries of the Affected Joint 
The total number of surgical procedures per subject performed on the joint treated for PJI for any 
reason will be reported. 
5.1.3.2 The HOOS and KOOS 
The HOOS is a self-reported measure consisting of a 40-item questionnaire that assesses pain, 
symptoms, function in activities of daily living (ADLs), function in sport and recreation 
(Sport/Rec), and QoL over the previous week. Dimensions are scored separately on a scale of 0 
to 100 (higher score is better). The instrument is valid and responsive in total hip replacement 
patients [52]. 
The KOOS is a self-reported measure consisting of a 42-item questionnaire that assesses the 
knee through dimensions of pain, function in ADLs, function in sport and recreation (Sport/Rec), 
other symptoms, and knee-related QoL. Dimensions are scored separately on a scale of 0 to 100 
(higher is score better). The instrument is valid and responsive in total knee replacement patients 
[53]. 
5.1.3.3 Clinical Lab Data 
Clinical lab data will be obtained at scheduled follow-up visits, including serum creatinine (sCr), 
complete blood count (CBC) with differential, and BUN. 
5.1.3.4 Bacterial Culture Data 
Results of cultures from intraoperative samples of tissue and synovial fluid during Stage 1 and 
Stage 2 surgeries will be collected. 
5.1.3.5 Serum Levels of Experimental Antibiotics 
In the Experimental Arm only, serum levels of vancomycin HCl and tobramycin sulfate will be 
measured during irrigation therapy to monitor for toxic systemic levels.  
5.1.3.6 Opioid Prescriptions 
Duration and cumulative Morphine Milligram Equivalents of prescribed opioids will be collected 
in both Arms as part of the concomitant medications log. 
5.1.3.7 Duration of Antibiotic Therapy 
Duration and dose of antibiotic prescriptions will be collected in both Arms as part of the 
concomitant medications log. 

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5.1.3.8 Transfusions  
The number of units of blood transfusions administered in the perioperative period (within 1 
week post-operative to Stage 1 and Stage 2 surgeries) will be collected. 
5.1.4 Healthcare Service Costs 
Healthcare service utilization for inpatient, outpatient, physician, SNF, home healthcare, physical 
therapy, hospice services, and medical equipment will be obtained from claims data for subjects 
enrolled in Medicare. The healthcare service utilization will be calculated from the time of Stage 
1 surgery (inclusive) to the 365-day follow-up visit (inclusive). At the time of the 365-day 
follow-up visit, all subjects who are enrolled in Medicare will be asked to provide consent for the 
Sponsor to gain access to claims data using Blue Button® 2.0. Blue Button® 2.0 is Medicare’s 
data service which allows patients to access and share their claims data with healthcare providers 
and researchers. Subjects who do not grant access to their claims data will complete all other 
final follow-up visit tasks as detailed in this Protocol. There will be no penalty or loss of benefit 
for subjects who are eligible for, but do not participate in, the healthcare service utilization data 
effort. Data collected as part of this study effort will be collected independently of the electronic 
case report forms (eCRFs).  
5.2 Safety 
Safety will be monitored throughout the study. The Investigators will assess the occurrence of 
AEs at each follow-up visit. The IMSM will evaluate all SAEs to determine the event’s causality 
to the investigational drugs, device, and procedures, and to determine whether the event meets 
the definition of a Serious Unexpected Adverse Reaction or Unanticipated Serious Adverse 
Device Effect. 
The DSMB will periodically monitor and evaluate the safety data throughout the study. 
 
6 Subject Population and Selection 
Skeletally mature patients with PJI of a hip or knee joint who meet all the following inclusion 
and none of the exclusion criteria will be recruited for this study. 
6.1 Inclusion Criteria 
1. Scheduled for two-stage exchange arthroplasty due to hip or knee PJI2; 
2. Signed informed consent; 
 
 
2 For this study, a scheduled two-stage exchange arthroplasty consists of two planned surgical procedures for 
treatment of PJI in which the first stage includes surgical removal of an implant from the infected joint, and the 
second stage includes implantation of a permanent replacement prosthesis. The implant removed in the first stage 
may be either i) a permanent implant or, ii) a temporary spacer implanted during the first stage of a prior two-stage 
exchange arthroplasty that has failed. 

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3. 22 to 84 years of age (inclusive); 
4. Medical clearance for surgery; 
5. Preoperative diagnosis of PJI of the hip or knee per the ICMMI 2018 definition of 
Periprosthetic Hip and Knee Infection, which is one of the following 2 major criteria: 
a. The presence of a sinus tract communicating with the prosthesis;  
b. Two positive growths of the same organism from at least 2 separate fluid 
or tissue samples from different areas of the affected joint using standard 
culture methods;  
OR 
- 
A pre-Stage 1 score ≥6 from all minor criteria for Periprosthetic Hip and Knee 
Infection listed in the table below, including intraoperative criteria from procedures 
performed prior to Stage 1 [2]. 
Preoperative Diagnosis: Minor Criteria 
Score 
Serum 
Elevated CRP (>1 mg/dL) or D-dimer (>860 
ng/mL) 
2 
Elevated ESR (>30 mm/h) 
1 
Synovial 
Elevated synovial WBC (>3000 
cells/µL) or LE (++) 
3 
Positive alpha-defensin (signal-to-cutoff ratio 
>1) 
3 
Elevated synovial PMN (>80%) 
2 
Elevated synovial CRP (>6.9 mg/L) 
1 
Intraoperative Diagnosis: *Inconclusive 
Pre-op Score or Dry Tap 
Score 
Preoperative score 
- 
Positive histology** 
3 
Positive purulence 
3 
Single positive culture 
2 
Abbreviations: CRP = c-reactive protein; ESR = erythrocyte 
sedimentation rate; WBC = white blood cell; LE = leukocyte 
esterase; PMN = polymorphonuclear leukocytes 
* Patients with a score ≥6 from any preoperative or intraoperative minor criteria 
obtained prior to Stage 1 surgery meet the ICMMI criteria. Patients with a 
score of <6 prior to Stage 1 surgery do not meet the inclusion criteria for this 
clinical study. 
** More than 5 neutrophils per high-power field in 5 high-power fields observed 
from histologic analysis of periprosthetic tissue at 400X magnification. 

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6.2 Exclusion Criteria 
1. Patients with 2 or more prior one-stage or two-stage exchange arthroplasties of the 
infected joint; 
2. Patients with acute PJI, defined as total joint arthroplasty surgery within 4 weeks 
prior to enrollment (Stage 1) in this study; 
3. Patients with bacteremia or positive bacterial blood culture in the last 30 days; 
4. Patients with concurrent PJI of more than one joint; 
5. Patients with ongoing active infection of an IV site; 
6. Patients who require long-term anticoagulation or antiplatelet therapy, and for whom 
bridging or withholding therapy is not recommended based on the individual’s 
clinical condition; 
7. Patients with advanced renal insufficiency (CKD Stage 4 or greater or GFR <30 
mL/min); 
8. Patients on chemotherapy for malignant disease; 
9. Patients on systemic glucocorticoid therapy (prednisone >10 mg/day or equivalent); 
10. Patients with immunodeficiency (e.g., splenectomy, sickle cell anemia, Stage 3 HIV 
infection, primary immunodeficiency disease), except immunodeficiency due to 
immunosuppressive therapy; 
11. Patients who have an allergy to vancomycin HCl or tobramycin sulfate (Note: prior 
history of red man syndrome is not considered an allergy); 
12. Patients who have an allergy to titanium, titanium alloys, polymethylmethacrylate, 
polyethylene, or polyurethane; 
13. Patients who are pregnant or planning to become pregnant in the next 12 months; 
14. Patients in whom NPWT is contraindicated; 
15. Patients with a fungal PJI as determined by fluid and/or tissue culture;  
16. Patients who have a skeletal defect of greater than 150 mm in length in the tibia or femur 
of the infected joint; 
17. Patients who have a planned surgical procedure within 6 months of enrollment that 
can impact the conduct of the study; 
18. Patients who are breastfeeding at the screening visit; 
19. Patients who are incarcerated or are facing impending incarceration; 
20. Patients who have been in treatment or referred to treatment for substance abuse within 
the past year; 
21. Patients who have any medical condition including schizophrenia or another 
psychiatric disorder with hallucinations and/or delusions that would interfere with the 
interpretation of the study results, the conduct of the study, or study participation 

