The VIBLOK SAfety and perFormancE Trial
Phase: NA
Conditions: HSV-2 Infection, Genital Herpes
Sponsor: CLJI Worldwide

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
1 of 49 
VIBLOK SAFE Trial Protocol  
 
 
 
 
CLINICAL PROTOCOL 
(Clinical Investigational Plan) 
Study Number: 2015-01 
Revision: Version 5.0 
Date: 01/MAY/2017 
 
Product name: 
VIBLOK 
 
Investigation Sponsor: 
CLJI WORLDWIDE 
1141 Kane Concourse, Suite 203 
Bay Harbor Islands, Florida 33154 
 
 
 
 
 
 
 
 
 
 
 
 
 
PROPRIETARY DATA: This document and the information contained herein may not be reproduced, 
used or disclosed without written permission from CLJI WORLDWIDE. 
CLJI Worldwide, CLJI Corporation, and VIBLOK™ are trademarks of CLJI Corporation. 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
2 of 49 
 
 
 
REVISION HISTORY 
Change # 
Version 
Change Description 
Date 
 ----- 
1.1 
Initial version 
29-Jun-2016 
1 
1.2 
Correction sample size estimates. 
Alignment swab instructions with materials. 
Clarification exploratory parameters. 
Added sentence on aim to enrol equal amount of 
men and women. 
18-Jul-2016 
2 
1.3 
Clarified project scope, improved swabbing 
instructions for men, aligned instructions with IFU. 
20-Jul-2016 
3 
2.0 
Rephrasing of study participant follow-up, sentence 
how to ensure equal enrolment of both sexes, and 
the exploratory objective with respect to HSV-2 and 
HSV-1 co-infection.  
22-Jul-2016 
4 
3.0 
Better alignment phrasing primary study endpoint 
throughout the protocol (28 days -> minimally 26 
days). 
Improved specification of secondary endpoints (HSV 
-> HSV-2 DNA). 
Removed exploratory objective on HSV-1 as 
chances for simultaneous shedding in the external 
genital area are minimal. 
Rephrased inclusion criterion #3, to ensure proper 
understanding on what antiviral therapy is meant. 
Added inclusion criterion on willingness to use 
contraceptive throughout the study, to prevent any 
pregnancy after screening. 
Removed HIV serology measurement at screening to 
avoid any unnecessary ethical dilemmas. 
Added follow-up call with study participants 2-5 days 
after visit 1, to ensure proper understanding and 
execution of study procedures. 
Changed instructions for the 2nd swab from 15-60 to 
5-60 minutes after applying the cream to better align 
with the intended use. 
Removed the redundant red circle indicating the 
swabbing area for men. 
Rephrased the section concerning the treatment in 
case of a recurrence, to clarify that participants will 
receive standard of care treatment via the usual 
health care channels.  
Changed instructions on storage of samples from in 
the refrigerator to at room temperature. 
08-Sep-2016 
5 
4.0 
Statistical sections concerning the primary and 
secondary endpoints have been improved upon EC 
(IRBN) questions. 
Risk evaluation concerning possible risks and 
mitigation associated with study procedures has 
been added upon EC questions. 
Additional instructions for study participants to wash 
hands (and to complete the diary) after taking the 
samples has been added. 
18-Oct-2016 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
3 of 49 
6 
4.1 
Typo statistical sections corrected 
24-oct-2016 
7 
4.2 
Adjustment VIBLOK package information (sachet 
instead of Easysnap). 
02-Jan-2017 
8 
4.3 
Adjustment VIBLOK package information (figure 1): 
change from 4.25 g to 5 ml due to different package. 
Changed wording in inclusion criteria from drug to 
device.  
Change address CLJI Worldwide. 
01-Mar-2017 
9 
4.4 
Added the study procedure external genital exam for 
unscheduled visit and added for women possible 
internal genital exam at V1, V2, V3 and unscheduled 
visit. 
Added sentence that pregnancy test and use of 
contraceptives is not applicable for women that are 
more than 1 year post-menopausal. 
30-Mar-2017 
10 
5.0 
Raised number to be enrolled from 48 to 84 due to 
high number of subjects enrolled turning out being 
HSV-2 negative. 
01-May-2017 
 
 
 
Signature 
Date 
Position 
Name 
 
 
 
Clinical Project Manager 
Dr Annet 
Muetstege 
Author 
 
 
RA/QA consultant 
Adi Berkovitch 
Reviewed 
 
 
MD 
Dr Craig Lichtblau 
Reviewed 
 
 
Clinical Virologist 
Prof. A. Wald 
Reviewed 
 
 
Statistician 
Joop Pfeil 
Reviewed 
 
 
President & CEO CLJI 
Ty Cross 
Approved 
 
 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
4 of 49 
 
Table of content 
Study Synopsis ........................................................................................................................ 7 
1.  
Introduction ................................................................................................................. 11 
1.1. 
Study Purpose ......................................................................................................... 11 
1.2. 
Clinical Background ................................................................................................. 11 
1.2.1. 
Disease Process ............................................................................................... 11 
1.2.2. 
Alternative Therapies/Techniques ..................................................................... 12 
2. 
Study Device ................................................................................................................... 12 
2.1. 
Device Description ................................................................................................... 12 
2.2. 
Prior Non-Clinical Testing ........................................................................................ 13 
2.3. 
Clinical History ......................................................................................................... 13 
3. 
Study Objectives ............................................................................................................. 13 
3.1. 
Primary Endpoint ..................................................................................................... 14 
3.2. 
Secondary Endpoints ............................................................................................... 14 
3.3. 
Exploratory Parameters ........................................................................................... 14 
4. 
Study Population ............................................................................................................. 14 
4.1. 
Inclusion Criteria ...................................................................................................... 14 
4.2. 
Exclusion Criteria ..................................................................................................... 15 
5. 
Investigational Plan ......................................................................................................... 15 
5.1. 
Study Design ........................................................................................................... 15 
5.2. 
Study Procedures .................................................................................................... 16 
5.2.1. 
Informed Consent ............................................................................................. 16 
5.2.2. 
Participant Screening - Visit 0-1 ........................................................................ 17 
5.2.3. 
Treatment start - Visit 1 ..................................................................................... 18 
5.2.4. 
Treatment - Follow-up call................................................................................. 18 
5.2.5. 
Treatment – Visits 2 and 3 ................................................................................ 18 
5.2.6. 
Genital herpes recurrence – Unscheduled visits ............................................... 19 
5.3. 
Follow-Up Visits ....................................................................................................... 19 
5.3.1. 
Missed Visits ..................................................................................................... 20 
5.3.2. 
Study Termination ............................................................................................. 21 
6. 
Study Material & Methods ............................................................................................... 21 
6.1. 
Study Device ............................................................................................................ 21 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
5 of 49 
6.2. 
Storage & Labeling .................................................................................................. 21 
6.3. 
Device Accountability ............................................................................................... 21 
7. 
Evaluation of Safety ........................................................................................................ 22 
7.1. 
Definitions ................................................................................................................ 22 
7.2. 
Adverse Event Assessments ................................................................................... 22 
7.3. 
Device Deficiency .................................................................................................... 23 
7.4. 
Adverse Event Reporting ......................................................................................... 23 
8. 
Risk Evaluation ............................................................................................................... 24 
8.1. 
Potential Risks to Study Participants ........................................................................ 24 
8.1.1. 
Risks/ Adverse Events associated with the disease state ................................. 24 
8.1.2. 
Risks/ Adverse Events associated with VIBLOK cream .................................... 24 
8.1.3. 
Risks associated with study procedures ............................................................ 25 
8.2. 
Methods to Minimize Risk ........................................................................................ 25 
8.3. 
Benefits .................................................................................................................... 26 
8.4. 
Risk-Benefit Analysis ............................................................................................... 26 
8.5. 
Definitions ................................................................................................................ 26 
9. 
Statistical Considerations ................................................................................................ 28 
9.1. 
Sample Size Determination ...................................................................................... 28 
9.2. 
Timing ...................................................................................................................... 28 
9.3. 
Analysis Sets ........................................................................................................... 28 
9.4. 
Missing Data ............................................................................................................ 29 
9.5. 
Endpoints ................................................................................................................. 29 
9.5.1. Primary Endpoint ..................................................................................................... 29 
9.5.2. Secondary Endpoints ............................................................................................... 29 
9.5.3. Exploratory Endpoints .............................................................................................. 29 
9.6. 
Endpoint Analysis .................................................................................................... 30 
10. 
Study Administration.................................................................................................... 30 
10.1. General Study Organization ..................................................................................... 30 
10.2. Steering Committee ................................................................................................. 30 
10.3. Data Monitoring Committee ..................................................................................... 30 
10.4. Core Laboratories .................................................................................................... 31 
10.5. Clinical Sites ............................................................................................................ 31 
10.6. Site Training............................................................................................................. 31 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
6 of 49 
10.7. Study Monitoring ...................................................................................................... 31 
10.8. Data Management ................................................................................................... 33 
10.9. Publication Policy ..................................................................................................... 33 
11. 
Ethical & Regulatory Considerations ........................................................................... 33 
11.1. Ethics Committee Approval ...................................................................................... 34 
11.2. Informed Consent .................................................................................................... 34 
11.3. Confidentiality .......................................................................................................... 34 
11.4. Records and Reports ............................................................................................... 34 
11.4.1. 
Records ......................................................................................................... 34 
11.4.2. 
Reports ......................................................................................................... 35 
11.5. Protocol Deviations .................................................................................................. 35 
11.6. Protocol Amendments .............................................................................................. 36 
11.7. Record Retention Policy........................................................................................... 36 
12. 
References .................................................................................................................. 36 
Appendix 1: English master Informed Consent....................................................................... 38 
Appendix 2: Daily Home PCR Instructions for Women ........................................................... 39 
Appendix 3: Daily Home PCR Instructions for Men ................................................................ 42 
Appendix 4. Participant Diary ................................................................................................. 46 
Appendix 5. Participant questionnaire .................................................................................... 49 
 
