MATRIX-002: Trial to Assess Acceptability and Safety of Two Placebo Prototype Vaginal Films
Phase: EARLY_PHASE1
Conditions: Safety, Acceptability, Usability
Sponsor: Rohan, Lisa, PhD

Study Title MATRIX-002: Trial to Assess Acceptability and Safety of Two Placebo Prototype Vaginal 
Films 
Protocol Version V1.0 24May2023 
NCT Number: NCT06046053 
Document Date: 24May2023 

 
 
MATRIX-002 
 
Trial to Assess Acceptability and Safety of Two Placebo Prototype Vaginal 
Films 
 
 
MATRIX: A USAID Project to Advance the Research and Development of Innovative 
HIV Prevention Products for Women 
 
 
Funding Agency: 
US Agency for International Development (USAID) 
 
 
 
Award/Grant Number(s): 
Cooperative Agreement #7200AA22CA00002 
 
 
 
 
A Non-IND Study 
 
 
 
Pharmaceutical Collaborator: 
University of Pittsburgh (Pitt) / Magee-Womens Research Institute and Foundation 
(MWRIF) 
 
 
 
Protocol Co-Chair: 
Nyaradzo M. Mgodi, MBChB, MMed 
 
 
Protocol Co-Chair: 
Alexandra Minnis, PhD 
 
 
 
Version 1.0 
 
24 May 2023 
 

 
 
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MATRIX-002 
 
Trial to Assess Acceptability and Safety of Two Placebo Prototype Vaginal 
Films 
 
TABLE OF CONTENTS 
 
 
LIST OF ABBREVIATIONS AND ACRONYMS ........................................................................... v 
PROTOCOL TEAM ROSTER .................................................................................................. vii 
INVESTIGATOR SIGNATURE FORM ..................................................................................... xvi 
PROTOCOL SUMMARY ....................................................................................................... xvii 
1 
KEY ROLES ............................................................................................................ 1 
1.1 
Protocol Identification ............................................................................................ 1 
1.2 
Funding Agency and Monitor Identification .............................................................. 1 
1.3 
Laboratory(ies) ...................................................................................................... 1 
1.4 
Data Management ................................................................................................. 2 
1.5 
Clinical Research Management ............................................................................... 2 
2 
INTRODUCTION .................................................................................................... 3 
2.1 
Background ........................................................................................................... 3 
2.2 
Description of Placebo Prototype Vaginal Films ........................................................ 4 
2.3 
Acceptability of Vaginal Film Formulations ............................................................... 4 
2.4 
Rationale for Study Design ..................................................................................... 5 
3 
OBJECTIVES .......................................................................................................... 6 
3.1 
Primary Objective .................................................................................................. 6 
3.2 
Secondary Objectives ............................................................................................. 6 
3.3 
Exploratory Objectives ........................................................................................... 6 
4 
STUDY DESIGN ..................................................................................................... 6 
4.1 
Identification of Study Design ................................................................................. 6 
4.2 
Summary of Major Endpoints.................................................................................. 7 
4.3 
Description of Study Population .............................................................................. 8 
4.4 
Time to Complete Accrual ...................................................................................... 8 
4.5 
Study Groups ........................................................................................................ 8 
4.6 
Expected Duration of Participation .......................................................................... 8 
4.7 
Sites ..................................................................................................................... 8 
5 
STUDY POPULATION ............................................................................................. 8 
5.1 
Selection of the Study Population ........................................................................... 8 
5.2 
Inclusion Criteria ................................................................................................... 9 
5.3 
Exclusion Criteria ................................................................................................. 10 
5.4 
Co-enrollment Guidelines ..................................................................................... 11 
6 
STUDY PRODUCT ................................................................................................ 12 
6.1 
Regimen ............................................................................................................. 12 
6.2 
Administration ..................................................................................................... 12 
6.3 
Study Product Formulation and Storage ................................................................ 12 
6.4 
Supply and Accountability .................................................................................... 13 
6.5 
Ancillary Study Supplies ....................................................................................... 13 
6.6 
Concomitant Medications ..................................................................................... 13 
6.7 
Prohibited Medications, Products and Practices ...................................................... 13 

 
 
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7 
STUDY PROCEDURES ........................................................................................... 14 
7.1 
Screening Visit ..................................................................................................... 14 
7.2 
Enrollment Visit – Visit 2 (Day 0) .......................................................................... 15 
7.3 
Follow-up Visits/Contacts ..................................................................................... 17 
7.4 
Follow-up Procedures for Participants Who Permanently Discontinue Study Product . 22 
7.5 
Interim Visits/Contacts ......................................................................................... 23 
7.6 
Behavioral Evaluations ......................................................................................... 23 
7.7 
Protocol Adherence Counseling ............................................................................. 25 
7.8 
Clinical Evaluations and Procedures ...................................................................... 25 
7.9 
Laboratory Evaluations ......................................................................................... 26 
7.10 
Specimen Management ........................................................................................ 27 
7.11 
Laboratory Oversight ........................................................................................... 27 
7.12 
Biohazard Containment ........................................................................................ 27 
8 
ASSESSMENT OF SAFETY ..................................................................................... 27 
8.1 
Safety Monitoring ................................................................................................ 27 
8.2 
Clinical Data and Safety Review ............................................................................ 28 
8.3 
Adverse Events Definitions and Reporting Requirements ........................................ 28 
8.4 
Pregnancy and Infant Outcomes ........................................................................... 30 
8.5 
Regulatory Requirements ..................................................................................... 31 
8.6 
Social Harms Reporting ........................................................................................ 31 
9 
CLINICAL MANAGEMENT ...................................................................................... 31 
9.1 
Grading System ................................................................................................... 31 
9.2 
Dose Modification Instructions .............................................................................. 31 
9.3 
General Criteria for Permanent Discontinuation of Study Product ............................ 32 
9.4 
Permanent Discontinuation in Response to Observed Adverse Events ..................... 32 
9.5 
Other Clinical Findings ......................................................................................... 32 
9.6 
HIV Infection ....................................................................................................... 33 
9.7 
Pregnancy ........................................................................................................... 33 
9.8 
Criteria for Early Termination of Study Participation ............................................... 33 
10 
STATISTICAL CONSIDERATIONS .......................................................................... 34 
10.1 
Overview and Summary of Design ........................................................................ 34 
10.2 
Study Endpoints .................................................................................................. 34 
10.3 
Sample Size and Power Calculations ..................................................................... 35 
10.4 
Randomization Procedures ................................................................................... 36 
10.5 
Participant Accrual, Follow-up and Retention ......................................................... 36 
10.6 
Data and Safety Monitoring and Analysis ............................................................... 36 
11 
DATA HANDLING AND RECORDKEEPING .............................................................. 38 
11.1 
Data Management Responsibilities ........................................................................ 38 
11.2 
Source Documents and Access to Source Data/Documents ..................................... 39 
11.3 
Quality Control and Quality Assurance................................................................... 39 
12 
CLINICAL SITE MONITORING ............................................................................... 39 
13 
HUMAN SUBJECTS PROTECTIONS ........................................................................ 40 
13.1 
Institutional Review Boards/Ethics Committees ...................................................... 40 
13.2 
Protocol Implementation ...................................................................................... 41 
13.3 
Study Coordination .............................................................................................. 41 
13.4 
Risk Benefit Statement ......................................................................................... 42 
13.5 
Informed Consent Process ................................................................................... 43 
13.6 
Participant Confidentiality ..................................................................................... 44 

 
 
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13.7 
Special Populations .............................................................................................. 44 
13.8 
Compensation ..................................................................................................... 45 
13.9 
Reporting ............................................................................................................ 45 
13.10 Access to HIV-related Care ................................................................................... 45 
13.11 Study Discontinuation .......................................................................................... 46 
14 
PUBLICATION POLICY ......................................................................................... 46 
15 
APPENDICES ....................................................................................................... 46 
APPENDIX I:  SCHEDULE OF STUDY VISITS AND EVALUATIONS ........................................... 47 
APPENDIX II:  ALGORITHM FOR HIV TESTING – SCREENING/ENROLLING/FOLLOW-UP ......... 49 
APPENDIX III:  SAMPLE INFORMED CONSENT FORM (SCREENING, ENROLLMENT, LONG-TERM 
STORAGE AND FUTURE TESTING) ...................................................................................... 50 
APPENDIX IV:  SAMPLE INFORMED CONSENT FORM (SEXUAL PARTNER SUBSET) ................. 69 
REFERENCES ..................................................................................................................... 76 
 
LIST OF FIGURES 
  
FIGURE 1: STUDY VISIT SCHEDULE ................................................................................ XVIII 
FIGURE 2: STUDY PRODUCT REGIMEN ............................................................................... 12 
FIGURE 3: STUDY VISIT SCHEDULE .................................................................................... 14 
 