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would not be in the best interest of the patient in the opinion of the Site PI;  
22. Patients who will participate in another clinical study of an investigational drug or 
investigational device or have participated in another clinical study of an investigational 
drug or investigational device within the past 30 days that would interfere with the 
interpretation of the study results or the conduct of the study; 
23. Patients who are judged by the Investigator to be unsuitable for the study. 
24. Patients receiving immunosuppressive therapy for bone marrow or another transplant; 
25. Patients currently or previously enrolled in this study. 
26. Patients who receive therapy including any of the following drugs, which will not be 
withheld for a period beginning at least one dosing cycle (minimum 7 days) prior to 
planned surgery and ending at least 14 days following planned surgery: 
Adalimumab (Humira)                Tocilizumab (Actemra) 
Etenercept (Enbrel)                     Anakinra (Kineret) 
Golimumab (Simponi)                Secukinimab (Cosentyx) 
Infliximab (Remicade)                Ustekinumab (Stelara) 
Abatacept (Orencia)                    Rituximab (Rituxan) 
Certolizumab (Cimzia)                Tofacitinib (Xeljanz) 
 Belimumab (Benlysta) 
 
6.3 Subject Completion 
A subject will be considered to have completed the study if he/she has completed the 365-day 
follow-up visit.  
6.4 Subject Discontinuation  
Once enrolled, every effort will be made to keep the subject in the study until the required 
follow-up period is complete. The subject has the right to withdraw from the study at any time 
without penalty or loss of benefit. The following events will result in terminating the subject’s 
follow-up:  
• Subject voluntarily withdraws; 
• Subject is lost to follow-up; 
• Subject dies; or 
• Study is terminated. 
 
The Sponsor must be notified of the reason for subject withdrawal. The Study Site will document 
this information on the Subject Withdrawal Form and make every effort to give a full description 
of the reason for withdrawal. Investigators must also report this information to the local IRB as 
defined by their institution’s procedure. 
Withdrawn subjects will not be replaced by enrolling additional subjects. Investigational drugs 
assigned to the withdrawn subject shall not be assigned to another subject. The remaining 
investigational drugs for the subject will be kept at the Study Site to be processed according to 

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the Sponsor’s disposal or return instructions. 
A subject who withdraws from the study for any reason, will be assessed for safety evaluation 
purposes. For investigational subjects, this assessment shall occur within 24 hours of the last 
dose of the investigational drugs if at all possible. 
 
7 Study Treatment Procedures 
7.1 Summary of Study Treatment 
Experimental Arm: Stage 1 surgery consists of surgical removal of an implant (permanent 
prosthesis or temporary spacer) from the infected joint, debridement per SOC, and 
 
  
Administration of 7-days local antibiotic irrigation 
 
  
 
 
 
  
The daily investigational drug regimen is repeated on consecutive days until the time of the 
Stage 2 surgery and is not discontinued before the 7th day of investigational drug therapy. The 
Stage 2 surgery may occur at any time during the 7th day of investigational drug therapy, such 
that the 7th day of investigational therapy may be less than a complete 24-hour period. 
 
 
Stage 2 surgery is performed at the completion of the local antibiotic therapy and consists of 
removal of the VT-X7 Spacer, debridement, and replacement with a permanent prosthesis, unless 
reimplantation is contraindicated by an intraoperative clinical finding during the Stage 2 
procedure. Note: Because of the short duration of the Interstage period in the Experimental Arm, 
common inflammatory markers such as ESR and CRP are typically still elevated at time of Stage 
2 surgery and therefore should not influence the decision to proceed with Stage 2. 
All subjects in the Experimental Arm receive 12 weeks of systemic antibiotics post-Stage 2 
(typically 6 weeks IV therapy and 6 weeks culture-specific, highly bioavailable oral therapy).  
Specific post-Stage 2 antibiotic selection, dose, and route of administration are determined by the 
treating physician supported by the local infectious disease and pharmacy teams. 
 

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Control Arm: Stage 1 surgery consists of surgical removal of an implant (permanent prosthesis 
or temporary spacer) from the infected joint, debridement, and insertion of an antibiotic-
impregnated cement spacer per SOC of the Study Site. 
Stage 1 surgery is immediately followed by systemic antibiotic administration for 6 weeks 
followed by a minimum 2-week antibiotic holiday. Post-Stage 1 antibiotics in the Control Arm 
are typically administered by IV, but culture-specific, highly bioavailable oral antibiotics may be 
used if appropriate. Specific post-Stage 1 antibiotic selection, dose, and route of administration is 
determined by the treating physicians. 
Stage 2 surgery consists of removal of the cement spacer, debridement, and replacement with a 
permanent prosthesis. Stage 2 surgery is scheduled following the 2-week antibiotic holiday and 
performed when deemed clinically appropriate by the Investigator. It is recommended that the 
Stage 2 surgery be preliminarily scheduled at the time of Stage 1 surgery to avoid unnecessary 
delay due to schedules of operating staff or facilities. 
All subjects in the Control Arm receive 12 weeks of systemic antibiotics post-Stage 2 (typically 
12 weeks culture-specific, highly bioavailable oral therapy). Specific post-Stage 2 antibiotic 
selection, dose, and route of administration are determined by the treating physicians. 
Both Arms: Complications associated with the temporary spacer, such as dislocation, loosening, 
or mechanical failure may occur between Stage 1 and Stage 2. Such complications may or may 
not have clinical implications or relevance and therefore may or may not require an unplanned 
surgical intervention prior to the Stage 2 surgery. The decision to perform surgery to address 
such complications is made by the Investigator based upon available clinical information and the 
Investigator’s best clinical judgment. Perioperative blood transfusions may be required for some 
subjects.  It is recommended that 1 unit of blood be administered based upon the clinical 
judgment of the treating physician when hemoglobin levels are confirmed at less than 7 
grams/deciliter. 
 
8 Schedule of Visits 

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8.1 Treatment and Data Collection Table 
The study treatment and data collection for each scheduled visit in the Experimental Arm are 
summarized in Table 2 and in the Control Arm in Table 3.  
Table 2 Treatment and Data Collection in the Experimental Arm 
Events 
Screening 
and Baseline 
Visit 
Stage 1 
Surgery 
Interstage 
Period 
Stage 2 
Surgery 
90-Day 
Follow-up 
Visit 
180 Day 
Follow-up 
Visit 
365-Day 
Follow-up 
Visit 
Visit window 
 
Day 0 
Days 0-7 
 
Day 7 
Days 90-104 Days 180-210 Days 365-395 
Obtain informed consent 
(and HIPAA) 
X 
 
Verify 
Inclusion/Exclusion 
X 
 
Administer pregnancy 
test3 
X 
Obtain medical history 
and CCI score  
X 
 
 
Perform Randomization4  
X 
 
 
Administer 1g IV TXA 
pre-op and intra-op 
X 
X 
Obtain 2 synovial fluid 
cultures5 
X 
X 
Obtain 2-3 tissue cultures5 
X 
X 
Record Operative time 
X 
X 
Implant VT-X7 
Spacer 
X 
Place irrigation line 
and NPWT sponges 
X 
Document implant and 
local antibiotics/cement 
X 
Administer local 
tobramycin sulfate and 
vancomycin HCl;6 
record date and time 
Start intra-
op Stage 1 
X 
 
Administer tailored 
IV antibiotics 
per IDSA, if culture + 7 
Start post-
op Stage 1 
X 
 
 
 
 
 
3 Applicable only if subject is female of child-bearing age. 
4 Subject is to be blinded to randomization until completion of Stage 1 procedure.  
5 Samples to be cultured for fungal and bacterial pathogens. 
6 The interstage period shall be completed on the 7th day after Stage 1 whenever possible. The last irrigation cycle 
of antibiotics should be given the day of the Stage 2 surgery. Vancomycin HCl may be administered for less than a 
full day on the 7th day to accommodate a Stage 2 surgery time that is earlier in the day than the Stage 1 surgery 
time. 
7 If subjects have positive cultures from previous aspirations, non-nephrotoxic IV or highly bioavailable oral 
antibiotics safe for use with vancomycin HCl and tobramycin sulfate are allowed at any time, including during the 
interstage period, for ancillary treatment of specific organisms according to IDSA recommendations. Rifampin is 
not allowed during the interstage period due to interaction with anesthetic in Stage 2. Non-nephrotoxic oral 
companion therapy of rifampin for Staphylococci or fluoroquinolones per IDSA recommendations for gram negative 
infections may be added during post-Stage 2 systemic antibiotic therapy. 