 
 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
7 of 49 
 
Study Synopsis 
Title 
CLJI VIBLOK SAfety and perFormancE Trial (SAFE Trial) 
Background 
Genital herpes has a high prevalence in industrialized as well as developing 
countries. 
Genital herpes causes genital ulcers, increases risk for acquiring HIV 
infection, and may be transmitted mother to child during birth with possible 
serious consequences. 
Medical treatments and condoms only partially reduce the risk for 
transmission from/ to sexual partners. Genital herpes transmission despite 
use of condoms is thought to be due to transfer via skin-to-skin contact in 
unprotected areas, and HSV-2 transmission may be enhanced by current 
shaving habits in the genital area leading to micro lesions (lacerations) of 
the skin. 
VIBLOK™ is a cream designed to impede the passage of viruses, such as 
HSV-2, across the skin. Bench and animal experiments indicate that it can 
block virus transmission (HIV, HPV, HSV) up to 98%.  
The objective of this clinical trial is to assess the safety and performance of 
VIBLOK in adults with HSV-2 infection by comparing virus detection in the 
extra-genital area before and after application of the barrier cream.  
Primary 
objective 
To assess safety of VIBLOK in HSV-2 infected adults. 
Secondary 
objective 
To evaluate the performance of VIBLOK as a barrier for virus transmission 
in men and women. 
Study design 
The VIBLOK SAfety and perFormancE Trial is a prospective, non-
randomized, comparative multi-center safety and performance study. Up to 
84 adults with a suspected HSV-2 infection are planned to be enrolled at up 
to 6 participating investigational centers in The Netherlands and Germany. 
Participants with a confirmed HSV-2 infection are planned to be followed for 
26-31 days, using VIBLOK for minimally 26 days in a row. Safety will be 
assessed by collecting all adverse events, and HSV will be measured from 
daily self-collected external genital swabs before and after application of 
VIBLOK. 
Study device 
VIBLOK cream 
Study scope 
Minimally 1 and maximally 6 sites in The Netherlands and Germany are 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
8 of 49 
planned to participate in this study. 
Study duration 
The study is anticipated to last 12 months from first-subject-in to last-
subject-out. Study participants are planned to be followed for 26 to 31 days. 
Study 
Population 
Adults with recurrent genital HSV-2 infections that meet all the inclusion 
and none of the exclusion criteria. 
Number 
of 
subjects 
Up to 84 men and women are to be enrolled, ensuring 46 participants with 
confirmed eligibility applying VIBLOK.  
Inclusion 
Criteria 
1. 
Participant is male or female and at least 18 years of age 
2. 
HSV-2 seropositive by the UW Western blot or Alegria assay  
3. 
History of recurrent genital herpes with at least 3 recurrences in the 
last year or, if currently on suppressive/ prophylactic therapy, prior to 
starting the therapy (antiviral therapy has to be stopped at least 7 
days prior to initiation of the trial product).    
4. 
General good health at the discretion of the investigator. 
5. 
Willing to not use any topical genital therapy aside from the study 
device for the duration of the trial. 
6. 
Willing to not use any systemic anti HSV therapy during the entire 
study starting 7 days prior to baseline. 
7. 
Willing to obtain 2 swabs from external-genital areas once daily for 
the duration of the trial. 
8. 
Willing to keep a daily trial diary during the treatment period. 
9. 
Negative pregnancy test for women at screening. 
10. Willing to use contraceptives for the duration of the study. 
11. Subject must be willing and able (in the opinion of the investigator) to 
understand the patient information and informed consent form and to 
comply with the clinical trial protocol and procedures. 
12. Subject must be willing to give written informed consent. 
Exclusion 
Criteria 
1. 
Serious medical conditions, such as diabetes, significant autoimmune 
disease, cancer or immunosuppression, etc. that at the discretion of 
the investigator will likely affect study outcomes 
2. 
Treatment with systemic steroids or other immune-modulating agents 
3. 
Participation in any investigational drug or device trial within 30 days 
prior to screening. 
4. 
Pregnancy or breastfeeding, in case of women. 
5. 
Any other conditions that in the judgment of the investigator would 
preclude successful completion of the clinical trial. 
Primary 
Endpoint 
Serious Adverse Device Effect incidence during the period using VIBLOK 
cream.  
Secondary 
• 
Comparison of HSV-2 DNA detection rate on days with asymptomatic 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
9 of 49 
Endpoints
shedding prior and after applying VIBLOK 
• 
Comparison of HSV-2 DNA copy number on days with asymptomatic 
shedding prior and after applying VIBLOK 
• 
Safety (Nature, frequency, duration, severity, seriousness and causality 
of adverse events) 
Exploratory 
Parameters 
• 
Sub-analyses to explore relation of device performance to 
o Gender 
o Time between VIBLOK application and sampling 
o Shaving and waxing habits 
o HSV symptoms 
 
• 
Participant satisfaction using VIBLOK as assessed on the participant 
questionnaire 
Assessments 
Treatment Period 
Activity 
Screening 
Visit 1 
FUP call 
Visit 2 
Visit 3 
Informed Consent 
X 
  
  
  
  
Review 
Inclusion/Exclusion 
Criteria 
X 
  
  
  
  
Medical 
History 
(including HSV history) 
X 
  
  
  
  
Interim 
History 
(including HSV history) 
  
X 
  
X 
X 
Targeted 
Physical 
Exam 
(including 
external genital exam) 
X 
X* 
  
X* 
X* 
HSV serology  
X 
  
  
  
  
Urine pregnancy test 
X 
  
  
  
  
Provide Study Device 
and/or training 
  
X 
X 
X 
  
Review 
device 
use 
adherence 
  
  
  
X 
X 
AE assessment 
  
 
User Questionnaire 
  
  
  
  
X 
Daily Swab Collection 
& Diary  
  
 
* for women possibly including internal genital exam if symptomatic 
Subject visits 
Visit
Exams
Visit window
0 
Screening 
Subject information and consent 
1 
Day 1 
<21 days after ICF sign off 
N/A 
Day 3 
2-5 days following visit 1 
2 
Day 14 
12-16 days following Visit 1 
3 
Day 28 
26-31 days following Visit 1 
 
 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
10 of 49 
Statistical 
analyses 
With a sample size of 36, an exact two-sided 95.0% confidence interval for 
a single proportion will show that the SADE incidence is below 10% at an 
expected incidence of 0.1%. Taking into account a drop-out rate of 15%, 
the estimated sample size needed is 42 study participants applying the 
VIBLOK cream. 
 
Comparing HSV-2 detection within participants before and after applying 
VIBLOK using Wilcoxon signed rank testing, with an 8% anticipated 
asymptomatic shedding rate, 80% power and type I error of 5%, 40 
participants are needed to show a 50% reduction post-intervention 
(VIBLOK). 
Taking into account a drop-out rate of 15%, up to 46 adults applying 
VIBLOK cream are needed. 
 
Taking into account a screenfailure rate of 45% due to absence of an HSV-
2 infection, up to 84 subjects will need to be enrolled. 
Study Steering 
Committee 
members 
Prof. C. Boucher, Prof. A. Wald, Dr A. Wensing, Dr A. Muetstege, and Dr C. 
Lichtblau. 
Coordinating 
Investigator 
Dr V. van de Walle, MD, PhD, CPI.  
PT&R, Elsstraat 47, 6191 JW Beek  
The Netherlands 
Study Sponsor 
CLJI Worldwide, 1141 Kane Concourse, Suite 203, Bay Harbor Islands, 
Florida 33154 
 
 
 
 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
11 of 49 
 
1.  
Introduction 
1.1. 
Study Purpose 
The purpose of this trial is to assess the safety and performance of the CLJI VIBLOK cream in 
HSV-2 infected adults. Clinical safety and performance data will be submitted for the purposes 
of obtaining CE marking approval. Following CE mark approval, the subsequent clinical follow-
up will continue to fulfill the post-market safety and surveillance reporting commitments.  
 
1.2. 
Clinical Background 
Sexually transmitted viral infections (viral STIs) have a high prevalence in industrialized as 
well as developing countries. They are associated with substantial morbidity and mortality, as 
well as a high risk for transmission from mother to child during birth. Genital lesions due to 
herpes are often painful, and can lead to substantial psychological morbidity [1]. The virus can 
also be passed from mother to child during birth, and neonatal infection can be very serious 
[2]. Without treatment, 80% of infants with disseminated disease die, and those who do 
survive are often brain damaged [3].  
In addition, genital herpes is associated with an increased risk of HIV acquisition by two- to 
threefold, HIV transmission on a per-sexual act basis by up to fivefold, and may account for 
40–60% of new HIV infections in high HSV-2 prevalence populations [4–9]. Indeed, the impact 
of suppressing HSV-2 shedding and associated disease on the rate of HIV acquisition has 
been tested in clinical trials using suppressive antiviral therapy, with disappointing results [10]. 
The most common STI encountered in practice are herpes simplex virus (HSV), type 1 and 2. 
Despite increased strategies to enhance patient awareness regarding safer sex practices and 
the liberal prescription of various antiviral medications like valacyclovir and acyclovir, the 
incidence of HSV infections has not decreased significantly in the last 2 decades. 
Virologists have long known that the HSV may well gain entrance to the host by fissures and 
lacerations in the skin [11]. These lesions oftentimes are imperceptible to the host. The 
defects in the intact skin may be produced during common grooming practices or, as a result 
of friction during sexual intercourse. Condoms have been shown to reduce the risk of 
transmitting HSV; however, significant transmission occurs from skin to skin contact not 
shielded by the condom [12]. 
 
1.2.1. Disease Process 
HSV-2 infection is acquired through direct contact with an active lesion or body fluid of an 
infected person principally through sexual activity. Herpes transmission occurs between 
discordant partners; a person with a history of infection (HSV seropositive) transmits the virus 
to an HSV seronegative person, the virus travels retrograde in the sensory nerves to establish 
a latent infection primarily in the sacral ganglia. Data suggest that the virus may reach ganglia 
far removed from the site of primary infection. The molecular mechanisms underlying HSV 
latency are incompletely understood [13]. 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
12 of 49 
1.2.2. Alternative Therapies/Techniques 
No method eradicates the herpes virus from the body, and disease management focusses on 
symptom relief, healing of the lesions, reducing recurrent episodes, and reducing viral 
transmission. Episodic treatment with antiviral medications, such as valacyclovir and acyclovir, 
has shown to reduce the duration, and severity of outbreaks. Acyclovir and valacyclovir 
therapy has shown to reduce the duration of viral shedding, and time to healing of the lesions 
with days [4, 14-15]. 
Treatment of HSV is complicated by the fact that many people infected by HSV may not be 
aware they are shedding: Asymptomatic viral shedding rates have been reported to occur on 
up to 25% of days in HSV-2 seropositive patients [16]. Antiviral medication also reduces the 
frequency of asymptomatic shedding of HSV in the genital tract when used as suppressive 
therapy up to 80% [17-18]. 
Several clinical trials have tested vaccines against genital herpes infection, but there is 
currently no commercially available vaccine that is protective against genital herpes infection.  
Condom use also reduces the transmission risk significantly; Condom users are reported to 
have a 30% lower risk of HSV-2 acquisition compared to those who never used condoms. 
That being far less when compared to the HIV acquisition rate, is explained by the fact that 
HSV-2 is primarily transmitted through direct skin-to-skin or skin-to-mucosa contact, and HSV-
2 transmission can occur when viral shedding is present in areas not covered by the condom 
[12, 19]. A recent study in discordant couples where condom efficacy was measured on a per 
act basis indicates there is a sex differential protective effect: risk of transmission from men to 
women can be reduced as high as 96% with condom use, but only to 65% from women to 
men [20].  
The above clinical data indicate that the VIBLOK cream can be a valuable addition to the 
current treatment and preventative strategies. 
 