LIST OF TABLES 
  
TABLE 1: SCREENING VISIT ............................................................................................... 15 
TABLE 2: ENROLLMENT VISIT – VISIT 2 (DAY 0) ................................................................. 16 
TABLE 3:  PHONE CHECK-IN (24-72 HOURS AFTER 1ST INSERTION) – VISIT 3 ...................... 17 
TABLE 4: 1-WEEK AND 2-WEEK TELEPHONE CONTACTS – VISITS 4 AND 5 (7 AND 14 DAYS 
AFTER VISIT 2) .......................................................................................................... 17 
TABLE 5: 4-WEEK VISIT – VISIT 6 (28 DAYS AFTER VISIT 2) ............................................... 18 
TABLE 6:  PHONE CHECK-IN (24-72 HOURS AFTER 2ND INSERTION) – VISIT 7 .................... 19 
TABLE 7: 6-WEEK TELEPHONE CONTACT – VISIT 8 (14 DAYS AFTER VISIT 6) ...................... 20 
TABLE 8: 8-WEEK VISIT – VISIT 9 (28 DAYS AFTER VISIT 6) ............................................... 20 
TABLE 9: FINAL CONTACT/SEV – VISIT 10 (7 DAYS AFTER VISIT 9) ..................................... 21 
TABLE 10: IDI VISIT WITH SEXUAL PARTNER SUBSET ........................................................ 22 
TABLE 11: SUMMARY OF BEHAVIORAL ASSESSMENTS ......................................................... 24 
TABLE 12: RANGE OF POTENTIAL EFFECT SIZES FOR EACH ENDPOINT ............................... 36 
 

 
 
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MATRIX-002 
 
Trial to Assess Acceptability and Safety of Two Placebo Prototype Vaginal 
Films 
LIST OF ABBREVIATIONS AND ACRONYMS 
 
ACRO  
African Clinical Research Organisation 
AE 
 
Adverse event 
AIDS  
Acquired immunodeficiency syndrome 
ALT 
 
Alanine transaminase 
API 
 
Active pharmaceutical ingredient 
AST 
 
Aspartate aminotransferase 
BV 
 
Bacterial vaginosis 
CAB 
 
Community advisory board 
CBC 
 
Complete blood count 
CDC 
 
Centers for Disease Control and Prevention (US) 
CDM 
 
Clinical data manager 
CFR 
 
Code of Federal Regulations 
CLIA 
 
Clinical Laboratory Improvement Act 
CQA 
 
Critical quality attributes 
CRF 
 
Case report form 
CRM 
 
Clinical research manager 
CRS 
 
Clinical research site 
CT 
 
Chlamydia trachomatis 
CV 
 
Cervicovaginal 
CVF 
 
Cervicovaginal fluid 
DAIDS  
Division of AIDS 
DRA 
 
Drug regulatory authority 
ECS-HSR 
Education and Compliance Support for Human Subject Research 
FDA 
 
U.S. Food and Drug Administration 
GC 
 
Neisseria gonorrhea 
GCP 
 
Good Clinical Practice 
GDP 
 
Good Documentation Practices 
GMP 
 
Good Manufacturing Practice 
GRAS  
Generally regarded as safe 
HHRC  
Harare Health and Research Consortium 
HIPAA  
Health Insurance Portability and Accountability Act 
HIV 
 
Human Immunodeficiency Virus 
IATA 
 
International Air Transport Association 
ICH E6  
International Conference for Harmonization Guideline for Good Clinical Practice 
IDI 
 
In-depth interview 
IEC 
 
Independent Ethics Committee 
IND 
 
Investigational New Drug 
IoR 
 
Investigator of Record 
IRB 
 
Institutional Review Board 
ISP 
 
Independent Safety Physician 
IUD 
 
Intrauterine device 

 
 
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KEMRI  
Kenya Medical Research Institute 
KOH 
 
Saline/potassium hydroxide 
LDMS  
Laboratory Data Management System 
LTFU  
Loss-to-follow-up 
MWRIF 
Magee-Womens Research Institute and Foundation 
NAAT  
Nucleic acid amplification test 
NIH 
 
National Institutes of Health 
OHRP  
Office for Human Research Protections 
PEP 
 
Post-exposure prophylaxis 
PHI 
 
Protected health information 
PI 
 
Principal Investigator 
PID 
 
Pelvic inflammatory disease 
PrEP 
 
Pre-exposure prophylaxis 
PSRT  
Protocol Safety Review Team 
PTID  
Participant identifier 
QA 
 
Quality assurance 
QC 
 
Quality control 
RTI 
 
Reproductive tract infection 
SAE 
 
Serious adverse event 
SEV 
 
Study Exit Visit 
SMS 
 
Short message service 
SOP 
 
Standard operating procedures 
SSA 
 
Sub-Saharan Africa 
SSP 
 
Study specific procedures 
STI 
 
Sexually transmitted infection 
UPT 
 
Urine pregnancy test 
USAID  
US Agency for International Development 
UTI 
 
Urinary tract infection 
VALUE  
Vaginal film as A Low-cost, User-administered, and Extended-release product 
Wits RHI 
Wits Reproductive Health and HIV Institute 
 
 

 
 
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MATRIX-002 
 
Trial to Assess Acceptability and Safety of Two Placebo Prototype Vaginal 
Films 
PROTOCOL TEAM ROSTER 
 
 
Protocol Co-Chair 
 
Nyaradzo M. Mgodi, MBChB, MMed 
Protocol Co-Chair 
Zengeza Clinical Research Site (CRS) 
7723 Cheuka Street 
Zengeza 3 Clinic 
Chitungwiza, Zimbabwe 
Phone: +263-772-264616 
Email: nmgodi@uz-ctrc.org 
 
 
Protocol Co-Chair 
 
Alexandra Minnis, PhD 
Protocol Co-Chair 
RTI International 
2150 Shattuck Avenue, Suite 800 
Berkeley, CA 94704 USA 
Phone: 1-919-485-1323 
Email: aminnis@rti.org 
 
 
 

 
 
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Clinical Research Site (CRS) Investigators  
 
 
University of Pittsburgh (Pitt)/Magee-Womens Research Institute and Foundation 
(MWRIF) CRS 
 
Katherine Bunge, MD, MPH 
Site Investigator of Record 
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  
 
Ingrid Macio, PA-C 
Site Investigator 
Department of Obstetrics, Gynecology and Reproductive Sciences 
University of Pittsburgh School of Medicine 
300 Halket Street 
Pittsburgh, PA 15213 USA 
Phone: 412-641-4242 
Fax: 412-641-2319 
Email: maciis@upmc.edu 
 
 
Harare Health and Research Consortium (HHRC) CRS 
 
Nyaradzo M. Mgodi, MBChB, MMed 
Site Investigator of Record 
Zengeza CRS 
7723 Cheuka Street 
Zengeza 3 Clinic 
Chitungwiza, Zimbabwe 
Phone: +263-772-264616 
Email: nmgodi@uz-ctrc.org 
 
 
 
 
 
 

 
 
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The Aurum Institute CRS 
 
Raesibe Agnes Pearl Selepe, MBChB 
Site Investigator of Record 
Klerksdorp Clinical Research Centre 
201 Jade Square Centre 
Cnr Margaretha Prinsloo and OR Tambo Drive 
Klerksdorp, North West Province 
South Africa 2571 
Phone: +27 87 135 1596 
Fax: +27 87 231 4977 
Email: pselepe@auruminstitute.org 
 
Heeran Makkan, MSc 
Site Investigator 
Tembisa CRS 
Corner Rev RTJ Namane and Flint Mazibuko Drive 
Tembisa Hospital, Hospital View, Tembisa 
Johannesburg, Gauteng 
South Africa 1632 
Phone: +27 10 590 1331 
Email: hmakkan@auruminstitute.org 
 
 
Wits Reproductive Health and HIV Institute (Wits RHI) CRS 
 
Thesla Palanee-Phillips, MMedSci, PhD, MSc 
Site Investigator 
Wits RHI Research Centre 
7 Esselen Street, 3rd-5th Floors 
Hillbrow, Johannesburg 
South Africa 2038 
Phone: +2711 358 5471 
Fax: +2786 554 1093   
Email: tpalanee@wrhi.ac.za   
 
Nkosiphile Ndlovu, MBChB, HIV Dip Man (SA) 
Site Investigator of Record 
Wits RHI Research Centre 
7 Esselen Street, 3rd-5th Floors 
Hillbrow, Johannesburg 
South Africa 2038 
Phone: +2784 722 5877 
Email: nkndlovu@wrhi.ac.za   
 
 
 

 
 
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Kenya Medical Research Institute (KEMRI) CRS 
 
Kenneth Ngure, PhD 
Site Investigator 
Jomo Kenyatta University of Agriculture and Technology (JKUAT)-College of Health Sciences 
P.O. Box 19704-00202 
Nairobi, Kenya 
Phone: 254-722362219  
Email: Kngure@pipsthika.org   
 
Nelly Rwamba Mugo, MBChB, MMed, MPH 
Site Investigator of Record  
Kenya Medical Research Institute (KEMRI) 
OAU Road  
Thika, Kenya  
Phone: 254-733629665  
Email: rwamba@uw.edu 
 
 
 

 
 
