A Randomized, Double Blinded Study of the Safety and Pharmacokinetics of Two Vaginal Film Formulations Containing the Integrase Inhibitor MK-2048
Phase: PHASE1
Conditions: Pharmacokinetics, Safety
Sponsor: Hillier, Sharon, PhD

Safety and Pharmacokinetics of Two Vaginal Film Formulations Containing the 
Integrase Inhibitor MK-2048 (FAME103) 
 
NCT04319718 
 
Document/IRB Approval Date: April 23, 2020 
 
 

 

FAME 103 Protocol Version 1.0 20Dec2019 
 
 
A RANDOMIZED, DOUBLE BLINDED STUDY OF THE SAFETY AND PHARMACOKINETICS 
OF TWO VAGINAL FILM FORMULATIONS CONTAINING  
THE INTEGRASE INHBITOR MK-2048   
 
DAIDS-ES  38680 
 
 
Funding Agency: 
Division of AIDS, US National Institute of Allergy and Infectious Diseases 
US National Institutes of Health 
 
Grant Number: A120249 
 
pIND Number: 144816 
IND holder: Sharon Hillier 
Pittsburgh, PA USA 
 
Protocol Chair: 
Katherine Bunge, MD MPH 
University of Pittsburgh 
Pittsburgh, PA USA 
 
 
Protocol Co-Chair: 
Sharon Hillier, PhD 
University of Pittsburgh 
Pittsburgh, PA USA                                                                                    
 
 
Study Site: 
UPMC Magee-Womens Hospital 
University of Pittsburgh Medical Center 
Pittsburgh, PA 
Phone:  412-641-4242 
Fax:  412-641-1133 
 
 
Version 1.0 
December 20, 2019

                                                                                                                    Page 2 of 59 
 
  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
 
A randomized, double blinded study of the safety and pharmacokinetics of two 
vaginal film formulations containing the integrase inhibitor MK-2048 
  
Table of Contents 
PROTOCOL SIGNATURE PAGE………………………………………………………………………5 
LIST OF ABBREVIATIONS AND ACRONYMS ..........................................................................6 
PROTOCOL TEAM ROSTER .....................................................................................................7 
PROTOCOL SUMMARY ............................................................................................................9 
1 
KEY ROLES .....................................................................................................................11 
1.1 
Protocol Identification ...................................................................................... 11 
1.2 
Funding ........................................................................................................... 11 
1.3 
Protocol Chair ................................................................................................. 11 
1.4 
Laboratory ....................................................................................................... 11 
2 
INTRODUCTION ...............................................................................................................13 
2.1 
HIV prevention and microbicides .................................................................... 13 
2.2 
Integrated Preclinical/Clinical Program ........................................................... 14 
2.3 
Rationale  ........................................................................................................ 14 
2.4 
Safety Data: Placebo Eudragit® platform ....................................................... 15 
2.5 
Safety and PK Data: MK-2048 ........................................................................ 16 
2.6 
Summary......................................................................................................... 18 
3 
OBJECTIVES ...................................................................................................................18 
3.1 
Primary Objectives: ......................................................................................... 18 
3.2 
Primary Endpoints: .......................................................................................... 19 
3.3 
Secondary Objectives: .................................................................................... 19 
3.4 
Secondary Endpoint: ....................................................................................... 19 
3.5 
Exploratory Objectives: ................................................................................... 19 
3.6 
Exploratory Endpoints: .................................................................................... 19 
4 
STUDY DESIGN ...............................................................................................................19 
4.1 
Identification of Study Design.......................................................................... 20 
4.2 
Summary of Major Endpoints .......................................................................... 20 
4.3 
Description of Study Population ...................................................................... 20 
4.4 
Time to Complete Accrual ............................................................................... 20 
4.5 
Study Groups .................................................................................................. 20 
4.6 
Expected Duration of Participation .................................................................. 20 
4.7 
Site .................................................................................................................. 20 
5 
STUDY POPULATION ......................................................................................................20 
5.1 
Selection of the Study Population ................................................................... 20 
5.2 
Recruitment ..................................................................................................... 20 
5.3 
Retention......................................................................................................... 20 
5.4 
Inclusion Criteria ............................................................................................. 21 
5.5 
Exclusion Criteria ............................................................................................ 21 
6 
STUDY PRODUCT ...........................................................................................................22 
6.1 
Regimen.......................................................................................................... 22 
6.2 
Administration ................................................................................................. 22 
6.3 
Study Product Formulation.............................................................................. 23 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
6.4 
Study Product Supply and Accountability........................................................ 23 
6.5 
Study Product Dispensing ............................................................................... 24 
6.6 
Concomitant Medications ................................................................................ 24 
7 
STUDY PROCEDURES ....................................................................................................24 
7.1 
Pre-Screening ................................................................................................. 24 
7.2 
Visit 1: Screening Visit .................................................................................... 24 
7.3 
Visit 2: Enrollment ........................................................................................... 25 
7.4 
Visit 3, 4, 5, 6, 7 and 8: Follow-Up Visits ......................................................... 27 
7.5 
Participants Who Become Pregnant ............................................................... 28 
7.6 
Interim Visits ................................................................................................... 28 
7.7 
Clinical Evaluations and Procedures ............................................................... 28 
7.8 
Laboratory Evaluations ................................................................................... 29 
7.9 
Specimen Collection and Processing .............................................................. 29 
7.10 
Biohazard Containment................................................................................... 29 
8 
ASSESSMENT OF SAFETY AND CLINICAL MANAGEMENT ........................................29 
8.1 
Safety Monitoring ............................................................................................ 29 
8.2 
Clinical Data Safety Review ............................................................................ 30 
8.3 
Adverse Events Definitions ............................................................................. 31 
8.4 
Reporting of Critical Events to DAIDS ............................................................. 32 
8.5 
Clinical Management of Adverse Events......................................................... 32 
8.5.1 Product Hold ................................................................................................. 33 
8.6 
Social Harms Reporting .................................................................................. 33 
8.7 
Criteria for Early Termination of Study Participation ....................................... 33 
    8.8      Reporting to the FDA………………………………………………………………33 
9 
STATISTICAL CONSIDERATIONS ..................................................................................34 
9.1 
Review of Study Design .................................................................................. 34 
9.2 
Sample Size and Accrual ................................................................................ 34 
9.3 
Study Endpoints .............................................................................................. 35 
9.3.1 Primary Endpoint ........................................................................................... 35 
9.3.2 Secondary and Exploratory Endpoints .......................................................... 35 
9.4 
Blinding ........................................................................................................... 37 
9.5 
Emergency Unblinding .................................................................................... 37 
9.6 
Random Assignment ....................................................................................... 37 
9.7 
Data Monitoring and Analysis ......................................................................... 37 
9.6.1 Data Monitoring ............................................................................................. 37 
9.6.2 Primary Endpoint Analysis ............................................................................ 37 
9.6.3 Secondary and Exploratory Endpoint Analysis .............................................. 37 
9.6.4 Analysis Cohort ............................................................................................. 38 
10 HUMAN SUBJECTS CONSIDERATIONS ........................................................................39 
10.1 
Special Populations ........................................................................................ 39 
10.1.1 Men ............................................................................................................. 39 
10.1.2 Children ....................................................................................................... 39 
10.1.3 Prisoners ..................................................................................................... 39 
10.1.4 Pregnant women ......................................................................................... 40 
10.2 
Informed Consent Process.............................................................................. 40 
10.2.1 Risk/Benefit Statement ................................................................................ 40 
Pregnancy, Breastfeeding and Sexual Practices ..................................................................41 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
10.3 
Incentives ........................................................................................................ 42 
10.4 
Participant Confidentiality................................................................................ 42 
10.5 
Communicable Disease Reporting .................................................................. 43 
10.6 
Study Discontinuation ..................................................................................... 43 
11 LABORATORY SPECIMENS AND BIOHAZARD CONTAINMENT .................................43 
11.1 
Laboratory Specimens .................................................................................... 43 
11.1.1 Urine Samples ............................................................................................. 44 
11.1.2 Vaginal Samples ......................................................................................... 44 
11.1.3 Rectal Swabs .............................................................................................. 44 
11.1.4 Cervical Swabs ........................................................................................... 44 
11.1.5 Cervicovaginal Lavage Samples ................................................................. 44 
11.1.6 Cervical Tissue ............................................................................................ 45 
11.2 
Quality Control and Quality Assurance Procedures ........................................ 45 
11.3 
Specimen Storage and Possible Future Research Testing ............................. 45 
11.4 
Biohazard Containment................................................................................... 45 
12 ADMINISTRATIVE PROCEDURES ..................................................................................46 
12.1 
Protocol Registration ....................................................................................... 46 
12.2 
Data Coordination ........................................................................................... 46 
12.3 
Study Monitoring ............................................................................................. 46 
12.4 
Protocol Compliance ....................................................................................... 46 
12.5 
Investigator’s Records .................................................................................... 47 
12.6 
Use of Information and Publications ............................................................... 47 
12.7 
Training Procedures ........................................................................................ 47 
REFERENCES .........................................................................................................................48 
APPENDIX 1:  SCHEDULE OF STUDY VISITS AND PROCEDURES ................. 49 
APPENDIX II:  HIV TESTING AGORITHIM ........................................................... 50 
        APPENDIX III:  SAMPLE INFORMED CONSENT…………………….…………..…49 
         
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                    Page 5 of 59 
 
  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
 
 
 
 
 
Protocol Signature Page 
 
 
Protocol Title:   
A randomized, double blinded study of the safety and 
pharmacokinetics of two vaginal film formulations containing the integrase inhibitor MK-
2048 
 
DAIDS #:   
 
DAIDS-ES # 38680 
 
Protocol Date:   
20December2019 
 
Protocol Version:   Version 1.0 
 
 
I will conduct the study in accordance with the provisions of this protocol and all 
applicable protocol-related documents. I agree to conduct this study in compliance with 
United States (US) Health and Human Service regulations (45 CFR 46); applicable U.S. 
Food and Drug Administration regulations; standards of the International Conference on 
Harmonization Guideline for Good Clinical Practice (E6); Institutional Review 
Board/Ethics Committee determinations; all applicable in-country, state, and local laws 
and regulations; and other applicable requirements (e.g., US National Institutes of 
Health, Division of AIDS) and institutional policies.  
 
 
 
_______________________________________________ 
Protocol Chair (PRINT NAME)  
 
 
 
_________________________________________________ 
Signature of Protocol Chair  
 
 
 
________________________ 
Date (Month/Day/Year) 
 
 

                                                                                                                    Page 6 of 59 
 
  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
A randomized, double blinded study of the safety and pharmacokinetics of two 
vaginal film formulations containing the integrase inhibitor MK-2048: 
FAME 103 
LIST OF ABBREVIATIONS AND ACRONYMS 
 
AE 
 
 
Adverse event 
AIDS  
 
Acquired Immunodeficiency Syndrome 
ARV 
 
 
Antiretrovirals 
BV 
 
 
Bacterial vaginosis 
CVL 
 
 
Cervicovaginal lavage 
CT 
 
 
Chlamydia trachomatis 
DAIDS  
 
Division of AIDS 
EAE 
 
 
Expedited adverse event 
GC 
 
 
Neisseria gonorrhoeae 
HIV 
 
 
Human Immunodeficiency Virus 
HSV-1, HSV-2  
Herpes Simplex Virus type 1, type 2 
IRB 
 
 
Institutional Review Board 
ITT 
 
 
Intent-to-treat 
N-9 
 
 
Nonoxynol-9 
NGU  
 
Nongonococcal urethritis  
NIAID  
 
National Institute of Allergy and Infectious Disease 
NIH 
 
 
National Institutes of Health 
PCR 
 
 
Polymerase chain reaction 
PSRT  
 
Protocol Safety Review Team 
RSC 
 
 
Regulatory Support Center 
SOP 
 
 
Standard operating procedure(s) 
STI 
 
 
Sexually transmitted infection 

                                                                                                                    Page 7 of 59 
 
  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
 A randomized, double blinded study of the safety and pharmacokinetics of two 
vaginal film formulations containing the integrase inhibitor MK-2048: FAME 103 
 
 PROTOCOL TEAM ROSTER 
Katherine Bunge, MD MPH 
Protocol Chair 
Department of Obstetrics,  
Gynecology and Reproductive Sciences 
University of Pittsburgh School of Medicine 
300 Halket Street 
Pittsburgh, PA 15213 USA 
Phone: 412-641-6967 
Fax: 412-641-1133 
Email: kbunge@mail.magee.edu  
 
Sharon Hillier, PhD 
Protocol Co-Chair 
Department of Obstetrics,  
Gynecology and Reproductive Sciences 
University of Pittsburgh School of Medicine 
204 Craft Avenue 
Pittsburgh, PA 15213 USA 
Phone: 412-641-8933 
Fax: 412-641-6170 
Email: shillier@mail.magee.edu 
 
Lisa Rohan, PhD 
Co-investigator 
Department of Pharmaceutical Sciences 
University of Pittsburgh School of Medicine 
204 Craft Avenue 
Pittsburgh, PA 15213 
Phone: 412-641-6108 
Fax: 12-641-6170 
Email:  lrohan@mwri.magee.edu 
 
 Julie S. Downs, PhD 
Co-investigator 
Dept. of Social and Decision Sciences 
Carnegie Mellon University 
208 Porter Hall (SDS) 
Pittsburgh, PA 15213-3890 
Office:  219-C Porter Hall 
Phone:  412-268-1862 
Fax:  412-268-6938 
Email:  downs@cmu.edu 
 
 
 
 
Bernard Moncla, PhD  
Co-investigator 
Department of Obstetrics, Gynecology and 
Reproductive Sciences 
Magee-Womens Research Institute 
204 Craft Avenue 
Pittsburgh, PA 15213 
Phone: 412-641-6025 
Fax: 412-641-6170 
Email:  bmoncla@mwri.magee.edu 
 
Leslie Meyn, PhD 
Biostatistician/Epidemiologist 
Department of Obstetrics,  
Gynecology and Reproductive Sciences 
University of Pittsburgh School of Medicine 
204 Craft Avenue 
Pittsburgh, PA 15213 
Phone:  42-641-4233 
Fax: 412-641-1133 
Email:  meynla@mwri.magee.edu  
 
Urvi Parikh, PhD 
Co-Investigator 
University of Pittsburgh 
3550 Terrace Street 
S804 Scaife Hall 
Pittsburgh, PA 15260 
Phone: 412-648-3103 
Fax: 412-648-8521 
Email: ump3@pitt.edu 
 
Peter L. Anderson, PharmD 
Co-investigator 
Department of Pharmaceutical Sciences 
Skaggs School of Pharmacy and 
Pharmaceutical Sciences 
University of Colorado Anschutz Medical 
Campus 
V20-C238, Room 4101 
12850 E. Montview Blvd.  
Aurora, CO 80045 
Phone:  303-724-6128 
Fax:  303-724-6135 
Email:  Peter.Anderson@ucdenver.edu  
 

                                                                                                                    Page 8 of 59 
 
  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
Merck 
Julie Strizki, PhD 
Principal Scientist, Clinical 
Microbiology/Virology 
Merck and Co. Inc 
770 Sumneytown Pike WP53-3020 
West Point, PA 19486 
Tel: 215 652-6058 
Email: Julie.strizki@merck.com 
 
NIH 
Hans M.L. Spiegel, MD 
Sr. Medical Officer, PMPRB/Prevention 
Sciences Program,  
Contractor, Kelly Government Solutions 
DAIDS, NIAID, NIH 
5601 Fishers Lane  
Room 8B51A 
Rockville, MD 20852 
Tel:  240-292-4633 
Fax: 240-627-3465 
Email: hans.spiegel@nih.gov 
 
Jim A. Turpin, PhD  
Branch Chief 
Preclinical Microbicides and Prevention 
Research Branch (PMPRB)  
NIAID/DAIDS  
Room 8B31/MSC 9831 
5601 Fishers Lane 
Rockville, MD 20852-9831 
Phone   (301) 451-2732 
Fax (240) 627-3465 
Email: jturpin@niaid.nih.gov  
 
Cherlynn Mathias, RN, BSN 
Program Officer/Nurse Consultant 
Prevention Science Program, NIH/DAIDS/PSP 
5601 Fishers Lane, 8B51B MSC 9831 
Rockville, MD 20852 
Phone: 240-292-4791 
Fax: 240-627-3465 
Email: cmathias@niaid.nih.gov  
 
Naana Cleland 
Prevention Sciences Program, NIH/DAIDS/PSP 
5601 Fishers Lane, Room 8B27 
Rockville, MD 20852 
Phone: 240 292-4779 
Email: clelandn@niaid.nih.gov 
 
Jeanna Piper, MD 
Sr. Medical Officer 
Clinical Microbicide Research Branch 
PSP/DAIDS/NIAID/NIH 
5601 Fishers Lane 
Room 8B68 
Rockville, MD 20852 
Tel: 240-292-4798 
E-mail: piperj@niaid.nih.gov 

                                                                                                                    Page 9 of 59 
 
  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
 
A randomized, double blinded study of the safety and pharmacokinetics of two 
vaginal film formulations containing the integrase inhibitor MK-2048: 
FAME 103 
 
PROTOCOL SUMMARY 
 
Short Title: 
 
      FAME 103 
 
Protocol Chair: 
Katherine Bunge, MD MPH  
 
Protocol Co-chair: 
Sharon Hillier, PhD 
 
Sample Size: 
Approximately 48  
 
Study Population:  
HIV-uninfected women, 18 – 45 years old 
 
Study Sites: 
UPMC Magee-Womens Hospital, Pittsburgh, PA 
 
 
Study Design: 
A phase I, 2 arm, single site, randomized clinical trial  
 
 
 
Study Duration: 
Accrual of approximately 48 participants is expected to take 9 months. The 
expected duration of study participation for each participant will be 
approximately 5-10 weeks. This includes the screening period. After 
enrollment, the study duration is 4 weeks 
 
Study Products: 
One dose MK-2048 vaginal film (2” x 2” size). Participants will be 
randomized to one of two formulations- high and low ammonio 
methacrylate copolymer type B (Eudragit®). Both films contain 30mg of 
MK-2048. 
 
 
 
 
  
Study Regimen: 
All participants will be randomized to receive a single dose of a vaginal 
film containing MK-2048 (either the high Eudragit® or low Eudragit® 
formulation). The film will be inserted by a clinician on the day of 
enrollment. Vaginal swabs and plasma will be collected at days 0, 3, 5, 7, 
10, 14 and 28 for all participants. On the day of enrollment, some 
participants may elect to participate in immediate post insertion sample 
collection (vaginal swab and plasma) at one or two time points within 6 
hours of insertion. Genital biopsy samples and a rectal swab will be 
obtained on day 7, and cervicovaginal lavage will be collected at 
screening and days 14 and 28.     
 