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Events 
Screening 
and Baseline 
Visit 
Stage 1 
Surgery 
Interstage 
Period 
Stage 2 
Surgery 
90-Day 
Follow-up 
Visit 
180 Day 
Follow-up 
Visit 
365-Day 
Follow-up 
Visit 
Administer post-op Stage 
2 systemic antibiotics per 
treating physician and 
Study Treatment Guide 
 
12 weeks8 
 
 
Obtain tobramycin sulfate 
peak serum level 
(taken 2 hours after the 
local tobramycin irrigation 
treatment on the specified 
Interstage days) 
X 
Q48 (days 
1, 3, 5, 7) 
 
Obtain tobramycin sulfate 
trough serum level 
(taken prior to the local 
tobramycin irrigation 
treatment on the specified 
Interstage days) 
X 
(at any time 
prior to the 
local 
irrigation 
treatment) 
Q48 (days 
1, 3, 5, 7) 
 
Obtain vancomycin HCl 
serum level 
(taken at any time daily 
during the Interstage 
period) 
X 
(at any time 
prior to the 
local 
irrigation 
treatment)
Daily 
 
Obtain transfusion record 
For 1 week 
post-Stage 1 
 
For 1 week 
post-Stage 2 
 
 
 
Obtain sCr, BUN and 
CBC with differential 
(taken at any time on the 
specified days) 
X 
X9 
Day 1, day 
2, then Q48 
until 
discharge 
Post op day 1, 
day 2, then 
Q48 until 
discharge 
X 
 
 
Obtain GFR 
X 
 
 
 
 
 
 
Document concomitant 
medications, including 
opioid use 
X 
X 
X 
X 
X 
X 
X 
Document AEs and 
complications 
X 
X 
X 
X 
X 
X 
Perform PJI assessment10 
 
 
X 
X 
X 
Obtain EQ-5D-3L 
X 
 
X 
X 
X 
Obtain HOOS/KOOS 
X 
 
X 
X 
X 
Obtain Blue Button® 
consent for claims data 
 
 
 
 
X 
HIPAA = Health Insurance Portability and Accountability Act; CCI = Charlson Comorbidity Index; AEs = 
adverse events; NPWT = negative pressure wound therapy; IV = intravenous; IDSA = Infectious Diseases 
Society of America; sCr = serum creatinine; BUN = blood urea nitrogen; CBC = complete blood count; Q48 = 
every 48 hours; TXA = tranexamic acid 
 
 
 
8 Total of 12 weeks (inclusive) of systemic antibiotic therapy post-Stage 2: typically, 6 weeks culture-specific, IV 
therapy per IDSA guidelines followed by 6 weeks culture-specific highly bioactive oral therapy.  
9 If baseline blood tests are taken within 48 hours of Stage 1 surgery, new blood tests are not required the day of 
Stage 1 surgery. 
 10 If clinical evidence of infection is present, use ICMMI 2018 for definitive PJI diagnosis. 

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Table 3 Treatment and Data Collection in the Control Arm 
Events 
Screening 
and 
Baseline 
Visit 
Stage 1 
Surgery 
Interstage 
Period 
Stage 2 
Surgery 
90-Day 
Follow-up 
Visit 
180-Day 
Follow-up 
Visit 
365-Day 
Follow-up 
Visit 
Time range permitted 
for logistical purposes 
 
Day 0 
Day 0 -
Stage 2 
Day 57 or 
later11 
Days 90-104 Days 180-210 Days 365-395 
Obtain informed consent 
(and HIPAA) 
X 
 
Verify Inclusion/ 
Exclusion 
X 
 
Obtain medical history 
and CCI score 
X 
 
Administer pregnancy 
test12 
X 
 
Perform treatment for 
PJI per SOC 
 
X 
X 
X 
X 
 
 
Perform randomization 
 X13   
 
 
 
Administer 1g IV 
TXA pre-op and intra-
op 
 
X 
 
X 
Obtain 2 synovial fluid 
cultures14 
X 
 
X 
Obtain 2-3 tissue 
cultures14 
X 
X 
Record Operative time 
X 
X 
Administer IV 
antibiotics per IDSA 
per SOC 
 
6 weeks15 
 
Administer 12 weeks 
post-op Stage 2 systemic 
antibiotics per treating 
physician and Study 
Treatment Guide 
 
 
X16 
 
Document implant and 
local antibiotics/cement 
 
X 
Obtain transfusion record 
For 1 week 
post-Stage 1 
 
For 1 week 
post-Stage 2 
 
 
 
Obtain sCr, BUN and 
CBC with differential 
X 
X17 
Day 1, 2, 
then Q48 
until 
discharge 
Day 1, 2, 
then Q48 
until 
discharge 
X 
 
 
Obtain GFR 
X 
 
 
 
 
 
 
 
 
11 Stage 2 procedure may occur later than one or more follow-up visits. Maintain schedule of follow-up visits on 
days specified, independent of Stage 2 procedure date. 
12 Applicable only if subject is female of child-bearing age. 
13 Subject is to be blinded to randomization until completion of Stage 1 procedure.  
14 Samples to be cultured for fungal and bacterial pathogens. 
15 Systemic antibiotic therapy using culture-specific, IV antimicrobial therapy for 6 weeks per IDSA guidelines and 
SOC, followed by antibiotic holiday for minimum of 2 weeks. Use of biofilm active companion drugs is encouraged 
when isolate is known to be susceptible.  
16 Total of 12 weeks (inclusive) of culture-specific, highly bioactive oral antibiotic therapy post-Stage 2. 
17 If baseline blood tests are taken within 48 hours of Stage 1 surgery, new blood tests are not required the day of 
Stage 1 surgery. 
 

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Events 
Screening 
and 
Baseline 
Visit 
Stage 1 
Surgery 
Interstage 
Period 
Stage 2 
Surgery 
90-Day 
Follow-up 
Visit 
180-Day 
Follow-up 
Visit 
365-Day 
Follow-up 
Visit 
Document concomitant 
medications, including 
opioid use 
X 
X 
X 
X 
X 
X 
X 
Document AEs  
X 
X 
X 
X 
X 
X 
Perform wound check and 
PJI assessment18 
 
 
 
 
X 
X 
X 
Obtain EQ-5D-3L 
X 
 
 
X 
X 
X 
Obtain HOOS/KOOS 
X 
 
 
X 
X 
X 
Obtain Blue Button® 
consent for claims data 
 
 
 
 
 
X 
HIPAA = Health Insurance Portability and Accountability Act of 1996; CCI = Charlson Comorbidity Index; AEs 
= adverse events; NPWT = negative pressure wound therapy; IV = intravenous; IDSA = Infectious Diseases 
Society of America; sCr = serum creatinine; BUN = blood urea nitrogen; CBC = complete blood count; TXA = 
tranexamic acid; Q48 = every 48 hours 
All study time-points, follow-up visits and time-based outcomes are defined from the day of Stage 1. 
 
8.2 Unscheduled Visits 
Visits made to the Study Site’s Emergency Department or to the operating surgeon’s office 
for a medical condition related to the index joint surgery, including SOC post-operative 
follow-up visits, are considered Unscheduled Visits, and the following should be documented 
in the relevant eCRF:  
• Reason for visit; 
• Result of wound check; 
• Concomitant medications; and 
• AEs/SAEs/UADEs. 
 
9 Data and Safety Monitoring Board  
The DSMB is composed of independent physicians and a biostatistician who will not participate 
in the study and who are not affiliated with the Sponsor, the Investigators, or any of the Study 
Sites. The DSMB will have access to study data, will review the study on a periodic basis, will 
be responsible for making recommendations regarding any safety or compliance issues 
throughout the course of the study, and may recommend to the Sponsor to modify or stop the 
study. Final decisions regarding study modifications or study termination rest with the Sponsor.  
Cumulative safety data will be reported to the DSMB and reviewed by the DSMB on periodic 
basis periods to ensure subject safety. Every effort will be made to allow the DSMB to conduct 
 
 
18 If clinical evidence of infection is present, use ICMMI 2018 for definitive PJI confirmation. 

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an unbiased review of subject safety information.  
The DSMB will meet according to the schedule specified in the DSMB Charter. 
 