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MATRIX 
 
 
Sharon Hillier, PhD 
MATRIX Executive Director and Clinical Trials Hub Co-lead 
Magee-Women’s Research Institute and Foundation (MWRIF) 
204 Craft Avenue, Room B511 
Pittsburgh, PA 15213 USA 
Phone: 1-412-641-6435 
Fax: 1-412-641-6170 
Email: hillsl@mwri.magee.edu 
 
Thesla Palanee-Phillips, PhD, MSc  
MATRIX Deputy Director 
Wits Reproductive Health and HIV Institute (Wits RHI) 
Hillbrow Health Precinct 
22 Esselen Street 
Johannesburg, 2001 South Africa  
Phone: 27-11-358-5471 
Fax: 27-086-554-1093 
Email: tpalanee@whri.ac.za 
 
Nyaradzo M. Mgodi, MBChB, MMed  
MATRIX Clinical Trials Hub Co-lead 
Harare Health and Research Consortium (HHRC) 
4 Ascot Road, Avondale 
Harare, Zimbabwe 
Phone: 263-24-2704920 
Fax:  263-24-2704897 
Email: nmgodi@uz-ctrc.org 
 
Leila E. Mansoor, B.Pharm, PhD 
MATRIX Design to Delivery (D2D) Pillar 2 Co-lead 
Centre for the AIDS Programme of Research in South Africa (CAPRISA) 
University of KwaZulu-Natal, 2nd Floor, Doris Duke Medical Research Institute 
719 Umbilo Road 
Durban, KwaZulu-Natal, 4001 South Africa 
Phone: 27-(0)31-655-0517 
Email: Leila.Mansoor@caprisa.org 
 
Alexandra Minnis, PhD 
MATRIX D2D Pillar 2 Co-lead 
RTI International 
2150 Shattuck Avenue, Suite 800 
Berkeley, CA 94704 USA 
Phone: 1-919-485-1323 
Email: aminnis@rti.org 
 

 
 
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Catherine Chappell, MD 
Protocol Safety Physician 
Department of Obstetrics, Gynecology and Reproductive Sciences 
University of Pittsburgh 
300 Halket Street 
Pittsburgh, PA 15213 
Phone: 412-641-1403 
Email: chappellca@upmc.edu 
 
Leslie Meyn, PhD 
Biostatistician/Epidemiologist 
MWRIF 
204 Craft Avenue 
Pittsburgh, PA 15213 
Phone: 412-641-4233 
Fax: 412-641-1133 
Email: meynla@mwri.magee.edu 
 
Tracy Zamborsky 
Data Manager 
MWRIF 
204 Craft Avenue 
Pittsburgh, Pennsylvania 15213 USA 
Email: zambtx@upmc.edu 
 
Edward Livant, BSMT (ASCP), MPH 
MATRIX Laboratory Quality Assurance/Quality Control (QA/QC) Coordinator 
MWRIF 
204 Craft Avenue, Room A536 
Pittsburgh, PA 15213 USA 
Phone: 412-641-3772 
Fax: 412-641-5290 
Email: elivant@mwri.magee.edu 
 
May Beamer, BS  
Laboratory Manager/Supervisor  
MWRIF  
204 Craft Avenue 
Pittsburgh, PA 15213 USA  
Phone: 412-641-6042  
Fax: 412-641-6170  
Email: mbeamer@mwri.magee.edu 
 
 
 
 
 
 

 
 
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Ingrid Macio, PA-C 
MATRIX Clinical Research Manager (CRM) 
MWRIF  
204 Craft Avenue 
Pittsburgh, PA 15213 USA 
Phone: 412-641-5455 
Fax: 412-641-2319  
Email: maciis@upmc.edu 
 
Sharon Riddler, MD, MPH 
Independent Safety Physician (ISP) 
Division of Infectious Diseases 
University of Pittsburgh School of Medicine 
Keystone Building, Suite 510 
3520 Fifth Avenue 
Pittsburgh, PA 15213 USA 
Phone: 412-383-1741 or 412-383-1675 
Fax: 412-383-2900 
Email: riddler@pitt.edu 
 
 
 

 
 
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USAID 
 
 
Shannon Allen, PhD 
MATRIX Agreement Officer Representative (AOR) 
Bureau of Global Health, Office of HIV AIDS, Research Division, USAID 
500 D Street Southwest 
Washington, DC 20547 USA 
Phone: 1-202-916-2201 
Email: shallen@usaid.gov 
 
Mary Latka, PhD, MPH 
Chief, Microbicides Branch 
Bureau of Global Health, Office of HIV AIDS, Research Division, USAID 
500 D Street Southwest 
Washington, DC 20547 USA 
Email: mlatka@usaid.gov 
 
Kristin Vahle, MPH 
Project Program Analyst 
Bureau of Global Health, Office of HIV AIDS, Research Division, USAID 
500 D Street Southwest 
Washington, DC 20547 USA 
Email: kvahle@usaid.gov 
 
 
 
 
 

 
 
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Pitt / MWRIF 
 
 
Lisa C. Rohan, PhD 
VALUE (Vaginal film as A Low-cost, User-administered, and Extended-release 
product) Project Principal Investigator (PI) 
Department of Pharmaceutical Sciences 
University of Pittsburgh School of Pharmacy 
Magee-Womens Research Institute 
204 Craft Avenue 
Pittsburgh, PA 15213 USA 
Phone: 1-412-641-6108 
Fax: 1-412-641-6170 
Email: lrohan@mwri.magee.edu 
 
Sravan K. Patel, PhD 
VALUE Project Co-PI 
Department of Pharmaceutical Sciences 
University of Pittsburgh School of Pharmacy 
Magee-Womens Research Institute 
204 Craft Avenue 
Pittsburgh, PA 15213 USA 
Phone: 1-412-641-8276 
Fax: 1-412-641-6170 
Email: patels10@mwri.magee.edu 
 
 
 
 

 
 
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MATRIX-002 
 
Trial to Assess Acceptability and Safety of Two Placebo Prototype Vaginal 
Films 
INVESTIGATOR SIGNATURE FORM 
Version 1.0; 24 May 2023 
 
MATRIX: A USAID Project to Advance the Research and Development of Innovative 
HIV Prevention Products for Women 
 
Funded by: 
US Agency for International Development (USAID) 
 
A Non-IND Study 
 
I, the Investigator of Record, agree to conduct this study in full 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); USAID 
regulations (2 CFR 200 and 22 CFR 225); standards of the International Conference for 
Harmonization Guideline for Good Clinical Practice (ICH E6); Institutional Review 
Board/Independent Ethics Committee (IRB/IEC) determinations; all applicable in-country, state, 
and local laws and regulations; and other applicable requirements (e.g., USAID) and institutional 
policies. 
 
I agree to maintain all study records in accordance with protocol-specified protections of 
participants’ confidentiality and with site IRB/IEC policies and procedures. Study records must be 
maintained on-site for the entire implementation period of the study and a minimum of at least 
three years after completion of research. Pitt/MWRIF will inform the investigator/institution as to 
when these documents no longer need to be retained. 
 
I have read and understand the information in this protocol, including the potential risks and side 
effects of the products under investigation, and will ensure that all associates, colleagues, and 
employees assisting in the conduct of the study are informed about the obligations incurred by 
their contribution to the study. 
 
 
 
___________________________________ 
Name of Investigator of Record (print) 
 
 
_________________________________     _____________________________ 
Signature of Investigator of Record      Date 

 
 
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MATRIX-002 
 
Trial to Assess Acceptability and Safety of Two Placebo Prototype Vaginal 
Films 
PROTOCOL SUMMARY 
 
Short Title:  
VALUE Placebo Film Study  
 
Pharmaceutical  
Collaborator: 
Pitt/MWRIF 
 
Funders: 
 
USAID 
 
Protocol Co-Chair: Nyaradzo M. Mgodi, MBChB, MMed 
 
Protocol Co-Chair:  Alexandra Minnis, PhD 
 
Sample Size:  
MATRIX-002 will enroll approximately 100 evaluable participants. MATRIX- 
 
 
 
002 will also enroll a subset of up to 30 sexual partners of evaluable  
 
 
 
participants for in-depth interviews (IDI). 
 
Study Population: HIV seronegative adult (18-45 years old) persons assigned female sex at  
 
 
 
birth who are at low risk of acquiring HIV infection (henceforth referred to  
 
 
 
as “participants”), and sexual partners of evaluable participants  
 
 
 
(henceforth referred to as “sexual partners”). 
 
Study Sites:  
Five sites in the US and sub-Saharan Africa (SSA): 
 
 
 
University of Pittsburgh (Pitt)/Magee-Womens Research Institute and  
 
 
 
Foundation (MWRIF) clinical research site (CRS); 
 
 
 
Aurum Institute CRS; 
 
 
 
Harare Health and Research Consortium (HHRC) CRS; 
 
 
 
Wits Reproductive Health and HIV Institute (Wits RHI) CRS; and 
 
 
 
Kenya Medical Research Institute (KEMRI) CRS. 
 
Study Design: 
Two-arm, randomized, multi-center trial of monthly vaginal administration 
of two placebo prototype films. 
 