 
 
 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Screen 
Enroll 
Day 0 
Day 3 
Day 5 
Day 7 
Day 10 
Day 14 
Day 28 

                                                                                                                    Page 10 of 59 
 
  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
Primary Objectives: 
• 
To assess the safety of a single dose of two formulations of an MK-2048 vaginal film which 
is intended for extended release of the antiretroviral drug 
 
Endpoints: 
• 
Grade 2 or higher Adverse Events 
 
Secondary Objectives: 
• 
To describe the pharmacokinetics of MK-2048 drug at 0, 3, 5, 7, 10, 14, and 28 days 
after film insertion  
• 
To describe the acceptability of two formulations of the MK-2048 vaginal film and identify 
qualities associated with higher or lower degrees of acceptability 
 
Secondary Endpoint: 
• 
MK-2048 concentrations in plasma, cervical tissue homogenate, CVL, rectal and vaginal 
swab eluents 
• 
Self-reported assessment of qualities of the experience with the films drawn from 
existing survey on microbicidal films, and general acceptability ratings drawn from 
market research methodology 
 
Exploratory Objectives: 
 
• 
To compare the effects of two formulations of the MK-2048 vaginal film on the vaginal 
microbiota and glycome pre and post study product use 
• 
To describe the pharmacokinetics of Eudragit® polymer to ensure that polymer 
persistence is proportional to drug release. 
• 
To describe the protective effect of MK-2048 film against HIV in an ex vivo biopsy 
challenge model using one cervical tissue biopsy 
 
Exploratory Endpoints: 
 
• 
Vaginal Microenvironment 
• 
Quantitative vaginal cultures and quantitative PCR for selected microbiota from 
vaginal swab 
• 
Nugent score from vaginal swab 
• 
Levels of anti-HIV viral activity in CVL 
• 
Levels of glycoproteins and mucins in CVL 
• 
Levels of biomarkers of innate immunity in CVL 
• 
Eudragit® pharmacokinetics 
• 
Eudragit® levels in CVL 
• 
Ex vivo challenge: HIV infection of cervical tissue as measured by HIV-1 p24 replication 
by ELISA and confirmed either by immunohistochemistry or quantitative PCR 
assessment of integrated provirus in HIV-1 exposed cervical biopsies 
 
 
 

                                                                                                                    Page 11 of 59 
 
  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
1 
KEY ROLES 
 
1.1 Protocol Identification 
Protocol Title: 
A randomized, double blinded study of the safety and pharmacokinetics 
of two vaginal film formulations containing the integrase inhibitor MK-2048 
 
Short Title: 
FAME 103 
  
 
1.2 Funding 
Funding Agency: 
DAIDS/NIAID/NIH 
 
 
            5601 Fishers Lane 
                                   Rockville, MD 20892-9831 
 
 
1.3 Protocol Chair 
Protocol Chair: 
Katherine Bunge, MD MPH 
Department of Obstetrics,  
Gynecology and Reproductive Sciences 
University of Pittsburgh School of Medicine 
300 Halket Street 
Pittsburgh, PA 15213 USA 
Phone: 412-641-6967 
Fax: 412-641-1133 
Email: kbunge@mail.magee.edu  
 
 
Protocol Co-Chair: 
Sharon L. Hillier, PhD 
 
 
 
University of Pittsburgh School of Medicine 
 
 
 
Magee-Womens Hospital 
 
 
 
300 Halket Street 
 
 
 
Pittsburgh, PA 15213 
 
 
 
Phone: 412-641-6435 
 
 
 
Fax: 412-641-1133 
 
 
 
Email:  shillier@mail.magee.edu 
  
1.4 Laboratory 
Local/Clinical Labs: 
UPMC Presbyterian Shadyside CP PUH 
 
 
UPMC Clinical Laboratory Building 
 
 
3477 Euler Way 
 
 
Pittsburgh, PA 15213 USA 
 
 
 
 
 
UPMC Magee Womens Hospital 
 
 
 
300 Halket Street 
 
 
 
Pittsburgh, PA  15213-3108 
 
Clinical and Translational Research Center 
 
 
 
University of Pittsburgh Medical Center 
 
 
 
300 Halket Street, Room 5521 
 
 
 
Pittsburgh, PA  15213 USA 

                                                                                                                    Page 12 of 59 
 
  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
 
Pharmacology: 
Anderson Laboratory 
 
 
 
University of Colorado 
 
 
 
12850 E. Montview Blvd.  
Aurora, CO 80045 USA 
 
Anti-viral 
Studies: 
Parikh Laboratory 
 
 
University of Pittsburgh 
                                   Magee-Womens Research Institute 
                                   204 Craft Avenue  
 
 
Pittsburgh, PA 15213 USA 
 
Microbiology 
Studies: 
Hillier Laboratory 
 
 
University of Pittsburgh 
                                   Magee-Womens Research Institute 
 
 
204 Craft Avenue 
 
 
Pittsburgh, PA 15213 USA 
 
Glycome 
Studies: 
Moncla Laboratory 
 
 
University of Pittsburgh 
                                   Magee-Womens Research Institute 
 
 
204 Craft Avenue 
 
 
Pittsburgh, PA 15213 USA 
 
                                     

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
2 
INTRODUCTION 
 
2.1  HIV prevention and microbicides 
Each year millions of people worldwide are newly infected with HIV, most recently 1.7 million 
people in 20171. Sexual transmission accounts for the majority of new HIV infections worldwide. 
Women are disproportionately impacted by the sexual transmission of HIV 2. This disproportionate 
impact arises from a combination of biologic, social, and economic factors.   Women at risk face 
formidable challenges in protecting themselves from HIV infection, including power differentials, 
gender norms, and economic dependence.  
 
 
Topical microbicides are agents designed to prevent or substantially reduce the acquisition and 
transmission of HIV when applied to the genital or gastrointestinal mucosa. In addition to 
preventing HIV infection, topical microbicides may satisfy two critical needs: affordability and 
female control. Topical microbicides also have the potential for high acceptability for both male 
and female partners. Acceptability and utility of topical microbicides can be maximized by the 
development of an array of dosing formulations. For all dosing formulations, safety, stability, and 
efficacy must be established. 
 
Vaginal films are an attractive dosing option for several reasons. In terms of manufacturing, films 
are inexpensive, scalable, physically and chemically stable, uniform with regards to product 
content, and amenable to combinations of active ingredients. In terms of use, films are discreet, 
portable, and easy to store. Vaginal films can deliver fixed doses of microbicidal agents with 
minimal mess and without an applicator. The small volume of vaginal films may also result in less 
dilution of endogenous antiviral or antibacterial properties of vaginal fluids compared to vaginal 
gels. In studies of spermicidal film, women have found vaginal films to be acceptable3-5. When 
Vaginal Contraceptive Film (VCF) was compared to foaming tablets containing nonoxynol-9 (N-
9), contraceptive film was preferred in three different countries 3. Ninety-seven percent of 59 
Mexican women, 60 percent of 52 Dominican women, and 86 percent of 51 Kenyan women 
reported liking contraceptive film.  In particular, they cited the following favorable characteristics: 
ease of use, general feel or comfort, additional lubrication, and lack of side effects 3. Over eighty 
percent of Cameroonian sex workers, who participated in a large randomized placebo-controlled 
trial of N-9 film, reported that they would use the film were it found to be effective against HIV4. In 
Zambian focus groups, placebo vaginal film was preferred over placebo vaginal tablets and soft-
gel capsules after each product was used once daily for one week 5. In a study evaluating the 
acceptability of placebo microbicidal film, soft gel capsule and tablet, African women were 
instructed to use each of the three products once daily for 7 consecutive days. The film and soft-
gel capsule were chosen significantly more often than the tablet as the preferred dosage form 
(39%, 37% and 25%, respectively). In this particular study, film and soft gel were preferred 
because of faster dissolving time and easier insertion5.  In other studies, participants found vaginal 
films to be less messy than foaming tablets or gel3,6. The Quatro study was a randomized 
crossover study conducted in Zimbabwe and South Africa to assess relative preferences of four 
vaginal placebo dosage forms. Two hundred participants were asked to use pre‐coitally inserted 
film, vaginal table and gel once per week for a month, and a monthly ring (for the entire month) 
during a four‐month crossover period. Participants subsequently chose one preferred product for 
the final study month. Preferences varied within and across countries, and there was no clear 
favorite reiterating the need for a variety of products to meet different women’s preferences Just 
under half of the women in Zimbabwe chose the vaginal film and ranked it their favorite product; 
in South Africa, the vaginal tablet was the most preferred7. 
 
 
 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
2.2 Integrated Preclinical/Clinical Program  
The Film Antiretroviral Microbicide Evaluation (FAME) program brings together an inter-
disciplinary group of research scientists from four academic institutions: University of Pittsburgh, 
University of Washington, Carnegie Mellon University, and the University of Colorado. The long-
term goal of the program is to develop and evaluate an extended delivery vaginal film containing 
an integrase inhibitor which could provide protection from HIV for one week or more following a 
single application. The first iteration of the FAME IPCP established proof of concept that vaginal 
films containing the antiretrovirals (ARVs) dapivirine and tenofovir could deliver drug to target 
tissues as effectively as gel formulations of those same ARVs. The second iteration of the 
program featured FAME-101, a clinical trial which established proof of concept for the extended 
release placebo vaginal film. In FAME-101, 64 participants received a single dose of the extended 
release vaginal film and were randomized to the timing of follow-up (3,7,10 or 14 days). The 
extended release placebo film was well tolerated and visible in 56% of the participants 
randomized to follow-up at 7 days and 25% randomized to follow up at 14 days. The goal of the 
second iteration of the FAME IPCP is to leverage this extended release film platform to establish 
proof of concept that an extended release formulation of an antiretroviral drug could provide 
coverage for 7 days or longer after a single application. An extended release formulation could 
address the challenges associated with daily use of products which have undermined adherence, 
and therefore effectiveness, in clinical trials. For this proof of concept study, the integrase inhibitor 
MK-2048 will be evaluated in the extended release film formulation although the extended release 
film format could be used as a delivery method for a wide range of antiretroviral drugs.  
 
 
2.3 Rationale   
This is a phase I randomized trial assessing the safety and acceptability of two formulations of 
MK-2048 vaginal film. As with all phase 1 studies, the primary objective is to evaluate the safety 
of the product. However, the overarching objective of this study is to provide proof of concept that 
an ARV can be delivered in an extended release film formulation to provide drug delivery for 7 
days or more after a single application. Whether or not Merck elects to pursue development of 
MK-2048, the extended release film formulation could provide a novel means to deliver 
antiretroviral drugs vaginally.   
This study is intended to provide proof of concept that an extended release film could provide 7 
days of drug delivery. Despite the shift in HIV prevention biomedical interventions towards long-
acting methods, there is still a demand for short acting methods. Some women prefer shorter 
acting interventions because they don’t want long-term systemic exposure to medication. With a 
7-day product which women control themselves, it would be possible to provide protection at 
times of increased risk without necessarily being coitally dependent. In a survey of 300 women 
conducted as part of the FAME program, 73% of women preferred a prevention method that 
would be available “when needed” and more women reported that seven days of protection 
would be preferable to one day so that a woman might use the product once and not have to 
worry about redosing for a week (Downs, unpublished data). 
 
MK-2048 is a potent second-generation integrase inhibitor that was advanced as a clinical 
candidate in 2005. However, in a single dose oral Phase 1 study, MK-2048 failed to achieve 
target plasma concentrations and further development was discontinued. Importantly, MK-2048 
remains an attractive choice for topical microbicide applications because it is highly potent 
against both wild type HIV-1 and raltegravir-resistant isolates, it is not currently being used for 
treatment and it has demonstrated a good safety profile in preclinical and clinical studies7. Free 
drug in ectocervical and colorectal explants demonstrated anti-viral activity. Full protection (6/6 
explants protected) was noted in the colorectal model at 1 μM; partial protection (4/6 explants 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
protected) was noted in the polarized ectocervical model at 100 μM. In an ex vivo challenge 
model conducted in eleven Chinese rhesus macaques, the level of virus growth in the tissue 
biopsies of MK-2048 gel-treated animals (n=5) was lower than that observed in tissues from the 
naïve (n=3) and placebo-treated animals (n=3). (DAIDS K-28 Gel Study, study identification #: 
14004-MK-2048 Biopsy Challenge Study dated February 20, 2019). Of note, protection was not 
noted in the ex vivo challenge model performed in the MTN-027 study of the intravaginal ring 
containing 30 mg of MK-2048 which released drug over 28 days of use.   
 
The current study will compare two extended release films each containing 30 mg of MK-2048 to 
be released over 7 days of use. The two films having either high (12.8%) or low (6.4%) Eudragit® 
formulations differ with respect to dissolution rate and spreadability. In in vitro dissolution testing, 
high Eudragit® film dissolves slower than the low Eudragit® film and shows decreased 
spreadability. Macaque data included in the investigators’ brochure includes data from pig-tailed 
macaques which support continued release of MK-2048 over a period of 7 days. 8   
 
The safety of the film polymer has been established in a previous clinical trial (FAME-101) and 
the safety of vaginal MK-2048 has been established in preclinical animal studies as well as two 
clinical trials (MTN-027 and MTN-028).  The established safety record of these products supports 
the direct comparison design of this trial without the need for a placebo arm. 
 
The primary objective of the proposed study will be to evaluate the safety of two formulations of 
MK-2048 vaginal film which differ with respect to rate of dissolution.   
 
Secondary objectives include evaluating the pharmacokinetics of the two film formulations as well.  
Understanding the immediate release profile of the films and how long the drug remains in the 
vagina will be integral to the study. 
 
In addition, the products’ acceptability and the films’ impact on the vaginal microenvironment, 
cellular immunity, inflammation and innate anti-HIV activity will also be assessed.  
   
Because the primary objective is safety and one of the secondary objectives is pharmacokinetics, 
the active vaginal film will be inserted by a clinician on the day of enrollment.  
  
2.4 Safety Data: Placebo Eudragit® platform 
The Eudragit® film has a proven safety record. 
 
Pre-Clinical Safety Data  
Safety evaluation of the extended release placebo film was performed in a nonhuman primate 
model.  Six pigtailed macaques were exposed to two films per week for two weeks, which is 
double the proposed human dosing (intended dosing is one film per week). In total, four films 
were delivered to each macaque over fourteen days. The vaginal microbiota, vaginal pH, and 
number of PMNs on gram stained vaginal smears were assessed before the first film placement 
and after the fourth film placement.  The integrity of the cervicovaginal tissues was assessed by 
colposcopy at each film placement. Of note, there was residual film visible in the vagina with each 
new film placement. No adverse events were noted by colposcopy; microbiota remained stable 
with no effect noted on the beneficial H202 producing microorganisms; vaginal pH remained 
within normal range; and PMN counts remained within the normal range even after more frequent 
administration than intended for use (Patton, personal communication). The entire study report is 
presented in Appendix IV. 
 
Clinical Safety Data 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
FAME-101 was a safety and acceptability study of the high (12.8%) Eudragit® placebo vaginal 
film. Sixty-four HIV uninfected, healthy women were enrolled. At enrollment the participants were 
randomized to timing of the follow-up visit. Participants returned either 3,7,10 or 14 days after film 
placement depending on their randomization and then all participants returned for a final safety 
assessment three weeks after enrollment. Safety assessments, acceptability parameters, and 
changes to the vaginal microenvironment were assessed at each visit. The persistence of the film 
by visual examination was noted as well. 
 
Eighty-four participants were screened and 64 enrolled. The median age was 26.5 years; 56% 
were white and 27% non-Hispanic black. The primary endpoint was Grade 2 or higher AEs. There 
were 6 Grade 2 events; these included bacterial vaginosis, vaginal itching, pelvic cramping (2), 
friable cervix and adnexal pain. Of these, only bacterial vaginosis and vaginal itching were 
attributed to study product use.  Forty-seven AEs were reported amongst 64 participants. Thirty-
one participants (48.5%) reported at least one AE; 22 reported at least one urogenital event. For 
the women randomized to the 3 and 7 day follow up visit approximately 50% of the participants 
had visible film on speculum exam (44% and 56%). In summary, the high Eudragit® film was very 
well tolerated with no concerning safety signals. 
 
2.5 Safety and PK Data: MK-2048 
Pre-Clinical Safety and PK Data 
MK-2048 was formulated as a gel to evaluate the potential local effects, systemic toxicity and 
toxicokinetics in rats and rabbits when administered intravaginally for 28 days. Gels containing 
0.059%, 0.117%, and 0.234% MK-2048 were developed for daily topical and vaginal 
administration.  In the 4-week rat study (study no. 1726-026) there was no evidence of systemic 
toxicity attributable to MK-2048 following daily intra-vaginal administration for 28 days. MK-2048 
appearance in plasma was rapid, with mean maximum concentrations of 0.38 to 0.76 µM (0.234% 
gel dose) that were achieved by 0.5 to 2 hours post dose. However, MK-2048 disappeared rapidly 
from plasma with mean trough concentrations (i.e., C24h) that were <LLQ (LLOQ = 0.0108 μM) 
at all doses.  The compound was well tolerated as there were no untoward local effects in vaginal 
tissues.  Because of the absence of any local or systemic toxicity in the rat model, the high dose 
gel of 0.234% MK-2048 is considered the no observed adverse effect level (NOAEL).   
 
Ten-day (study no. 1726-020) and 28-day (study no. 1726-027) Good Laboratory Practices (GLP) 
intravaginal studies were conducted in female rabbits in which gels containing 0.059%, 0.117%, 
and 0.234% MK-2048 were administered daily. In the initial 10-day vaginal irritation study, 
changes within female reproductive tissues occurred with similar incidence and severity in rabbits 
receiving gels containing MK-2048 compared to placebo gel. Because of the absence of a dose-
effect relationship and the absence of a difference between the placebo and the MK-2048-treated 
groups, the dose of 0.234% is considered the NOAEL for MK-20489.  
 