10 Statistical and Data Considerations 
10.1 Overall Statistical Design 
This study is a multi-center, prospective, parallel, concurrent RCT. Details of the statistical 
analysis, including the handling of missing values will be described in the Statistical Analysis 
Plan (SAP). This section provides key elements of the statistical approaches. 
10.2 Efficacy Endpoints 
10.2.1 Primary Efficacy Endpoint 
The primary endpoint is a composite of Overall Success at the 90-day follow-up visit, as 
described in Section 5. The study hypothesis is that the Investigational treatment will have 
superior outcomes compared to the Control treatment in terms of Overall Success at 90 days. 
The statistical null and alternative hypotheses are: 
H0: ΠI - ΠC ≤ 0  
vs. 
HA: ΠI - ΠC > 0, 
Where, 
ΠI is the proportion of subjects who meet criteria for Overall Success at 90 days in the 
Experimental Arm, and 
ΠC is the proportion of subjects who meet criteria for Overall Success at 90 days in the Control 
Arm.  
The hypotheses will be tested using a one-sided z-score test for independent samples for 
proportions at the 1-sided alpha level of 0.025. If the test value exceeds the nominal critical 
point, the H0 will be rejected. The 2-sided 95% CI for the difference in Overall Success between 
the Experimental and Control Arms will be calculated.  
10.2.2 Secondary Endpoints 
A pre-planned analysis of the secondary endpoints will be performed testing the superiority of 
Experimental Arm compared to Control Arm conditioned by success in testing of the primary 
efficacy endpoint. The multiplicity and Type 1 Error within the secondary endpoints’ family will 
be controlled using the fixed sequence approach and one-sided alpha value of 0.025. Refer to the 
SAP for details on the analysis of the secondary endpoints. 

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10.2.3 Exploratory endpoints 
Exploratory endpoints will be analyzed using t-test, McNemar’s test, chi-square test, and 
Fisher’s exact test, as appropriate. Longitudinal changes will be analyzed using mixed models 
for repeated measures (MMRM). 
10.3 Analysis Populations  
The following analysis populations are defined for the study: ITT, mITT, Per-protocol (PP), 
Completed Cases (CC), and Safety. Safety will be evaluated on the Safety population. The 
primary analysis of efficacy will be performed on the ITT population. The mITT, PP and CC 
populations will be used in a sensitivity analysis of the efficacy endpoints. 
• The ITT population includes all Randomized subjects, regardless of whether the subject 
received the treatment to which the subject has been randomly assigned.  
• The mITT population includes all Randomized subjects where the randomly assigned 
treatment has been attempted. 
• The PP population is a subset of the ITT population and includes all subjects who receive 
the assigned treatment and do not have any major protocol violations.  
• The CC population includes all subjects in the ITT population who have the 365-day 
follow-up visit.  
• The Safety population includes all ITT subjects. 
10.4 Type I Error 
The alpha level will be set to 0.05 based on the 2-sided testing and 0.025 for the one-sided 
approach, if not explicitly stated otherwise. Control for multiplicity in testing of secondary 
endpoints is based on fixed sequence approach. Unless otherwise indicated, all statistical 
inferences will be based on 2-sided 95% CIs.  
10.5 Sample Size and Power 
A sample size of 76 subjects will have 90% power to detect .35 (35%) difference in the 
proportion of subjects who are classified as Overall Success at 90-day follow-up, under the 
assumption that the proportion of subjects in the Control Arm who are classified as Overall 
Success is 50%. 
10.6 Missing Value Imputations 
Details concerning missing value imputations will be described in the SAP. 
10.7 Sub-group Analyses 
Pre-planned sub-group analyses will include analyzing the primary and secondary endpoints by 
joint and by drug resistance (none versus one or more multi-drug resistant pathogens at Stage 1). 

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10.8 Additional Analyses 
10.8.1 Interim Analysis of Stage 2 Success  
An interim analysis of percent success of Stage 2 implantation in the Experimental Arm will be 
initiated 10 days after the Stage 1 surgery of the 15th subject in the Experimental Arm.  The 
analysis will describe proportion of subjects who were not implanted with the permanent 
prosthesis, describe any unplanned surgical interventions, list the reasons for failure to perform 
the second stage surgery, and describe approaches to the management of these subjects 
10.8.2 Interim Safety Analysis 
An interim safety analysis will be performed when the 15th subject in the Experimental Arm 
reaches 90 days post-Stage 1 surgery.    The analysis will include, but not be limited, to the 
number of subjects retaining the prosthesis implanted at the second stage and describing any 
unplanned post-stage 2 interventions for all subjects. 
 
11 Risk-Benefit Analysis 
11.1 Potential Benefits 
There are significant potential benefits for Experimental subjects who participate in this clinical 
study. Subjects to be included in the present study have a serious and potentially life-threatening 
clinical condition. The investigational product, if effective as anticipated, will provide better 
outcomes compared to current SOC treatment. Subjects who are randomized into the Control 
Arm will receive SOC treatment and will not be worse off than if they did not participate in the 
study. Data from the Phase 2 study (JPS-001) showed an acceptable safety profile for the 
intervention. The efficacy findings from the Phase 2 study were also acceptable and are expected 
to be translated to this study, thus justifying the assumed benefit-to-risk ratio. 
There are potential societal benefits to a novel antimicrobial therapy application with the 
possibility of shortening treatment durations thus minimizing antimicrobial resistance and 
toxicity. PJI and its associated comorbidities are serious medical events that consume a large 
amount of health care resources. If the treatment is shown to be more effective and/or safer than 
the current SOC treatment, the investigational product will provide a therapeutic option that fills 
the treatment gap and thus contributes to overall management of PJI while advancing 
antimicrobial stewardship. Additionally, the shortened intervention duration has the potential to 
reduce opioid usage and misuse, a serious national crisis that affects public health as well as 
social and economic welfare.  
 
 
 

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• The study Protocol has built-in measures to control potential adverse effects, including 
study inclusion/exclusion criteria, clinical surveillance, and laboratory surveillance; 
• Training and technical support will be provided for device placement/removal 
procedures; 
• A DSMB is set up to monitor the safety of the subjects in the study; 
• An interim safety analysis has been implemented to compare safety outcomes early in 
the study. 
• Non-clinical studies of the investigational product components were performed to 
minimize or eliminate risks (see Table 5 Summary Table of Risks and Risk Mitigation 
Associated with the Investigational Product or Treatment); 
• The Phase 2 study (JPS-001) has not indicated any major risks associated with the 
investigational drugs; and 
• Clinical study results from the Phase 2 study (JPS-001) show that there were no 
investigational treatment-related AEs in any of the 15 enrolled subjects. 
 
In summary, subjects included in the present study have a clinical indication for two-stage 
arthroplasty. Prior clinical experience shows that the investigational product, VT-X7, can be 
used successfully, that subjects may achieve favorable outcomes, and that the complications are 
acceptable and can be managed clinically. The risks associated with the investigational product 
including the VT-X7 Spacer have been mitigated as much as possible. The current study design 
includes additional measures to further minimize risks.  
 
12 Discontinuation of Study, Study Sites, or Subjects 
12.1 Discontinuation of Study Sites 
Study Site participation may be discontinued if the Sponsor, the PI, or the IRB judges it 
necessary for any or no reason. Subjects at discontinued Study Sites will be followed up 
in accordance with Section 6.4. 
12.2 Treatment Discontinuation in the Experimental Arm 
If a subject is unable to continue the investigational treatment for any reason which requires 
premature removal of the investigational device, antibiotic irrigation shall be discontinued, the 
device shall be removed, and appropriate medical treatment shall be administered at the direction 
of the treating physicians.  
 