Study Duration: 
Approximately nine weeks of follow-up per participant is planned with a 
projected accrual period of approximately 3-6 months. The total duration of 
the study will be approximately 6-9 months. 
 
Study Products: 
Placebo vaginal films A and B, 2” x 2” in size, which differ by shape. 
 
 
 
 
Study Regimen: 
Participants will be randomized (1:1) to insert either placebo vaginal film A 
or placebo vaginal film B once monthly for two months. 
 

 
 
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Figure 1: Study Visit Schedule 
 
 
 
 
 
 
Primary Objective: 
 
 
Acceptability 
• 
To assess the acceptability of two placebo film types (A and B) when administered vaginally 
once monthly for two months. 
 
Primary Endpoint:  
 
Acceptability 
• 
Participant ratings of overall satisfaction with use of the placebo vaginal films. 
 
Secondary Objectives: 
 
Safety 
• 
To assess the safety of two placebo film types (A and B) when administered vaginally once 
monthly for two months. 
 
Usability 
• 
To assess participants’ ability to properly insert the placebo vaginal film. 
 
Secondary Endpoints: 
 
Safety 
• 
Proportion of participants with genitourinary Grade 2 or higher Adverse Events deemed 
related to study product. 
 
Usability 
• 
Proportion of participants with clinically assessed proper insertion (more than half of the 
vaginal film proximal to introitus). 
 
Scr
V1
Enr 
V2
24-72 hr 
Phone 
check
V3
Wk 1 
Phone 
check
V4
Wk 2
Phone 
check
V5
Wk 
3
Wk 4 
Clinic 
follow 
up
V6
24-72hr 
Phone 
check
V7
Wk 
5
Wk 6 
Phone 
check
V8
Wk 
7
Wk 8 
Clinic 
follow 
up
V9
Wk 9 
Final 
phone 
contact
V10
No sex or vaginal product use permitted 
 No restrictions on sex or vaginal product use 
≤45 days 
2nd Film 
1st Film 
Note: phone check visits may be converted to other remote contact method (e.g., SMS) or in-person as needed and preferred by sites and individual 
participants and in accordance with local regulatory requirements 

 
 
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Exploratory Objectives: 
 
Participant acceptability, attitudes and experiences 
• 
To explore multiple dimensions of acceptability of two placebo film types (A and B) and 
participants’ attitudes towards and experiences with the vaginal film. 
 
Sexual partner attitudes and experiences 
• 
To explore sexual partners’ attitudes towards and experiences with the vaginal film. 
 
Vaginal microenvironment 
• 
To assess the impact of placebo film use on participants’ vaginal microenvironment when 
administered vaginally once monthly for two months. 
 
Social harms and social benefits 
• 
To describe the reported experiences of social harms and social benefits over the course 
of vaginal film use. 
 
Exploratory Endpoints: 
 
Participant acceptability, attitudes and experiences 
• 
Participant responses to quantitative acceptability assessments and IDI questions. Multiple 
dimensions will be explored, including: 
o Vaginal film attributes, including acceptability (e.g., ease of insertion, burden, 
perceived effectiveness of film as delivery form) and preferences 
o Experience and comfort with inserted vaginal film (e.g., expulsions, leakage, 
awareness of film during daily activities) 
o Experience during sex and menses 
o Vaginal practices and concomitant vaginal product use while using vaginal film 
o Perception of sexual partners’ attitudes towards vaginal film 
o Perceived benefits and concerns/challenges with the vaginal film as a future HIV 
prevention option 
o Interest in using vaginal film as a future HIV prevention option 
 
Sexual partner attitudes and experiences 
• 
Sexual partner responses during IDI related to: 
o Vaginal film attributes, including acceptability and preferences 
o Perception of participant’s experience using the vaginal film during the study 
o Physical sensation of the participant’s vaginal film use during sex (as relevant) 
o Perceived benefits and concerns/challenges with the vaginal film as a future HIV 
prevention option 
 
Vaginal microenvironment 
• 
Change from baseline in vaginal pH following film use during the two study phases (i.e., 
with and without sexual abstinence requirement). 
• 
Change from baseline in quantity of selected vaginal microbiota following film use during 
the two study phases (i.e., with and without sexual abstinence requirement). 
• 
Change from baseline in Nugent score following film use during the two study phases (i.e., 
with and without sexual abstinence requirement). 

 
 
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Social harms and social benefits 
• 
Participant self-report of social harms (i.e., non-clinical adverse consequences of study 
participation or product use that may manifest in social, psychological or physical ways). 
• 
Participant or sexual partner self-report of social benefits (e.g., positive consequences of 
product use disclosure, self-confidence, improved communication with intimate partner) 
resulting from vaginal film use and/or study participation. 
 
 

 
 
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1 
KEY ROLES 
 
1.1 Protocol Identification 
 
Protocol Title:   
Trial to Assess Acceptability and Safety of Two Placebo Prototype 
Vaginal Films 
 
Protocol Number: 
 
MATRIX-002 
 
Short Title: 
 
VALUE Placebo Film Study 
 
Date:  
 
24 May 2023 
 
1.2 Funding Agency and Monitor Identification 
 
Funding Agency: 
USAID  
Bureau of Global Health, Office of HIV/AIDS, Research Division 
500 D Street Southwest 
Washington, DC 20547 USA 
 
 
Pharmaceutical Collaborator: Pitt/MWRIF 
 
204 Craft Avenue 
 
Pittsburgh, PA 15213 USA 
 
Monitor – African sites: 
African Clinical Research Organisation (ACRO) 
 
Phase 3, Second Floor Offices, Centurion Science Park, 
 
1011 Pretorious Avenue, Lyttelton Manor, Centurion, 0157 
 
South Africa  
 
 
Monitor – US site: 
University of Pittsburgh Education and Compliance Support for 
Human Subject Research (ECS-HSR) 
 
Office of Research Protections 
 
Heiber Building, Suite 401 
 
3500 Fifth Avenue, 
 
Pittsburgh, PA 15213 USA 
 
1.3 Laboratory(ies) 
 
 
 
 
 
MATRIX/MWRIF 
204 Craft Avenue 
Pittsburgh, Pennsylvania 15213 USA 
 

 
 
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1.4 Data Management 
 
Quantitative Data Center: 
MATRIX/MWRIF 
204 Craft Avenue 
Pittsburgh, Pennsylvania 15213 USA 
 
Qualitative Data Center: 
RTI International 
 
 
 
2150 Shattuck Avenue, Suite 800 
 
 
 
Berkeley, CA 94704 USA 
 
1.5 Clinical Research Management 
 
 
 
 
 
MATRIX/MWRIF 
204 Craft Avenue 
Pittsburgh, Pennsylvania 15213 USA 
 
 
 
 

 
 
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2 
INTRODUCTION 
 
2.1 Background 
 
Topical microbicides are agents designed to prevent or at least substantially reduce the risk of 
sexual acquisition and transmission of HIV when applied to the genital or rectal mucosa. Vaginal 
films are an attractive dosing option for topical (vaginal) delivery of anti-HIV drugs. In terms of 
costs of production and manufacturing, films are relatively inexpensive, scalable, physically and 
chemically stable, and amenable to a range of active ingredients including combinations of 
excipients. In terms of use, films are discreet, portable, and easy to store. Vaginal films can 
deliver fixed doses of pharmacologically active agents with minimal mess or leakage and without 
an applicator. Due to their small volume, films also generate no significant alterations in innate 
microbiome as shown in previous clinical evaluation for our FAME program (U19 AI0826391, U19 
AI1202492), and incur less dilution of endogenous antiviral or antibacterial properties in vaginal 
fluids as compared to vaginal gels. Feedback from women in several clinical and focus-group 
studies – NCT01231763 (FACE)3, NCT02908503 (FLAG)4, NCT02602366 (Quatro)5, PASII6, 
NCT01334827 (MIST)7,8, NCT01548560 (FAME 02)9, FAME 02B10, NCT02579083 (VAST)11, 
NCT01989663 (FAME 04)12, NCT02280109 (FAME 05)13, NCT03537092 (FAME 101)14, FAME 102 
(unpublished data), NCT04319718 (FAME 103)15, NCT04391036 (FAME 103B)16 – supported the 
willingness for women to use such products and the advancement and development of vaginal 
films for discrete HIV prevention.5,6,9-11 
 
The long-term goal of the VALUE (Vaginal film as A Low-cost, User-administered, and Extended-
release product) project is to develop and evaluate an extended-release vaginal film containing 
dapivirine, a potent NNRTI, which could provide protection from HIV for at least one month 
following a single application. Previously, the Pitt/MWRIF team developed and evaluated quick 
dissolve films for on-demand vaginal administration of several anti-HIV drug candidates including 
dapivirine.9,10,12,13 We have also confirmed the feasibility of design of a monthly film platform 
(LATCH R61/33 AI142687)17 in a nonhuman primate (macaque) model. Furthermore, retention 
of films within the vagina was established during menses and sex in the macaque model. The 
VALUE project aims to design a one-month vaginal film containing dapivirine as the active 
pharmaceutical ingredient (API) to provide a low cost and convenient option for women for 
protection from HIV infection through sex. Previous studies have supported the acceptability and 
safety of the quick dissolve and 7-day sustained release films, but there is limited data regarding 
a monthly vaginal film. 
   