2. 
Study Device 
VIBLOK is an over-the-counter, non-sterile, single use medical device which is designed to 
impede the passage of viruses across the skin, such as HSV (herpes simplex virus), by 
creating a mechanical barrier on the skin. This barrier is achieved as a result of a compound 
cream which covers the desired area that is to be protected.  
 
2.1. 
Device Description 
VIBLOK is a medical device, applied on the external genital, pubic, and perianal areas of men 
and women prior to sexual activity in order to cover minor cuts, scrapes and irritations of the 
skin including the ones associated with grooming of these areas, and to help protect against 
STIs caused by viruses such as Herpes Simplex. The main ingredients of the cream are a 
water repelling, high weight, silicone and a water repelling surface treated zinc oxide, similar 
to the zinc oxide used in diaper rash creams. 
 
 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
13 of 49 
 
 
Figure 1 – VIBLOK cream package 
 
The VIBLOK cream is supplied for single-use only, and is packaged in a sachet (Figure 1). 
The VIBLOK cream is intended to be applied before sexual activity to all external genital, 
pubic, and perianal areas – with or without hair -, hereinafter referred to as “skin”, that will 
come in contact with the partner. 
The CLJI VIBLOK cream shall be used per the Instructions for Use (IFU) and after training has 
been achieved as determined by the study sponsor. Further description of the VIBLOK cream 
is provided in the IFU and the Investigator’s Brochure (IB). 
 
2.2. Prior Non-Clinical Testing 
Results of the in vitro and in vivo animal testing support the safety and performance of the 
VIBLOK cream. Further details are provided in the IB. 
 
2.3. Clinical History 
The VIBLOK cream has been evaluated for its irritation/ sensitization potential in human 
subjects with 53 enrollments. The study provides data on 10 consecutive 24 hours product 
exposures in 3 consecutive weeks, followed by another 48 hours exposure on a previously 
unexposed test site in 50 subjects. No adverse reactions of any kind were noted during the 
course of the study. 
 
3. 
Study Objectives 
The objective of the study is to assess the safety and performance of the VIBLOK cream in 
HSV-2 infected adults. It is expected that data from this study will support an application for 
the CE Mark. 
 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
14 of 49 
3.1. Primary Endpoint 
The primary safety endpoint will be number of Serious Adverse Device Effects during 
minimally 26 days of VIBLOK use.  
 
3.2. Secondary Endpoints 
Device performance: 
• 
Comparison of HSV-2 DNA detection rate on days with asymptomatic shedding prior 
and after applying VIBLOK 
• 
Comparison of HSV-2 DNA copy number on days with asymptomatic shedding prior 
and after applying VIBLOK 
 
Safety endpoints:  
• 
Total number, type, and duration of AEs after 24 days of VIBLOK use. 
 
3.3. Exploratory Parameters 
• 
Sub-analyses to explore relation of device performance to 
o Gender 
o Time between VIBLOK application and sampling 
o Shaving and waxing habits 
o HSV symptoms 
• 
Participant satisfaction using VIBLOK as assessed on the participant questionnaire 
(appendix 5). 
 
4. 
Study Population 
Participants will be screened and selected from men and women with a (suspected) HSV-2 
infection. 
For the sake of the sub-analysis on a possible relation of device performance to gender, an 
effort will be made to enroll an equal amount of men and women. Therefore enrolment will be 
tracked to ensure enrolment of a minimum of 16 participants of the less represented sex. 
 
4.1. Inclusion Criteria  
Candidates for this study must meet all of the following inclusion criteria:  
1. Participant is male or female and at least 18 years of age 
2. HSV-2 seropositive by the UW Western blot or Alegria assay  
3. History of recurrent genital herpes with at least 3 recurrences in the last year or, if currently 
on suppressive/ prophylactic therapy, prior to starting the therapy (antiviral therapy has to 
be stopped at least 7 days prior to initiation of the trial product).    

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
15 of 49 
4. General good health at the discretion of the investigator. 
5. Willing to not use any topical genital therapy aside from the study device for the duration of 
the trial. 
6. Willing to not use any systemic anti HSV therapy during the entire study starting 7 days 
prior to baseline. 
7. Willing to obtain 2 swabs from external-genital areas once daily for the duration of the trial. 
8. Willing to keep a daily trial diary during the treatment period. 
9. Negative pregnancy test for women at screening. 
10. Willing to use contraceptives for the duration of the study. 
11. Subject must be willing and able (in the opinion of the investigator) to understand the 
patient information and informed consent form and to comply with the clinical trial protocol 
and procedures. 
12. Subject must be willing to give written informed consent. 
 
4.2. Exclusion Criteria 
Candidates for the study will be excluded if any of the following conditions are present: 
1. Serious medical conditions, such as diabetes, significant autoimmune disease, cancer or 
immunosuppression, etc. that at the discretion of the investigator will likely affect study 
outcomes 
2. Treatment with systemic steroids or other immune-modulating agents 
3. Participation in any investigational drug or device trial within 30 days prior to screening 
4. Pregnancy or breastfeeding, in case of women 
5. Any other conditions that in the judgment of the investigator would preclude successful 
completion of the clinical trial. 
 
5. 
Investigational Plan 
5.1. Study Design 
This is a prospective, non-randomized, comparative multi-center safety and performance trial. 
Up to 84 participants are planned to be enrolled at up to 6 participating investigational centers 
in Europe. The enrollment period is expected to be approximately 11 months and participant 
follow-up for subjects with a confirmed HSV-2 infection will last for 26 to 31 days. Participants 
will be assessed at the following intervals: at screening, during the first application, and 
approximately 14 and 28 days after first application.  
Fourty six adults with recurrent genital herpes due to HSV-2 will be instructed to apply daily 
VIBLOK. Participants will obtain external genital skin swabs once daily, before and 5-60 
minutes after applying the cream in the external genital area, and maintain a diary of genital 
signs and symptoms (Figure 3 and 4, Appendices 2, 3, and 4). 
 
 
 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
16 of 49 
 
 
 
 
Figure 3: Female genitals with the VIBLOK application area (grey) 
 
 
 
 
Figure 4: Male genitals with the VIBLOK application area (grey) 
 
 
5.2. Study Procedures 
5.2.1. Informed Consent  
The study investigator(s) and support staff will approach adults with (suspected) HSV-2 
infection to assess their interest in participating in the study. If the potential participant is 
interested, they will be provided with the informed consent and the study background, 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
17 of 49 
benefits, risks and study procedures will be explained. If the potential participant is 
comfortable with proceeding, then they will be asked to sign the approved informed consent, 
and subject screening will commence. Informed consent must be obtained prior to any 
screening procedures or tests that are specific to this study. 
If new information becomes available that can significantly affect a participant’s future health 
and medical care, then that information will be provided to the participants in written form.  
5.2.2. Participant Screening - Visit 0-1 
The screening of potential participants will be conducted by one or more study team members. 
The site research team will be responsible for ensuring and reporting screening of men and 
women for study eligibility. Cumulative screening and enrollment logs will be maintained by 
research sites. Reasons for screen failures will be documented in study logs. 
All anti-viral therapies shall be stopped minimally 7 days prior to Visit 1. 
Women that are more than 1 year post-menopausal will be considered as having no child 
bearing potential, and the pregnancy test and use of contraceptives is not applicable for them. 
Table 2 lists the schedule of events for participants from the initial screening and baseline 
measures through their bi-weekly follow-up visits. These measures are more fully described in 
the subsequent sections.  
Table 2. Schedule of Events 
Treatment Period 
Activity 
Screening 
Visit 1 
FUP call 
Visit 2 
Visit 3 
Informed Consent 
X 
  
  
  
  
Review Inclusion/Exclusion Criteria 
X 
  
  
  
  
Medical History (including HSV history) 
X 
  
  
  
  
Interim History (including HSV history) 
  
X 
  
X 
X 
Targeted 
Physical 
Exam
(including
external genital exam) 
X 
X* 
  
X* 
X* 
HSV serology  
X 
  
  
  
  
Urine pregnancy test 
X 
  
  
  
  
Provide Study Device and/or training 
  
X 
X 
X 
  
Review device use adherence 
  
  
  
X 
X 
AE assessment 
  
 
User Questionnaire 
  
  
  
  
X 
Daily Swab Collection & Diary  
  
 
* for women possibly including internal genital exam if symptomatic 
 
The following screening data will be collected for all study subjects prior to enrollment to 
assess possible eligibility: 
• 
Medical history, standard of care physical examination, including external genital exam 
 
A subject will be considered as “enrolled”, once (s)he has signed the Informed Consent. Study 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
18 of 49 
specific data will not be collected for subjects who fail any of the eligibility criteria and do not 
apply the study product; these subjects will be recorded on a Screening Log where the reason 
for screening failure will be documented. 
 
5.2.3. Treatment start - Visit 1 
Once participant’s eligibility is confirmed, i.e. HSV-2 serology is positive, select assessments 
and laboratory tests will be done prior to document baseline status. These include: 
• 
Physical examination, including a genital examination that for women may include an 
internal genital examination if symptomatic; 
• 
(Interim) medical history; 
• 
Urine pregnancy test; 
• 
Adverse Events assessment 
 
After the examination, the participant will receive instructions by the site research staff as to 
how to take swabs and to apply VIBLOK, watch the instruction video, and subsequently takes 
the first swab, applies VIBLOK, and takes a second swab 5-60 minutes after applying VIBLOK 
while at the research site. These procedures will be monitored by one person from the site 
research staff to ascertain that the cream was applied correctly and that the swabs were 
obtained in the right way. Participants will also be instructed in how to label the swabs and 
vials. Once the swabbing procedures are correctly done, the participant will be provided the 
following: 
• 
The study device along with instructions for use; 
• 
The swabbing kits along with instructions for use; 
• 
Diary. 
 
Participants with a negative HSV-2 serolgy will be considered screen failures and exit the 
study. 
 
5.2.4. Treatment - Follow-up call 
Two-five days after visit 1, participants will receive a follow-up call by some-one from the site 
research staff to verify that participants have a full understanding and no remaining questions 
concerning the study procedures, specifically with respect to: 
• 
Swabbing procedures 
• 
Application of the VIBLOK cream 
• 
Completion of the diary 
In addition, any AEs will be recorded. 
 
5.2.5. Treatment – Visits 2 and 3 
During the treatment periods, participants should: 
• 
Complete their diary daily; 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
19 of 49 
• 
Take swabs daily, before and 5-60 minutes after applying the cream on the external 
genitals according to the instructions; 
• 
Visit the clinical trial site every other week 
 
Clinical trial site visits will occur approximately 14 and 28 days after Visit 1. 
During the clinic visits the following examinations/ evaluations and procedures will be done by 
site research staff: 
• 
Adverse Events review; 
• 
Targeted physical examination, including a genital examination that for women may 
include an internal genital examination if symptomatic; 
• 
(Interim) medical history; 
• 
Review and collection of subject’s diary; 
• 
Collection of subject swabs; 
• 
Device accountability; 
 
New trial devices and diary will be provided during Visit 2. 
 