 
 
 

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12.3 Treatment Discontinuation in the Control Arm 
If a subject is unable to continue treatment for any reason which requires premature removal of 
the cement spacer or discontinuation of antibiotic therapy in the Control Arm, appropriate 
medical treatment shall be administered at the direction of the treating physicians. 
12.4 Subject Lost to Follow-Up 
A subject will be considered lost to follow-up if he/she does not appear for the scheduled study 
visit and study personnel are unable to contact the subject. Study personnel must make a 
reasonable effort to contact the subject and document the following contact attempts prior to 
declaring a subject to be lost to follow-up: 3 phone calls with at least 2 days in between each call 
followed by a certified letter. The first phone call must occur no more than 3 business days after 
the subject has failed to show up for a visit.  
When possible, study personnel will aim to determine the reason for the subject being lost to 
follow-up and record any information obtained. 
12.5 Study Discontinuation 
The study will be discontinued if the Sponsor decides it necessary for medical, safety, regulatory, 
no reason, or other reasons consistent with applicable laws, regulations, and Good Clinical 
Practice (GCP).  
 
13 Adverse Events 
13.1 Basis of Adverse Event Management  
The definitions, recording, assessment, and reporting of AEs required in this Protocol are based 
on requirements from FDA 21 Code of Federal Regulations (CFR) 312.32 (Revised as of April 
1, 2018), FDA 21 CFR 812 (Revised as of April 1, 2018), ISO 14155:2020, and Guidance for 
Industry and Investigators: Safety Reporting Requirements for IND and 
Bioavailability/Bioequivalence (BA/BE) Studies (FDA, December 2012, Drug Safety) [54]. 

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13.2 Definitions 
Adverse Event (AE): Any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. It 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. Or,  
An untoward medical occurrence, unintended disease or injury, or untoward clinical signs 
(including abnormal laboratory findings) in subjects, users or other persons, whether or not 
related to the investigational medical device and whether anticipated or unanticipated. 
Suspected Adverse Reaction: Any AE for which there is a reasonable possibility that the drug 
caused the AE. Reasonable possibility means there is evidence to suggest a causal relationship 
between the drug and the AE. A suspected adverse reaction implies a lesser degree of certainty 
about causality than adverse reaction, which means any AE caused by a drug. 
Adverse Reaction: Any AE caused by a drug. Adverse reactions are a subset of all suspected 
adverse reactions where there is reason to conclude that the drug caused the event. 
Unexpected Adverse Reaction: An AE or suspected adverse reaction is considered 
“unexpected” if it is not listed in the Investigator’s Brochure (IB) or is not listed at the specificity 
or severity that has been observed. For the investigational drugs in this study, because they are 
marketed and approved in the U.S., ordinarily FDA-approved prescription drug labeling is used 
as the basis for determining whether an event is unexpected for reporting purposes.  
Adverse Device Effect (ADE): An AE related to the use of an investigational medical device 
includes AEs resulting from insufficient or inadequate instructions for use (IFU), deployment, 
implantation, installation, or operation, or any malfunction or any event resulting from use error 
or from intentional misuse of the investigational medical device. 
Serious Adverse Device Effect (SADE): An ADE that has resulted in any of the consequences 
characteristic of an SAE.  
Unanticipated Adverse Device Effect or Unanticipated Serious Adverse Device Effect 
(UADE or USADE): Any serious adverse effect on the health or safety of a subject, or any life-
threatening problem or death caused by, or associated with, a device, if that effect, problem, or 
death was not previously identified in nature, severity, or degree of incidence in the Protocol or 
any other unanticipated serious problem associated with a device that relates to the rights, safety, 
or welfare of subjects. 
Serious Adverse Event (SAE): An AE or suspected adverse reaction is considered “serious” if, 
in the view of either the Investigator or sponsor, it:  
• Leads to death; 
• Is life threatening, or places the participant at immediate risk of death; 
• Requires inpatient hospitalization or prolongation of existing hospitalization; or 

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• Results in a persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions, or a congenital anomaly/birth defect.  
 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, they 
may jeopardize the subject and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition.  
13.3 Adverse Event Recording 
AE information will be collected throughout the study. The Investigator or his/her designee will 
record all AEs on the appropriate Source Worksheet (SW) and enter this data on an eCRF. The 
applicable SW will capture the event term, date of onset, duration, seriousness, severity, actions 
taken, outcome, and causality to the investigational product (drug, implanted spacer, or the 
investigational procedure) or NPWT. The Investigator is responsible for determination of 
seriousness, severity, and causality.  
The Investigator will assess subjects at each study visit for the occurrence of AEs. In order to 
avoid bias in eliciting AEs, subjects should be asked non-leading questions. All AEs reported by 
the subject or found on examination or in a laboratory report must be recorded.  
All AEs must be followed until resolved or a stable clinical outcome is reached. All treatments 
and outcomes of the AE must be recorded.  
All AEs and SAEs must be followed until one of the following occurs: 
• AE is resolved (i.e., return to normal/baseline values);  
• AE is declared clinically insignificant; 
• AE has stabilized; 
• Subject is lost to follow-up or withdraws consent; 
• Subject completes the study, including required follow-up visits; or 
• Study is closed. 
 
The Investigator must follow GCP guidelines and continue to treat (or refer the subject to an 
appropriate practitioner for continuing treatment) any AE that remains unresolved after the 
subject has completed study participation.  
13.4 Adverse Event Assessment 
The Investigator is responsible for identifying and reporting all AEs from his/her site. The 
Investigator is responsible for the determination of severity, seriousness, and causality for each 
event reported.  
The Sponsor or Sponsor’s designee will routinely review AE information as reported by the 
Investigators. The Sponsor or Sponsor’s designee will also review and assess SAEs for 
seriousness and causality. Further, he/she will determine whether the event is “unexpected” for 

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IND safety reporting purposes and whether the event meets the definition of a UADE. 
If the Investigator and Sponsor/Sponsor’s designee have different assessments of the seriousness 
or life-threatening nature of an event, the more serious assessment will prevail and be evaluated 
by the Sponsor for possible expedited reporting for IND safety report purposes. 
If the Investigator and Sponsor have different assessments of event causality, for IND safety 
report purposes, the Sponsor’ judgement will override the Investigator’s assessment.  
The causality assessment is defined below: 
• Unrelated: known consequences of the underlying disease or condition under 
investigation or other events that commonly occur in the study population 
independent of investigational product or procedure; 
• Reasonable possibility: there is evidence to suggest a causal relationship between the 
investigational product and/or study procedure to the AE;  
• Definitely related: there is reason to conclude that the investigational product and/or 
study procedure caused the event. 
13.5 Adverse Event Reporting 
The Investigator is responsible for the collection and submission of AE and SAE data to the 
Sponsor/Contract Research Organization (CRO).  
AE data will be entered into the electronic data capture (EDC) system. 
The Investigator must report to the Sponsor/CRO any SAE within 24 hours of the Investigator 
becoming aware of the SAE, whether or not it is considered investigational product-related, 
including those listed in the Protocol or IB. The Investigator  must include an assessment of 
whether there is a reasonable possibility that the investigational product and/or study procedure 
caused the event. SAE data will be entered into the EDC system and submitted on a Serious 
Adverse Event Report to the Sponsor/CRO. 
The Investigator is responsible for all reporting required as per IRB. The Sponsor/CRO is 
responsible for advising the Investigator if an AE is an unanticipated problem that needs to be 
reported to the IRB. In general, an AE observed during the conduct of a study should be 
considered an unanticipated problem involving risk to human subjects, and reported to the IRB, 
only if it was unexpected, serious, and would have implications for the conduct of the study 
(Guidance for Clinical Investigators, Sponsors, and IRBs, Adverse Event Reporting to IRBs — 
Improving Human Subject Protection, FDA, January 2009, Procedural).  
13.6 Device Deficiency 
13.6.1 Definition of Device Deficiency  
A device deficiency is the inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety, or performance. This may include malfunctions, use errors, and 