In the 28-day GLP rabbit study (study no. 1726-027) there was no evidence of systemic toxicity 
following intra-vaginal administration of MK-2048.  There were no test article-related gross or 
microscopic findings in tissues. Administration of MK-2048 gels at the higher concentrations of 
0.234% and 0.117% had subtle effects on the distal mucosa characterized by leukocyte infiltration 
and/or focal erosion of distal mucosa.  Therefore, the low concentration of MK-2048 at 0.059% is 
the NOAEL, which is the equivalent of a 5.5 mg/kg total cumulative dose corresponding to a dose 
multiple of 11.  Although findings were reported at the higher dose levels for MK-2048 in the 
proximal mucosa of rabbits, the proximal mucosa in the rabbit is a unique tissue and is not 
representative of vaginal tissues in other species, including women.  In summary, the absence of 
relevant changes in distal mucosa and stratified squamous epithelium of the rabbit and the 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
absence of changes in both the rat and sheep models, which are more representative of vaginal 
tissues in women, are more relevant findings. 
Data generated in macaque nonclinical studies provide evidence of local tolerability of MK-2048 
extended release films in the vagina.  Human 2”x2” sized extended release films were produced 
for animal studies. Films were cut to 1”x1” sized extended release film so as to be compatible with 
pigtail macaques.  In six macaque studies, in which 23 animals received extended release MK-
2048 films, there were no safety concerns8. 
The highest concentration administered to macaques during nonclinical studies of MK-2048 
extended release film was 25 mg. This is comparable to 100 mg of human dose based on 4x 
scaling between macaque and human microbicide products. This has been a general conversion 
factor (2-4x) used among researchers in this field based on anatomical scaling. At this dose, no 
local toxicity in vaginal tissue nor adverse events during the follow-up of non-human primates 
were reported by colposcopy analysis of vaginal tissues. Macaques exposed to extended release 
film loaded with 7.5 or 25 mg of MK-2048 experienced good local tolerability (observations with 
colpophotograpy) with no tissue adverse responses.    
The observation of the presence of the extended release film in the vagina using 
colpophotography documented the appearance of film product as long as it is distinct from vaginal 
exudate. The presence of the film was observed for a week or more in the majority of animals in 
all nonclinical studies performed in macaques.  Notably, film product was retained during 
menstruation. Further, in the coital study, the films remained in place even after animals had 
coitus. 
The administration of MK-2048 extended release film via intravaginal route in macaques led to 
drug plasma levels similar to those observed with ring studies.  These plasma concentrations 
have not led to any safety issues and were much lower than those observed in rat nonclinical 
study. 
To compare to these results, no systemic toxicity was reported in oral safety studies   
demonstrating MK-2048 plasma concentrations of 0.443 - 3.1 ng/mL are unlikely to evoke any 
safety issues.8. 
 
Clinical Safety and PK Data 
MTN-027 was a multi-site, single-blind, four-arm, randomized, placebo-controlled Phase 1 safety 
and PK trial of the vicriviroc (VCV)(MK4176) vaginal ring containing 182 mg vicriviroc (MK-4176); 
the MK-2048 vaginal ring, containing 30 mg MK-048; the MK-2048A vaginal ring, containing 182 
mg vicriviroc (MK-176) and 30 mg MK-2048; and the Placebo vaginal ring10. The study enrolled 
48 healthy, 18-45 year old women who were HIV-uninfected, non-pregnant, sexually abstinent, 
and using adequate contraception. Women were randomized to one of four study regimens in a 
1:1:1:1 ratio. The vaginal ring was worn for approximately 28 consecutive days. The primary 
objectives were to assess the safety and to determine the concentration of drug in vaginal fluid, 
plasma and cervical tissue after 28 days of continuous use, followed by 7 days off product. Safety 
was evaluated as the proportion of women with related genitourinary AEs and proportion of 
women with any grade 2 or higher AEs. Secondary objectives were to evaluate acceptability and 
adherence over 28 days of use. 
 
Thirteen Grade 1 and 2 Grade 2 related genitourinary AEs were observed in 9 women. Of the 
Grade 1 AEs, vaginal burning, pruritis, and application site erythema and pain were noted. Both 
Grade 2 related genitourinary AEs were due to vulvovaginal candidiasis. There were no 
statistically significant differences in the number of participants with related genitourinary AEs or 
any Grade 2 AEs between the placebo arm and treatment arms. There were no Grade 3 or higher 
AEs. 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
 
MK-2048 peak concentrations, from both the single and combination IVR, were substantially 
higher in vaginal fluids than in plasma (30× higher) and rectal fluid suggesting less risk for 
systemic toxicity Plasma MK-2048 concentration with the MK-2048-alone vaginal ring achieved 
peak concentrations more rapidly when compared to the combination vaginal ring (Tmax 
median 27 and 47 hours, respectively), followed by a similar decline in concentration after VR 
removal (median terminal decay half-life of 3 and 2 hours, respectively). The antiviral activity of 
MK-2048 was not correlated with tissue-associated drug concentrations in an ex vivo HIV-1 
challenge assay.  
 
MTN-028 was a phase 1, single-blind, 2-arm PK trial of 2 combination vaginal rings containing 
different dose strengths of VCV and MK-204811. Eighteen women were randomized 2:1 to a low-
dose ring, containing 91 mg of VCV and 10 mg of MK-2048, or the original-dose ring, containing 
182 mg of VCV and 30 mg of MK-2048. Participants used the rings continuously for 28 days and 
were followed up for approximately 7 days after ring removal.  
 
There were a total of 2 grade 1 and 3 grade 2 product-related genitourinary AEs observed in 5 
women. These AEs occurred in 3 participants (23%) in the low-dose arm (application site pain, 
vulvovaginal pruritis, and dysmenorrhea), and 2 (33%) in the original-dose arm (diarrhea and 
vaginal discharge). There were an additional 7 unrelated grade 2 AEs (5 in the low-dose arm; 2 
in the original-dose arm); no grade ≥3 AEs were reported. There were no statistically significant 
differences in the number of participants with product-related genitourinary AEs (3 of 13 vs 2 of 6 
participants) or any grade ≥2 AEs (6 of 13 vs 3 of 6) between the low-dose and original-dose 
arms, respectively (P > .99). 
 
The original dose ring treatment arm offered higher plasma AUC, cervical tissue concentration, 
and greater drug released (based on residual drug levels). Both arms had similar CVF AUCs. 
Plasma and CVF concentrations of MK-2048 decreased rapidly after ring removal. The extended 
release films containing 30 mg of MK-2048 will deliver this drug over a shorter period of time (7 
days) vs the 28 day ring, effectively delivery a higher level of drug daily than was possible using 
the ring. The preclinical data from the pigtailed macaques suggest that levels of MK-2048 in the 
tissues and vaginal fluid can be achieved after film administration which are similar to those which 
have been reported to correlate with protection for other integrase inhibitors such as raltegravir.12. 
For that reason, the proposed study will have value for the HIV prevention field in providing 
additional data on topical delivery of integrase inhibitors as well as the use of extended release 
film formulations for vaginal delivery of ARVs.  
 
2.6 Summary 
The current study is a proof of concept study to determine whether an extended release film could 
deliver drug for seven days. Two film formulations which differ by dissolution and spreadability 
will be compared. It is appropriate to advance these two formulations of MK-2048 film into a 
clinical trial for safety given that the individual ingredients used in the film have a history of safe 
use in the vaginal compartment. The extended release platform may prove to be an effective drug 
delivery system with the potential to be used with many medications 
 
3 
OBJECTIVES 
3.1 Primary Objectives: 
 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
• 
To assess the safety of a single dose of two formulations of an MK-2048 vaginal film which 
is intended for extended release of antiretroviral drugs. 
 
3.2 Primary Endpoints: 
 
• 
Grade 2 or higher Adverse Events 
 
3.3 Secondary Objectives: 
 
• 
Pharmacokinetics: To describe the pharmacokinetics of MK-2048 drug at 0, 3, 5, 7, 10, 
14, and 28 days after film insertion  
 
• 
Acceptability: To describe the acceptability of two formulations of the MK-2048 vaginal film 
and identify qualities associated with higher or lower degrees of acceptability 
 
3.4 Secondary Endpoint: 
• 
MK-2048 concentrations in plasma, tissue homogenate, CVL, and rectal and vaginal 
swab eluents, comparing the two film types 
 
• 
Acceptability: Self-reported assessment of qualities of the experience with the films drawn 
from existing survey on microbicidal films, and general acceptability ratings drawn from 
market research methodology 
 
3.5 Exploratory Objectives: 
 
• 
To compare the effects of two formulations of the MK-2048 vaginal film on the vaginal 
microbiota and glycome pre and post study product use 
• 
To describe the pharmacokinetics of Eudragit® polymer to ensure that polymer 
persistence is proportional to drug release.  
• 
To describe the protective effect of MK-2048 film against HIV in an ex vivo biopsy 
challenge model using cervical tissue  
 
3.6 Exploratory Endpoints: 
 
• 
Vaginal Microenvironment 
• 
Quantitative vaginal cultures and quantitative PCR for selected microbiota from 
vaginal swab 
• 
Nugent score from vaginal swab 
• 
Levels of anti-viral activity in CVL 
• 
Levels of glycoproteins and mucins in CVL 
• 
Levels of biomarkers of innate immunity in CVL 
• 
Eudragit® pharmacokinetics 
• 
Eudragit® levels in CVL 
• 
Ex vivo challenge: HIV infection of cervical tissue as measured by HIV-1 p24 replication 
by ELISA and confirmed either by immunohistochemistry or quantitative PCR assessment 
of integrated provirus in HIV-1 exposed cervical biopsies 
 
4 
STUDY DESIGN 
 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
4.1 Identification of Study Design 
This is, single site, double blinded study. 
 
 
4.2 Summary of Major Endpoints 
Grade 2 or higher Adverse Events  
 
4.3 Description of Study Population 
The study population will be HIV-uninfected women who meet criteria outlined in Section 5. 
 
4.4 Time to Complete Accrual 
Accrual is expected to be completed in approximately 9 months. 
 
4.5 Study Groups 
All participants will be randomized to one of two MK-2048 films: a high Eudragit® film or a low 
Eudragit® film.   
 
4.6 Expected Duration of Participation 
The duration of study participation per woman is expected to be approximately 5-10 weeks. This 
includes the screening period. 
 
4.7 Site 
There is a single study site: UPMC Magee-Womens Hospital, Pittsburgh, PA.   
 
 
5 
STUDY POPULATION 
 
5.1 Selection of the Study Population 
The inclusion and exclusion criteria in this section will be utilized to ensure the appropriate 
selection of study participants.  
 
5.2 Recruitment 
Participants will be recruited from a variety of sources including the ambulatory clinic of Magee-
Womens Hospital and the surrounding population. Participants will also be referred to the study 
from other local research projects and other health and social service providers serving the target 
study population.  Recruitment strategies will be used that have been shown to be successful in 
several prior studies of topical microbicides. Recruitment materials will be approved by the 
University of Pittsburgh Institutional Review Board. 
 
5.3 Retention 
Once a participant is enrolled, the study site will make every effort to retain her in follow-up to 
minimize possible bias associated with loss-to-follow-up. The site will implement the following 
procedures to enhance retention:    
 
• 
Thorough explanation of the study visit schedule and procedural requirements during the 
informed consent process and re-emphasis at each study visit.      
• 
Thorough explanation of the importance of both groups to the overall success of the study. 
• 
Collection of detailed locator information at the study screening visits, and active review and 
updating of this information at each subsequent visit. 
• 
Use of appropriate and timely visit reminder mechanisms. 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
• 
Immediate follow-up on missed visits. 
 
Study sites will use a participant tracking mechanism to facilitate visit scheduling and timely 
identification and follow-up on missed visits.   
 
5.4 Inclusion Criteria 
Women must meet all the following criteria to be eligible for inclusion in the study: 
 
1) Age 18 through 45 years (inclusive) at screening 
 
2) Able and willing to provide written informed consent. 
 
3) Willing to use an effective method of birth control throughout the duration of the study.  
Examples of effective methods include:  hormonal methods (other than NuvaRing®), IUD, 
bilateral tubal ligation, same sex partner, partner with a vasectomy, abstinence (defined as 
no vaginal sex for one month prior to screening).   
 
4) Able and willing to provide adequate locator information  
 
5) HIV-uninfected based on testing performed by study staff at screening (per algorithm in 
Appendix II) 
 
6) In general good health as determined by the site clinician 
 
7) Agree to be sexually abstinent, including use of sex toys, from V2 (Enrollment) until V7 (7 
days after the biopsy visit) and 48 hours prior to all study visits. 
 
8) Agree to refrain from use of vaginal device or products (for example, lubricants, creams, 
suppositories)  throughout participation in the study.   Tampons may be used except between 
V5 (biopsy visit) and V7 (day 14).  
 
9)  Willingness to undergo all study-related assessments and follow all study-related 
procedures 
 
10) At screening and enrollment, agrees not to participate in other research studies involving 
drugs, medical devices, or vaginal products while enrolled in this trial 
 
11) Participants over the age of 21(inclusive) must have documentation of a satisfactory Pap 
within three years prior to Enrollment consistent with Grade 0 according to the Female Genital 
Grading Table for Use in Microbicide Studies Addendum 1 (Dated November 2007) to the 
DAIDS Table for Grading Adult and Pediatric Adverse Events, Corrected Version 2.1, July 
2017, or satisfactory evaluation with no treatment required of grade 1 or higher Pap results. 
If no documentation of a Pap smear can be provided, a Pap smear will be collected at the 
screening visit.   
 
5.5 Exclusion Criteria 
 
Women who meet any of the following criteria will be excluded from the study. Of note, the study 
is limited to premenopausal women with an intact uterus because the mucosal immune 
environment differs substantially between pre- and post- menopausal women. Therefore, 
inclusion of post-menopausal women would introduce heterogeneity into the population. 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
 
1.) Menopause (as defined as amenorrhea for one year or more without an alternative etiology) 
 
2.) Hysterectomy 
 
3.) Participant report of any of the following: 
a) Known adverse reaction to any of the study products (ever) 
b) Non- therapeutic injection drug use in the 12 months prior to Screening 
c) Surgical procedure involving the pelvis in the 60 days prior to enrollment (includes 
dilation and curettage or evacuation, and cryosurgery; does not include cervical biopsy 
for evaluation of an abnormal pap smear)   
d) Participation in a drug, spermicide and/or microbicide study in the 30 days prior to 
enrollment  
e) Currently pregnant or pregnancy within 42 days prior to enrollment  
f) Currently lactating 
g) Use of a diaphragm, NuvaRing®, or spermicide for contraception 
 
4.) Urogenital infection or suspected infection within 7 days of enrollment including: symptomatic 
candidiasis, trichomonas vaginalis, and symptomatic bacterial vaginosis; or cervical 
infection, including N. gonorrhoeae (GC), C. trachomatis (CT), or mucopurulent cervicitis; 
syphilis; HSV lesions, or other sores (Note: seropositive HSV without active lesions will not 
be excluded); acute pelvic inflammatory disease; urinary tract infection; recent exposure to 
a partner with GC, CT, Trichomonas, syphilis, or NGU 
 
5.) Antibiotic or antifungal therapy (vaginal or systemic) within 7 days of enrollment 
 
6.) As determined by the PI, has any significant uncontrolled active or chronic cardiovascular, 
renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine *including poorly 
controlled diabetes), respiratory, immunologic disorder or infectious disease 
 
7.) Menses-like bleeding at the time of the Enrollment visit* or expected menses-like bleeding 
within 14 days of the Enrollment visit 
(*Women who have vaginal bleeding at the scheduled Enrollment visit may return at a 
different date to be re-examined and possibly enrolled provided they are still within the 
screening window and meet all criteria.) 
 
8.) Any condition that, in the opinion of the Investigator, would preclude provision of consent, 
make participation in the study unsafe, complicate interpretation of study outcome data, or 
otherwise interfere with achieving the study objectives 
 
6 
STUDY PRODUCT 
 
6.1 Regimen 
Each participant will receive one vaginal film containing MK-2048 in either a high dose Eudragit® 
(12.8%) film or low dose Eudragit® (6.4%) film  
 
6.2 Administration 
After eligibility is confirmed, site staff will randomize the participant to one of two film formulations: 
high dose Eudragit® or low dose Eudragit®. The site staff will retrieve the film from the pharmacy. 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
To ensure appropriate placement, the clinician will place the film in the proximal third of the vagina 
using a speculum.  
 
6.3 Study Product Formulation   
Participants will be randomized to one of two formulations- high (12.8%) or low (6.4%) Eudragit® 
polymer. Both films contain 30mg of MK-2048. The films are 2” x2.”  
 
Calculated composition of MK-2048 30 mg extended release vaginal film (low ammonio methacrylate 
copolymer type B) 
Component  
Quantity 
(mg/film) 
Function 
MK-2048 
30.0 
API 
Hydroxypropyl methylcellulose E5 (VIVAPHARM® HPMC E5, 
Hypromellose 2910) 
36.7 
Film forming 
polymer/base 
Hydroxyethyl cellulose (HEC, NATRASOLTM 250L PHARM) 
36.7 
Film forming 
polymer/base 
Hydroxypropyl methylcellulose (BENECEL™ K4M HPMC 
Type 2208 
45.4 
Film forming 
polymer/base 
Hydroxypropyl cellulose (HPC, KLUCEL™ JXF PHARM) 
73.4 
Film forming 
polymer/base 
Ammonio methacrylate copolymer dispersion type B 
(Eudragit® RS 30D)a   
41.5 
Extended release 
polymer 
Polyethylene glycol 400 (PEG 400) 
39.3 
Plasticizer/dispersant 
Propylene glycol (PG) 
28.7 
Plasticizer/dispersant 
Purified Waterb 
11.0 
Solvent 
Total unit weight  
 
 
Calculated composition of MK-2048 30 mg extended release vaginal film high ammonio methacrylate 
copolymer type B) 
Component  
Quantity 
(mg/film) 
Function 
MK-2048 
30.0 
API 
Hydroxypropyl methylcellulose E5 (VIVAPHARM® HPMC E5, 
Hypromellose 2910) 
30.1 
Film forming 
polymer/base 
Hydroxyethyl cellulose (HEC, NATRASOLTM 250L PHARM) 
30.1 
Film forming 
polymer/base 
Hydroxypropyl methylcellulose (BENECEL™ K4M HPMC 
Type 2208 
37.2 
Film forming 
polymer/base 
Hydroxypropyl cellulose (HPC, KLUCEL™ JXF PHARM) 
60.3 
Film forming 
polymer/base 
Ammonio methacrylate copolymer dispersion type B 
(Eudragit® RS 30D)a   
68.1 
Extended release 
polymer 
Polyethylene glycol 400 (PEG 400) 
32.3 
Plasticizer/dispersant 
Propylene glycol (PG) 
23.6 
Plasticizer/dispersant 
Purified Waterb 
10.0 
Solvent 
Total unit weight 321.7 
 
 
6.4 Study Product Supply and Accountability 
Study product will be manufactured and package by Benefit Coatings, Stratford, CT, in 
compliance with cGMP. Product release testing includes GMP Microbial Limits Testing 
(USP61/62).  After product release, the packaged study product will be provided to the UPMC 
Magee-Womens Hospital Pharmacy.  All study product will be available to the study staff through 
the Magee Pharmacy. 
 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
The Magee research pharmacist will maintain complete accountability records of all study 
products received for this protocol and dispensed to participants.  Additional documentation will 
be required for study product returns, destruction (if applicable) and other related issues as 
outlined in instructions for DAIDS clinical trials. All unused study products must be returned to the 
Pharmacy after the study is completed or terminated.   
 
The film is packaged into a foil-lined pouch and stored at room temperature of 20-25°C (68-77°F). 
GMP stability testing will be conducted for the clinical trial product material. Research and 
development level stability testing is available for the film and shows the product to remain within 
target specifications at all time points evaluated to date.  
 
6.5 Study Product Dispensing  
Study products will be dispensed to clinic staff only upon receipt of a written prescription signed 
by an authorized prescriber.   
 
6.6 Concomitant Medications  
Enrolled study participants may use concomitant medications during study participation.  All 
concomitant medications, over-the-counter preparations, vitamins and nutritional supplements, 
recreational drugs, and herbal preparations will be recorded on the concomitant medications log 
form.  
 