MATRIX-002 is a randomized trial assessing the acceptability and safety of two vaginal placebo 
film products that differ in shape. Specifically, the 2"x2" films differ with respect to shape of the 
corners. One film product is square in shape, while the second product has rounded edges on all 
four corners. These differences may impact product acceptability and usability. The proposed 
study will evaluate the acceptability, safety, and self-insertion success of these 1-month placebo 
film products when applied vaginally with and without sex at five clinical sites, one in the United 
States and four in South Africa, Zimbabwe, and Kenya. Building on the existing evidence base for 
the quick dissolve and 7-day extended-release films, multiple African sites will participate in 
MATRIX-002 alongside the US site, affording the opportunity to obtain critical information and 
feedback from women who have the greatest potential to benefit from access to a range of HIV 
prevention products. This study of the one-month placebo vaginal film will examine overall 

 
 
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satisfaction with the film after using it, multiple components and correlates of acceptability, as 
well as topics relevant to adherence and preference. The design of these assessments is informed 
by a recent systematic review of the Theoretical Framework of Acceptability (Sekhon),18 published 
by Ortblad et al.19 
 
Additionally, by investigating the attitudes and experiences that sexual partners had while 
MATRIX-002 participants used the vaginal film, this study hopes to gain a deeper understanding 
of how partners’ opposition or support may affect a user’s ability to safely, correctly and 
consistently use a vaginal film for HIV prevention in the future. This, in turn, can contribute to 
efforts to mitigate concerns and cultivate support among men for HIV prevention research, HIV 
prevention products, and microbicide use. Data from in-depth interviews (IDI) may also provide 
insight to the strategies and counseling messages that could be used in couples’ education and 
counseling for future trials, with the objective of promoting use of the vaginal film. 
 
2.2 Description of Placebo Prototype Vaginal Films 
 
2.2.1 
Placebo Vaginal Film A 
 
Placebo Vaginal Film A is made of film-forming polymers, release-modifying polymers, and 
plasticizers. It differs from Placebo Vaginal Film B by the shape (square vs. rounded edges). All 
the 
excipients 
used 
have 
a 
history 
of 
pharmaceutical 
use 
(https://www.accessdata.fda.gov/scripts/cder/iig/index.cfm). The formulations contain multiple 
excipients, namely, hydroxypropyl cellulose, Hypromellose, hydroxyethyl cellulose, ammonio 
methacrylate copolymer type B, propylene glycol, and polyethylene glycol. A vaginal film 
containing similar excipients was utilized in the FAME 101 study (ClinicalTrials.gov Identifier: 
NCT03537092)14 without any adverse outcomes in healthy participants. 
 
2.2.2 
Placebo Vaginal Film B 
 
Placebo Vaginal Film B is also made of film-forming polymers, release-modifying polymers, and 
plasticizers. It differs from Placebo Vaginal Film A by the shape (square vs. rounded edges). 
 
2.3 Acceptability of Vaginal Film Formulations 
 
End-user acceptability of vaginal films as an option for women has been confirmed through input 
from nearly 3000 women.5,6,9-11 Prior end-user acceptability data was collected primarily through 
programs evaluating HIV prevention products to gain insight regarding the acceptability of the 
vaginal film platform when applied for HIV prevention. Some of the data also include preferences 
associated with multipurpose prevention platforms. In these studies, we have obtained data 
comparing films with other dosage forms, explored end-user acceptability in the context of sexual 
intercourse and obtained information from end-users that has directed our target critical quality 
attributes (CQAs) including size, color and texture. We also gained insights that informed film use 
instructions and explored the relationship between formulation modification, end-user 
acceptability, and ease of use experiences with the product. Overall, women have found the 
vaginal film platform to be acceptable and easy to use. 
 

 
 
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2.4 Rationale for Study Design 
 
The primary objective of this study is to assess the acceptability of two placebo film types (A and 
B) when administered vaginally once monthly for two consecutive months. Previous research has 
supported the safety of the film excipients, but there is little data on the acceptability of a monthly 
vaginal film. The study is designed to assess acceptability parameters in the first month in ideal 
conditions (i.e., pelvic rest). During this phase, we anticipate that participants will be unaware of 
the film’s presence in the vagina based on prior clinical research with vaginal film products; 
however, it is possible that with time the film might contribute to discharge as it dissolves and/or 
be expelled during menses. The first month, during which participants are instructed to refrain 
from putting anything into the vagina, will provide valuable insight into user experiences with the 
film without extraneous interruptions. The second month, during which participants are allowed 
to have sexual intercourse and use vaginal products, will provide important information about 
user experience with the film with vaginal stimuli. We anticipate that the film will stay in place 
despite potential disruptors but can only understand this through the second month of use. By 
evaluating two placebo films we hope to understand if there are differences in performance (e.g., 
acceptability and insertion success) and what attributes potentially contribute to these outcomes. 
Aspects of the film that lead to better performance will be incorporated into future film design. 
 
This study has been designed to add to our knowledge about potential end-users’ acceptability 
of and perceptions towards long-term (1 month) use of films with different shapes. Acceptability 
will be assessed through quantitative questionnaires and IDIs with users and, among a subset, 
IDIs with their sexual partners. Instructional materials will be utilized to familiarize users with the 
insertion process. These materials were designed based on participant feedback from previous 
trials. Product misplacement such as partial insertion has been noted in clinical trials of vaginal 
films previously conducted at the University of Pittsburgh.4 While most participants could 
successfully insert the vaginal films, incorrect film placement was noted for some. In some 
instances, the vaginal film stuck to the finger after attempted insertion and in other instances the 
film was visualized on the external genitalia, which illustrates the importance of assessing ease 
of proper insertion and film attributes relevant to usability in this placebo study. Since the film is 
intended to provide HIV protection for a month after a single application, identification of any 
adverse effects will also be an integral part of this study. Importantly, experiences of the 
participants and their partners in the context of sex will also be explored. Previous studies have 
found the vaginal film to be safe and acceptable as quick dissolve and 7-day sustained release 
formulations, but the 1-month long vaginal film has never been tested in women. This placebo 
study will provide critical information on acceptability, safety, usability, and user experience, 
which will be incorporated in the dapivirine film development and clinical evaluation program. 
Finally, although NCT02702895 (MTN-032) and other studies have shown that male partners play 
an important role in women’s adherence to microbicides,20 more research is needed to understand 
how this manifests specifically in the context of women’s use of extended-release vaginal films. 
Therefore, perceptions of the vaginal film will also be elicited from sexual partners of study 
participants. 
 
 

 
 
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3 
OBJECTIVES  
 
3.1 Primary Objective 
 
 
Acceptability 
• 
To assess the acceptability of two placebo film types (A and B) when administered 
vaginally once monthly for two months. 
 
3.2 Secondary Objectives 
 
Safety 
• 
To assess the safety of two placebo film types (A and B) when administered vaginally 
once monthly for two months. 
 
Usability 
• 
To assess participants’ ability to properly insert the placebo vaginal film. 
 
3.3 Exploratory Objectives 
 
Participant acceptability, attitudes and experiences 
• 
To explore multiple dimensions of acceptability of two placebo film types (A and B) and 
participants’ attitudes towards and experiences with the vaginal film. 
 
Sexual partner attitudes and experiences 
• 
To explore sexual partners’ attitudes towards and experiences with the vaginal film. 
 
Vaginal microenvironment 
• 
To assess the impact of placebo film use on participants’ vaginal microenvironment when 
administered vaginally once monthly for two months. 
 
Social harms and social benefits 
• 
To describe the reported experiences of social harms and social benefits over the course 
of vaginal film use. 
 
 
4 
STUDY DESIGN 
 
4.1 Identification of Study Design 
 
MATRIX-002 is a two-arm, randomized, multi-center trial to assess acceptability, safety and 
usability of two placebo prototype films when administered vaginally once monthly for two 
months. 
 

 
 
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4.2 Summary of Major Endpoints 
 
Primary Endpoints: 
 
Acceptability 
• 
Participant ratings of overall satisfaction with using the placebo vaginal films. 
 
Secondary Endpoints: 
 
Safety 
• 
Proportion of participants with genitourinary Grade 2 or higher Adverse Events deemed 
related to study product. 
 
Usability 
• 
Proportion of participants with clinically assessed proper insertion (more than half of the 
vaginal film proximal to introitus). 
 