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inadequacy in the information supplied by the manufacturer including labelling. For the purposes 
of this study, this definition includes device deficiencies related to the investigational medical 
device (i.e., the VT-X7 Spacer) and medical devices used as part of therapy (i.e., the NPWT 
system) or in the Control Arm in the clinical investigation.  
13.6.2 Device Deficiency Report  
The Investigator is responsible for documenting all device deficiencies related to both the 
investigational device (i.e., the VT-X7 Spacer) and the medical device used as part of therapy 
(i.e., the NPWT system), or the medical devices used in the Control Arm throughout the clinical 
investigation. The reporting shall be done using the Device Deficiency Report form provided by 
the Sponsor or designee, and via entry into the EDC system.  
The data from the Device Deficiency Report will be periodically reviewed by the DSMB. When 
applicable, appropriate corrective and preventive actions (CAPAs) will be taken to protect the 
safety of subjects, users, and other persons. The sponsor or designee will arrange for the safe 
return of the investigational device that is subject to a device deficiency. 
13.6.3 Timing for Reportable Event 
The Investigator is responsible for assessing the reportability of each event, and submitting the 
Device Deficiency Report when the deficiency meets the following criteria:  
• For any device deficiency that led to a SAE, the Investigator must submit both an SAE 
report and the associated Device Deficiency Report to the Sponsor/designee following 
the timeline as described in Section 13.5. 
• For any device deficiency that might have led to an SAE if either: 
o suitable action had not been taken, 
o intervention had not been made, or 
o circumstances had been less fortunate, 
The Investigator must submit the Device Deficiency Report to the Sponsor/CRO as soon as 
possible, but not later than 5 business days following the date of awareness of the event.  
The Investigator is responsible for reporting the device deficiency to the IRB, if required per IRB 
regulations.  
The Sponsor will promptly evaluate the report to determine further actions.   
The Investigator is reminded that mandatory reporting to the FDA, as per 21 CFR Part 803, is 
required for the NPWT pumps throughout the course of the study. 
 
14 Investigational Product Accountability 

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14.1 Investigational Drug 
The Study Site will maintain an inventory of the investigational drugs. This inventory will 
include: 
• Name of person designated as responsible for the inventory of the investigational 
products; 
• Amount received including date and lot number(s); 
• Amount currently in inventory; 
• Amounts dispensed to each subject, identified by the subject identification number; 
• Amount destroyed, if applicable (this should not occur without prior notification to 
Sponsor/CRO); 
• Non-study disposition (e.g., wasted, broken); 
• Amount returned to Sponsor or designee, if applicable. 
Investigational drugs must be stored in a secure space with double lock and limited access. 
Neither the Investigator nor any member of the study staff will distribute any of the 
investigational drug to any person not participating in this study. The drugs should be stored at a 
controlled room temperature of 20° to 25°C (68° to 77°F). 
The Sponsor or designee will provide forms to facilitate investigational drug product inventory 
control. All completed investigational drug accountability forms and treatment logs must be 
retained in the Study Site’s pharmacy binder or equivalent information retained in the electronic 
medical record. These records must be available for inspection by the Sponsor, its designees, 
and/or by regulatory agencies at any time.  
14.2 Investigational Device and Instruments 
The VT-X7 Spacer will be provided by the Sponsor to the Study Site at the time of Stage 1 
surgery. The VT-X7 Spacer will be available in multiple sizes because the choice of size of 
spacer components is determined during the Stage 1 surgery. The required surgical instruments 
for insertion and removal of the VT-X7 Spacer will be provided non-sterile in a surgical tray. 
The surgical instruments tray will be provided to the Study Site ahead of the planned Stage 1 and 
Stage 2 surgeries to allow time for the cleaning and sterilization of the tray.  
The VT-X7 Spacer removed during Stage 2 surgery should be discarded per the Study Site’s 
biohazardous material handling procedures unless it appears broken or the irrigation line is 
detached from the Spacer, in which case the device is to be shipped for evaluation per the 
Sponsor’s instructions. 
Documentation of the investigational device and instrument accountability will be maintained on 
logs provided by the Sponsor. 
 
15 Selection of Study Sites and Principal Investigators 

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The Sponsor will select PIs who are qualified by training and experience to perform clinical 
research in this field and to participate in the clinical investigation. Study Sites will be selected 
based upon an assessment of the qualifications of the PI and the facilities at each Study Site. All 
PIs will be trained on the investigational product, the Protocol, and all study procedures prior to 
enrolling subjects. 
A Site Initiation Visit (SIV) will be conducted at each Study Site to ensure the Investigators and 
study personnel understand the obligations for using and managing the investigational product, 
following the study Protocol, obtaining informed consent, adhering to FDA and IRB regulations, 
and conducting clinical research.  
15.1 Training 
15.1.1 Site Training 
All Investigators/study personnel are required to attend Sponsor training sessions, which may be 
conducted at an Investigator’s meeting, an SIV, or other appropriate training sessions. Remote 
over-the-phone or web-based training will take place as necessary. Training of 
Investigators/study personnel will include, but is not limited to, the study Protocol, enrollment 
(including review of inclusion and exclusion criteria), subject retention, investigational product 
usage, investigational product accountability, source documentation and eCRF completion, and 
study personnel responsibilities. All Investigators and relevant site personnel must sign a training 
log (or equivalent) upon completion of the training.  
15.1.2 Monitor Training 
The Sponsor or designee will engage Clinical Research Associates (CRAs) who are qualified by 
appropriate training and experience to review the conduct and quality of the study. Prior to 
working on the study, CRAs will be trained on the Protocol, SWs/eCRFs, and the 
drug/device/procedure. Such training will be documented. 
15.2 Study Monitoring 
The Sponsor and/or a designee (e.g., a CRO) will monitor the clinical study in a manner 
consistent with FDA regulations and GCP standards. A Monitoring Plan will be generated to 
document the monitoring process to ensure compliance with all procedures required by the 
Protocol and to verify data quality. 
A risk-based approach will be used to determine the site monitoring frequency. Monitoring and 
Source Data Verification (SDV) may be performed remotely or on-site.  
The Investigator and his/her personnel will be expected to cooperate with Sponsor’s personnel or 
designee and to be available during the monitoring visits to answer questions sufficiently and to 
provide any missing information. 
15.3 Source Data Verification  
SDV ensures accuracy and credibility of the data obtained. During SDV, reported data are 

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reviewed for accuracy, completeness, attributability, and verifiability. 
Source data includes all information in source documents (original records, certified copies of 
original records, appointment books, original laboratory records, and original data recorded on 
customized worksheets) and includes all original recordings or copies of clinical findings, 
observations, or other activities necessary for the reconstruction and evaluation of the study. 
15.4 Direct Access to Source Data/Documents 
The PI(s)/institution(s) will permit direct access to source data/documents for study-related 
monitoring, audits, and IRB and regulatory inspection(s). The process for direct access to source 
documents in the electronic medical record (EMR) will be determined during site qualification as 
this process varies by Study Site procedure. 
Consenting subjects agree to allow the Sponsor or designee access and copying rights to 
pertinent information in their medical records relevant to study participation. As part of the 
informed consent, the Investigator or designee will obtain permission for regulatory authorities 
to review any records identifying subjects in this study. The Sponsor will not otherwise release 
any personal information.  
15.5 Protocol Deviations 
It is the Investigator’s responsibility to ensure that there are no deviations from the Protocol 
except in cases of medical emergencies when the deviation is necessary to protect the life or 
physical well-being of the subject. In the event of any deviation from the Protocol, a Protocol 
Deviation Report will be completed. The occurrence of protocol deviations will be assessed by 
the Sponsor for evaluation of Investigator compliance to the Protocol and to GCP and regulatory 
requirements. Protocol deviations will be designated as significant or minor. The Investigator 
will inform his/her IRB of protocol deviations according to the requirements of each reviewing 
IRB.  
Significant protocol deviations for this Protocol consist of, but are not limited to, the following:  
• Failure to obtain subject’s informed consent prior to enrolling into the study;  
• Enrollment of subjects who do not meet all eligibility requirements; 
• Failure to conduct Protocol-required procedures and clinical follow-ups;  
• Failure to report SAEs according to Protocol requirements.  
In the event of any deviation from the Protocol, the Sponsor will be notified of the Study Site’s 
non-compliance. Corrective actions will be recommended if indicated, and the methods, plan, or 
other activities implemented to ensure non-recurrence will be documented by the Investigator 
and forwarded to the Sponsor or designee. Repeated protocol deviations despite re-education of 
Study Site personnel and/or significant protocol deviations may result in termination of the Study 
Site’s study participation. Subjects already enrolled at these Study Sites will continue to be 
followed for safety per Protocol guidelines. 
 