All participants will be counseled to avoid the use of spermicide and other non-study vaginal 
products (other than tampons during menstruation and female condoms) while participating in the 
study.  Participants who report use of these products will be counseled regarding the use of 
alternative methods; however reported use of these products does not require any change in 
study product administration or follow-up procedures.  Condoms, if provided by study staff, will 
not be coated with any type of spermicide.   
 
7 
STUDY PROCEDURES 
This section describes visit-specific study procedures.     
 
7.1 Pre-Screening  
As part of participant outreach and recruitment strategies, study staff may pre-screen potential 
study participants (e.g. via telephone). During these interactions, study staff may explain the study 
to participants and ascertain elements of presumptive eligibility, to be confirmed at an on-site 
screening visit. If the participant is eligible based on a screening script her name and appointment 
time will be placed on the script.  If she signs consent, the telephone script will then become part 
of her research record. If she does not sign consent, the form will be de-identified. 
 
7.2 Visit 1: Screening Visit 
Screening may take place up to 45 days prior to Enrollment.  Screening procedures may occur 
over several visits. A combined written informed consent for screening and enrollment will be 
obtained before any screening procedures are initiated.  For participants who do not meet the 
eligibility criteria, screening will be discontinued once ineligibility is determined. 
 
The table below outlines procedure to take place at the Screening visit.     
 
 
 
 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
 
 
   Table 1:  Visit 1 Procedures 
VISIT 1:  SCREENING VISIT 
Component 
Procedure/Analysis 
 
 
 
 
 
 
 
ADMINISTRATIVE 
• 
Written Informed Consent 
• 
Assign Study Number (PTID) 
• 
Review Eligibility 
• 
Collect Contact Information 
• 
Medical history and concomitant medications 
• 
Visit Questionnaire 
• 
HIV Pre-/Post-Test Counseling 
• 
Screening Results 
• 
Protocol counseling (including effective birth control, 
sexual practices restrictions and vaginal product use) 
• 
Schedule Next Study Visit, prn 
• 
Participant Reimbursement 
 
URINE 
• 
Pregnancy test 
• 
Urine dipstick, as clinically indicated 
SALIVA 
• 
Rapid HIV 
BLOOD 
• 
Confirmatory HIV, as clinically indicated 
 
VAGINAL 
• 
pH 
• 
Wet Mount, as clinically indicated 
• 
Trichomonas (NAAT) 
• 
Vaginal sample for Future Use* 
 
CERVICAL 
• 
GC/CT (NAAT) 
• 
Cervical sample for Future Use* 
• 
Pap smear, as indicated 
 
 
CVL 
• 
Levels of antiviral activity 
• 
Levels of glycoproteins and mucins 
• 
Levels of cytokines & innate immunity factors 
• 
Assessment of drug assay specificity for MK-2048 and 
Eudragit® 
 
PHYSICAL EXAM 
• 
Physical Exam 
• 
Vital Signs (BP) 
• 
Height & Weight 
 
PELVIC EXAM 
• 
Bimanual Exam, as clinically indicated 
• 
External Genital & Speculum Exam 
      * For participants who have consented to the collection of samples for future use and use of left-over samples for future 
studies. 
 
7.3  Visit 2: Enrollment 
Subjects who meet the inclusion and exclusion criteria following the Screening visit may schedule 
an Enrollment visit.  Care will be taken to schedule the Enrollment visit at a time when the 
participant is not expecting to be actively bleeding or anticipating her menses within 14 days. 
 
Before performing any enrollment procedures, study staff will confirm eligibility.  The participant 
will undergo a pelvic examination. Pelvic specimens as described below will be collected and the 
study staff will assess for bleeding.  If no bleeding or other exclusionary findings are evident, the 
participant will then be randomized to study product. The act of randomization is considered the 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
act of enrollment for this study. Subjects with menses like vaginal bleeding at the Enrollment visit 
will not be randomized/enrolled at that time.  These subjects may be rescheduled if vaginal 
bleeding resolves before 45 days from Screening have elapsed. If vaginal bleeding does not 
resolve during the window period, and the subject expresses interest in enrollment for the study, 
she may be rescreened.   
 
After eligibility is confirmed, the site staff will go to the Pharmacy to obtain the study product. The 
clinician will insert a speculum and then place the film in the proximal third of the vagina under 
direct visualization per the SOP. After film placement, participants will be scheduled for Visit 3. 
Participants who agree to optional additional PK sampling will undergo blood draw and blind 
vaginal swab sampling for drug levels at 1-2 time points within the first 6 hours post insertion.   
 
   Table 2:  Visit 2 Procedures 
VISIT 2:  ENROLLMENT – DAY 0 (Day 1 of Product Use) 
Component 
Procedure/Analysis 
 
 
 
ADMINISTRATIVE 
• 
Review/Confirm Eligibility 
• 
Collect/Update Contact Information 
• 
Visit Questionnaire 
• 
Update medical history and concomitant medications 
• 
Screening Results 
• 
Protocol counseling (including effective birth control, 
sexual practices restrictions and vaginal product use) 
• 
Assess/Document Adverse Events 
• 
Schedule Next Study Visit 
• 
Participant Reimbursement 
ACCEPTABILITY 
• 
Acceptability Questionnaire (post film insertion) 
BLOOD 
• 
Baseline MK-2048 level 
• 
Optional MK-2048 level * 
 
URINE 
• 
Pregnancy test 
• 
Urine dipstick, as clinically indicated 
 
 
VAGINAL 
• 
pH 
• 
Wet Mount, as clinically indicated 
• 
Gram Stain 
• 
Quantitative Vaginal Culture 
• 
Quantitative PCR for microbiota 
• 
MK-2048 level 
• 
Optional vaginal swab(s) for MK-2048 **  
• 
Vaginal sample for Future Use*** 
CERVICAL 
• 
Cervical sample for Future Use*** 
 
PHYSICAL EXAM 
• 
Physical Exam, as clinically indicated 
• 
Vital Signs (BP) 
 
PELVIC EXAM 
• 
Bimanual Exam, as clinically indicated 
• 
External Genital & Speculum Exam 
RANDOMIZATION 
• 
Randomization to study product 
 
STUDY PRODUCT 
• 
Study Product Distribution 
• 
Clinician-inserted with speculum 
*Participants may opt to have one additional blood draw at 1, 2, 3, 4, 5 or 6 hours post film insertion for MK-2048 levels.  
**Participants may opt to have additional vaginal swabs collected at one or two time points (1, 2, 3, 4, 5, or 6 hours) post film 
insertion.  The swabs will be collected by a clinician without a speculum.  
***For participants who have consented to the collection of samples for future use and use of left-over samples for future studies. 
 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
 
7.4 Visit 3, 4, 5, 6, 7 and 8: Follow-Up Visits 
Visit 3, 4, 5, 6,7 and 8 procedures are outlined in Table 4.  The windows around these study visits 
are as follows:  
Visit 3: Day 3 (2-4) 
Visit 4: Day 5 (5-6) 
Visit 5: Day 7 (7-8) 
Visit 6: Day 10 (9-12) 
Visit 7: Day 14 (13-16) 
Visit 8: Day 28 (24-32) 
Two cervical biopsies will be obtained at Visit 5 only. A CVL will be performed at Visits 7 and 8. 
Residual drug, if present, will be removed during the CVL at Visit 7. The purpose of Visit 8 is to 
provide a final safety assessment. 
 
   Table 3:  Follow-up Visit Procedures 
VISIT 3, 4, 5, 6, 7, 8  FOLLOW-UP VISITS 
Component 
Procedure/Analysis 
 
 
ADMINISTRATIVE 
• 
Collect/Update Contact Information 
• 
Visit Questionnaire 
• 
Update medical history and concomitant medications 
• 
Protocol counseling excluding Visit 8 (including effective 
birth control, sexual practices restrictions and vaginal 
product use) 
• 
Assess/Document Adverse Events 
• 
Schedule Next Study Visit (excluding Visit 8) 
• 
Participant Reimbursement 
ACCEPTABILITY 
• 
Acceptability Questionnaire (Visit 5 ONLY; prior to biopsy) 
BLOOD 
• 
MK-2048 level 
 
URINE 
• 
Pregnancy test (Visit 5 & 8 and as clinically indicated) 
• 
Urine dipstick, as clinically indicated 
 
 
VAGINAL 
• 
pH 
• 
Wet Mount, prn 
• 
Trichomonas (NAAT), as clinically indicated 
• 
Gram Stain 
• 
Quantitative Vaginal Culture 
• 
Quantitative PCR for microbiota 
• 
Vaginal swab for MK-2048 level 
• 
Vaginal sample for Future Use* 
RECTAL 
• 
Rectal swab for MK 2048 (Visit 5 ONLY) 
 
CERVICAL 
• 
GC/CT (NAAT), as clinically indicated 
• 
Cervical biopsies- two adequate (Visit 5 ONLY) 
• 
Cervical sample for Future Use* 
 
 
CVL (Visits 7 and 8 only) 
• 
Levels of antiviral activity  
• 
  
• 
Levels of glycoproteins and mucins  
• 
Levels of cytokines & innate immunity factors  
• 
MK-2048 level  
• 
Eudragit® levels 
PHYSICAL EXAM 
 
• 
Physical Exam, as clinically indicated 
• 
Vital Signs (BP) 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
 
PELVIC EXAM 
• 
Bimanual Exam, as clinically indicated 
• 
External Genital & Speculum Exam 
      * For participants who have consented to the collection of samples for future use and use of left-over samples for future 
studies. 
 
 
7.5 Participants Who Become Pregnant 
Urine pregnancy tests will be performed at screening, enrollment, Visit 5, Visit 8, and as clinically 
indicated. Participants who become pregnant will be referred for care. Should the pregnancy be 
diagnosed during study follow-up, pelvic exams will only be performed to evaluate a participant's 
reported symptom. No genital specimens will be collected in a pregnant participant. 
Participants will be terminated from the study but will be contacted after their study participation 
to ascertain the pregnancy outcome. 
 
Study staff will report pregnancy details to the Antiretroviral Pregnancy Registry should an 
enrolled participant become pregnant during follow-up.   
7.6 Interim Visits 
Interim visits may be performed at any time during the study (and study procedures repeated as 
clinically indicated), for the following or other reasons: 
 
• 
For administrative reasons, e.g., a participant may have questions for study staff, or may 
need to re-schedule a follow-up visit. 
• 
In response to AEs.  When interim contacts or visits are completed in response to 
participant reports of AEs, study staff will assess the reported event clinically and provide 
or refer the participant to appropriate medical care.   
• 
In the event of laboratory processing issues (i.e. inconclusive STD testing, lost or 
inadequate sample 
• 
For other reasons at participant request. 
 
 Details of the interim visit will be recorded in the chart notes. 
 
7.7 Clinical Evaluations and Procedures 
Physical exams will include the following assessments:   
 
• 
Vital signs: 
o Blood pressure 
 
• 
Measurements of: 
o Weight (at Screening only) 
o Height (at Screening only) 
  
• 
Focused physical exam (at Screening only): 
o General appearance 
o Cardiac exam   
o Respiratory exam   
o Abdomen  
 
Additional assessments may be performed at the discretion of the examining clinician in 
response to symptoms or illnesses present at the time of the visit/exam. 
 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
7.8    Laboratory Evaluations 
 
Local/Clinical Laboratory 
Urine pregnancy test  
Rapid saliva HIV test  
Wet mount if clinically indicated 
Vaginal pH 
Dipstick urinalysis if clinically indicated 
Confirmatory HIV testing if indicated  
Pap smear if indicated 
 
MWRI Laboratories 
Cervical NAAT for chlamydia, gonorrhea 
Vaginal NAAT for trichomonas 
Vaginal Gram stain  
Quantitative vaginal cultures 
Quantitative vaginal PCR for selected microbiota 
Levels of cytokines and innate immunity factors from CVL 
Levels of glycoproteins and mucins in CVL 
Anti-viral activity from CVL 
Ex vivo HIV challenge of cervical tissue 
 
University of Colorado Lab 
MK-2048 levels in CVL, cervical tissue, rectal fluid, vaginal fluid and plasma 
Eudragit® levels in CVL 
 
7.9 Specimen Collection and Processing 
The site will adhere to the standards of DAIDS  good clinical laboratory practice and site standard 
operating procedures for proper collection, processing, labeling, handling, transport, and storage 
of specimens.  In cases where laboratory results are not available due to administrative or 
laboratory error, sites are permitted to re-draw and/or re-collect specimens. 
 
7.10 Biohazard Containment 
As the transmission of HIV and other blood-borne pathogens can occur through contact with 
contaminated needles, blood, and blood products, appropriate blood and secretion precautions 
will be employed by all personnel in the drawing of blood and shipping and handling of all 
specimens for this study as recommended by the CDC and NIH.  All biological specimens sent to 
the University of Colorado lab will be transported using packaging mandated by CFR 42 Part 72.  
Biohazardous waste will be contained according to institutional, transportation/carrier, and all 
other applicable regulations.   
 
8 
ASSESSMENT OF SAFETY AND CLINICAL MANAGEMENT 
 
8.1 Safety Monitoring 
The study site investigators are responsible for continuous close safety monitoring of all study 
participants, and for alerting the Protocol Team if unexpected concerns arise. A sub-group of the 
Protocol Team, including the Protocol Chair or designee, the DAIDS Medical Officer, and the 
External Safety Monitor (see section 8.2) will serve as the Protocol Safety Review Team (PSRT). 
Close cooperation among the PSRT and the study site will be necessary to monitor participant 
safety and respond to occurrences of toxicity in a timely manner. Appropriate safety monitoring 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
will be contingent upon excellent communication between study participants and study staff, and 
upon cooperation among study staff, investigators, the External Safety Monitor, and the DAIDS 
Medical Officer. Grade 3 or higher AEs will be reported by the site to the independent safety 
physician, DAIDS medical officer and Merck as appropriate no later than 48 hours after 
identification to ensure timely evaluation of safety data. 
 
8.2 Clinical Data Safety Review 
An External Safety Monitor who is familiar with the pertinent scientific literature related to the study 
product will be responsible for the first review of data and safety monitoring.  This physician, 
independent of the study sponsor, will be available to monitor data from this site.  His/her minimum 
qualifications will include experience as a physician and experience in the conduct of clinical 
research. This individual will not receive salary or other support from the grant. The External 
(Independent) Safety Monitor model has been used successfully for other Magee-Womens 
Hospital Reproductive Infectious Disease studies involving investigational products. The 
proposed individual will meet the qualifications outlined above and have training in the importance 
of the objective treatment of clinical safety data.   
 
The Data Management team for this site will generate data summaries for the Protocol Chair, the 
External Safety Monitor, and the DAIDS Medical Officer on  at least a monthly basis. More 
frequent ad hoc safety reviews can be implemented during the initial enrollment and throughout 
the study as needed. These data summaries will include adverse event, accrual and retention 
data. The External Safety Monitor will evaluate adverse event data independently as well to 
recommend to the PSRT whether the study protocol should continue as originally designed, 
should be changed, or should be terminated.   
 
Approximately once a month the PSRT will convene via email or telephone to review adverse 
event data. Only masked safety data will be reviewed by the PSRT.  If more urgent safety matters 
arise, telephone calls can occur more frequently.    
 
The IRB will be notified of any serious and unexpected adverse events according to the policies 
outlined in the University of Pittsburgh IRB Policy and Procedure Manual9. 
 
The following information will be submitted to the University of Pittsburgh IRB at the time of 
renewal of a research protocol, as required by the IRB guidelines: 
 
 
• 
The frequency of monitoring during the renewal interval, including the dates of data and 
safety monitoring; 
• 
A summary of any assessment performed to evaluate external factors or other relevant 
information that may have an impact on the safety of study volunteers or the ethics of the 
research study; 
• 
A summary of the outcome of procedural reviews conducted to ensure subject privacy and 
research data confidentiality; 
• 
Any conclusions regarding changes to the anticipated benefit-to-risk ratio of study 
participation and final recommendations related to continuing, changing, or terminating 
the study, with accompanying rationales as appropriate. 
 
Furthermore, should two Grade 3 or higher related AEs be reported, enrollment will be paused 
and an emergency meeting of the PSRT be called to order. The PSRT will review the cumulative 
data and give serious consideration to discontinuing enrollment. 
 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
 
8.3 Adverse Events Definitions   
An AE is defined as any untoward medical occurrence in a clinical research participant 
administered an investigational product and which does not necessarily have a causal relationship 
with the investigational product.  As such, an AE can be an unfavorable or unintended sign 
(including an abnormal laboratory finding, for example), symptom or disease temporally 
associated with the use of an investigational product, whether or not considered related to the 
product.  This definition is applied to all groups beginning from the time of randomization.   
 
Study participants will be provided instructions for contacting the study site to report any untoward 
medical occurrences they may experience, except for possible life-threatening events, for which 
they will be instructed to seek immediate emergency care.  Where feasible and medically 
appropriate, participants will be encouraged to seek evaluation at UPMC Magee-Womens 
Hospital, where the study clinicians are based, and to request that a study clinician be contacted 
upon their arrival.  All participants reporting a clinically significant untoward medical occurrence 
will be followed either in person or by phone until the occurrence resolves (returns to baseline) or 
stabilizes over a four week period. 
 
Study site staff will document  AEs reported by or observed in enrolled study participants 
regardless of severity and presumed relationship to study product.   
 
For each study participant, AE documentation and reporting will be undertaken throughout the 
scheduled duration of follow-up, i.e., through Visit 8. 
 
The PI/designee will grade the severity of each AE and the relationship of the AE to study product:   
 
AE severity will be graded per the DAIDS Table for Grading Adult and Pediatric Adverse Events, 
Version 2.1, July 2017 and the Female Genital Grading Table for Use in Microbicide Studies 
(Appendix 1, version 1.0, November 2007) except that asymptomatic BV will not be considered 
an AE. AEs not included in the Female Genital Grading Table will be graded by the DAIDS AE 
Grading Table Version 2.1, July 2017.  In cases where a genital AE is covered in both tables, the 
Female Genital Grading Table for Use in Microbicide Studies will be the grading scale utilized.   
 
The relationship of all reported AEs will be assessed based on the Manual for Expedited 
Reporting of Adverse Events to DAIDS (Version 2.0, dated January 2010) and the clinical 
judgment of the PI/designee.   
 
The relationship categories that will be used for this study are:  
Related: There is a reasonable possibility that the AE may be related to the study agent(s)  
Not related: There is not a reasonable possibility that the AE is related to the study agent(s)  
The study products that must be considered when AE relationships are assigned are the MK-
2048 films.   
 