Exploratory Endpoints: 
 
Participant acceptability, attitudes and experiences 
• 
Participant responses to quantitative acceptability assessments and IDI questions. Multiple 
dimensions will be explored, including: 
o Vaginal film attributes, including acceptability (e.g., ease of insertion, burden, 
perceived effectiveness of film as delivery form) and preferences 
o Experience and comfort with inserted vaginal film (e.g., expulsions, leakage, 
awareness of film during daily activities) 
o Experience during sex and menses 
o Vaginal practices and concomitant vaginal product use while using vaginal film 
o Perception of sexual partners’ attitudes towards vaginal film 
o Perceived benefits and concerns/challenges with the vaginal film as a future HIV 
prevention option 
o Interest in using vaginal film as a future HIV prevention option 
 
Sexual partner attitudes and experiences 
• 
Sexual partner responses during IDI related to: 
o Vaginal film attributes, including acceptability and preferences 
o Perception of participant’s experience using the vaginal film during the study 
o Physical sensation of the participant’s vaginal film use during sex (as relevant) 
o Perceived benefits and concerns/challenges with the vaginal film as a future HIV 
prevention option 
 
Vaginal microenvironment 
• 
Change from baseline in vaginal pH following film use during the two study phases (i.e., 
with and without sexual abstinence requirement). 
• 
Change from baseline in quantity of selected vaginal microbiota following film use during 
the two study phases (i.e., with and without sexual abstinence requirement). 
• 
Change from baseline in Nugent score following film use during the two study phases (i.e., 
with and without sexual abstinence requirement). 

 
 
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Social harms and social benefits 
• 
Participant self-report of social harms (i.e., non-clinical adverse consequences of study 
participation or product use that may manifest in social, psychological or physical ways).  
• 
Participant and sexual partner self-report of social benefits (e.g., positive consequences 
of product use disclosure, self-confidence, improved communication with intimate partner) 
resulting from vaginal film use and/or study participation. 
 
4.3 Description of Study Population 
 
The study population will consist of HIV seronegative adult (18-45 years old) persons assigned 
female sex at birth who meet the criteria outlined in Sections 5.2.1 and 5.3, and sexual partners 
who meet eligibility criteria as described in Section 5.2.2. 
 
4.4 Time to Complete Accrual 
 
The time to complete accrual at all sites is anticipated to be approximately 3-6 months. 
 
4.5 Study Groups 
 
MATRIX-002 will enroll approximately 100 evaluable participants, randomized (1:1) to either 
placebo vaginal film A or B. MATRIX-002 will also enroll a subset of up to 30 sexual partners for 
an IDI. See Section 10.3 for more details. 
 
4.6 Expected Duration of Participation 
 
Once randomized to placebo film A or B, participants will complete approximately nine weeks of 
follow-up. The total duration of the study will be approximately 6-9 months. 
 
4.7 Sites 
 
The following five sites in the United States and sub-Saharan Africa (SSA) will take part in 
MATRIX-002: University of Pittsburgh (Pitt)/Magee-Womens Research Institute and Foundation 
(MWRIF) clinical research site (CRS), Aurum Institute CRS, Harare Health and Research 
Consortium (HHRC) CRS, Wits Reproductive Health and HIV Institute (Wits RHI) CRS, and Kenya 
Medical Research Institute (KEMRI) CRS. 
 
 
5 
STUDY POPULATION 
 
5.1 Selection of the Study Population 
 
The inclusion and exclusion criteria in Sections 5.2 and 5.3 will be used to ensure the appropriate 
selection of study participants. In addition, a sample of up to 30 sexual partners for whom 
participants have given permission to contact will be selected for participation in an IDI. 
 

 
 
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5.1.1 
Recruitment 
 
Participants will be recruited from a variety of sources across sites including, but not limited to, 
existing databases (as permitted by local guidelines on protected health information [PHI]), 
primary care health clinics, family planning clinics, HIV testing facilities, gynecology clinics, 
institutions of higher learning, other community-based organizations, and through community 
outreach activities. Recruitment materials will be approved by site Institutional Review 
Boards/Independent Ethics Committees (IRB/IEC) prior to use per local requirements. Community 
education strategies, including group sessions, may be employed as part of participant/partner 
outreach. Sites will develop and implement local standard operating procedures (SOP) to target 
potential participants for recruitment. 
 
5.1.2 
Retention 
 
Once a participant is enrolled in MATRIX-002, study sites will make every effort to retain the 
participant in follow-up to minimize possible bias associated with loss-to-follow-up (LTFU). An 
average retention rate of 95% will be targeted across sites. Sites will develop and implement local 
SOPs to target and ensure high rates of retention. 
 
5.2 Inclusion Criteria 
 
5.2.1 
Participants 
 
Potential participants must meet all the following criteria prior to Enrollment (unless otherwise 
specified): 
 
1) Aged 18 to 45 years (inclusive) at Screening, verified per site SOP. 
 
2) Assigned female sex at birth. 
 
3) Able and willing to provide written informed consent to be screened for and enrolled in 
MATRIX-002 in one of the study languages (as specified in site SOP). 
 
4) Able and willing to provide adequate contact/locator information, as defined in site SOP. 
 
5) Able and willing to comply with all protocol requirements, including: 
• 
Abstaining from all receptive sexual intercourse (vaginal, anal, digital, oral) for the first 
month of product use. 
• 
Abstaining from using other intravaginal products for the first month of product use. 
• 
Abstaining from engaging in intravaginal practices for the first month of product use. 
• 
Refraining from participation in other research studies for the duration of the study 
unless approved by the Protocol Safety Review Team (PSRT). 
• 
Responding to scheduled phone/short message service (SMS) contacts. 
• 
Attending all clinic follow-up visits. 
 
6) HIV-uninfected based on testing performed at Screening and Enrollment (per protocol 
algorithms in Appendix II). 
 
7) Per participant report, if in a relationship, must be in a mutually monogamous relationship 
with a partner who is not known to be HIV positive or to currently have a sexually transmitted 
infection (STI). 

 
 
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8) Negative urine pregnancy test at Screening and Enrollment. 
 
9) Participants over the age of 21 (inclusive) must have documentation of a Grade 0 Pap smear 
within the past 3 years prior to Enrollment, or a Grade 1 Pap smear at Screening with no 
treatment required, per 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. 
 
10) Protected from pregnancy starting two weeks before Screening and continuing for the 
duration of study participation by an effective contraceptive method as confirmed by site SOP; 
effective methods include: 
• 
Hormonal methods except vaginal rings 
• 
Copper intrauterine device (IUD) 
• 
Sterilization of participant 
• 
Correct and consistent condom use (for US site only) 
• 
Abstinence from penile-vaginal intercourse 
 
5.2.2 
Sexual Partners 
 
Potential participants for the sexual partner IDI subset must meet all of the following criteria to 
be eligible for inclusion in the study: 
1. Identifies as a sexual partner of a MATRIX-002 participant. 
2. Identified by participant as a sexual partner during MATRIX-002 for whom the participant 
has given permission to contact (as specified in site SOP). 
3. Able and willing to provide written informed consent in one of the study languages (as 
specified in site SOP). 
4. Able and willing to complete the required study procedures. 
5. Must be 18 years old or above at the time of their study participation, verified per site 
SOP. 
 
5.3 Exclusion Criteria 
 
Potential participants must not meet any of the following criteria prior to Enrollment (unless 
otherwise specified):  
 
1) Per participant report at Screening and Enrollment, intends to do any of the following during 
the study participation period: 
• 
Become pregnant. 
• 
Breastfeed. 
• 
Relocate away from the study site. 
• 
Travel away from the study site for a time period that would interfere with product 
resupply and/or study participation. 
 
2) Positive HIV test at Screening or Enrollment. 
 
3) Positive test for Trichomonas vaginalis (TV), Neisseria gonorrhea (GC), Chlamydia trachomatis 
(CT), or Treponema pallidum (Syphilis) at Screening or (per participant report) treated for 
potential STI within past 12 months. 
 
4) Diagnosed with urinary tract infection (UTI), pelvic inflammatory disease (PID), or 
reproductive tract infection (RTI) requiring treatment per WHO guidelines at Enrollment. 

 
 
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Note: Otherwise eligible participants diagnosed during screening with a UTI, symptomatic 
yeast infection or symptomatic BV infection are offered treatment consistent with WHO 
recommendations. If treatment is completed and symptoms have resolved within 45 days of 
obtaining informed consent for screening, the participant may be enrolled. 
 
5) Clinically apparent Grade 2 or higher pelvic exam finding per the DAIDS Table for Grading 
Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 and/or Addenda 1 
(Female Genital  Grading Table for Use in Microbicide Studies [Dated November 2007]) at 
Enrollment. 
 
Note: Otherwise eligible participants with exclusionary pelvic exam findings at Screening may 
be enrolled/randomized if treatment is begun at least 7 days prior to enrollment and findings 
have improved to a non-exclusionary severity grading or resolved by the time of enrollment. 
Spotting/bleeding will be considered exclusionary only if greater than what would be expected 
from contraceptive use. 
 