During Visit 3, subjects will be asked to complete a questionnaire regarding the usability of the 
cream (refer to Appendix 5). 
 
5.2.6. Genital herpes recurrence – Unscheduled visits 
If a lesion develops that is consistent with genital herpes, swabs should be obtained from the 
lesion. Participants who have such a recurrence (i.e., papules, vesicles or pustules, ulcers,or 
crusts) during the treatment period are requested to contact and return to the clinic for an 
examination as soon as possible. That examination includes a genital examination, and for 
women may include an internal genital examination. 
In case of a recurrence, participants will be instructed to apply their usual treatment or refer to 
their treating physician whichever is applicable, in order to receive treatment per standard 
practice. If the subject is successfully treated within 21 days, and meets the inclusion criteria 
and none of the exclusion criteria, subject may re-enter the study. The concerning follow-up 
period is prolonged with the number of days the treatment required. These visits shall be 
recorded as an unscheduled visit. 
In case of a second recurrence, the subject shall exit the study. 
 
5.3. Follow-Up Visits 
 
Visit
Exams
Visit window
0 
Screening 
Subject information and consent 
1 
Day 1 
<21 days after ICF sign off 
N/A 
Day 3 
2-5 days following visit 1 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
20 of 49 
2 
Day 14 
12-16 days following Visit 1 
3 
Day 28 
26-31 days following Visit 1 
 
Upon Visit 1 and at each follow-up assessment, study staff will confirm the participant's 
availability for future follow-up and an appointment for the follow-up call will be made. 
Planned absences from the area should be recorded to facilitate continued ability to contact a 
study participant. If a participant cannot be reached for a follow-up visit, the investigator will 
document on the follow-up data form, the efforts undertaken to contact the participant, 
referring physicians, family members, or other alternate contacts noted in the study 
participant’s records. These efforts should include 3 attempts of telephone contacts at 
separate dates and times, and a registered letter. 
If the participant cannot be reached in any way for their follow-up visits and misses the 
scheduled visit, new efforts will be undertaken to locate them at subsequent follow-up visits for 
safety purposes. 
 
5.3.1. Missed Visits 
Participants who miss a follow-up visit will not be considered to be withdrawn from the trial and 
contact with the participant should continue to be established for the follow-up examinations if 
applicable. Every participant that started applying VIBLOK, should be encouraged to remain in 
the study until they have completed the protocol-required follow-up period. If the participant 
discontinues prematurely from the study, the reason for discontinuation must be documented 
on the appropriate case report form (CRF). Possible reasons for premature discontinuation 
may include, but are not limited to the following: 
• 
Withdrawal of consent: Participant decides to withdraw from the study. If a participant 
withdraws from the clinical investigation, the reason(s) should be recorded. If such 
withdrawal is due to problems related to the investigational device safety, the investigator 
shall ask for the participant’s permission to follow his/her status/condition outside the 
investigation. 
• 
Lost to follow-up – All participants should be encouraged to return to the clinic for 
evaluation during follow-up. If a participant is unable to return to the clinic, 3 separate 
telephone calls (or emails) should be made to attempt to bring the participant back into the 
clinic or obtain safety information. All attempts should be documented in the source 
documents. If the participant does not respond to the 3 telephone calls then the 
Investigator should send a certified letter to the participant. If applicable, a new round of 
attempts to contact the participant for return to the clinic for evaluation should be made 
when the subsequent visit is due. 
Patients who discontinue prematurely will be included in the analysis of results, and will not be 
replaced. 
 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
21 of 49 
5.3.2. Study Termination 
The Data Monitoring Board and Sponsor have the right to discontinue a site or terminate the 
trial for the following reasons: 
• 
The DMB and Sponsor may terminate the study for safety reasons 
• 
A decision on the part of the Sponsor to suspend or discontinue testing, evaluation, or 
development of the product for any reason 
• 
The Sponsor may decide to close a study site when the Investigator fails to enroll patients 
into the study at an acceptable rate 
• 
Failure of the Investigator to comply with pertinent regulations of appropriate regulatory 
authorities 
• 
Insufficient adherence to protocol requirements  
• 
Submission of knowingly false information from the research facility to the Sponsor, Study 
Monitor, or appropriate regulatory authority 
If the study is terminated early, all specified follow-up data on participants enrolled prior to 
termination will be collected and reported. 
  
6. 
Study Material & Methods 
6.1. Study Device 
Investigational devices will be supplied to the research site by DelaRange on behalf of CLJI. 
The trial devices will be labeled as Investigational Use Only (specific language will vary based 
on geography). Each device will have a unique product identifier, and this information will be 
included both in the participant’s medical file as well as given to them after the procedure. The 
Instructions for Use for the VIBLOK cream are provided.  
6.2. Storage & Labeling 
The VIBLOK cream is to be stored as specified on the unit labels, and in a secure location 
where only study personnel can access the device for use. The VIBLOK cream will be 
appropriately labeled to identify their investigational nature. 
6.3. Device Accountability  
The Investigator shall maintain records of the receipt and disposition of the investigational 
device. A device disposition log supplied by CLJI to the research site will be used to record 
devices received from DelaRange, participant hand-out, use, and discards, and devices 
returned to DelaRange. The participants should return all devices, including emptied packages 
to research site, and the Investigator shall return to CLJI used and unused devices/ packages, 
along with the completed device disposition log at completion of the investigation. Use of the 
VIBLOK cream is prohibited outside of this protocol. 
Device disposition will be verified by the clinical monitor periodically throughout the study.   
 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
22 of 49 
7. 
Evaluation of Safety 
7.1. Definitions 
An Adverse Event (AE) is any 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.  
A Serious Adverse Event (SAE) is any adverse event that: 
a) leads to death  
b) leads to a serious deterioration in the health of the subject that 
1. results in a life-threatening illness or injury 
2. results in a permanent impairment of a body structure or a body function 
3. requires in-patient hospitalization or prolongation of existing hospitalization 
4. results in medical or surgical intervention to prevent permanent impairment to a 
body structure or a body function 
c) leads to fetal distress, fetal death, congenital abnormality or birth defect  
Adverse Device Effects and Serious Adverse Device Effects are those AEs and SAEs 
that occur as an untoward or unintended response to a medical device. These events 
include those which result from insufficiencies or inadequacies in the Instructions for 
Use or deployment of the device as well as user error. 
Unanticipated Serious Adverse Device Effect (USADE) is defined as any serious 
adverse effect on health or safety or any life-threatening problem or death caused by – 
or associated with – the device, if that effect, problem or death was not previously 
identified in nature, severity, or degree of incidence in the investigational plan (including 
documents such as the protocol, Investigator’s Brochure, informed consent form or other 
study-related documents), or any other unanticipated serious problem associated with 
the device that relates to the rights, safety or welfare of subjects.  
Adverse events may be volunteered by participants, elicited from questioning by Investigator 
or designee, or collected via observation by the Investigator. In addition, participants will be 
instructed to contact the investigator, and/or study coordinator if any significant adverse 
events occur between study evaluation visits. 
7.2. Adverse Event Assessments 
The Investigator will determine whether or not the event is related to the device and/or 
procedure, and whether or not the event meets serious criteria. Pre-existing medical 
conditions or symptoms reported prior to the participant’s enrollment will not be recorded as 
an AE. In the event there is a worsening in the pre-existing medical condition or symptoms 
then an AE must be recorded. 
If it is determined that an AE has occurred, the investigator should obtain all the information 
required to complete the study AE Form The causal relation of the event to either the 
investigational device or to the procedure will be categorized by the Investigator as follows: 
None – AE is not associated with the investigational device or procedure. 
Remote – AE had minimal or no temporal relationship to the use of the investigational 
device and/or a more likely alternative etiology exists. 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
23 of 49 
Possible – AE had a strong temporal relationship to the use of the investigational 
device or procedure and there is no contradicting evidence that can reasonably explain 
the subject’s condition. 
Probable or Definite – AE had a strong temporal relationship to the use of the 
investigational device or procedure and another etiology is highly unlikely. 
All AEs will be reviewed by the Study Safety Officer. The AE will be assessed as to its 
seriousness and relationship to the device, the procedure, and whether it was anticipated or 
not anticipated.  
7.3. Device Deficiency 
Device deficiency is an inadequacy of a medical device with respect to its integrity, quality, 
durability, reliability, safety or performance. It includes malfunctions, user errors and 
inadequate labeling. 
Device deficiencies that did not lead to an adverse event but could have led to a medical 
occurrence: 
a) If either suitable action had not been taken, 
b) If intervention had not been made, or 
c) If circumstances had been less fortunate. 
Reporting conventions for device deficiencies that could result in an SAE are the same as 
those for an actual SAE. 
7.4. Adverse Event Reporting 
AEs are reported beginning from enrollment until participant participation has ended (i.e. 
completion of study or withdrawal of consent). Adverse events must be followed until 
resolution, AE has stabilized, or the study has been completed. 
All Serious Adverse Events (SAE) must be reported to CLJI Worldwide within 24 hours of the 
Investigator becoming aware of the event or according to local regulations (whatever is more 
stringent). Information may be entered into the electronic adverse event form or reported 
directly to the Safety Officer of CEpartner4U: 
Ton Pennings 
Phone: +31 (0) 343 444 875 
Cell: +31 (0) 6 516 536 26 
Fax: +31 (0) 343 442 162 
e-mail: t.pennings@cepartner4u.com 
 
At the time of initial notification, the following minimal information must be provided: 
• 
Identifiable participant: participant number 
• 
Identifiable reporter: study site 
• 
Adverse event description 
• 
Causal relationship to device and procedure 
• 
Awareness date 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
24 of 49 
The site will provide to CLJI Worldwide (or designee) a copy of anonymized supporting 
documentation (such as hospital record, laboratory results, autopsy results) of all SAEs. 
SAEs will be reported to the ethics committee (EC) and regulatory authorities as required by 
national regulations or by the EC itself. 
All SADEs must be reported to CLJI Worldwide within 24 hours of the Investigator becoming 
aware of the event or according to local regulations (whatever is more stringent). The AE 
Forms of the CRF must be completed with 5 working days for all SADEs. The Investigator is 
also responsible for notifying his/her EC of all SADEs occurring at his/her site (and any 
additional information as required by EC or local regulations). All SADEs must be followed 
until resolution or until a stable clinical endpoint is reached. All required treatments and 
outcomes of the SADE must be recorded. 
CLJI will notify all participating clinical Investigators, ECs, and competent authorities as 
necessary of all SADEs that occur during this study within with the specified reporting time 
after he/she first receives notice of the effect. Investigators are responsible for reviewing 
information received about SADEs. 
Device deficiencies which could have led to a serious adverse device effect should undergo 
the same reporting as serious adverse events, i.e., they should be reported to CLJI Worldwide 
within 24 hours of awareness; and to the ethics committee and regulatory authorities as 
required by national regulations or by the ethics committee. 
 