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16 Data Handling and Record Keeping 
16.1 Subject Coding 
The eCRFs and all other documents/data sent to the Sponsor will not contain identifying study 
subject information. Each subject will be assigned a unique subject identification number that 
reflects the Study Site number and subject number. The subject identification number will 
consist of 8 characters in an alphanumeric combination. Each Study Site will be assigned a 3-
digit alphabetic code.  
The Study Site will maintain a log that links the subject identification number to the 
name of each subject. An example is shown in Table 5. 
Table 5 Example of the Subject Identification Number 
Site Code 
Connector 
Sequential Number 
A 
B 
C 
- 
0 
0 
0 
1 
16.2 Data Handling and Record Keeping 
For the study duration, the Investigator will maintain complete and accurate documentation as 
required per International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) GCP E6(R2). 
The following materials should be included in the subject record:  
• Signed ICF; 
• SWs including but not limited to dated and signed notes from each subject’s visit (for 
specific results of procedures and exams and investigational drug dosing and 
investigational device accountability data);  
• Medical records for subject medical history/physical condition prior to study 
involvement, study progress records, laboratory reports, medication record, and 
investigational device use record; 
• AEs and their outcome including supporting documents;  
• Subject’s condition upon study completion or withdrawal and information regarding 
the subject’s discontinuation or completion. 
16.3 Electronic Case Report Form Completion 
Accurate data recording will be performed by Study Site personnel trained on the Protocol and 
electronic case report form (eCRF) completion. All data fields will be completed. However, if 
data are not available (i.e., missed visit, etc.), the Study Site will receive instructions regarding 
how to properly document these facts.  
Error messages will be generated for the modification and/or verification of the entered data. 

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Queries will be generated using an electronic data query system that includes an automated audit 
trail of the corrections. The Investigator will certify that the data are complete and accurate by 
applying an electronic signature to the eCRF. Any subsequent alterations, corrections, or 
additions will be reviewed and electronically signed by the Investigator prior to the database 
lock. 
The Sponsor or designee will provide clinical monitoring to include eCRF review and parity 
checks with the source documentation. 
16.4 Record Retention 
The Investigator/Site will maintain all records pertaining to this study for the later of: (a) 2 years 
following study completion; (b) 2 years after the study has been terminated by the Sponsor; (c) 
as otherwise instructed by the Sponsor; or (d) as required by local laws or regulations. The 
Investigator will be notified by Sponsor of the date of completion or discontinuation of the study.  
To comply with these requirements, the Investigator will not dispose of or transfer any records 
relevant to this study without either (1) written permission from the Sponsor, or (2) providing an 
opportunity for the Sponsor to archive the records with an external vendor.  
 
17 Ethical Considerations 
17.1 Subject Compensation 
Study subjects may be compensated for certain activities required of them during their 
participation in the clinical study. 
17.2 Informed Consent 
Written informed consent will be obtained from each subject before any study-specific 
procedures or assessments are done and after the aims, methods, anticipated benefits, and 
potential hazards are explained. The subject’s willingness to participate in the study will be 
documented in writing on the ICF, which will be signed by the subject with the date of that 
signature indicated, as well as the dated signature of the study personnel who obtained the 
consent. The Investigator will keep the original ICF and a copy will be given to the subject. As 
part of the informed consent process, study personnel will explain to the subject that he/she is 
free to refuse entry into the study and free to withdraw from the study at any time without 
prejudice to future treatment. Written and/or oral information about the study will be provided in 
understandable language to all subjects. 
17.3 Institutional Review Boards 
IRB approval for the Protocol and ICF will be obtained prior to subjects’ study participation. The 
approval letter must be obtained prior to beginning this study and a copy must be provided to the 
Sponsor. No changes will be made to the Protocol or ICF without appropriate approval from the 

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IRB, the Sponsor, and/or the regulatory agencies.  
As per IRB requirements, the Investigator will report study progress until it is completed. 
Further, any Protocol amendments as well as associated ICF changes will be submitted to the 
IRB and written approval must be obtained prior to implementation. 
17.4 Confidentiality and Protection of Study Files 
The identity of subjects enrolled in the study and the information contained in their study records 
will be kept confidential by the Sponsor.  
Each subject will be assigned a study identification number to be used on eCRFs and other study 
records sent to the Sponsor or designee.  
Confidentiality will be protected as much as possible throughout the study. Results of data 
collected will be reported as statistical information only. The subject’s name will not be used or 
otherwise disclosed unless required by U.S. law or regulation.  
 
18 Sponsor and Principal Investigator Reports 
18.1 Principal Investigator Reports 
The reports in Table 6 are required of each PI as described. 
Table 6 Investigator Reports 
Report 
Submit to 
Submission Schedule 
Screening and 
Enrollment 
CRO 
Weekly 
All study data 
EDC (CRO) Baseline data: within 48 hours; all others: no later than 7 days 
Serious 
Adverse Events 
(SAEs) 
CRO/IRB 
Report to CRO within 24 hours after the PI first learns of the 
event. Report to IRB according to IRB’s reporting roles, or if 
notified by the Sponsor/CRO that the SAE meets FDA’s IND 
safety report criteria.  
 
Device 
Deficiency 
Report 
CRO/IRB 
If associated with an SAE, use the same schedule for SAE 
reporting. Otherwise, within 5 days after the PI first learns of the 
event. Report to IRB according to IRB’s reporting roles, or if 
instructed by the Sponsor/CRO. 
Study protocol 
deviations  
CRO/IRB 
Report to CRO and IRB within 48 hours if the deviation affects 
the subject’s safety and well-being. Otherwise, report to CRO no 
later than 7 days; report to IRB according to IRB’s reporting 
roles.  
Subject withdrawal  
CRO/IRB 
Report to CRO and IRB within 48 hours if the deviation affects 
the subject’s safety and well-being. Otherwise, report to CRO no 
later than 7 days; report to IRB according to IRB’s reporting 
roles.  

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IRB submission for 
continued approval  
IRB/CRO 
Submit to IRB annually or as required during and at the end of the 
study. Submit IRB’s approval document to CRO within 5 working 
days of receipt.  
IRB suspensions or 
terminations of 
approvals 
CRO 
Report to the Sponsor/CRO within 48 hours of receiving any IRB 
communications of suspensions or termination of approvals. 
Sponsor/CRO will report to the FDA. 
18.2 Sponsor Safety Reports 
The Sponsor is responsible for timely review of safety information and determining whether the 
safety information submitted from the Study Sites meets the IND safety reporting criteria as 
defined in FDA 21 CFR 321.32:  
• Suspected adverse reaction; 
• Serious;  
• Unexpected. 
 
The Sponsor is responsible for ensuring any serious and unexpected suspected adverse reaction 
is reported to the FDA in an IND safety reporting format and to all participating Investigators as 
soon as possible, but in no case later than 15 calendar days after the Sponsor determines that the 
information qualifies for reporting according to FDA 21 CFR 321.32I(1)(i). For any unexpected 
fatal or life-threatening suspected adverse reactions, the Sponsor must also notify the FDA as 
soon as possible but in no case later than 7 calendar days after the Sponsor's initial receipt of the 
information according to FDA 21 CFR 321.32(c)(2).  
The Sponsor will notify the central IRB and advise all participating Study Sites to notify the 
local IRBs for the aforementioned IND safety report.  
In addition, the Sponsor will report the results of an evaluation of a UADE to the FDA and all 
reviewing IRBs and Investigators within 10 working days after the Sponsor first receives notice 
of the adverse effect according to FDA 21 CFR 812.150(b)(1).  
If the Sponsor determines that a UADE presents an unreasonable risk to subjects, the Sponsor 
will terminate all investigations or parts of investigations presenting that risk as soon as possible. 
Termination shall occur no later than 5 working days after the Sponsor makes this determination 
and no later than 15 working days after the Sponsor first received notice of the effect as defined 
in FDA 21 CFR 812.46(b)(2).  
 