6) Participant report and/or clinical evidence of any of the following: 
• 
Known adverse reaction to any of the study product materials (ever). 
• 
Hysterectomy. 
• 
Surgical procedure involving the pelvis in the 30 days prior to Enrollment. 
• 
Use of diaphragm, NuvaRing, or (for African sites only) spermicide for contraception 
in the two weeks prior to Screening. 
• 
Antibiotic or antifungal (oral or intravaginal) therapy within 7 days of Enrollment. 
• 
Prior use of post-exposure prophylaxis (PEP) or oral pre-exposure prophylaxis (PrEP) 
(including FTC/TDF) in the 4 weeks prior to Screening or any prior use of long-acting 
systemic PrEP (including cabotegravir or islatravir). 
• 
Use of any of the following in the 12 months prior to Screening: stimulants (cocaine 
[including crack], methamphetamine, or non-physician prescribed pharmaceutical-
grade stimulants), or inhaled nitrates, or illicit injection drug use of any kind. 
• 
At Screening or Enrollment, as determined by the Investigator of Record 
(IoR)/designee, has any significant uncontrolled active or chronic cardiovascular, 
renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, 
respiratory, immunologic disorder or infectious disease. 
 
7) Has any of the following laboratory abnormalities at Screening: 
• 
Grade 2 or higher Aspartate aminotransferase (AST), alanine transaminase (ALT), 
creatinine, or Hemoglobin per the DAIDS Table for Grading Adult and Pediatric Adverse 
Events, Corrected Version 2.1, July 2017. 
 
8) Has any other condition that, in the opinion of the IoR/designee, would preclude informed 
consent, make study participation unsafe, complicate interpretation of study outcome data, 
or otherwise interfere with achieving the study objectives. 
 
5.4 Co-enrollment Guidelines 
 
Participants must not take part in other research studies involving drugs, medical devices, vaginal 
products, or vaccines starting two weeks before the Screening Visit and while taking part in 
MATRIX-002, unless approved by the PSRT. Participants must not take part in observational or 
qualitative studies while taking part in MATRIX-002, unless approved by the PSRT. Each site will 
be responsible for defining procedures for management and prevention of co-enrollment prior to 
initiation. 
 

 
 
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Should any participant report concurrent participation in contraindicated studies after enrolling in 
MATRIX-002, the IoR/designee will consult the PSRT regarding ongoing product use and other 
potential safety considerations associated with co-enrollment, or regarding potential product 
acceptability considerations associated with co-enrollment. 
 
 
6 
STUDY PRODUCT 
 
6.1 Regimen 
 
The products being used in this study are the placebo prototype vaginal films A and B. The two 
films differ by the shape (square vs. rounded edges). At each of the study sites, participants will 
be randomized (1:1) to receive either placebo vaginal film A or B. Each participant will receive 
one dose per month for two consecutive months, for a total of 2 doses of placebo vaginal film. 
 
Figure 2: Study Product Regimen  
 
 
 
 
 
 
 
6.2 Administration 
 
After eligibility is confirmed and the participant is randomized to one of two films (Placebo Film A 
or B) site staff will retrieve the assigned film from the pharmacy. Participants will self-insert the 
film at the study clinic, and film placement will be checked visually by a study clinician. If less 
than half of the vaginal film is proximal to introitus, participants will have the film removed and 
asked to try again with a new film. If less than half of the vaginal film is proximal to introitus a 
second time, participants will have the film removed and a third film inserted by the clinician 
using a speculum. 
 
6.3 Study Product Formulation and Storage    
 
Films are composed of film-forming polymers, release modifying polymers, and plasticizers. The 
2”x2” films will be packaged into foil-lined pouches and stored at room temperature. Good 
Scr
V1
Enr 
V2
24-72 hr 
Phone 
check
V3
Wk 1 
Phone 
check
V4
Wk 2
Phone 
check
V5
Wk 
3
Wk 4 
Clinic 
follow 
up
V6
24-72hr 
Phone 
check
V7
Wk 
5
Wk 6 
Phone 
check
V8
Wk 
7
Wk 8 
Clinic 
follow 
up
V9
Wk 9 
Final 
phone 
contact
V10
No sex or vaginal product use permitted 
 No restrictions on sex or vaginal product use 
≤45 days 
2nd Film 
1st Film 
Note: phone check visits may be converted to other remote contact method (e.g., SMS) or in-person as needed and preferred by sites and individual 
participants and in accordance with local regulatory requirements 

 
 
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Manufacturing Practice (GMP) stability testing will be conducted for the clinical trial product 
material as per ICH guidelines. 
 
6.4 Supply and Accountability 
 
6.4.1 
Study Product Supply 
 
Study product will be manufactured and packaged 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 clinical sites.   
 
6.4.2 
Study Product Dispensing 
 
Study product will be dispensed to clinic staff only upon receipt of a written prescription signed 
by an authorized prescriber.   
 
6.4.3 
Study Product Accountability 
 
The clinical study site pharmacist(s) 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). 
 
6.4.4 
Retrieval of Unused Study Products 
 
All unused study products must be accounted for by the site Pharmacy after the study is 
completed or terminated.   
 
6.5 Ancillary Study Supplies 
 
Clinic staff will offer male condoms to all participants after the first month of vaginal film use.  
 
6.6 Concomitant Medications 
 
All concomitant medications will be recorded on case report forms (CRF) for participants starting 
at Screening. Concomitant medications include any prescription, over the counter or 
herbal/traditional medication or preparation. Enrolled study participants may use concomitant 
medications during study participation but will be asked to abstain from medications and products 
noted as prohibited in Section 6.7. 
 
6.7 Prohibited Medications, Products and Practices 
 
Participants will be instructed to practice “pelvic rest” during the first month of participation. This 
means nothing should enter the vagina: fingers, penis, tampon, toys, etc. Participants will be 
asked to abstain from any penetrative sex (i.e., penile or with the use of an instrument that 
penetrates past the labia majora), intravaginal practices (e.g., douching), and use of all 
intravaginal medications and products during the first month of participation. If a participant 
reports receptive sexual activity, douching, or use of an intravaginal medication or product, the 
site staff will counsel the participant about the importance of adhering to the protocol (if reported 

 
 
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during first month of product use) and record these behaviors on the appropriate CRF. During 
the second month of participation there are no restrictions on sexual activity, intravaginal 
practices or products. Please reference the MATRIX-002 Study Specific Procedures (SSP) Manual 
for additional details. 
 
 
7 
STUDY PROCEDURES 
 
An overview of the study visits and evaluations schedule is provided in Appendix I. Presented in 
this section is additional information on visit-specific study procedures. Detailed instructions to 
guide and standardize procedures across sites as well as to specify the visit windows are provided 
in the MATRIX-002 SSP Manual. 
 
Figure 3: Study Visit Schedule 
 
 
 
 
 
 
 
7.1 Screening Visit   
 
Potential participants will provide written informed consent prior to any study procedures 
including all screening assessments to determine their eligibility to take part in the study. 
Participants will be counselled to abstain from sex and from use of intravaginal products (see 
Section 6.7) for the first month of study product use. Eligibility determination will include baseline 
demographics and medical history, physical and pelvic examination, urine pregnancy test (UPT), 
and HIV/STI screening. If eligible, potential participants will return within 45 days for their 
Enrollment Visit. For women with a regular menstrual cycle, the Enrollment Visit (and subsequent 
clinic visits if enrolled) will ideally be scheduled when the potential participant is not on her period. 
 
Note: Multiple visits may be conducted within the screening window to complete all required 
screening procedures, including any procedures that need to be repeated (e.g., blood draw), if 
necessary. 
 
Note: Potential participants who fail their first screening attempt may be re-screened once. 
 
Scr
V1
Enr 
V2
24-72 hr 
Phone 
check
V3
Wk 1 
Phone 
check
V4
Wk 2
Phone 
check
V5
Wk 
3
Wk 4 
Clinic 
follow 
up
V6
24-72hr 
Phone 
check
V7
Wk 
5
Wk 6 
Phone 
check
V8
Wk 
7
Wk 8 
Clinic 
follow 
up
V9
Wk 9 
Final 
phone 
contact
V10
No sex or vaginal product use permitted 
 No restrictions on sex or vaginal product use 
≤45 days 
2nd Film 
1st Film 
Note: phone check visits may be converted to other remote contact method (e.g., SMS) or in-person as needed and preferred by sites and individual 
participants and in accordance with local regulatory requirements 

 
 
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Table 1: Screening Visit 
Screening Visit – Visit 1  
Component 
Procedures 
Administrative and Regulatory 
• Obtain written informed consent for screening and enrollment (sites 
may split screening and enrollment consent if requested/required by 
IRB/IEC) 
• Assign a unique Participant Identification (PTID) number 
• Assess eligibility 
• Collect demographic information 
• Collect locator information 
• Provide reimbursement 
• Schedule next visit/contact* 
Behavioral/Counseling 
• HIV pre- and post-test counseling  
• HIV/STI risk reduction counseling 
• Protocol counseling (including regarding pelvic rest in Month 1) 
Clinical 
• Collect medical and menstrual history  
• Collect concomitant medications 
• Perform full physical examination  
• Perform pelvic examination (including bimanual exam) 
• Treat or prescribe treatment for RTI/UTI/STIs* 
• Provide available test results 
Laboratory 
Saliva 
• HIV test(s) (only at sites with CLIA certification) 
Urine 
• Urine pregnancy test 
• Urine dipstick/culture* 
Blood 
• HIV test(s) (not required for sites that conduct saliva testing) 
• Complete blood count (CBC) 
• Serum creatinine 
• AST/ALT 
• Syphilis serology 
Pelvic 
• Nucleic acid amplification test (NAAT) for GC/CT/TV 
• Pap test^ 
• Saline/potassium hydroxide (KOH) wet mount for candidiasis and/or 
bacterial vaginosis (BV)* 
*If indicated and/or per local standard of care; ^ if indicated (if participant is unable to provide documentation of a 
normal Pap test within 3 years prior to enrollment) 
 