8. 
Risk Evaluation  
8.1. Potential Risks to Study Participants 
For purposes of this study, adverse events that may be anticipated are associated with the 
use of VIBLOK cream as well as the procedures used to deploy the cream.  
Anticipated risks have been minimized to the furthest extent possible (full details of the risk 
management procedures can be found in the CIB), but the nature of the patient’s disease 
state has inherent risks [22]. 
8.1.1. Risks/ Adverse Events associated with the disease state  
Complications associated with an HSV-2 infected population may include, but are not limited 
the following: 
• 
Recurrences of genital herpes 
• 
Systemic symptoms, including fever headache, malaise and myalgia’s 
• 
Local pain and itching 
• 
Dysuria 
• 
Tender lymphadenopathy 
 
8.1.2. Risks/ Adverse Events associated with VIBLOK cream 
In addition to the events listed in the previous section, the additional adverse events listed 
below are specifically associated with the VIBLOK cream and its application. The lack of data 
associated with long term VIBLOK usage prevents predicting the incidence of these risks. 
Additional complications include, but may not be limited to: 
• 
Toxic, hypersensitive or allergic reaction 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
25 of 49 
• 
Epithelial sensitization 
 
8.1.3. Risks associated with study procedures 
Study procedures may impose additional risks to study participants. In case of the SAFE Trial 
this theoretically could concern an increased risk for HSV infection of 
• 
housemates, or  
• 
other places than the extra-genital region 
due to the frequent sampling and/ or touching of the extra-genital area. 
 
HSV is transmitted via direct contact with infected secretions, such as during sexual 
intercourse. Casual contact, sharing of bathroom, toilet seats, etc. have not been implicated in 
HSV transmission. Furthermore, sampling and cream application is only done when 
participants are asymptomatic, which in principle is not different from normal hygienic or 
sexual behavior. Therefore,  swabbing of the genital area by a study participant does not pose 
a risk to housemates. 
The likelihood of spreading the virus to another part of the body is nil, since autoinoculation 
does not occur in persons who are infected outside of the primary episode as then immunity 
has been established. Of note, in that respect is that the University of Washington the HSV 
research group has been using self-collected swabs for study of HSV for >25 years, and 
neither autoinoculation, nor exposure of housemates has ever been suspected as a result of 
these procedures. 
 
In summary, the likelihood for imposing additional risks to study participants and their 
housemates due study procedures is considered negligible. 
 
 
8.2. Methods to Minimize Risk 
Product handling and procedure guidance are provided in the Training Materials, and will be 
used for device training to minimize risks associated with device use.  
Additionally, efforts will be made to minimize and/ or early capture of these possible risks 
through site/investigator selection and management. Site and investigator selection criteria are 
established to ensure that the study personnel and their institutions are qualified to screen, 
perform and manage the study procedures as well as support the associated requirements for 
research. Also trial management structure is designed to provide disciplined oversight of the 
trial activities including monitoring of site and personnel performance. 
Site and investigator criteria include the following: 
• 
Investigational site personnel must be experienced and skilled in treating participants with 
viral STI’s. 
• 
Good collaboration with general practitioners to ensure proper participant follow-up. 
• 
The study site must have an adequately staffed research department with a minimum of 
one dedicated study coordinator. 
• 
Able to enroll a minimum of 5 participants 
 
Although the risk associated with the study procedures is considered negligible as compared 
to normal practice, the study participants will be instructed to wash their hands thoroughly 
after their (daily) sampling. 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
26 of 49 
 
8.3. Benefits  
There are no proven benefits from participation in this study and usage of the investigational 
device.   
The study may indirectly be of benefit to study participants if they are determined to be a 
frequent asymptomatic shedder of HSV-2 and, therefore, a potential transmitter of infection 
while not having symptoms 
Possible benefits for future people using the VIBLOK cream will be based upon results of this 
and other studies of VIBLOK. 
Information gained from the conduct of this study may be of benefit to patients with the same 
medical condition in the future. The long-term results of using the VIBLOK cream are not 
known at the present time. There are no alternative treatments. The Clinical Investigator’s 
Brochure has a full assessment of the clinical risk associated with the VIBLOK cream. 
 
8.4. Risk-Benefit Analysis  
Use of VIBLOK according to the instructions is expected to reduce the risk for HSV-2 transfer 
from one person to the other via skin-to-skin contact during sexual intercourse. However, as 
indicated in section 8.3 there is no proven benefit for the study participants. 
Participants enrolled in this clinical study will be at risk of those events listed in section 8.1.2. 
These risks are considered at an acceptable level with no known residual risk as all VIBLOK 
ingredients have been used for many years, and the ingredient zinc oxide is listed in the 
European Pharmacopeia (also refer to the VIBLOK Investigator’s Brochure). All adverse 
events will be carefully monitored throughout the study. 
Hence it is believed that the participants participating in this study are not at greater risk than 
any other people with an HSV-2 infection. 
 
 
8.5. Definitions  
The definitions used in this protocol are consistent with those referenced in ISO 14155:2011. 
 
Term 
Definition 
Reference/ 
Justification 
Adverse Event (AE) 
Any 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 device.  
ISO 
14155: 
2011 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
27 of 49 
Term 
Definition 
Reference/ 
Justification 
Serious Adverse Event 
(SAE) 
Adverse Event that:  
a) led to a death, 
b) led to a serious deterioration in the health of a study subject that  
• resulted in a life-threatening illness or injury, 
• resulted in permanent impairment of a body structure or body 
function, 
• required in-patient hospitalization or prolongation of existing 
hospitalization, 
• resulted in a medical or surgical intervention to prevent 
permanent impairment to body structure or a body function. 
c) leads to fetal distress, fetal death or a congenital abnormality or 
birth defect 
The following is not considered an SAE: Hospitalization for 
diagnostic or elective surgical procedures, planned at or before the 
enrollment for a pre-existing condition. 
ISO 
14155: 
2011 
 
Adverse Device Effect 
(ADE) 
Adverse event related to the use of an investigational medical 
device.  
This definition also includes adverse events resulting from 
insufficient or inadequate instructions for use, deployment, 
implantation, installation, or operation, or any malfunction of the 
investigational device. And events resulting from use error or from 
intentional misuse. 
ISO 
14155: 
2011 
Serious Adverse Device 
Effect (SADE) 
Adverse Device Effect that resulted in any of the consequences 
characteristics of a Serious Adverse Event. 
ISO 
14155: 
2011
Unanticipated Adverse 
Device Effect (UADE) 
Any serious adverse effect on health or safety 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 investigational plan or 
application (including a supplementary plan or application), or any 
other unanticipated serious problems associated with a device that 
relates to the rights, safety, or welfare of patients. 
ISO 
14155: 
2011 
Device 
Malfunction 
or 
deterioration 
Failure of a device to perform in accordance with its intended 
purpose when used in accordance with the manufacturer's 
instructions. 
GHTF/SG2/N
54R8:2006 
 
Endpoints, 
Clinical 
Safety (after 26 days) 
• 
SADE incidence 
• 
Nature, frequency, duration, severity, seriousness and causality 
of adverse events 
 
Endpoints, Performance 
(after 26 Days) 
• 
Comparison of HSV detection rate on days with asymptomatic 
shedding prior and after applying VIBLOK 
• 
Comparison of HSV copy number on days with asymptomatic 
shedding prior and after applying VIBLOK 
 
 
Pre-Existing Condition 
A pre-existing condition is one that is present at the start of study 
treatment. A preexisting condition is not an adverse event unless it 
worsens as a result of the study treatment. 
 
Recurrent 
Hospitalization 
Re-Hospitalization 
Re-hospitalization for HSV-2 recurrences and/or complications 
related to the cream. 
 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
28 of 49 
 
9. 
Statistical Considerations 
This clinical study is a prospective, non-randomized, comparative multi-center safety and 
performance trial. 
  
9.1. Sample Size Determination 
The primary endpoint is the SADE incidence at 28 days of VIBLOK usage. 
With a sample size of 36, an exact two-sided 95.0% confidence interval for a single proportion 
will show that the SADE incidence is below 10% at an expected incidence of 0.1%. Taking into 
account a drop-out rate of 15%, the estimated sample size needed is 42 study participants 
applying the VIBLOK cream. 
The secondary endpoint is VIBLOK performance. 
Statistical analysis will evaluate whether the disagreement rate in positivity between the pre- 
and post-treatment swabs is indicative of a decrease in detection frequency.  For each person, 
the number of swabs on which shedding occurs only pre-intervention will be assessed, and 
then the number of swabs on which shedding occurs only post-intervention will be subtracted. 
If this number averages above zero, it indicates that the detection rate is decreased following 
intervention, and therefore a protective effect of the intervention with regard to shedding.  
Since this number is not distributed according to a known distribution, we will compare it to 
zero using a non-parametric test, the Wilcoxon signed-rank test. With an 8% anticipated 
asymptomatic shedding rate, 80% power and type I error of 5%, 40 participants taking 
samples for 28 days are needed to show a 50% reduction post-intervention, i.e. after applying 
VIBLOK. 
Taking into account a drop-out rate of 15%, up to 46 adults applying VIBLOK cream are 
needed. 
Total number of subjects to be enrolled. 
Taking into account an overall screenfailure rate of 45% for absence of a confirmed HSV-2 
infection, up to 84 subjects will be enrolled to get to the required minimum of 46 adults 
applying VIBLOK. 
 
9.2. Timing 
Participants will undergo screening and, once the HSV-2 infection is confirmed, baseline visits, 
and then follow-up visits at 14, and 28 after baseline, in addition there will be a follow-up call 
after 2-5 days after the baseline visit. 
 
9.3. Analysis Sets  
The As Treated (AT) Population will consist of all participants that were enrolled in the trial and 
that applied VIBLOK at least once.  
The Per Protocol (PP) Population will consist of all participants who fulfil the protocol in the 
terms of the eligibility and that applied VIBLOK for at least 26 days. 
The primary and secondary endpoints will be reported based on the AT population. 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
29 of 49 
Descriptive and summary statistical analysis will also be performed on all primary and 
secondary endpoints on the PP population.  
Prior to final statistical analysis, designated staff will develop a memo that describes the 
exclusions from analysis populations.  
9.4. Missing Data 
All possible steps will be taken to minimize missing data in the study, including monitoring of 
data forms for completeness and efforts to track and maintain contact with study participants 
during the follow-up period. Missing data will not be imputed and the data will be analyzed as 
is. An investigation may be made concerning the sensitivity of the results of analysis to the 
method of handling missing values, especially if the number of missing values is substantial. 
 