The DAIDS Table for Grading Adult and Pediatric Adverse Events, the Female Genital Grading 
Table for Use in Microbicide Studies is available on the DAIDS Regulatory Support Center (RSC) 
web site:https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables   
 
All AEs will be captured on an AE log.  AEs should be reviewed at each study visit and updated 
as needed.  For any Grade 3 or higher AEs that are continuing at a participant’s study exit visit, 
the Protocol Chair/designee must establish a clinically appropriate follow-up plan for the AE and 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
review with the DAIDS Medical Officer.  At a minimum, the AE must be re-assessed by study staff 
at least 2 weeks after the participant’s study exit visit (Visit 8); additional evaluations also may 
take place at the discretion of the PI/designee.  The same approach must be taken for any AEs 
deemed related to study product that are still ongoing at the study exit visit (Visit 8).  For those 
AEs requiring re-assessment, if the AE has not resolved or stabilized at the time of re-assessment, 
study staff will continue to re-assess the participant at least once per month while the study is 
ongoing.     
 
8.4 Reporting of Unanticipated Problems and Serious AEs to DAIDS 
 
Relevant unanticipated problems such as study product concerns will be reported to the DAIDS 
MO within 1 business day. The following information about the critical event will be submitted to 
DAIDS MO:  
 
A detailed description of the problem and actions the study site is taking or plans to take to 
address the problem, such as suspending participant enrollment, termination of research, revising 
study protocol or informed consent documents, increasing monitoring of the study participant, etc. 
Any revisions to the study protocol and informed consent must be reviewed and approved by the 
DAIDS MO and study site IRB prior to implementation.  
 
Serious or continuing noncompliance and suspension/termination of IRB approval must be 
reported as critical events as well. 
 
Serious Adverse events will be reported to the DAIDS MO within 24 hours of the site becoming 
aware of the event.  As per the International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use ICH definition, a Serious Adverse Event (SAE) is any 
untoward medical occurrence that at any dose: 
-results in death, 
 
-is life-threatening 
 
-requires inpatient hospitalization or prolongation of existing hospitalization, 
 
-results in persistent or significant disability/incapacity, 
 
Or 
 
-is a congenital anomaly/birth defect 
 
 
8.5 Clinical Management of Adverse Events   
By definition, an adverse event can be either new finding or symptom or a worsening of a pre-
existing condition. In order to accurately capture adverse events in follow-up, a thorough baseline 
history will be obtained at Visit 1 and Visit 2.  For example, for participants who endorse a history 
of headache, site staff will probe for and record details surrounding the condition such as 
frequency, location, duration, medication use, triggers, etc. Only by eliciting a full description will 
study staff be equipped to determine whether a subsequent event in follow-up is a clinically distinct 
event or not. 
 
Adverse events will be elicited at each follow-up visit. Referral to appropriate care will be offered 
to participants as needed The study site is well equipped to manage treatment of all sexually 
transmitted infections and vaginitis identified during screening or during study participation except 
for HIV.  Participants who are found to be HIV infected will be referred for care.   The PI/designee 
should manage STI/RTI per CDC guidelines, available at http://www.cdc.gov.  Observed single 
dose treatment should be provided whenever possible.  Vaginally applied medications should not 
be used if possible.  
 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
8.5.1 Product Hold 
In the unlikely event that a participant is intolerant of the study product immediately after 
placement, the site clinician will perform a pelvic exam to remove all visible product. 
 
 
8.6 Social Harms Reporting 
Although study sites make every effort to protect participant privacy and confidentiality, it is 
possible that participants' involvement in the study could become known to others, and that social 
harms may result (i.e., because participants could become known as HIV-infected or at "high risk" 
for HIV infection). For example, participants could be treated unfairly or discriminated against, or 
could have problems being accepted by their families and/or communities and/or employer. 
 
Social harms that are judged by the study site investigator to be serious or unexpected will be 
reported to the DAIDS Medical Officer and the responsible site IRB at least annually or according 
to individual IRB requirements.  In the event that a participant reports social harm, every effort will 
be made by study staff to provide appropriate care and counseling to the participant, and/or 
referral to appropriate resources for the safety of the participant as needed 
 
8.7 Criteria for Early Termination of Study Participation 
Participants may voluntarily withdraw from the study for any reason at any time.  The Site 
PI/designee also may withdraw participants from the study to protect their safety and/or if they 
are unwilling or unable to comply with required study procedures. Participants also may be 
withdrawn if the study sponsors, government or regulatory authorities, including the Office of 
Human Research Protections (OHRP), or site IRBs/ECs terminate the study prior to its planned 
end date.  Every reasonable effort is made to complete a final evaluation of participants who 
withdraw or are withdrawn from the study prior to completing follow-up.  Study staff members will 
record the reason(s) for all withdrawals in participants’ study records.   
 
8.8 Reporting to the FDA 
The IND holder will be responsible for reporting any safety concerns to the FDA. 
 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
 
9 
STATISTICAL CONSIDERATIONS 
 
9.1 Review of Study Design 
 
The primary aim of this study is to assess the safety of a single dose of a MK-2048 vaginal film.  
All participants will be randomized to receive a single dose of a vaginal film containing MK-2048 
(either the high Eudragit® or low Eudragit® formulation). The film will be inserted by a clinician 
on the day of enrollment. Vaginal swabs and plasma will be collected at days 0, 3, 5, 7, 10, 14 
and 28. Rectal swab and genital biopsy samples will be obtained on day 7 and cervicovaginal 
lavage will be collected at screening, day 14 and day 28. 
 
9.2 Sample Size and Accrual 
 
The primary aim of the study is to assess the local and systemic safety of a single dose of two 
formulations of an MK-2048 vaginal film. The primary endpoint is the proportion of participants 
who experience a Grade 2 or higher adverse event. The proposed total sample size is N=48 
divided into 2 arms (low and high Eudragit® content assigned at a 1:1 ratio).  Based on previous 
studies of vaginal products conducted at the study site, the accrual of 48 eligible subjects with 
normal reproductive tracts is expected to require the screening of approximately 90 
volunteers.  Since unevaluable participants will be replaced, it is anticipated that 48 women 
exposed to study product will be evaluable for the primary endpoint.   
 
The sample size is based on the exact binomial probability of observing Grade 2 or higher adverse 
events. Table 4 gives the upper and lower bounds for the 95% exact binomial confidence intervals 
of the true Grade 2 or higher adverse event rate at all possible numbers of observed events in a 
group of size 24 or in the full cohort of 48. Note that the results for more than 50% of events in 
each group are not listed, but by symmetry can be calculated as 1- the listed rate and 95% CI for 
the number of non-events. If none of the 48 subjects experience Grade 2 or higher adverse 
events, the 95% exact 2-sided upper confidence bound for the Grade 2 adverse event rate is 
7.4%. In a previous study of a single dose of the high Eudragit® content placebo film, 6 grade 2 
adverse events were reported in a cohort of 64 women for an event rate of 9.4%. If similar event 
rates are observed in the proposed study, we will be able to rule out grade 2 or higher adverse 
event rates greater than 22.6% in the full cohort and 32.4% in each study arm. 
 
 
 
TABLE 4:  95% confidence intervals for the true rate at all possible observed Grade 2 or higher 
adverse event rates 
 
 
Number of 
observed 
events 
Rate (95% CI) 
Number of 
observed 
events 
Rate (95% CI) 
0/24 
0 (0, 14.2%) 
0/48 
0 (0, 7.4%) 
1/24 
4.2% (0.1%, 21.1%) 
1/48 
2.1% (0%, 11.1%) 
2/24 
8.3% (1.0%, 27.0%) 
2/48 
4.2% (0.5%, 14.3%) 
3/24 
12.5% (2.7%, 32.4%) 
3/48 
6.2% (1.3%, 17.2%) 
4/24 
16.7% (4.7%, 37.4%) 
4/48 
8.3% (2.3%, 20.0%) 
5/24 
20.8% (7.1%, 42.2%) 
5/48 
10.4% (3.4%, 22.6%) 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
6/24 
25.0% (9.8%, 46.7%) 
6/48 
12.5% (4.7%, 25.2%) 
7/24 
29.2% (12.6%, 51.1%) 
7/48 
14.6% (6.1%, 27.8%) 
8/24 
33.3% (15.6%, 55.3%) 
8/48 
16.7% (7.5%, 30.2%) 
9/24 
37.5% (18.8%, 59.4%) 
9/48 
18.8% (8.9%, 32.6%) 
10/24 
41.7% (22.1%, 63.4%) 
10/48 
20.8% (10.5%, 35.0%) 
11/24 
45.8% (25.6%, 67.2%) 
11/48 
22.9% (12.0%, 37.3%) 
12/24 
50.0% (29.1%, 70.9%) 
12/48 
25.0% (13.6%, 39.6%) 
 
 
13/48 
27.1% (15.3%, 41.8%) 
 
 
14/48 
29.2% (17.0%, 44.1%) 
 
 
15/48 
31.2% (18.7%, 46.3%) 
 
 
16/48 
33.3% (20.4%, 48.4%) 
 
 
17/48 
35.4% (22.1%, 50.5%) 
 
 
18/48 
37.5% (24.0%, 52.6%) 
 
 
19/48 
39.6% (25.8%, 54.7%) 
 
 
20/48 
41.7% (27.6%, 56.8%) 
 
 
21/48 
43.8% (29.5%, 58.8%) 
 
 
22/48 
45.8% (31.4%, 60.8%) 
 
 
23/48 
47.9% (33.3%, 62.8%) 
 
 
24/48 
50.0% (35.2%, 64.8%) 
 
 
9.3 Study Endpoints 
9.3.1 Primary Endpoint   
Grade 2 Adverse Events 
The safety/toxicity endpoint is clinical or laboratory evidence of a Grade 2 or higher Adverse Event 
as defined by the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 2.1, July 
2017 and the Female Genital Grading Table for Use in Microbicide Studies (Appendix 1 to the 
DAIDS Table for Grading Adult and Pediatric Adverse Events, (Dated November 2007). 
9.3.2 Secondary and Exploratory Endpoints 
The secondary and exploratory endpoints of this study are as follows: 
 
Secondary: MK-2048 pharmacokinetics 
 
MK-2048 concentrations in plasma, tissue homogenate, and CVL rectal and vaginal swab eluents, 
comparing the two film formulations sampled at enrollment and post-enrollment time-points 
through Visit 8  
 
Secondary: Acceptability 
Reports of overall acceptability of the film and qualities of the experience with the film will be 
measured using a self-report survey drawing items from two sources. Overall acceptability is 
measured using standard language in market research methodology, each using a 5-point 
agreement scale followed by an open-ended explanation. Assessment of film-specific qualities of 
the experience is assessed by a 9-item scale drawn from previous research with participant-
inserted films. Questions assess perceptions of leaking, vaginal dryness, and sensation of the 
film inside the vagina during and after insertion. 
Exploratory: Vaginal Microenvironment 
Given that there is no non-product use arm, participants will serve as their own control. 
Assessment of baseline microenvironment will take place during the Enrollment visit with the 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
exception of CVL properties. CVL will be obtained at the Screening visit so that the 
microenvironment can recover prior to study product administration at the enrollment visit.  
 
Levels of lectin binding and mucins measured in CVL samples 
Endogenous and exogenous glycolytic enzymes, formulated microbicide products, and microbial 
flora interact with mucins and may alter their structure and function. These alterations may be 
detected with lectins, which are sugar specific binding molecules, and can be bound to reporter 
molecules (such as horseradish peroxidase) in an ELISA type assay.  
 
Nugent Score 
Clinically significant changes in vaginal flora will be evaluated by a change in the Nugent score 
baseline (Visit 2, pre-exposure) through Visit 7.  The Nugent score is graded 1 to 10 as follows: 
Normal, 0 to 3 
Intermediate, 4 to 6 
BV, 7-10 
 
Any shift from normal at baseline to intermediate or BV at Visit 3, 4, 5, 6, 7, or 8 or shift from 
intermediate or BV to normal at Visit 3, 4, 5, 6, 7, or 8 will be considered a scientifically meaningful 
change in vaginal microbiota.   
 
Quantitative vaginal cultures and quantitative PCR 
Meaningful changes will be defined by greater than or equal to 1 log changes in dominant 
members of the microbiota, including Lactobacillus species, Gardnerella vaginalis, key anaerobic 
microorganisms, Enterococcus species, Escherichia coli, Staphylococcus aureus, Group B 
Streptococcus, and Candida species. 
 
Levels of anti-viral activity   in CVL 
In-vitro anti-HIV activity will be determined by the TZM-bl assay. 
 
The TZM-bl assay will determine HIV-1 infection by luciferase for single round of replication. To 
assess the potency of the CVL, serial dilutions will be made and tested to determine the IC50. 
 
Levels of biomarkers of innate immunity 
Changes in cervical cytokine expression and innate immunity factors in cervicovaginal lavage will 
be assessed.  Changes within each group will be reported. The factors to be analyzed will be 
determined on the scientific evidence at the time of the analysis. 
 
Exploratory: Pharmacokinetic (PK)/ Persistence of Eudragit® in CVL 
Persistence of polymer will be determined as detected levels of polymer in vaginal fluid collected 
through cervicovaginal lavage.  
 
Exploratory: Ex vivo challenge 
HIV infection of cervical biopsies as measured by HIV-1 p24 replication by ELISA and 
confirmation either by immunohistochemistry or quantitative PCR assessment of integrated 
provirus in HIV-1- exposed cervical biopsies. 
 
 

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9.4 Blinding 
All participants will receive a single dose of the MK-2048 vaginal film. They will be blinded to the 
formulation with respect to Eudragit® content. Evaluators of the study endpoints will also be 
blinded to the film formulation.  
 
 
9.5 Emergency Unblinding 
The Principal Investigator can proceed with unblinding for safety concerns, without prior 
consultation of the PSRT. Details of emergency unblinding are specified in an SOP. 
 
9.6 Random Assignment 
The randomization scheme will be generated and maintained by a member of the Data 
Management Center at the study site. and supplied to the Pharmacy.  Women will be randomized 
to one of the two arms at a 1:1 ratio using a permuted block design with random block sizes of 2, 
4, and 6.  In order to minimize bias in group assignment, participants will be given study 
identification numbers.  A study staff member will allot the identification numbers in sequential 
order as participants become eligible to enroll in the study. Numbered study film product packages 
will include sealed envelopes enclosing documentation of the randomized assignment to film 
formulation. The randomization scheme will be created for a total of 54 participants; the overage 
will be created to compensate for participant withdrawals or unusable products. 
 
9.7 Data Monitoring and Analysis 
9.7.1 Data Monitoring 
This clinical trial will be conducted in compliance with the protocol, GCP guidelines, and applicable 
regulatory requirements.  All research charts are maintained in locked files in a locked room. The 
research staff, under the direction of the primary investigator, will create and maintain electronic 
databases using REDCap (Research Electronic Data Capture) which is a secure, web-based 
application designed for clinical trial data collection that is validated for each study protocol. The 
databases will be backed up every night onto the University of Pittsburgh’s server’s back-up 
system.  Appropriate firewall and virus scanning software are installed and updated routinely by 
the university support staff. 
 
This study will utilize electronic data capture. Site staff will enter data as collected directly into a 
data entry system.  Study data management staff will review the electronic data elements for 
completeness and accuracy.  If there are any responses that are incomplete, unclear, or 
inconsistent with related data elements, the staff person will speak with the clinician in question 
as soon as possible to resolve the problem.  If necessary, the study staff will make the appropriate 
change in the electronic database which tracks time and date if a change is made.   
 
9.7.2 Primary Endpoint Analysis 
The number of adverse events will be summarized by severity, body system, and relationship to 
study product using frequencies and percent. Individual participants will contribute once to the 
calculation of event rates. Differences in the prevalence of adverse events between the study 
arms will be assessed using Fisher’s exact test. 
 
9.7.3 Secondary and Exploratory Endpoint Analysis 
Summary statistics of frequencies and percentages will be provided for categorical data.  Means 
and standard deviations or medians and ranges will be provided for continuous data. Methods for 
the analyses of the secondary endpoints are described below.  

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Student’s t- and Mann-Whitney U tests will be used, where appropriate, to evaluate differences 
in the following continuous variables between the study arms: MK-2048 concentrations in 
plasma, rectal and vaginal swab eluents, and genital tissue, levels of glycoproteins and mucins 
in CVL, levels of cytokines and innate immunity factors, and antiviral activity in CVL. Between 
group pre- to post-exposure changes in the above endpoints will also be evaluated using 
Student’s t- and Mann-Whitney U tests, where appropriate, while paired Student’s t- and 
Wilcoxon signed-rank tests will be used to evaluate these changes within each study arm. 
Mixed effects linear regression will be used to evaluate associations between days of exposure 
to study product and these outcomes.  
 
Nugent score will be categorized as follows: normal (score 0-3), intermediate (score 4-6), and 
bacterial vaginosis (score 7-10). Differences in the categorized Nugent score pre and post 
exposure levels will be evaluated using Fisher’s exact, while McNemar’s tests will be used to 
evaluate pre- to post-exposure shifts between normal (score 0-3) and abnormal (score 4-10) 
vaginal microflora within each study arm. Generalized estimating equations will be used to 
evaluate differences in the marginal post exposure prevalence of bacterial vaginosis between the 
two film formulations.  
 
Prevalence of microorganisms at each visit as assessed through culture and qPCR will be 
compared between the study arms using Fisher’s exact tests, while pre- to post-exposure shifts 
will be evaluated within each group using McNemar’s tests. Differences between the study arms 
in the quantity of microorganisms at each visit, as well as the change in quantity, will be evaluated 
using Mann-Whitney U tests. Meaningful changes will be defined by greater than  or equal to 1 
log changes in dominant members of the microbiota, including Lactobacillus species by 
quantitative PCR (qPCR), Prevotella species by qPCR, Gardnerella vaginalis (qPCR), Atopobium 
vaginae (qPCR) and Megasphaera phylotype I) qPCR).  Candida species, facultative gram 
negative rods, staphylococci and streptococci will be evaluated by cultivation based methods. 
Fisher’s exact tests will be used to evaluate differences in these changes between study arms.  
Mixed effects linear regression (for continuous outcomes) and generalized estimating equations 
(for binary outcomes) will be used to evaluate associations between days of exposure to study 
product and these outcomes. 
 
Descriptive statistics will be performed for HIV infection of cervical biopsies as measured by HIV-
1 p24 replication for each study arm and the combined cohort. Differences in HIV-1 p24 replication 
between study arms will be evaluated using Student’s t-or Mann-Whitney U test, as appropriate.  
 
9.7.4 Analysis Cohort 
The intent-to-treat cohort (ITT) will be defined as those who were randomized.  It will be used for 
analyses of baseline characteristics, protocol deviations and violations, and trial conduct. The 
evaluable cohort (Eval) is a subset of ITT participants. Evaluable participants will be defined as 
participants who complete the Screening and Enrollment visits and return for their day 7 visit 
within the window for a safety assessment.  Non-evaluable participants will be replaced.   
 