19 Reporting and Publication of Results 
All unpublished information provided to the Investigators by the Sponsor shall not be published 
or disclosed to a third party without the prior written consent of the Sponsor.   
The publication of results in academic journals and any patent application(s) based on the results 
of the trial submitted by the Investigator will be guided by the Investigational Site Agreements 

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between the Sponsor and the Investigator.  
The Sponsor or its designee will prepare a Clinical Study Report that will comprehensively 
describe the trial findings. When the Sponsor generates reports from the data collected in this 
trial for presentation to regulatory authorities, drafts may be circulated to the Investigator for 
comments and suggestions.   
20 Literature Cited 
1. Diaz-Ledezma C, Higuera CA, Parvizi J. Success after treatment of periprosthetic joint 
infection: a Delphi-based international multidisciplinary consensus. Clin Orthop Relat 
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2. Parvizi J, Tan TL, Goswami K, Higuera C, Della Valle C, Chen AF, Shohat N. The 2018 
Definition of Periprosthetic Hip and Knee Infection: An Evidence-Based and Validated 
Criteria. J Arthroplasty. 2018;33(5):1309-1314.e2. doi: 10.1016/j.arth.2018.02.078.  
 
3. Tande AJ, Patel R. Prosthetic joint infection. Clin Microbiol Rev. 2014 Apr;27(2):302-
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4. Genetic and Rare Diseases Information Center. Prosthetic joint infection. Available from: 
https://rarediseases.info.nih.gov/diseases/11977/prosthetic-joint-infection [October 14, 
2020].  
 
5. Davidson DJ, Spratt D, Liddle AD. Implant materials and prosthetic joint infection: the 
battle with the biofilm. EFORT Open Rev. 2019;4(11):633-639. 
 
6. Arciola CR, Campoccia D, Montanaro L. Implant infections: adhesion, biofilm formation 
and immune evasion. Nat Rev Microbiol. 2018;16(7):397-409. 
 
7. Gbejuade HO, Lovering AM, Webb JC. The role of microbial biofilms in prosthetic joint 
infections. Acta Orthop. 2015;86(2):147-58. 
 
8. Cochran AR, Ong KL, Lau E, Mont MA, Malkani AL. Risk of Reinfection After 
Treatment of Infected Total Knee Arthroplasty. J Arthroplasty. 2016;31(9 Suppl):156-61. 
doi: 10.1016/j.arth.2016.03.028. 
 
9. Landersdorfer CB, Bulitta JB, Kinzig M, Holzgrabe U, Sörgel F. Penetration of 
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11. Laverty G, Alkawareek MY, Gilmore BF. The In Vitro Susceptibility of Biofilm Forming 
Medical Device Related Pathogens to Conventional Antibiotics. Dataset Papers in 
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15. Tunney MM, Ramage G, Patrick S, Nixon JR, Murphy PG, Gorman SP. Antimicrobial 
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10.1128/AAC.42.11.3002. 
 
16. Gomez MM, Tan TL, Manrique J, Deirmengian GK, Parvizi J. The Fate of Spacers in the 
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17. van Hal SJ, Paterson DL, Lodise TP. Systematic review and meta-analysis of 
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18. Andersson AE, Bergh I, Karlsson J, Nilsson K. Patients' experiences of acquiring a deep 
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19. Cancienne JM, Werner BC, Bolarinwa SA, Browne JA. Removal of an Infected Total 
Hip Arthroplasty: Risk Factors for Repeat Debridement, Long-term Spacer Retention, 
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20. Cancienne JM, Granadillo VA, Patel KJ, Werner BC, Browne JA. Risk Factors for 
Repeat Debridement, Spacer Retention, Amputation, Arthrodesis, and Mortality After 
Removal of an Infected Total Knee Arthroplasty with Spacer Placement. J Arthroplasty. 
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21. Zmistowski B, Karam JA, Durinka JB, Casper DS, Parvizi J. Periprosthetic joint 
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2013;95(24):2177-84. doi: 10.2106/JBJS.L.00789. 
 

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22. Akindolire J, Morcos MW, Marsh JD, Howard JL, Lanting BA, Vasarhelyi EM. The 
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23. Puhto T, Puhto AP, Vielma M, Syrjälä H. Infection triples the cost of a primary joint 
arthroplasty. Infect Dis (Lond). 2019;51(5):348-355. doi: 
10.1080/23744235.2019.1572219. 
 
24. Rennert-May ED, Conly J, Smith S, Puloski S, Henderson E, Au F, Manns B. The cost of 
managing complex surgical site infections following primary hip and knee arthroplasty: 
A population-based cohort study in Alberta, Canada. Infect Control Hosp Epidemiol. 
2018;39(10):1183-1188. doi: 10.1017/ice.2018.199. 
 
25. Vanhegan IS, Malik AK, Jayakumar P, Ul Islam S, Haddad FS. A financial analysis of 
revision hip arthroplasty: the economic burden in relation to the national tariff. J Bone 
Joint Surg Br. 2012;94(5):619-23. doi: 10.1302/0301-620X.94B5.27073. 
 
26. Peel TN, Dowsey MM, Buising KL, Liew D, Choong PF. Cost analysis of debridement 
and retention for management of prosthetic joint infection. Clin Microbiol Infect. 
2013;19(2):181-6. doi: 10.1111/j.1469-0691.2011.03758.x. 
 
27. Klouche S, Sariali E, Mamoudy P. Total hip arthroplasty revision due to infection: a cost 
analysis approach. Orthop Traumatol Surg Res. 2010;96(2):124-32. doi: 
10.1016/j.rcot.2010.02.005. 
 
28. International Organization for Standardization. ISO 7206-4:2010. Implants for surgery - 
Partial and total hip joint prostheses - Part 4: Determination of endurance properties and 
performance of stemmed femoral components. Geneva: ISO; 2010. 
 
29. International Organization for Standardization. ISO 7206-6:2013. Implants for surgery - 
Partial and total hip joint prostheses - Part 6: Endurance properties testing and 
performance requirements of neck region of stemmed femoral components. Geneva: ISO; 
2013. 
 
30. International Organization for Standardization. ISO 7206-13:2016. Implants for surgery - 
Partial and total hip joint prostheses - Part 13: Determination of resistance to torque of 
head fixation of stemmed femoral components. Geneva: ISO; 2016. 
 
31. International Organization for Standardization. ISO 7206-10:2018. Implants for surgery - 
Partial and total hip-joint prostheses - Part 10: Determination of resistance to static load 
of modular femoral heads. Geneva: ISO; 2018. 
 
32. ASTM International. ASTM F1264-16. Standard specification and test methods for 
intramedullary fixation devices. West Conshohocken, PA; 2016. 
 

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33. International Organization for Standardization. ISO 10555-1:2013. Intravascular 
catheters - Sterile and single-use catheters - Part 1: General requirements. Geneva: ISO; 
2013. 
 
34. International Organization for Standardization. ISO 11137-1:2006. Sterilization of health 
care products - Radiation - Part 1: Requirements for development, validation and routine 
control of a sterilization process for medical devices. Geneva: ISO; 2006. 
 
35. International Organization for Standardization. ISO 11607-1:2019. Packaging for 
terminally sterilized medical devices - Part 1: Requirements for materials, sterile barrier 
systems and packaging systems. Geneva: ISO; 2019. 
 
36. International Organization for Standardization. ISO 11607-2:2019. Packaging for 
terminally sterilized medical devices - Part 2: Validation requirements for forming, 
sealing and assembly processes. Geneva: ISO; 2019. 
 
37. U. S. Food and Drug Administration. Reprocessing Medical Devices in Health Care 
Settings: Validation Methods and Labeling; Guidance for Industry and Food and Drug 
Administration Staff. 2015. 
 
38. International Organization for Standardization. ISO 10993-1:2009. Biological Evaluation 
of Medical Devices - Part 1: Evaluation and testing within a risk management process. 
Geneva: ISO; 2009. 
 
39. International Organization for Standardization. ISO 10993-1:2018. Biological Evaluation 
of Medical Devices - Part 1: Evaluation and Testing Within a Risk Management Process. 
Geneva: ISO; 2018. 
 
40. International Organization for Standardization. ISO 10993-12:2012. Biological 
Evaluation of Medical Devices - Part 12: Sample Preparation and Reference Materials. 
Geneva: ISO; 2012. 
 
41. International Organization for Standardization. ISO 10993-18:2005. Biological 
evaluation of medical devices - Part 18: Chemical characterization of medical device 
materials within a risk management process. Geneva: ISO; 2005. 
 
42. International Organization for Standardization. ISO 10993-17:2009. Biological 
evaluation of medical devices. Establishment of allowable limits for leachable 
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Confidential 
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Protocol JPS-0301 
 
 
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