9.5. Endpoints 
9.5.1. 
Primary Endpoint 
The primary endpoint for this clinical study is SADE incidence after minimally 26 days of 
VIBLOK treatment in the AT population. This analysis will be repeated for the PP population. 
9.5.2. 
Secondary Endpoints 
Secondary endpoints with respect to device performance are: 
• 
Within-participant HSV-2 DNA detection rate on days with asymptomatic shedding  
• 
HSV-2 copy number on HSV DNA positive samples detected by quantitative real-time 
PCR on days with asymptomatic shedding  
 
The secondary endpoint with respect to safety is:  
• 
Total number and type of AEs after minimally 26 days of VIBLOK use. 
 
Secondary analyses will be performed in the AT population. The analyses will be repeated for 
the PP population. 
9.5.3. 
Exploratory Endpoints 
Subanalyses will be performed as follows: 
• 
To explore VIBLOK’s blocking ability in relation to 
o Gender 
o Time between VIBLOK application and sampling 
o Shaving and waxing habits 
• 
Participant satisfaction using VIBLOK as assessed on the participant questionnaire 
 
Exploratory analyses will be performed in the AT population. These analyses will not be 
repeated for the PP population. 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
30 of 49 
9.6. Endpoint Analysis 
All statistical analyses will be performed by CLJI or a designee. Participant data listings and 
tabular and graphical presentations of results will be provided. All clinically relevant baseline 
and follow-up variables will be tabulated.  Descriptive statistics will be used for continuous 
variables (e.g., mean, standard deviation, sample size, minimum, and maximum) and 
frequency tables or proportions for discrete variables.  
Swab samples will be analyzed by a core laboratory for HSV DNA and the mean HSV-2 copy 
number on HSV-2 DNA positive samples.  
Further details of the statistical methods will be provided in the Statistical Analysis Plan. 
 
10. 
Study Administration 
10.1. General Study Organization 
CLJI Worldwide is the Study Sponsor, and has the overall responsibility for the conduct of the 
study, including assurance that the study meets the regulatory requirements of the appropriate 
regulatory bodies. The Sponsor will have certain direct responsibilities and will coordinate 
other responsibilities to the specified committees, core labs and other support services as 
necessary. 
CLJI Worldwide will be responsible for submitting the Investigational Plan and all changes to it 
to the national competent authority and local EC to obtain ongoing approvals as needed. 
CLJI Worldwide and Core Laboratories will maintain copies of correspondence, data, 
shipment of devices, adverse device effects and other records related to the clinical trial as 
appropriate.  
CLJI Worldwide will submit all reports required by the appropriate regulatory authorities as 
identified in this section of the regulation. This may include unanticipated and serious adverse 
device effects, withdrawal of EC approval, current investigators list, annual progress reports, 
recall information, final reports and protocol violations. 
10.2. Steering Committee 
The Steering Committee will be responsible for general oversight of the trial. This committee 
will meet periodically to monitor clinical site progress, and protocol compliance. This 
committee will be responsible for reviewing the final results, determining the methods of 
presentation and publication, and selection of secondary projects and publications. The 
committee will be comprised but not limited of Prof. C. Boucher, Prof. A. Wald, Dr A. Wensing, 
and Dr A. Muetstege with at least one of the medical doctors (MD) being a study investigator. 
10.3. Data Monitoring Committee  
The Data Monitoring Committee (DMC, also known as the Data Safety Monitoring Board, 
DSMB) will consist of at least 3 members, with minimally one member independent from the 
Sponsor, the investigators, or anyone involved in the clinical care of the study participants. 
(S)he will not have scientific, financial, or other conflict of interest related to the Sponsor or the 
investigators.  

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
31 of 49 
The DMC committee will review all safety data and will monitor the rates of SAEs, device and 
procedure failures, and any device-related adverse events from this clinical study and make 
recommendations based upon the safety analyses. It will also be responsible for the 
developing a charter and deciding on early termination of the trial as necessary. The 
frequency of the DMC meetings will be determined prior to study commencement; however, 
the DMC may call a meeting at any time if there is reason to suspect safety is an issue. DMC 
oversight for this trial is expected to be rigorous with frequent review of all essential safety 
data. 
10.4. Core Laboratories 
A Core laboratory will be established for the analyses of the swabs, and serology. 
Standardized protocols for acquiring and transmitting electronic records will be developed and 
documented prior to study initiation.  
10.5.  Clinical Sites 
CLJI Worldwide will select qualified investigators, ship devices only to participating 
investigators, obtain a signed Clinical Study Agreement and provide the investigators with the 
information and training necessary to conduct the study. CLJI Worldwide will retain copies of 
all study-related correspondence with study sites. 
10.6. Site Training 
Clinical sites will be chosen that have had experience with patients with viral STIs. Additional 
training of appropriate clinical site personnel will be the responsibility of the Sponsor. To 
ensure proper device usage, uniform data collection, and protocol compliance, the Sponsor 
will present a formal training session to study site personnel which will review the instructions 
for use of the device, the Investigational Plan, techniques for the identification of eligible 
patients, instructions on in-hospital data collection, standardized data collection for core 
laboratory analysis, methods for soliciting data from alternative sources, schedules for follow-
up with the study site coordinators, and regulatory requirements. Detailed feedback regarding 
completion of forms will be provided by the Sponsor, and through regular site monitoring. The 
sponsor reserves the right to enforce retraining for sites who have demonstrated study or 
procedure compliance issues. 
10.7. Study Monitoring 
CLJI Worldwide, or its designee, will conduct investigational site monitoring to ensure that all 
investigators are in compliance with the protocol and the Investigator’s Agreement, and that all 
study participants have been properly consented with the current version of the informed 
consent document. CLJI Worldwide will evaluate circumstances where an investigator 
deviates from the clinical protocol and will retain the right to remove either the investigator or 
the investigational site from the study. 
Routine on-site monitoring visits shall include verification of the following: 
• 
Compliance with the protocol, any subsequent amendment(s), ISO14155 and 
maintenance of regulatory requirements; deviations shall be discussed with the principal 
investigator(s) or authorized designee, documented and reported; 
• 
Only authorized individuals are participating in the clinical investigation; 
• 
The investigational device is being used according to the protocol and instructions for use;  

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
32 of 49 
• 
Investigational site resources, equipment and the investigational site team, remain 
adequate throughout the duration of the clinical investigation; 
• 
Signed and dated informed consent forms have been obtained from each participant at the 
point of enrollment or before any clinical-investigation-related procedures are undertaken, 
using an informed consent form approved by the ethics committee; 
• 
Source documents and other clinical investigational records are accurate, complete, up to 
date, stored and maintained appropriately;  
• 
CRFs and queries are complete, recorded in a timely manner, and consistent with source 
documents; (hence the monitor will perform 100% source verification of the 
inclusion/exclusion criteria, all adverse events and all endpoints. Further, a random sample 
of at least 10% of the participants (at least 2 participants per site) will be fully source 
verified); 
• 
All adverse events and device deficiencies are reported to CLJI without unjustified delay; 
• 
All serious adverse events and deviations are reported to the EC, if required; 
• 
The storage and investigational device accountability are correct and the device 
accountability process is being followed; 
• 
All other required reports, notifications, applications, submissions and correspondence are 
maintained in the investigator's files and are accurate, complete, timely, legible, dated and 
identify the clinical investigation; 
• 
Current laboratory normal values, laboratory certifications, accreditations, or other 
validations are present in the investigator's file;  
• 
Participant withdrawal has been documented; the monitor shall discuss this with the 
principal investigator or his/her authorized designee; 
• 
Participant non-compliance with the requirements stated in the informed consent has been 
documented; the monitor shall discuss this with the principal investigator or his/her 
authorized designee; 
• 
Suitability of the attempts to contact lost to follow-up participants and any intermediaries; 
• 
The principal investigator and investigation site team are informed and knowledgeable of 
all relevant document updates concerning the clinical investigation, and 
• 
Any corrective and preventive actions, as needed, have been implemented and are 
effective. 
Monitors shall be appropriately qualified per the following requirements: 
• 
Qualified in the field of the applicable regulations and ISO14155:2011 through training and 
experience as well as scientific or clinical knowledge; 
• 
Knowledgeable on the use of the investigational device(s) and relevant requirements, 
protocol and informed consent process; 
• 
Trained on the CLJI' clinical quality assurance and quality control system  
All monitoring activities shall be documented in a written report. The frequency of monitoring 
visits will depend on enrollment and center compliance, but each center will at least be visited 
once per year. Further details are laid out in the monitoring plan. 
CLJI Worldwide will review significant new information, including unanticipated adverse events 
and ensure that such information is provided to the DMC, study investigators and to all 
reviewing ECs and regulatory agencies as necessary. 
Efforts will be made to ensure that data collection compliance is monitored and communicated 
to the Investigators in a timely manner throughout the trial. 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
33 of 49 
10.8. Data Management 
CLJI Worldwide will provide data management through an electronic data capture (EDC) 
system.  
 
CLJI Worldwide will prepare written progress reports and a final report based on data in the 
database and will also coordinate with the DMC to ensure data reports are available in a 
timely manner for all reviews. The core laboratory will be also coordinated by the Sponsor 
and/or respective vendor so that core lab data for each participant is recorded in the e-CRF.  
10.9. Publication Policy  
The Study Steering Committee members will plan and review the study publication strategy 
and review proposed papers and presentations. The committee co-chairmen will develop the 
format for submission and review of proposed publications. The committee will ensure 
accuracy of data reporting and will provide editorial assistance and review as needed. 
Investigators will be required to submit requests for presentation or publication for committee 
review and approval. 
Publication or presentation of the overall clinical study results and/or site specific results of 
study devices which have not been released, and which still may be undergoing development, 
requires the prior written approval of CLJI Worldwide. After CLJI Worldwide has had the 
opportunity to review and comment upon the publication or presentation of the overall clinical 
and/or site-specific results then Institutions and Investigators will comply with the 
publication/presentation protocol set forth in the Clinical Study Agreement. 
In the event that the multicenter publication has not been completed within one (1) year from 
the date of the completion or termination of the Study, then notwithstanding the foregoing, the 
site may individually publish a Proposed Publication regarding its individual results from the 
Study, provided that the Proposed Publication is first reviewed by Sponsor. 
During agreed upon interval and at the conclusion of the trial, a multicenter abstract reporting 
the primary results will be prepared and presented at a major conference. A multicenter 
publication will also be prepared for publication in a reputable scientific journal. No publication 
of results from any single center experience will be allowed until the primary endpoint and 
secondary endpoints are analyzed, in order to allow for preparation and publication of the 
multicenter results. The analysis of other pre-specified and non-pre-specified endpoints will be 
performed by CLJI Worldwide. Additional proposed investigations will require the approval of 
CLJI Worldwide. 
CLJI Worldwide will provide statistical support for the publication process.  
 