TABLE 5: Statistical Analysis Plan 
Endpoint 
Variable 
Statistics 
Primary 
 
Adverse Events 
Frequency, Percent 
Secondary 
MK-2048 concentration 
Mean, SD, Median, Range, 
Acceptability 
Frequency, Percent 

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  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
Exploratory 
Persistence of Eudragit® in CVL defined 
as any concentration above the lower 
limit of quantification 
Mean, SD, Median, Range  
Levels of glycoproteins and mucins, in 
CVL 
Mean, SD, Median, Range 
Antiviral activity in CVL 
Mean, SD, Median, Range 
 
Change in vaginal flora (Nugent score) 
Frequency, Percent, Median, 
Range 
 
Culture/qPCR results from vaginal 
organisms - prevalence 
Frequency, Percent 
Culture/qPCR results from vaginal 
organisms - concentration 
Mean, SD, Median, Range 
 
Change in cytokine and innate immunity 
factors 
Mean, SD, Median, Range 
HIV infection of cervical biopsies in ex 
vivo challenge 
Mean, SD, Median, Range 
10 HUMAN SUBJECTS CONSIDERATIONS 
 
The investigators will make efforts to minimize risks of these products to human subjects.  
Volunteers will take part in a thorough informed consent process throughout their participation in 
the study.  Before beginning the study, the investigators will have obtained IRB approval. The 
investigators will permit audits by the NIH or any of their appointed agents. 
  
10.1 Special Populations 
Study staff will offer screening to eligible women of all ethnic and racial groups.  Members of the 
study staff are not seeking the screening or enrollment of women in special or vulnerable 
populations.  The following section also discusses special considerations for male partners of 
participants. 
 
10.1.1 Men  
Men are not included as subjects in the study because the study is testing a vaginal application 
of the study product.  The male sexual partners of women participating in this study will not be 
consented or monitored for several reasons.  Protocol-specified guidelines for abstinence are 
expected to protect male partners from exposure to the study product.  In addition, based on 
preclinical data, no toxicity is anticipated from the study product.   
 
10.1.2 Children 
The NIH has mandated that children be included in research trials when appropriate.  This study 
will enroll women aged 18 to 20 who are able to give informed consent.  This study meets 
“Justifications for Exclusion” criteria for younger children as set forth by the NIH.  Specifically, "the 
research topic to be studied is irrelevant to (young) children" and "a separate, age-specific study 
in (adolescent) children is warranted and preferable" at a later time. 
 
10.1.3 Prisoners 
Prisoners will not be included in this study (for screening or enrollment).  Any participants 
incarcerated during the course of participation in the trial will not be followed during their 
incarceration and will be discontinued from the study.  Participants who have been released from 

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incarceration will be permitted to return for any protocol specified follow-up or safety visits per the 
guidelines of the local IRB. 
 
10.1.4 Pregnant women 
Pregnancy is an exclusion criterion as the vaginal microenvironment in pregnancy differs 
substantially from the non-pregnant state. Including pregnant participants would make the 
interpretation of study results difficult. Women who become pregnant during the study period 
following randomization will be terminated from the study. Participants who become pregnant 
during the course of the study will be contacted periodically after study termination in order to 
determine the pregnancy outcome. 
 
 
10.2 Informed Consent Process 
Written informed consent will be obtained from all potential study participants prior to the initiation 
of any study-related procedures. Only listed investigators who are physicians may obtain 
consent.  The informed consent process will give individuals all of the relevant information they 
need in order to decide whether to participate, or to continue participation, in this study.  Potential 
research participants will be permitted to ask questions and to exchange information freely with 
the study investigators.  Only listed study investigators may obtain informed consent from 
potential study participants.  The investigators will keep research participants fully informed of any 
new information that could affect their willingness to continue study participation.   
 
10.2.1 Risk/Benefit Statement 
Risks 
It is not expected that this trial will expose human subjects to unreasonable risk.  The intervention 
used in this study is unlikely to cause uncomfortable side effects and is only given once. However, 
there may be unknown risks or side effects associated with the use of the vaginal film.  Some 
women who used the film in other studies have reported vaginal discharge, and irritation and 
discomfort.  Women in studies involving the MK-2048 vaginal ring reported bacterial vaginosis, 
vulvovaginal candidiasis, vaginal burning, vaginal erythema, vaginal pain, and vaginal itching 
which investigators attributed to the study product. Only the vaginal candidiasis was Grade 2; the 
other AEs were Grade 1. 
 
Below is a list of potential risks of participation.  There may be other risks associated with 
participation that are not yet known.  
Procedure 
Risk  
Pregnancy Test 
• 
Anxious or nervous having test or waiting for results 
• 
Denial, depression or worry with unexpected positive result 
Pelvic Exam 
• 
Discomfort with speculum  
Genital and rectal 
specimens  
• 
Minimal discomfort from collection of specimens 
Cervical Biopsy 
• 
Generally well tolerated but may cause pain (or pinching) 
• 
Cramping similar to menstrual cramps 
o Cramping typically resolves within minutes after procedure 
o May take ibuprofen prior to biopsy to minimize cramping 
• 
Vaginal spotting or bleeding for a couple days 
o Typically less than a period but if heavier, instructed to 
contact study staff 
• 
Infection of biopsy area 

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o Unlikely but if foul odor or unusual discharge, instructed to 
contact study staff 
• 
A cut in the vagina can increase the risk of getting HIV if exposed 
• 
Risk of dislodging an IUD (if present) 
o If displaced, a new one would be inserted at no charge 
Vaginal use of  
MK 2048 film 
• 
Vaginal discharge, irritation, discomfort 
• 
Vaginal burning, itching, redness and/or pain  
• 
Yeast or bacterial infection 
• 
Allergic reaction 
Blood draw  
• 
Bruising, soreness, pain/discomfort, bleeding, infection at the site 
• 
lightheadedness, fainting 
Participation in 
research, 
collection and 
storage of private 
health 
information, 
biospecimens and 
internet 
communication* 
• 
Inconvenient 
• 
Breach of confidentiality  
Questionnaires 
• 
Discomfort with personal nature of questions 
 
STD/HIV testing 
• 
Worry or anxiety 
• 
Sadness, depression or denial with a positive test result 
o Positive gonorrhea and chlamydia test results will be reported 
to the Allegheny County Health Department according to the 
Commonwealth of Pennsylvania reporting requirements 
o May be contacted and asked questions about sexual partners 
*We will make reasonable efforts to protect the privacy of information on social media. Each platform has 
their own privacy policies and terms of use that may change at any time. The University of Pittsburgh cannot 
guarantee the privacy and confidentiality of information shared on social media in this research study. 
Participants information may not remain private. Participants will be instructed to visit site privacy policies 
and update privacy settings, as necessary. Social media retains information shared across accounts for an 
unknown length of time and it may be shared with others including targeted advertisers. 
 
Pregnancy, Breastfeeding and Sexual Practices 
The vaginal film is not a birth control method.  We do not know what effect the study drug may 
have on pregnancy, including the effect of the study drug on the fetuses of women who use the 
vaginal film when pregnant, or the babies of women who use the vaginal film when breastfeeding.  
Because of this, pregnant women and women who are breastfeeding may not join this study.  
Women who join the study must agree to avoid sexual intercourse from V2 (enrollment) until V7 
(7 days after the biopsy visit) as well as 48 hours prior to study visits, use an effective method of 
birth control and have scheduled pregnancy tests while in the study. Effective methods of birth 
control include hormonal methods (like "the pill" or Depo-Provera injections), the IUD, sterilization 
(or "tied tubes"), abstinence (or not having sex), same sex partner, or having a partner who has 
had a vasectomy. Effective methods of birth control cannot include use of a diaphragm, NuvaRing, 
or spermicide. Participants must agree to use an effective method of birth control until the last 
study visit, approximately 4 weeks after enrollment.  
 
In the unlikely event that a participant becomes pregnant during the study, study staff will refer 
her to available medical care and other services as needed.  The study does not pay for this care.  

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Participants will be terminated from the study; however, since the outcome of the pregnancy is 
important to study staff; women will be followed through the outcome of the pregnancy.  
 
If a participant were to become HIV infected while using the study product, the HIV virus may 
develop resistance to MK-2048.  Developing MK-2048 resistance means that the MK-2048 may 
not be able to treat HIV however, MK-2048 is not currently used to treat HIV. Participants who are 
diagnosed with HIV in follow-up will be referred for care and exited from the study.   
 
Benefits 
As this is a Phase I study and it will be the first time these investigational films will be tested in 
humans, there is no expectation of potential direct benefit from the study intervention, only the 
potential for ancillary benefits. Information learned from this study may help in the development 
of vaginal products for women.  Women will have exams and HIV/STD testing as part of 
participation in this study. 
 
10.3 Incentives 
Volunteers will not be charged for any of the study visits, study supplies or examinations.  There 
are no costs to participants in this study.  Pending IRB approval of these compensation guidelines, 
women will be compensated for their time and inconvenience and for their travel needs while 
participating in the protocol.  The approved amounts of compensation for the time commitment of 
participants will be given out at each visit.  The visits will be pro-rated and partial payment given 
in the event that the participant only completes a portion of the study visits.  The following 
proposed compensation amounts were created based on common institutional practice for studies 
investigating vaginal products, as well as studies utilizing observation periods in the Clinical 
Translational Research Center.  
 
Visit 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
Compensation 
$30 
$40 
$30 
$30 
$100 
$30 
$30 
$40 
Incentive if all visits in window 
 
 
 
 
 
 
 
$40 
Optional procedures 
 
* 
 
 
 
 
 
 
* V2 INCLUDES OPTIONAL SAMPLING: Two vaginal swabs collected without a speculum and 
one blood sample collected following film insertion.   
o Optional collection times are at 1, 2, 3, 4, 5, or 6 hrs.   
o Additional compensation will be provided for each sample collected ($10 per vaginal 
swab and $20 for blood draw plus an additional $10 for each sample collected between 
4 – 6 hours). 
 
Total compensation for all required visits = $370.  Potential compensation for all visits, including 
the maximum compensation for optional visits = $440. 
 
If a participant completes a visit outside of the protocol window for that visit, $10 will be deducted 
from the scheduled visit payment.  
 
In addition, a parking pass, bus pass or assistance with transportation will be provided to 
participants as needed.  
 
10.4 Participant Confidentiality 
Members of the study staff are all trained in patient confidentiality.  The log of study subject names 
and other protected health information is kept in a locked area.  All computer information about 
study volunteers is kept on a computer with log-on passwords.  Laboratory specimens are labeled 
with study numbers and date, and are delivered by study staff.   In addition to the research study 

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staff, the NIH, study monitors, University of Pittsburgh Research Conduct and Compliance Office, 
the Office of Human Research Protections, and/or the University of Pittsburgh IRB may have 
access to participant’s health information. Each member of the staff has log-on identification and 
password, logs off before leaving a computer screen unattended, and closes their office door 
when out of the office.  All research records will be kept for a minimum of seven years following 
closure of this study (per University of Pittsburgh policy).    
 
10.5 Communicable Disease Reporting 
Study staff members will comply with all local requirements to report communicable diseases 
including chlamydia, gonorrhea, and HIV identified among study participants to the Allegheny 
County Health Department.  Study investigators will include discussion of mandated reporting 
during the study informed consent process. 
 
10.6 Study Discontinuation 
NIAID or the University of Pittsburgh Institutional Review Board may discontinue this study at any 
time.  Ongoing safety monitoring will track the incidence of AEs and EAEs.  In the event of an 
abnormal number of reported AEs and/or EAEs judged to be related to study product the External 
Safety Monitor will contact the Principal Investigator to initiate a temporary hold on further 
enrollment. 
11 LABORATORY SPECIMENS AND BIOHAZARD CONTAINMENT 
 
11.1 Laboratory Specimens 
Laboratory specimens will be handled in a manner consistent with institutional, OSHA, and GLP 
guidelines.  Study staff members are trained in the appropriate handling of laboratory specimens.  
Samples such as urine that will be divided for multiple analyses will be divided according to site 
SOP. 
   TABLE 6:  Laboratory Test Methods 
SAMPLE 
METHOD 
LABORATORY 
 
URINE 
Pregnancy test 
Clinical Research Center 
CLIA #39D1031322 
Urine dipstick 
 
SALIVA 
Rapid HIV 
Clinical Research Center 
CLIA #39D1031322 
 
BLOOD 
Confirmatory HIV 
 
 
UPMC Presbyterian Shadyside CP PUH 
CLIA# 39D0911193 
MK-2048 Level 
University of Colorado  
(non-diagnostic laboratory) 
RECTAL 
MK 2048 Level 
University of Colorado  
(non-diagnostic laboratory) 
 
 
 
 
VAGINAL* 
pH 
Clinical Research Center 
CLIA #39D1031322 
Wet Mount 
 
 
 
Magee-Womens Research Institute 
CLIA #39D1004688 
Trichomonas (NAAT) 
Gram Stain 
Quantitative Vaginal Culture 
Quantitative PCR for 
microbiota 
MK 2048 Level in CVL 
University of Colorado  
(non-diagnostic laboratory) 
 
 
 
GC/CT (NAAT) 
Magee-Womens Research Institute 
CLIA #39D1004688 

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CERVICAL* 
 
Cervical biopsy tissue for ex 
vivo challenge 
Magee-Womens Research Institute 
(non-diagnostic laboratory) 
Cervical biopsy tissue for 
MK 2048 level 
University of Colorado  
(non-diagnostic laboratory) 
Pap smear 
UPMC Magee-Womens Hospital  
CLIA# 39D0177794 
 
 
 
 
 
 
CVL 
Levels of antiviral activity 
Magee-Womens Research Institute/Parikh 
Laboratory 
(non-diagnostic laboratory) 
Levels of glycoproteins and 
mucins 
Magee-Womens Research Institute/Moncla 
Laboratory (non-diagnostic laboratory)   
Levels of cytokines & innate 
immunity factors 
Magee-Womens Research Institute/Hillier 
Laboratory  
(non-diagnostic laboratory) 
MK-2048 level 
University of Colorado  
(non-diagnostic laboratory) 
Eudragit® level 
University of Colorado  
(non-diagnostic laboratory) 
      *Future Use Samples will be stored at Magee-Womens Research Institute; use and processing lab to be determined 
11.1.1 Urine Samples 
Study staff at the clinical site will utilize dipstick urinalysis to screen for possible urinary tract 
infection as clinically indicated.  Urine will be tested for HCG via the Sure-Vue® test or equivalent. 
 
11.1.2 Vaginal Samples 
The assessment of vaginal flora will be based on the Nugent Scoring System for Gram Stained 
Vaginal Smears as well as assessment of several groups of organisms by cultivation (culture) 
based methods.  In addition, selected microbiota will be detected using a quantitative polymerase 
chain reaction (qPCR) test which has been developed and validated within the laboratory.  MK-
2048 vaginal concentrations will be measured according to SOP. 
 
Collection will be done as gently and carefully as possible so as to collect an adequate sample 
that is unlikely to disturb the mucosa or overall vaginal microenvironment or the vaginal film in 
situ.  Trichomonas vaginalis will be detected using an amplified DNA assay and handled 
according to policies outlined in SOPs for this study. 
 
11.1.3 Rectal Swabs 
MK-2048 concentrations will be quantified according to the SOP. 
 
11.1.4 Cervical Samples 
C. trachomatis and N. gonorrhoeae  will be detected using an amplified DNA assay and handled 
according to policies outlined in SOPs for this study.  
 
Pap smears collected as part of screening will be processed and resulted by UPMC Magee-
Womens Hospital cytology department.  
  
11.1.5 Cervicovaginal Lavage Samples 
MK-2048 Content in CVL 
Aliquots of lavage samples will be tested for MK-2048 levels (according to SOP).   

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Eudragit® Content in CVL 
Aliquots of lavage samples will be tested for Eudragit® levels (according to SOP) 
 
Anti-viral Activity in CVL 
Aliquots of lavage samples will be tested for anti-viral and antibacterial activity as outlined in the 
site SOPs.  
 
Cervical Cytokines and Innate Factors in CVL 
Cytokines (for example, IL-1β and TNFα) along with innate immune factors (for example, 
antiproteases) that could contribute to a proinflammatory milieu or changes in the glycomic 
signatures may be evaluated. The factors to be analyzed will be determined on the scientific 
evidence at the time of the analysis. 
 
Glycome Studies 
Aliquots of lavage samples will be tested for glycoproteins and mucins. 
 
11.1.6 Cervical Tissue 
MK-2048 Concentration in Cervical Tissue 
Tissue from cervical biopsies will be processed at the University of Colorado and concentrations 
of MK-2048 measured. 
 
Ex-vivo Challenge 
The efficacy of study product to prevent HIV infection will be based on an ex vivo HIV biopsy 
challenge model as outlined in the site SOP.  
 
11.2 Quality Control and Quality Assurance Procedures 
Dr. Sharon Hillier, who completed a training program in clinical and public health microbiology 
certified by the American Board of Medical Microbiology (ABMM), directs the Infectious Disease 
Research Laboratory at Magee-Womens Research Institute.  This laboratory is CLIA-inspected 
and maintains its own CLIA license.  Thus, all testing done in this research laboratory is performed 
with the same level of quality control as required in a licensed clinical laboratory.   
 
11.3 Specimen Storage and Possible Future Research Testing 
Part of the consent form will include an explanation of future use of vaginal and cervical specimens 
and blood samples.  Any future use or residual samples will be stored at Magee-Womens 
Research Institute, Microbiology Laboratory, 5th floor for an indefinite period of time.  The principal 
investigator will assume primary responsibility for control of this area. 
 
Any results from research done on future use or leftover specimens will not be placed in health 
records and will be kept confidential. The language and format employed in the consent for these 
purposes are an IRB-approved means commonly employed in studies performed at this and other 
study sites within our institution to obtain permission for use of stored samples.  All primary study 
endpoints, protocol-specified testing, and QA/QC testing will be ascertained prior to any additional 
testing of stored specimens.   
 
11.4 Biohazard Containment 
Biohazardous waste will be contained according to institutional and all other applicable 
regulations. 
 

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12 ADMINISTRATIVE PROCEDURES 
The study proposal for funding, this protocol, the informed consent document, data collection 
forms, and advertising flyers are all reviewed by the University of Pittsburgh Institutional Review 
Board prior to enrollment of participants in the study. 
 
12.1 Protocol Registration 
Prior to implementation of this protocol, and any subsequent full version amendments, the study 
site must have the protocol and the protocol consent form(s) approved, as appropriate, by their 
local institutional review board (IRB)/ethics committee (EC) and any other applicable regulatory 
entity (RE). Upon receiving final approval, the site will submit all required protocol registration 
documents to the DAIDS PRO at the Regulatory Support Center (RSC).  The DAIDS PRO will 
review the submitted protocol registration packet to ensure that all of the required documents 
have been received. 
 
Site-specific informed consent forms (ICFs) WILL NOT be reviewed or approved by the DAIDS 
PRO, and sites will receive an Initial Registration Notification when the DAIDS PRO receives a 
complete registration packet. Receipt of an Initial Registration Notification indicates successful 
completion of the protocol registration process. The site will not receive any additional notifications 
from the DAIDS PRO for the initial protocol registration. A copy of the Initial Registration 
Notification should be retained in the site's regulatory files. 
 