11. 
Ethical & Regulatory Considerations 
The VIBLOK cream is not commercially available in any country. The clinical investigation 
shall be conducted in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki (as updated in Fortaleza Brazil in 2013) and in compliance with 
ISO14155:2011 and any regional or national regulations. The clinical investigational plan 
(including the Investigator’s Brochure, protocol, and informed consent document) to study the 
VIBLOK cream must be reviewed and approved by the appropriate national competent 
authority and local or regional Ethic Committee (EC) where the clinical investigation is to be 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
34 of 49 
conducted before enrollment of participants may begin. Any additional requirements imposed 
by the ethics committee or regulatory authority shall be followed. 
Changes to the investigational plan that may increase the risk or present new risks to the 
participant must be approved in writing by CLJI Worldwide, the regulatory authorities and the 
EC before the change is implemented. 
11.1. Ethics Committee Approval 
Ethics Committee (EC) approval or acknowledgement of the lead EC approval to participate in 
this trial is required from each institution joining this investigation. Prior to participant 
enrollment, a signed copy of the EC approval letter must be submitted to CLJI Worldwide 
certifying investigational plan approval. Investigators are responsible for submitting and 
obtaining initial and continuing review if necessary (at intervals not greater than once a year) 
of the clinical investigation by their reviewing EC. 
11.2. Informed Consent 
Subject Information/Informed Consent is mandatory and must be obtained from all subjects 
prior to their participation in this trial.  
Any modifications to the Informed Consent must be approved by CLJI Worldwide, and as 
necessary by the EC. Copies of revised versions and the final Subject Information/Informed 
Consent must be provided to CLJI. 
A copy of the EC approved Informed Consent along with a copy of each patient’s signed 
consent must be maintained by each investigator. A signed copy of the consent form must be 
given to each participant. 
11.3. Confidentiality 
The participant’s name and personal data will remain confidential and will not be published in 
any way. Participants will be identified on all e-CRFs by a unique reference number. E-CRFs 
are confidential documents. The sponsor’s monitor or representative and regulatory and 
Ethics Committee representatives, auditors and inspectors may have access to medical files 
in order to verify authenticity of data collected. Accordingly, data will only be available to the 
sponsor, the Investigator, Investigators’ staff, the investigation statistician, and if requested to 
the advisory committee and regulatory authorities.  
The Investigator will maintain as part of the investigation file a list identifying all patients 
entered into the study. 
11.4. Records and Reports 
11.4.1. Records 
Records to be maintained by the investigator include: 
• 
Clinical trial investigational plan and all amendments, all approved versions 
• 
Signed clinical trial agreement 
• 
EC approval letter, including final informed consent 
• 
EC membership list 
• 
Correspondence relating to the trial 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
35 of 49 
• 
CVs for all investigators and research coordinator 
• 
Site personnel signature list 
• 
Clinical monitor sign-in log 
• 
Patient screening/enrollment log 
• 
Reports (includes annual reports, final reports from investigator and sponsor) 
 
The following records must be maintained for each participant enrolled in the trial: 
• 
Signed Informed Consent (latest approved site version) 
• 
All completed e-CRFs 
• 
Supporting documentation of any complications and/or safety events. 
CLJI Worldwide requests that the investigator retain copies of procedure reports, procedure 
nursing notes and the results of any interventional procedures that occurs post trial procedure. 
CLJI Worldwide reserves the right to secure data clarification and additional medical 
documentation on participants enrolled in this trial. 
11.4.2. Reports 
Adverse event reporting requirements are discussed in Section 7.4.  
CLJI Worldwide will make reports on this investigation available to the DMC and Study 
Steering Committee when necessary and in accordance with the respective charters.   
CLJI Worldwide must be notified within 24 hours of any unanticipated adverse device effects, 
withdrawal of EC approval or major protocol violations.   
Upon completion or termination of the trial, the principal investigator for each site must submit 
a final written report to CLJI Worldwide and the Ethics Committee as required by the 
regulations. The report must be submitted within 3 months of completion or termination of the 
trial.   
11.5. Protocol Deviations 
The investigator will not deviate from the protocol without the prior written approval of CLJI 
Worldwide except in medical emergencies or in unforeseen, isolated instances where minor 
changes are made that will not increase the participant’s risk or affect the validity of the trial. In 
medical emergencies, prior approval for protocol deviations will not be required, but the CLJI 
Worldwide clinical research personnel must be notified within 24 hours of the incident.  
All protocol deviations need to be recorded in the respective section of the e-CRF and 
reported according national and ethics committee requirements. Periodic monitoring of 
protocol compliance will be performed for each site. The sponsor maintains the right to place a 
moratorium on enrollment in sites deemed to have excessive protocol compliance issues. In 
cases of major protocol violation, e.g., failure to obtain informed consent or violation of 
inclusion/exclusion criteria, the principal investigator is required to make a written statement 
attesting to retraining or other action(s) to be taken at his/her site to avoid such violations in 
the future. 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
36 of 49 
11.6. Protocol Amendments 
Changes to the protocol that may be made during the clinical study will be made by prior 
written agreement between CLJI Worldwide and the Principal Investigator. An amendment will 
be effective when: a) signed by the Principal Investigator and CLJI Worldwide and b) the 
amendment has been approved by the EC, if required by the Institution’s policies.   
11.7. Record Retention Policy 
All clinical sites will maintain study records for a minimum of fifteen years after marketing 
approval is obtained. Record retention dates will be provided to all parties concerned by CLJI 
Worldwide.  
 
12. 
References 
 
[1] Stanberry LR, Cunningham AL, Mindel A, Scott LL, Spruance SL, Aoki FY, et al., et al. 
Prospects for control of herpes simplex virus disease through immunization. Clin Infect 
Dis 2000; 30: 549-66 
[2] Brown ZA, Selke S, Zeh J, Kopelman J, Maslow A, Ashley RL, et al., et al. The acquisition 
of herpes simplex virus during pregnancy. N Engl J Med 1997; 337: 509-15 
[3] Brown Z. Preventing herpes simplex virus transmission to the neonate. Herpes2004; 11: 
175A-86A 
[4] Wald A, Link K. Risk of human immunodeficiency virus infection in herpes simplex virus 
type 2-seropositive persons: a meta-analysis. J Infect Dis 2002; 185: 45-52  
[5] Strick LB, Wald A, Celum C. Management of herpes simplex virus type 2 infection in HIV 
type 1-infected persons. Clin Infect Dis 2006; 43: 347-56 
[6] Celum C, Levine R, Weaver M, Wald A. Genital herpes and human immunodeficiency 
virus: double trouble. Bull World Health Organ 2004; 82: 447-53 
[7] Serwadda D, Gray RH, Sewankambo NK, Wabwire-Mangen F, Chen MZ, Quinn TC, et al., 
et al. Human immunodeficiency virus acquisition associated with genital ulcer disease and 
herpes simplex virus type 2 infection: a nested case-control study in Rakai, Uganda. J Infect 
Dis 2003; 188: 1492-7 
[8] Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ. Herpes simplex 
virus 2 infection increases HIV acquisition in men and women: systematic review and meta-
analysis of longitudinal studies. AIDS 2006; 20: 73-83. 
[9] Reynolds SJ, Quinn TC. Developments in STD/HIV interactions: the intertwining epidemics 
of HIV and HSV-2. Infect Dis Clin North Am 2005; 19: 415-25  
[10] Reynolds SJ. The role of HSV-2 suppressive therapy for HIV prevention.. Future 
Microbiol. 2009 ; 4: 1095–1097  
[11] Larson T et al. Fomites and Herpes Simplex Virus. J Infect Dis 1985 Apr; 151(4)  
[12] Martin E. et al. A Pooled Analysis of the Effect of Condoms in Preventing HSV-2 
Acquisition. Arch Intern Med. 2009 July 13; 169(13): 1233–1240 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
37 of 49 
[13] Berger JR, Houff S Neurological complications of herpes simplex virus type 2 infection. 
Arch Neurol. 2008 May;65(5):596-600. 
[14] Bryson YJ. et al. Current status and prospects for oral acyclovir treatment of first episode 
and recurrent genital herpes simplex virus. J Antimicrob Chemother. 1983 Sep;12 Suppl B:61-
65.  
[15] Mertz GJ et al., Double-blind placebo-controlled trial of oral acyclovir in first-episode 
genital herpes simplex virus infection. JAMA 1984 Sep 7;252(9):1147-51.   
[16] Koelle D.M. and Corey L. Herpes simplex: insights on pathogenesis and possible 
vaccines. Ann Rev Med. 2008;59:381-95. 
[17] Wald et al. Frequent genital herpes simplex virus 2 shedding in immunocompetent 
women. Effect of acyclovir treatment. J Clin Invest. 1997 Mar 1;99(5):1092-7 
[18] Wald et al. Suppression of subclinical shedding of herpes simplex virus type 2 with 
acyclovir. Ann Intern Med. 1996 Jan 1;124(1 Pt 1):8-15. 
[19] Wald, et al, Effect of Condoms on Reducing the Transmission of Herpes Simplex Virus 
Type 2 From Men to Women. JAMA 2001 
[20] Margaret AS. et al. Effect of Condom Use on Per-act HSV-2 Transmission Risk in HIV-1, 
HSV-2-discordant Couples. Clin Infect Dis 2016; 62 (4):456-461 
[21] Wald et al. Helicase–Primase Inhibitor Pritelivir for HSV-2 Infection. N Engl J Med 
2014;370:201-10. 
 
 
 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
38 of 49 
Appendix 1: English master Informed Consent 
 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
39 of 49 
Appendix 2: Daily Home PCR Instructions for Women 
 
Thank you for volunteering for this study. Please read this sheet over carefully to understand how 
the study is being done. 
Study Supplies 
You will receive the following supplies:  
• 
Dacron-tipped swabs (similar to Q-Tips) 
• 
Small plastic vials (with green, yellow, and red labels) 
• 
Color coded labels  
• 
A storage box 
• 
VIBLOK cream 
• 
Mirror 
• 
A bag for transport 
• 
A swab collection log 
• 
A study diary 
 
Sample Labels 
The labels are preprinted with your study, clinic, and participant number. For each sample you 
collect, please fill in the date and time you collected the sample.  
Study Diary 
It is important that you bring your study diary to each clinic visit. Fill out the diary immediately 
before you obtain your swab samples. Please record this information as accurately as 
possible. 
Storage of Samples 
Vials with and without swabs can be stored at room temperature. When you return to the clinic 
for your next appointment, please bring the storage box with all the swab samples and your 
diary. 
Communicating with the Clinic  
If you develop symptoms of a recurrence or have any questions, please contact the <specify 
the department>. If you have ANY unusual urinary, genital, or rectal symptoms, such as a 
urinary tract infection, rash, or bleeding, call the clinic as soon as possible for an appointment. 
Every effort will be made to accommodate your schedule for clinic visits. Please call in at the 
earliest sign of symptoms so that a visit can be scheduled as soon as possible. 
 