Upon receiving final IRB/EC and any other applicable RE approval(s) for an amendment, the 
study site should implement the amendment immediately. The site is required to submit an 
amendment registration packet to the DAIDS PRO at the RSC. The DAIDS PRO will review the 
submitted protocol registration packet to ensure that all the required documents have been 
received. Site-specific ICF(s) WILL NOT be reviewed and approved by the DAIDS PRO and sites 
will receive an Amendment Registration Notification when the DAIDS PRO receives a complete 
registration packet. A copy of the Amendment Registration Notification should be retained in the 
site's regulatory files. 
 
For additional information on the protocol registration process and specific documents required 
for initial and amendment registrations, refer to the current version of the DAIDS Protocol 
Registration Manual, available at http://rsc.tech-res.com/protocolregistration/   
 
12.2 Data Coordination 
Data management responsibilities will reside with the Data Management staff at Magee-Womens 
Hospital. 
 
12.3 Study Monitoring 
The University of Pittsburgh Education and Compliance Office for Human Subject Research 
(ECO-HSR) will assist with the monitoring as outlined in the study monitoring plan.  
 
The site investigator will make study documents (e.g., consent forms, drug distribution forms, 
eCRFs) and pertinent hospital or clinic records readily available for inspections by the local IRB, 
the site monitors, the FDA, NIAID/DAIDS, the OHRP, and other local, US, or international 
regulatory entities for confirmation of the study data. 
 
 
12.4 Protocol Compliance 
All protocol amendments will be submitted to and approved by the University of Pittsburgh IRB 
and  DAIDS prior to the implementation of an amendment. 

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12.5 Investigator’s Records 
The investigator will maintain, and store securely, complete, accurate and current study records 
throughout the study.  Study records will not be destroyed prior to receiving approval for record 
destruction from the Principal Investigator and they will be maintained for a minimum of seven 
years following completion of the study, per the University of Pittsburgh IRB policy.  Applicable 
records include source documents, site registration documents and reports, correspondence, 
informed consent forms, and notations of all contacts with the participant.   
 
12.6 Use of Information and Publications 
Publication of study results will be governed by DAIDS policies.  The investigators will submit any 
presentation, abstract, or manuscript to DAIDS for review prior to submission.  
 
12.7 Training Procedures 
Only study staff trained in applicable study procedures and staff experienced in HIV pre-test and 
post-test counseling will perform these study procedures.  Approved written materials consistent 
with the local clinical standard of care will support pre-test and post-test counseling.   

                                                                                                                    Page 48 of 59 
 
  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
 REFERENCES 
1. 
UNAIDS 
2017 
Global 
HIV 
and 
AIDS 
Statistics. 
Accessed 
at 
https://www.unaids.org/en/resources/fact-sheet     
2. 
UNAIDS 
Women 
and 
Girls 
and 
HIV. 
Accessed 
at 
https://www.unaids.org/sites/default/files/media_asset/women_girls_hiv_en.pdf 
3.  
Steiner M, Spruyt A, Joanis C, et al. Acceptability of spermicidal film and foaming tablets among 
women in three countries. International Family Planning Perspectives 1995;21:104-7. 
4. 
Visness CM, Ulin P, Pfannenschmidt S, Zekeng L. Views of Cameroonian sex workers on a woman-
controlled method of contraception and disease protection. Int J STD AIDS 1998;9:695- 
5. 
Nel AM, Mitchnick LB, Risha P, Muungo LT, Norick PM. Acceptability of vaginal film, soft-gel 
capsule, and tablet as potential microbicide delivery methods among African women. J Womens Health 
(Larchmt) 2011;20:1207-14. 
6.  
Raymond E, Alvarado G, Ledesma L, et al. Acceptability of two spermicides in five countries. 
Contraception 1999;60:45-50. 
7.  
Montgomery E, Beksinska M, Mgodi N, et al. End-user preference for and choice of four vaginally 
delivered HIV prevention methods among young women in South Africa and Zimbabwe: the Quatro 
Clinical Crossover Study. J Int AIDS Soc. 2019 May;22(5):e25283.  
8.          Magee-Womens Research Institute and Foundation MK-2048 30mg Extended Release Vaginal 
Film. 2019 
9. 
Merck Sharp & Dohme Corp. MK-2048 Investigational Brochure. 2014. 
10.  
Hoesley CJ, Chen BA, Anderson PL, et al. Phase 1 safety and pharmacokinetics study of MK-2048/ 
Vicriviroc (MK-4176)/MK-2048A intravaginal rings. Clinical Infectious Disease 2019;68:1136-1143. 
11. 
Liu AY, Zhang J, Anderson PL, et al. Phase 1 pharmacokinetic trial of 2 intravaginal rings containing 
different dose strengths of Vicriviroc  (MK-4176) and MK-2048. Clinical Infectious Disease 2019;68:1129-
1135. 
12.  
Dobard C, Sharma S, Parikh UM, et al. Postexposure protection of macaques from vaginal SHIV 
infection by topical integrase inhibitors. Sci Transl Med. 2014 Mar 12;6(227):227  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    
 

                                                                                                                    Page 49 of 59 
 
  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
APPENDIX 1:  SCHEDULE OF STUDY VISITS AND PROCEDURES 
Component 
Procedure/Analysis 
V1:  
Screen 
V2:  
Enroll 
V3-7 
V8 
 
 
 
 
 
 
ADMINISTRATIVE 
Written Informed Consent 
X 
 
 
 
Assign Study Number (PTID) 
X 
 
 
 
Review/Confirm Eligibility 
X 
X 
 
 
Collect/Update Contact Information 
X 
X 
X 
X 
Medical Hx/Concomitant Meds 
X 
X 
X 
X 
Visit Questionnaire 
X 
X 
X 
X 
HIV Pre-/Post-Test Counseling 
X 
 
 
 
Screening Results 
X 
X 
 
 
Protocol counseling 
X 
X 
X 
 
Assess/Document Adverse Events 
 
X 
X 
X 
Schedule Next Study Visit 
X 
X 
X 
 
Participant Reimbursement 
X 
X 
X 
X 
ACCEPTABILITY 
Acceptability Questionnaire 
 
X 
V5 ONLY 
 
 
URINE 
Pregnancy test 
X 
X 
^ & V5 
X 
Urine dipstick 
^ 
^ 
^ 
^ 
SALIVA 
Rapid HIV 
X 
 
 
 
BLOOD 
Confirmatory HIV 
^ 
 
 
 
MK-2048 levels 
 
X* 
X 
X 
 
 
 
VAGINAL SAMPLES 
 
pH 
X 
X 
X 
X 
Wet Mount 
^ 
^ 
^ 
^ 
Trichomonas (NAAT) 
X 
 
^ 
^ 
Gram Stain 
 
X 
X 
X 
Quantitative Vaginal Culture 
 
X 
X 
X 
Quantitative PCR for microbiota 
 
X 
X 
X 
Vaginal Sample for Future Use** 
X 
X 
X 
X 
MK-2048® level 
 
X* 
X 
X 
 
CERVICAL SAMPLES 
GC/CT (NAAT) 
X 
 
^ 
^ 
Cervical Sample for Future Use** 
X 
X 
X 
X 
Pap smear 
^ 
 
 
 
Cervical Biopsies 
 
 
V5 ONLY 
 
RECTAL SAMPLES 
MK-2048 level 
 
 
V5 ONLY 
 
 
 
CVL 
Levels of antiviral activity 
X 
 
V7 ONLY 
X 
Glycoproteins and mucins 
X 
 
V7 ONLY 
X 
Cytokines & innate immunity 
factors 
X 
 
V7 ONLY 
X 
Eudragit® level 
X 
 
V7 ONLY 
X 
MK-2048 level 
X 
 
V7 ONLY 
X 
 
PHYSICAL EXAM 
Physical Exam 
X 
^ 
^ 
^ 
Vital Signs (BP) 
X 
X 
X 
X 
Height & Weight 
X 
 
 
 
 
PELVIC EXAM 
Bimanual Exam 
^ 
^ 
^ 
^ 
External Genital & Speculum Exam 
X 
X 
X 
X 
STUDY PRODUCT 
Study Product Randomization 
 
X 
 
 
Film Distribution 
 
X 
 
 
Film Insertion by Clinician 
 
X 
 
 
X Required 
 
 
       
^ PRN/as clinically indicated 
* Additional OPTIONAL vaginal swabs (up to 2) and single blood sample at 1, 2, 3, 4, 5, 6hrs post film   
   Insertion 
** For participants who have consented to the collection of samples for future use and use of left-over samples for future studies. 

                                                                                                                    Page 50 of 59 
 
  FAME 103 Protocol Version 1.0 20Dec2019                                                                      
 
APPENDIX II:  HIV TESTING AGORITHIM 
 
 
 
START 
SAMPLE 1 
OraQUICK® Rapid 
HIV Test 
IF 
NEGATIVE 
→ 
STOP 
REPORT AS HIV-
UNINFECTED; 
ENROLL IN STUDY 
 
 
 
IF POSITIVE 
 
 
 
 
 
 
↓ 
 
REPORT AS 
INDETERMINATE, 
REQUIRES 
ADDITIONAL 
TESTING 
IF  
INDET. 
← 
SAMPLE 2 
HIV Ab/Ag Plasma 
Testing 
IF 
NEGATIVE 
 
 
 
 
IF POSITIVE 
 
 
 
 
↓ 
 
 
 
 
REPORT AS HIV-
POSITIVE, 
REQUIRES 
CONFIRMATORY 
TESTING 
 
 
 
 
 
↓ 
 
 
 
 
REFERRALFOR 
CARE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  

                                                                                                                    Page 51 of 59 
 
 
FAME 103 Protocol Version 1.020Dec2019 
 
 
 
 
 
 
 
 
 
 
APPENDIX III:  SAMPLE INFORMED CONSENT 
 
CONSENT TO ACT AS A PARTICIPANT IN A RESEARCH STUDY 
  
STUDY TITLE:   
A Randomized, Double Blinded Study of the Safety and Pharmacokinetics of Two 
Vaginal Film Formulations Containing the Integrase Inhibitor MK2048:  FAME 103 
 
INFORMED CONSENT VERSION:  Version 1.0, 12/20/2019 
 
PRINCIPAL INVESTIGATOR:  Katherine Bunge, MD 
    UPMC Magee-Womens Hospital, Dept of OB/GYN/RS,  
    300 Halket Street, PGH, PA  15213 
 
QUESTIONS ABOUT THE STUDY: Contact the research staff at 412-641-4242 or after hours at 412-463-
1337 
 
FUNDING AGENCY:  Division of AIDS, US National Institute of Allergy and Infectious Diseases, US National 
Institutes of Health 
 
 
KEY INFORMATION 
Participation is voluntary.  You are being asked to take part in a research study.  Research studies include 
only people who choose to take part.  The study team members will explain the study to you and will answer 
any questions you might have.  You should take your time to make your decision. 
 
Summary of study. This study includes approximately 48 healthy non-pregnant women aged 18 – 45 who 
agree to use a single investigational (experimental) vaginal film and return for 6 follow up visits.  The vaginal 
film, which is a thin square similar to a Listerine® breath strip, contains an investigational medication called 
MK2048.  MK2048 is not approved by the Food and Drug Administration (FDA). This study will assess the 
safety and acceptability of the film.    
 
Visits (8 in total) 
Time 
Key component(s) of visit 
Screen 
Today 
Determine eligibility; includes STD/HIV testing  
Enrollment 
Within 45 days 
Vaginal film insertion by a clinician 
Required Follow-up Visits 
Days 3, 5, 7, 10, 14, 
28 
Blood and genital* sample collection at each visit; 
Cervical biopsies and rectal swabs at Day 7 visit only  
*Genital samples refer to vaginal, cervical and/or rectal samples  
 
Risks. The main risks of participation include the risks of using an investigational vaginal film, blood draws and 
cervical biopsies.  The number of study visits may be inconvenient.   
 
Benefits.  There is no direct benefit to participating, however some participants may get satisfaction taking part 
in a study that involves women’s health.  
 

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FAME 103 Protocol Version 1.020Dec2019 
 
 
 
 
 
 
 
 
 
Right to withdrawal.  You may withdraw from the study at any time if you chose.   
 
Alternatives.  The alternative is not to participate in this study.     
 
**************************************************************************************** 
YOUR PARTICIPATION IS VOLUNTARY 
Participation in research is a personal decision; you are under no obligation to participate.  If you agree to take 
part, you will be asked to sign your name on this form and will be offered a copy to keep.  Your regular doctor 
may be part of this study team.  You should take your time to make a decision and discuss with others if needed. 
 
STUDY PRODUCTS AND PURPOSE OF STUDY 
Two different vaginal films will be tested in this study.  Both films contain the same amount of an investigational 
medication called MK2048.  MK2048 has been used in other studies to look at HIV prevention.  The two films 
differ in the amount of polymer (“binding” or “delivery” agent).   
 
Films 
MK2048 dose 
Size 
# of participants 
high polymer* 
30mg 
2” x 2” 
24 
low polymer  
30mg 
2” x 2” 
24 
*used in a previous placebo (blank, no drug) film study of 64 women and was safe and acceptable    
 
The Food and Drug Administration (FDA) has not approved MK2048 film for use.  While MK2048 has been 
tested in humans, including vaginal dosing via vaginal ring, this is the first time MK2048 has been tested in a film 
form in humans. Importantly, all the ingredients that make up the film, including the polymers have been tested 
in humans and have been found to be safe.   
 
This study is testing the safety of MK2048 film when used once.  Cervical biopsies, vaginal and rectal samples, 
and blood will be collected to see how much MK2048 gets into the genital tissue and/or bloodstream.  The 
cervical tissue will be exposed to HIV in the lab to understand whether the film can help to prevent HIV infection 
when tested outside the body.   
 
This study is not testing if MK2048 vaginal film prevents you from getting infected with HIV.  Researchers do not 
yet know if the film will work in humans to protect against HIV.  The best way to protect against getting HIV 
infection during sex is to use a condom every time you have sex. 
 
Eligible women will be randomized (50/50 chance, like flipping a coin) at visit 2 (V2) to have one of two films 
inserted (high polymer or low polymer).  You cannot choose your group.  Both films are packaged identically, so 
neither you nor study staff will know which group you are in.  All women will follow the same study visit schedule. 
 
 
STUDY VISIT HIGHLIGHTS 
• 
All research activities will take place at UPMC Magee-Womens Hospital.  
• 
A screening visit (V1) will determine if you are eligible to participate.  You are under no obligation to 
participate even if you are found to be eligible.  Screening can occur over more than one visit, if necessary. 
• 
If eligible and interested, you will be asked to return within 45 days to be enrolled (V2).  At V2, you will have 
the assigned vaginal film inserted into the vagina by a research clinician.   

                                                                                                                    Page 53 of 59 
 
 
FAME 103 Protocol Version 1.020Dec2019 
 
 
 
 
 
 
 
 
 
• 
There are 6 follow-up visits (V3 – V8).  Window periods for visits will allow some flexibility in scheduling 
study visits.  Genital and blood samples are collected to establish your baseline and to check drug levels 
throughout the study.   
• 
 
    This table outlines the visit schedule and study procedures.   
 
STUDY PROCEDURES 
STUDY VISIT 
SCREEN ENROLL 
FOLLOW-UP 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
Day 
-45 
0 
3 
5 
7 
10 
14 
28 
Length of Visit 
1hr 
1hr 
30m 
30m 
30m 
30m 
30m 
30m 
Medical History & Medication 
review 
x 
x 
x 
x 
x 
x 
x 
x 
Visit Questionnaire 
x 
x 
x 
x 
x 
x 
x 
x 
Collect/update contact information 
x 
x 
x 
x 
x 
x 
x 
x 
HIV Rapid Test 
x 
 
 
 
 
 
 
 
HIV Confirmatory Test 
^ 
 
 
 
 
 
 
 
Review Applicable Test Results 
x 
x 
 
 
 
 
 
 
Protocol Counseling  
x 
x 
x 
x 
x 
x 
x 
 
Urine pregnancy test 
x 
x 
 
 
x 
 
 
x 
Blood draw (MK2048 level) 
 
x 
x 
x 
x 
x 
x 
x 
Pelvic Exam with speculum 
x 
x 
x 
x 
x 
x 
x 
x 
Genital sample collection 
x 
x 
x 
x 
x 
x 
x 
x 
STD testing 
x 
 
 
 
 
 
 
 
Pap smear 
^ 
 
 
 
 
 
 
 
CVL (vaginal “wash” with saline) 
x 
 
 
 
 
 
x 
x 
Cervical Biopsies 
 
 
 
 
x 
 
 
 
Rectal Swab (MK2048 level) 
 
 
 
 
x 
 
 
 
Brief Physical Exam 
x 
 
 
 
 
 
 
 
Height and Weight 
x 
 
 
 
 
 
 
 
Blood pressure 
x 
x 
x 
x 
x 
x 
x 
x 
MK2048 
Film 
Insertion 
(by 
clinician) 
 
x 
 
 
 
 
 
 
Acceptability Questionnaire 
 
x 
 
 
x 
 
 
 
Compensation 
$30 
$40 
$30 
$30 
$100 
$30 
$30 
$40 
Incentive if all visits in window 
 
 
 
 
 
 
 
$40 
Optional procedures 
 
* 
 
 
 
 
 
 
 
^ as necessary 
* V2 INCLUDES OPTIONAL SAMPLING: You may choose to have up to two vaginal swabs collected without a 
speculum and one blood sample collected following film insertion.   
o Optional collection times are at 1, 2, 3, 4, 5, or 6 hours following film insertion.   
o Additional compensation will be provided for each sample collected as follows: 
 
1, 2, 3 hour collection 
4, 5, 6 hour collection 
Vaginal Swab 
$10 
$20 

                                                                                                                    Page 54 of 59 
 
 
FAME 103 Protocol Version 1.020Dec2019 
 
 
 
 
 
 
 
 
 