Weekdays: <specify contact information> 
After Hours: <specify contact information> 
 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
40 of 49 
Collecting Daily Swab Samples 
Please read the following instructions carefully, it is very important that you collect samples in 
the same order as given in the instructions. 
Please collect two extra-genital swabs per day: one before and one 5-60 minutes after 
VIBLOK application.  
Please also collect a swab from a herpes lesion during an outbreak: do not apply VIBLOK 
when you develop a lesion and contact the clinic when you first notice symptoms. 
Collect samples once a day before bathing or showering, or at least one hour after bathing or 
showering. Thoroughly wash and dry your hands before beginning. 
 
VIBLOK application area (grey area) 
 
 
 
Swabbing area (red circle) 
 
 
Figure 2.1. Female genitals with VIBLOK application and swabbing area. 
 
1/ To collect the EXTRA GENITAL swab in the green-labeled vial before VIBLOK: 
1. Unwrap 1 sterile swab and hold it by the plastic shaft. Try not to touch the Dacron tip with 
your hands.  
 
2. Gently put the swab on your labia.  
3. Rotate the swab in a full circle. Gently remove the swab from your labia. 
4. Rub the same swab from the outer (hairy) edges of your labia to the smooth skin below the 
vaginal opening, covering the entire area.   
5. Rub the swab over the skin between your vagina and anal opening (anus).  
6. Rub the swab in a circular motion over your rectal area, covering a radius of about 1.0 cm 
around the anus. 
 
2/ Closing the vials and labeling: 
1. Place the collected swab into the vial with the green color coded label. 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
41 of 49 
 
 
2. Pull the swab out of the vial 0.5 cm, break (or cut) off the end of the plastic shaft, and 
discard it in the trash.  
3. Securely replace the screw top of the vial. 
4. Complete the swab collection log, with the full date (for example: 17-AUG-2015) and time 
of collection.       
5. Place the labeled vial inside the grid box. 
 
3/ Apply VIBLOK   
1. Apply one packet of VIBLOK™ evenly and thoroughly to all external genital (including labia 
and clitoris), pubic, and perianal areas with or without hair.  
2. Ensure application from minimally 2 cm outside of the outer (hairy) edges of your labia to 
the smooth skin below the vaginal opening, covering the entire area, the skin between 
your vagina and anal opening (anus), and your rectal area, covering a radius of about 2,5 
cm around the anus. Apply more than one packet if needed.   
3. Wait 5 to 60 minutes. 
 
4/ To collect the EXTRA GENITAL swab in the yellow-labeled vial after VIBLOK:  
1. Repeat the procedure as described under 1/ and 2/ using the vial with the yellow color 
coded label 
2. Make sure to rub the swap only in the area where you applied VIBLOK: Keep a distance of 
at least 1 cm to the outer edges. 
3. Use the mirror from your sampling kit if needed.  
 
5/ To collect a LESION swab in the red-labeled vial: 
If you develop a herpes lesion, please rub a separate swab over this area and place the swab 
in one of the red-labeled vials. Do not apply VIBLOK when you develop a herpes lesion and 
call the clinic when you first notice symptoms. 
Repeat the procedure as described under 2/. 
 
6/ After collection of the swabs 
After you have collected the daily swabs, ensure to 
1. thoroughly wash and dry your hands 
2. have completed the participant diary 
 
 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
42 of 49 
Appendix 3: Daily Home PCR Instructions for Men 
 
Thank you for volunteering for this study. Please read this sheet over carefully to understand 
how the study is being done. 
Study Supplies 
You will receive the following supplies:  
• 
Dacron-tipped swabs (similar to Q-Tips) 
• 
Small plastic vials (with green, yellow, and red labels) 
• 
Color coded labels 
• 
A storage box 
• 
VIBLOK cream 
• 
Mirror 
• 
An bag for transport 
• 
A swab collection log 
• 
A study diary 
 
Sample Labels 
The labels are preprinted with your study, clinic, and participant number. For each sample you 
collect, please fill in the date and time you collected the sample.  
Study Diary 
It is important that you bring your study diary to each clinic visit. Fill out the diary immediately 
before you obtain your swab samples. Please record this information as accurately as 
possible. 
Storage of Samples 
Vials with and without swabs can be stored at room temperature. When you return to the clinic 
for your next appointment, please bring the storage box with all the swab samples and your 
diary. 
Communicating with the Clinic  
If you develop symptoms of a recurrence or have any questions, please contact the <specify 
the department>. If you have ANY unusual urinary, genital, or rectal symptoms, such as a 
urinary tract infection, rash, or bleeding, call the clinic as soon as possible for an appointment. 
Every effort will be made to accommodate your schedule for clinic visits. Please call in at the 
earliest sign of symptoms so that a visit can be scheduled as soon as possible. 
 
Weekdays: <specify contact information> 
After Hours: <specify contact information> 
 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
43 of 49 
Collecting Daily Swab Samples 
Please read the following instructions carefully, it is very important that you collect samples in 
the same order as given in the instructions. 
Please collect two extra-genital swabs per day: one before and one 5-60 minutes after 
VIBLOK application.  
Please also collect a swab from a herpes lesion during an outbreak: do not apply VIBLOK 
when you develop a lesion and contact the clinic when you first notice symptoms. 
Collect samples once a day before bathing or showering, or at least one hour after bathing or 
showering. Thoroughly wash and dry your hands before beginning. 
 
VIBLOK application area (grey area) 
 
 
 
 
 
 
Figure 3.1. Male genitals with VIBLOK application and swabbing area. 
 
1/ To collect the EXTRA GENITAL swab in the green-labeled vial before VIBLOK: 
1. Unwrap 1 sterile swab and hold it by the plastic shaft. Try not to touch the Dacron tip with 
your hands.  

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
44 of 49 
 
2. Rub the swab, starting at the tip of the penis, over the whole length of the penis to the 
base, covering the entire area. 
3. Rub the swab over the skin between your penis and anal opening (anus).  
4. Rub the swab in a circular motion over your rectal area, covering a radius of about 1 cm 
around the anus. 
 
2/ Closing the vials and labeling: 
1. Place the collected swab into the vial with the green color coded label. 
 
 
2. Pull the swab out of the vial 0.5 cm, break (or cut) off the end of the plastic shaft, and 
discard it in the trash.  
3. Securely replace the screw top of the vial. 
4. Complete the swab collection log, with the full date (for example: 17-AUG-2015) and time 
of collection.       
5. Place the labeled vial inside the grid box. 
 
3/ Apply VIBLOK   
1. Apply one packet of VIBLOK™ evenly and thoroughly to all external genital, penile shaft, 
pubic and perianal areas – with or without hair, minimally 2 cm outside of the swabbing 
area. 
2. Ensure application starting at the tip of the penis, over the whole length of the penis to the 
base, covering the entire area, the skin between your penis and anal opening (anus), and 
your rectal area, covering a radius of minimally 2,5 cm around the anus. Apply more than 
one packet if needed.   
3. Wait 5 to 60 minutes. 
 
4/ To collect the EXTRA GENITAL swab in the yellow-labeled vial after VIBLOK:  
1. Repeat the procedure as described under 1/ and 2/ using the vial with the yellow color 
coded label 
2. Make sure to rub the swap only in the area where you applied VIBLOK: Keep a distance of 
at least 1 cm to the outer edges. 
3. Use the mirror from your sampling kit if needed.  
 
5/ To collect a LESION swab in the red-labeled vial: 
If you develop a herpes lesion, please rub a separate swab over this area and place the swab 
in one of the red-labeled vials. Do not apply VIBLOK when you develop a herpes lesion and 
call the clinic when you first notice symptoms. 
 
 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
45 of 49 
6/ After collection of the swabs 
After you have collected the daily swabs, ensure to 
1. thoroughly wash and dry your hands 
2. have completed the participant diary 
 
 

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
46 of 49 
 
Appendix 4. Participant Diary 
 
 
 
 
Day of the month
1
2
3
4
5
6
7
8
9
10
Time Skin Swab Collected
Time VIBLOK Swab Collected
Time in case of genital area shaved
Time in case of genital area waxed
Time in case of other hair removal
Specify other hair removal method if 
applicable
Anti-HSV medication taken
Symptoms
No Symptoms
Itching, burning, tingling
Lesions (sores, blisters, ulcers, crusts)
Other (describe below)
Lesion Locations
Genital (Men: penis, scrotum; 
Women: vagina, labia, vulva, groin, pubis)
Rectal (perineum, perianal)
Buttock
Other: ______________________

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
47 of 49 
 
Day of the month
11
12
13
14
15
16
17
18
19
20
Time Skin Swab Collected
Time VIBLOK Swab Collected
Time in case of genital area shaved
Time in case of genital area waxed
Time in case of other hair removal
Specify other hair removal method if 
applicable
Anti-HSV medication taken
Symptoms
No Symptoms
Itching, burning, tingling
Lesions (sores, blisters, ulcers, crusts)
Other (describe below)
Lesion Locations
Genital (Men: penis, scrotum; 
Women: vagina, labia, vulva, groin, pubis)
Rectal (perineum, perianal)
Buttock
Other: ______________________

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
48 of 49 
 
 
 
 
 
 
 
 
Day of the month
21
22
23
24
25
26
27
28
29
30
31
Time Skin Swab Collected
Time VIBLOK Swab Collected
Time in case of genital area shaved
Time in case of genital area waxed
Time in case of other hair removal
Specify other hair removal method if 
applicable
Anti-HSV medication taken
Symptoms
No Symptoms
Itching, burning, tingling
Lesions (sores, blisters, ulcers, crusts)
Other (describe below)
Lesion Locations
Genital (Men: penis, scrotum; 
Women: vagina, labia, vulva, groin, pubis)
Rectal (perineum, perianal)
Buttock
Other: ______________________

CLJI WORLDWIDE 
VIBLOK SAfety and perFormancE Trial Protocol  
Date 01/MAY/2017 
 
 
Version 
CONFIDENTIAL  
Pages 
5.0 
2015-01 VIBLOK 
49 of 49 
Appendix 5. Participant questionnaire 
 
Participant questionnaire and debriefing: to be filled out by the participant during visit 4. 
Question  
Circle one option 
Free text 
I found VIBLOK 
1. Very easy to use 
2. Somewhat easy to use 
3. Difficult to use 
 
The use was 
1. Simple and clear 
2. Somewhat confusing 
3. Very confusing 
 
The VIBLOK user 
documentation was 
1. Excellent 
2. Adequate 
3. Inadequate 
 
If VIBLOK was available for 
use, I would 
1. Use it 
2. Use it only in very 
special cases 
3. Never use it 
 
What I liked best about 
VIBLOK was 
 
 
 
 
What I liked least about 
VIBLOK was 
 
 
 
 
What suggestions do you 
have for improving VIBLOK?