Blood Sample 
$20 
$30 
 
 
ADDITIONAL STUDY VISIT PROCEDURE INFORMATION 
• 
Visit Questionnaires include asking things like sexual history, vaginal product use, and vaginal symptoms 
• 
HIV testing will be done as part of the study. 
o A saliva sample will be tested for the antibody to HIV. An antibody is a substance that blood cells 
make to fight infection. Exposure (contact) to the HIV virus produces antibodies. 
o Results take 20 minutes.  Study staff will talk to you about the meaning of the result, how you feel, 
and ways to prevent HIV and other sexually transmitted infections. 
o Sometimes HIV test results are not clearly positive, but also not clearly negative.  In that case, blood 
will need drawn and sent to the lab for further testing which could take a week.    
o If the test shows you have HIV, you cannot join the study.  You will be referred for medical care and 
other services.  Your partner(s) may have access to free HIV counseling and testing, if needed.  
• 
You will only get the results of tests that are applicable to your clinical care, including pregnancy test, STD 
and HIV tests, and evaluation for vaginal complaints if performed.  You will not get the results of the other 
tests as they are done for research purposes only.  
• 
Protocol counseling includes visit reminders, STD/HIV and abstinence counseling, and vaginal product use. 
o You must agree to not have sex (vaginal, anal and receptive oral) from V2 – V7. 
o You must also agree to not have sex 48 hours before the other study visits.  
o You must agree not to use vaginal products during the study and no tampon use between V5 – V7. 
• 
Blood will be drawn to test MK2048 levels.  Approximately 2 teaspoons of blood will be drawn each time.  
• 
Genital sample collection includes collecting Q-tip like swabs from the vagina, cervix and rectum.  The 
samples will be used to look at bacteria and other markers.  
• 
STD (sexually transmitted disease) testing will include Chlamydia, Gonorrhea and Trichomonas. 
• 
CVL (cervicovaginal lavage) is a vaginal “wash” of the vagina with saline; the wash takes one minute. 
• 
Cervical biopsies will be collected by a physician investigator at V5. 
o Two adequate samples will be collected, approximately 3mm each or the size of a grain of rice. 
o The biopsy sites take approximately 7 days to heal.  As a reminder, do not put anything in the 
vagina (tampon, sex toy) and avoid any type of sex (vaginal, anal, receptive oral) for 7 days. 
• 
Study procedures can be repeated as needed (e.g. collection or processing error, or for clinical reasons). 
• 
Microscopic exam (looking under a microscope) of vaginal discharge, urine dipstick and bimanual exam (to 
feel uterus and ovaries) may be done as clinically indicated during the study. 
• 
Interim or unscheduled visits may occur if needed (e.g. abnormal results, repeat testing, side effects). 
• 
Study participation for the required visits end at Visit 8 (Day 28). 
• 
If you have ongoing side effects at V8, study staff may call you until the issue stabilizes or resolves. 
• 
In the unlikely event you become pregnant while participating in the study, the study staff will refer you for 
appropriate care.  You will be exited from the study, but study will need to follow up with you by telephone 
until the outcome of your pregnancy is known. 
• 
If you are found to have an Gonorrhea, Chlamydia or Trichomonas or a vaginal infection during the study, 
you may be provided with directly observed antibiotic treatment. 
• 
The samples for this research study will be sent to Magee-Womens Research Institute (MWRI) where most 
of the samples will be processed.  Some samples may be sent to outside investigators for processing or 

                                                                                                                    Page 55 of 59 
 
 
FAME 103 Protocol Version 1.020Dec2019 
 
 
 
 
 
 
 
 
 
analysis.  Importantly and regardless of lab, all samples are sent with a unique study number.  No personal 
identifiers (name, SSN, birthdate) will be on the samples.   
RISKS AND/OR DISCOMFORTS  
By participating in this study, you could have these side effects or other side effects that we do not know about. 
Procedure 
Risk  
Pregnancy Test 
• 
Anxious or nervous having test or waiting for results 
• 
Denial, depression or worry with unexpected positive result 
Pelvic Exam 
• 
Discomfort with speculum  
Genital and rectal 
specimens  
• 
Minimal discomfort from collection of specimens 
Cervical Biopsy 
• 
Generally well tolerated but may cause pain (or pinching) 
• 
Cramping similar to menstrual cramps 
o Cramping typically resolves within minutes after procedure 
o May take ibuprofen prior to biopsy to minimize cramping 
• 
Vaginal spotting or bleeding for a couple days 
o Typically less than a period but if heavier, contact study staff 
• 
Infection of biopsy area 
o Unlikely but if foul odor or unusual discharge, contact study staff 
• 
A cut in the vagina can put you at increased risk of getting HIV if exposed 
• 
If you have an IUD, there is a risk of dislodging it with performing the biopsies.  If 
displaced, a new IUD will be inserted at no cost to you 
Vaginal use of  
MK 2048 film 
• 
Vaginal discharge, irritation, discomfort 
• 
Vaginal burning, itching, redness and/or pain;  
• 
Yeast or vaginal infection 
• 
Allergic reaction 
Blood draw  
• 
Bruising, soreness, pain/discomfort, bleeding, infection at the site 
• 
lightheadedness, fainting 
Participation in 
research; 
collection and 
storage of private 
health information, 
biospecimens and 
internet 
communication* 
• 
Inconvenient 
• 
Breach of confidentiality  
Questionnaires 
• 
Discomfort with personal nature of questions 
STD/HIV testing 
• 
Worry or anxiety 
• 
Sadness, depression or denial with a positive test result 
o Positive gonorrhea and chlamydia test results will be reported to ACHD 
according to the Commonwealth of Pennsylvania reporting requirements 
o May be contacted and asked questions about sexual partners 
*We will make reasonable efforts to protect the privacy of information on social media. Each platform has their 
own privacy policies and terms of use that may change at any time. The University of Pittsburgh cannot 
guarantee the privacy and confidentiality of information shared on social media in this research study. Your 

                                                                                                                    Page 56 of 59 
 
 
FAME 103 Protocol Version 1.020Dec2019 
 
 
 
 
 
 
 
 
 
information may not remain private. You will be instructed to visit site privacy policies and update privacy settings, 
as necessary. Social media retains information shared across accounts for an unknown length of time and it may 
be shared with others including targeted advertisers. 
 
Pregnancy, Breastfeeding and Sexual Practices 
The vaginal film is not a birth control method.  We do not know what effect the study drug may have on pregnancy, 
including the effect of the study drug on the fetuses of women who use the vaginal film when pregnant, or the 
babies of women who use the vaginal film when breastfeeding.  Because of this, pregnant women and women 
who are breastfeeding may not join this study.  Women who join the study must agree to avoid sexual intercourse 
from V2 (enrollment) until V7 (7 days after the biopsy visit), and 48 hours prior to each study visit, use an effective 
method of birth control and have scheduled pregnancy tests while in the study. Effective methods of birth control 
include hormonal methods (like "the pill" or Depo-Provera injections), the IUD, sterilization (or "tied tubes"), 
abstinence (or not having sex), same sex partner, or having a partner who has had a vasectomy. You must 
agree to use this method of birth control until the last study visit, approximately 4 weeks after you are enrolled.  
 
If you do not think you can be sexually abstinent until at least 7 days after the biopsy visit, then you should not 
enroll in this study.  In the unlikely event that you become pregnant during the study, study staff will refer you to 
available medical care and other services you or your baby may need.  The study does not pay for this care.  
You will keep coming here for study visits as originally planned.  We will change the study procedures as needed 
to protect your health while you are pregnant. The outcome of your pregnancy is important to study staff; you 
will be followed through the outcome of your pregnancy.  
 
If you were to become HIV infected while using the study product, the HIV virus may develop resistance to 
MK2048.  Developing MK2048 resistance means that the MK2048 may not be able to treat HIV however, 
MK2048 is not currently used to treat HIV. 
 
BENEFITS 
You will not  directly benefit from participating in this study.  You may, however, feel satisfaction knowing that 
information learned from this study may help in the development of vaginal products for women.  You will also 
have exams and HIV/STD testing as part of your participation in this study.      
 
NEW INFORMATION 
You will be told about any new information learned that might affect your willingness to stay in the study.   
 
CLINICALLY RELAVENT RESEARCH RESULTS:  You will be given the results of your pregnancy, STD and 
HIV testing.  Counseling, referrals and treatment will be discussed as applicable.  There is no plan to provide 
you with your results for tests collected for research purposes only or results of the study in general once it is 
completed. 
 
STOPPING STUDY DRUG OR BEING WITHDRAWN EARLY 
The study staff may remove you from the study early without your permission if: 
• 
The study is stopped or cancelled  
• 
You are not able to keep appointments 

                                                                                                                    Page 57 of 59 
 
 
FAME 103 Protocol Version 1.020Dec2019 
 
 
 
 
 
 
 
 
 
• 
Other reasons that may prevent you from completing the study successfully or safely. This would include 
a newly diagnosed pregnancy or HIV.  If you become pregnant, although you will be terminated from 
further study visits, study staff will continue to contact you through the outcome of your pregnancy.   
Participants who withdraw or who are withdrawn from the study prior to completing follow up may be asked to 
complete a final study visit.   
 
COSTS TO YOU 
There is no cost to you or your insurance for study related visits or procedures.   
 
REIMBURSEMENT 
You will receive compensation for your time, effort, and travel expenses as detailed in the study procedure table 
above.  If you complete all the required study visits within the designated window periods, you will receive a total 
of $370.  If you complete all the required study visits and the optional V2 procedures, it is possible to be 
compensated up to $440.   If you complete a visit but are seen outside of the protocol window for that visit, $10 
will be deducted from the scheduled visit payment.  
 
Parking passes or assistance with transportation will be provided as needed.  
 
CONFIDENTIALITY 
Research records will be kept and accessed by the investigators for a minimum of seven years.  The 
computers that store any data that is collected are password and firewall protected.  Study related 
questionnaires and specimens are identified by a unique study number to protect your confidentiality.  The link 
to your name and study number will be kept in a separate, secure location that only the clinical research team 
has access to.  If data from this study is shared with other (outside) investigators interested in infections, the 
information will be shared without personal identifiers (for example name, date of birth, SSN).   
 
In unusual circumstances, your research records may be inspected by appropriate agencies. The University of 
Pittsburgh Education and Compliance Office for Human Subject Research (ECO-HSR) may review your 
identifiable research information (which may include your identifiable medical record information) for the 
purpose of monitoring the appropriate conduct of this research study.  The sponsor of the study or their 
designee may also review your identifiable research information but only for the purposes of monitoring the 
conduct and data collected for the study.  No information will be extracted from your medical record unless you 
sign a separate medical release and no information about your participation in this study will be placed in your 
medical record.  
 
We will do everything possible to keep your test results confidential but this cannot be guaranteed.  If others 
would become aware of your HIV status, it could result in discrimination which may impact your employability, 
insurability, or even prevent you from traveling to certain countries. If you test positive, Pennsylvania state law 
requires your name and results be reported to the local health department. All information will be handled in 
compliance with the Pennsylvania law on HIV-related confidential information. 
 
If you test positive for gonorrhea, chlamydia, or HIV, the Commonwealth of Pennsylvania requires that your 
name be given to the Allegheny County Health Department.  You may be contacted and asked questions about 
your sexual partner(s). 
 

                                                                                                                    Page 58 of 59 
 
 
FAME 103 Protocol Version 1.020Dec2019 
 
 
 
 
 
 
 
 
 
The investigators may use or disclose, for purposes described above, identifiable information (which may include 
identifiable medical information) related to your being in this study a minimum of 7 years and for as long 
(indefinite) as it may take to complete this study. 
 
A description of this clinical trial will be available on http://www.clinicaltrials.gov. This website will not include 
information that can identify you. At most, the website will include a summary of the results. You can search this 
website at any time. 
 
Your participation in this study may include whole genome sequencing.  Whole genome sequencing is the 
mapping out of a person’s unique DNA. Your genome is the unique blueprint for your body. Sometimes, because 
of new or inherited genetic mutations, your genes can cause a disease or increase your risk for disease. By 
sequencing your genome, health professionals can look at the unique variations found in your genes. Some of 
it matters. Some doesn’t matter. Some is still unknown or uncertain. 
 
RESEARCH-RELATED INJURY 
If you believe that the research procedures have resulted in an injury to you, immediately contact the Principal 
Investigator who is listed on the first page of this form.  Emergency medical treatment for injuries solely and 
directly related to your participation in this research study will be provided to you by the hospitals of UPMC.  Your 
insurance provider may be billed for the costs of this emergency treatment, but none of those costs will be 
charged directly to you.  If your research related injury requires medical care beyond this emergency treatment, 
you will be responsible for the costs of this follow-up care.  At this time, there is no plan for any additional financial 
compensation.  You do not give up your legal rights by signing this form. The US National Institutes of Health 
(NIH) does not have a mechanism to provide compensation for research related injury.    
 
HIPAA AUTHORIZATION:  We are requesting your authorization or permission to access your protected 
health information for research purposes.  This authorization will be valid for an indefinite period of time.  We 
may obtain information concerning your birth control method, age, level of education, past medical and 
gynecologic history and results of any tests that were already done as part of your standard evaluation.   
 
This information may be needed so that we can compare the data in your medical record to the data obtained 
for this study.  We may use the information to identify whether you meet the conditions for participation in this 
study.  We may also use your medical record to obtain new contact information for you while you are in the 
study. The information may be needed for retention purposes.   
 
The identifiable information will be made available to members of the research team, for an indefinite period of 
time and may be shared with other groups, possibly including authorized representatives of the sponsor of the 
study, National Institutes of Health (or authorized representative that they delegate, such as representatives 
from monitoring or auditing companies) or authorized officials from the University of Pittsburgh Research 
Conduct and Compliance Office.  We will protect your privacy and the confidentiality of your records, as 
described in this document but cannot guarantee the confidentiality of your research records, including 
information obtained from your medical records, once your personal information is disclosed to others outside 
UPMC or the University.   
 
Your research information and data may be shared with investigators conducting other research.  The shared 
information may be labeled by your unique study number and linked to the study data that matches the unique 

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FAME 103 Protocol Version 1.020Dec2019 
 
 
 
 
 
 
 
 
 
study number.  The link between your personal identifying information and the unique study number is 
maintained by the clinical research team and will not be shared with other investigators or laboratory staff.    
 
You can always withdraw your authorization to allow the research team to review your medical records by 
contacting the investigator listed on the first page and making the request in writing.  If you do so, you will no 
longer be permitted to participate in this study.  Any information obtained from you up to that point will continue 
to be used by the research team.   
 
YOUR RIGHTS AS A RESEARCH PARTICIPANT/VOLUNTEER 
Your participation in this research study is entirely voluntary.  You may want to discuss this study with your 
family and friends and your personal physician before agreeing to participate.  If there are any words you do 
not understand, feel free to ask us.  The investigators will be available to answer your current and future 
questions.   
 
Whether or not you provide your consent for participation in this research study will have no effect on your current 
or future relationship with the University of Pittsburgh, your current or future medical care at a UPMC hospital or 
affiliated health care provider or your current or future relationship with a health care insurance provider. 
 
CERTIFICATE OF CONFIDENTIALITY: 
To help us protect your privacy, we have obtained a Certificate of Confidentiality from the National Institutes of 
Health.  The researchers can use this Certificate to legally refuse to disclose information that may identify you 
in any federal, state, or local civil, criminal, administrative, legislative, or other proceedings, for example, if 
there is a court subpoena.  The researchers will use the Certificate to resist any demands for information that 
would identify you, except as explained below.   
 
The certificate cannot be used to resist a demand for information from personnel of the United States 
Government that is used for auditing or evaluation of federally-funded projects or for the information that must 
be disclosed in order to meet the requirements of the US Food and Drug Administration (FDA) and other 
regulatory authorities.  
 
You should understand that a Certificate of Confidentiality does not prevent you or a member of your family 
from voluntarily releasing information about yourself or your involvement in this research.  If an insurer, 
employer, or other person obtains your written consent to receive research information, then the researchers 
may not use the Certificate to withhold that information.   
 
The Certificate of Confidentiality will not be used to prevent disclosure to state or local authorities of child abuse 
and neglect, or harm to self or others. 
 
PROBLEMS OR QUESTIONS 
If you ever have any questions about the study, or if you have a research-related injury, you should contact 
Katherine Bunge, MD or the research staff at (412) 641-4242. If you ever have any questions about your rights 
as a research participant, you can contact the University of Pittsburgh IRB at 1-866-212-2668.   
 
 
 

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CONSENT FOR FUTURE USE 
As part of this study, there will be samples that are collected specifically for future use and there may also be 
leftover samples from the main testing that could be stored for future use. These samples may be used by 
investigators for future research on genital tract infections, for further understanding of STDs and how the body 
responds to infection and/or genetic testing and may include whole genome sequencing.  Whole genome 
sequencing is the mapping out of a person’s unique DNA. Your genome is the unique blueprint for your body. 
Sometimes, because of new or inherited genetic mutations, your genes can cause a disease or increase your risk for 
disease. By sequencing your genome, health professionals can look at the unique variations found in your genes. Some of 
it matters. Some doesn’t matter. Some is still unknown or uncertain.   
 
The specimens would be stored at Magee Womens Research Institute by study number; your name will not be 
on the sample.  Information linking your study number to your name will be kept in a separate, secure location 
in the clinical research area.   
 
Your study samples or genetic material may lead, in the future, to new inventions or products.  If the research 
investigators develop new products from the use of your biologic sample or genetic material, there are 
currently no plans to share with you any money or other rewards that may result from the development of the 
new product.    
 
You would not be informed of results of the future tests since the data may not be applied to a clinical setting 
and may not affect clinical care.  Any results from the research done on future use samples would not be put in 
your medical record and would be kept confidential.  Samples may be given to other investigators (secondary 
investigators), other than Magee and UNC investigators.  If samples were given to secondary investigators 
they would be made available without links to your personal identifying information.  
 
There are few risks to you from future use of your specimens.  Reports about research done with your 
specimens will not be put in your health record, but will be kept with the study records.  Results from future 
research using your specimens may be presented in publications and meetings, but your name will not be 
identified. 
 
PLEASE INITIAL YOUR CHOICE BELOW (chose one):  
 
 
_________        I agree to the future use of my specimens as described above 
                  initials 
                                                                                  OR 
_________      I DO NOT agree to the future use of my specimens as described above 
     initials 
 
***************************************************************************************** 
 

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PLEASE INITIAL WHICH, IF ANY, OPTIONAL RESEARCH PROCEDURES YOU AGREE TO BELOW:  
 
Optional Procedure 
Visit 
Timepoint(s) 
Initial if you agree 
Up to two additional vaginal swab(s) 
V2 
Enrollment 
1, 2, 3, 4, 5, 6 hrs after film 
placement 
 
One additional blood sample 
V2 
Enrollment 
1, 2, 3, 4, 5, 6 hrs after film 
placement 
 
 
****************************************************************************************** 
VOLUNTARY CONSENT 
The above information has been explained to me and all of my current questions have been answered.  I 
understand that I am encouraged to ask questions, voice concerns or complaints about any aspect of this 
research study during the course of this study, and that such future questions, concerns or complaints will be 
answered by a qualified member of the research team or by the principal investigator listed on the first page.  I 
understand that I may always request that my questions, concerns or complaints be addressed by the Principal 
Investigator.  At any time I may also contact the Human Subjects Protection Advocate of the IRB Office, 
University of Pittsburgh (1-866-212-2668) to discuss problems, concerns and questions; obtain information; offer 
input; or discuss situations in the event that the research team is unavailable.  By signing this form I agree to 
participate in this research study for the purposes described above.  A copy of this consent form will be offered 
to me. 
 
_______________________________________   
Printed Name of Participant  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
          
_______________________________________ 
_________________    ______________   
Participant Signature  
 
 
 
Date 
 
 
   Time AM/PM 
 
CERTIFICATION OF INFORMED CONSENT:  I certify that I have explained the nature and purpose of this 
research to the above individual and I have discussed the potential benefits and possible risks of study 
participation.  Any questions the individual has about this study have been answered, and we will always be 
available to address future questions as they arise.  I further certify that no research component of this protocol 
was begun until after this consent form was signed. 
 
 
________________________________________  
____________________ 
Printed Name of Person Obtaining Consent  
 
Role in Research Study 
 
 
________________________________________  
____________________ 
Signature of Person Obtaining Consent 
 
 
 
Date