7.2 Enrollment Visit – Visit 2 (Day 0) 
 
Within 45 days of the Screening Visit, willing and eligible participants will have their eligibility 
confirmed and be randomized (1:1) to placebo vaginal film A or B. Participants will again be 
counselled to abstain from sex and from use of vaginal products (see Section 6.7) for the first 
month of study product use. Study staff will review instructional materials about the film and film 
insertion with participants prior to insertion of the first film. Participants will be asked to provide 
a urine sample for a UPT, undergo HIV/STI screening and a pelvic examination, provide a blood 
sample for plasma archive, and complete an interviewer-administered baseline acceptability 
questionnaire about the film. Participants will then be asked to insert the film at the study clinic, 
and film placement will be checked visually by a study clinician. If less than half of the vaginal 
film is proximal to introitus, participants will have the film removed and asked to try again with a 

 
 
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new film. If less than half of the vaginal film is proximal to introitus a second time, participants 
will have the film removed and a third film inserted by the clinician using a speculum. Participant 
attempts to insert the film will be documented on the appropriate CRF. 
 
Table 2: Enrollment Visit – Visit 2 (Day 0) 
Enrollment Visit – Visit 2 (Day 0) 
Component 
Procedures 
Administrative and Regulatory 
 
• Review informed consent or (for sites that use separate screening and 
enrollment consent forms if requested/required by IRB/IEC) obtain 
written informed consent for enrollment 
• Assess and confirm eligibility  
• Review/update locator information 
• Randomization 
• Provide reimbursement 
• Schedule next visit/contact* 
Behavioral/Counseling 
• HIV pre- and post-test counseling 
• HIV/STI risk reduction counseling 
• Protocol counseling (including regarding pelvic rest in month 1 and 
product use) 
• Review instructional materials 
• Baseline behavioral questionnaire (acceptability and risk/protective 
behaviors) 
• Post-insertion behavioral assessment 
Clinical 
• Review/update medical and menstrual history  
• Review/update concomitant medications 
• Perform targeted physical examination* 
• Perform pelvic examination with speculum 
• AE assessment 
• Treat or prescribe treatment for RTI/UTI/STIs* 
• Visual examination by clinician to check vaginal film placement 
• Clinician film insertion assessment 
• Provide available test results 
Laboratory 
Saliva 
• HIV test(s) (only at sites with CLIA certification) 
Urine 
• Urine pregnancy test 
• Urine dipstick/culture* 
Blood 
• HIV test(s) (not required for sites that conduct saliva testing) 
• Plasma for archive 
• CBC* 
• Serum creatinine* 
• AST/ALT* 
Pelvic 
• NAAT for GC/CT/TV 
• Saline/KOH wet mount for candidiasis and/or BV* 
• Vaginal Gram stain 
• Vaginal swab(s) for microbiota 
• Vaginal pH 

 
 
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Enrollment Visit – Visit 2 (Day 0) 
Component 
Procedures 
Study Product/Supplies 
• Provide vaginal film for self-insertion at clinic 
• Clinician insertion of vaginal film at clinic (only if participant fails two 
attempts) 
*If indicated and/or per local standard of care 
 
7.3 Follow-up Visits/Contacts 
 
7.3.1 Phone check-in (24-72 hours after 1st insertion) – Visit 3 
 
Between 24 and 72 hours after the insertion of the first film, a member of the study team will 
contact the study participant via telephone or short message service (SMS) to assess experiences 
with the first vaginal film in situ. Participants who prefer to complete these procedures in-person 
may elect to do so. The staff member will ask the participant about initial experiences with the 
film in place, any concerns about product placement and leakage, and elicit any questions or 
other concerns. If conducted as a phone conversation, this is anticipated to be less than 5 
minutes. If conducted as an SMS exchange, this is anticipated to be less than 5 text messages 
from each party. If participants raise any concerns that require more in-depth discussion, the 
staff member will assess the proper follow-up method. 
 
Table 3:  Phone check-in (24-72 hours after 1st insertion) – Visit 3 
Phone check-in (24-72 hours after 1st insertion) – Visit 3 
Component 
Procedures 
Administrative and Regulatory 
• Provide reimbursement 
Behavioral/Counseling 
• Brief behavioral assessment (concerns and comfort with film use) 
 
7.3.2 1-week and 2-week Telephone Contacts – Visits 4 and 5 (7 and 14 days after 
Visit 2) 
 
Approximately one week and two weeks after Enrollment, the study team will contact the study 
participant via telephone or SMS to assess participant wellness, comfort with the film, and any 
concerns. Participants who prefer to complete these procedures in-person may elect to do so. 
Participants who report AEs or otherwise express concerns may be asked to come in for an Interim 
Visit, if willing, to conduct additional counseling and/or testing as needed. 
 
Table 4: 1-week and 2-week Telephone Contacts – Visits 4 and 5 (7 and 14 days after 
Visit 2) 
1-week and 2-week Telephone Contacts – Visits 4 and 5 (7 and 14 days after Visit 2) 
Component 
Procedures 
Administrative and Regulatory 
• Review/update locator information 
• Provide reimbursement 
• Schedule next visit/contact 
Behavioral/Counseling 
• Brief behavioral assessment (concerns and comfort with film use) 
• Protocol counseling* 

 
 
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1-week and 2-week Telephone Contacts – Visits 4 and 5 (7 and 14 days after Visit 2) 
Component 
Procedures 
Clinical 
• Review/update medical and menstrual history  
• Review/update concomitant medications 
• AE assessment 
• Provide available test results 
*If indicated and/or per local standard of care 
 
7.3.3 4-week Visit – Visit 6 (28 days after Visit 2)   
 
At least four weeks after Enrollment, participants will come to the clinic for acceptability and 
safety evaluation for the first film, the clinician will remove any visible film, and the participant 
will insert a second film. Study staff will once again review instructional materials about the film 
and film insertion with participants prior to insertion of the second film. The second film will be 
the same film shape the participant was randomized to at enrollment, and film placement will be 
checked visually by a study clinician. If less than half of the vaginal film is proximal to introitus, 
participants will have the film removed and asked to try again with a new film. If less than half 
of the vaginal film is proximal to introitus a second time, participants will have the film removed 
and a third film inserted by the clinician using a speculum. Participant attempts to insert the film 
will be documented on the appropriate CRF. During the second month, there are no restrictions 
on vaginal product use or sex. Participants will be asked to provide a urine sample for a UPT, 
undergo HIV/STI testing and a pelvic examination, and complete an interviewer-administered 
acceptability questionnaire about the film. 
 
Table 5: 4-week Visit – Visit 6 (28 days after Visit 2) 
4-week Visit – Visit 6 (28 days after Visit 2) 
Component 
Procedures 
Administrative and Regulatory 
 
• Review/update locator information 
• Provide reimbursement 
• Schedule next visit/contact 
Behavioral/Counseling 
• HIV pre- and post-test counseling 
• HIV/STI risk reduction counseling 
• Protocol counseling (including regarding sexual partner IDI 
component and product use) 
• Review instructional materials 
• Follow-up behavioral questionnaire (acceptability and product use 
experiences; intravaginal practices and sexual activity) 
• Post-insertion acceptability assessment 
Clinical 
• Review/update medical and menstrual history  
• Review/update concomitant medications 
• Perform targeted physical examination* 
• Perform pelvic examination with speculum 
• AE assessment 
• Treat or prescribe treatment for RTI/UTI/STIs* 
• Visual examination by clinician to check vaginal film placement 
• Clinician film insertion assessment 
• Provide available test results 

 
 
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4-week Visit – Visit 6 (28 days after Visit 2) 
Component 
Procedures 
Laboratory 
Saliva 
• HIV test(s) (only at sites with CLIA certification) 
Urine 
• Urine pregnancy test 
• Urine dipstick/culture* 
Blood 
• HIV test(s) (not required for sites that conduct saliva testing) 
• CBC* 
• Serum creatinine* 
• AST/ALT* 
Pelvic 
• NAAT for GC/CT/TV 
• Saline/KOH wet mount for candidiasis and/or BV* 
• Vaginal Gram stain 
• Vaginal swab(s) for microbiota 
• Vaginal pH 
Study Product/Supplies 
• Provide vaginal film for self-insertion at clinic 
• Clinician insertion of vaginal film at clinic (only if participant fails two 
attempts) 
• Offer male condoms 
*If indicated and/or per local standard of care 
 
7.3.4 Phone check-in (24-72 hours after 2nd insertion) – Visit 7 
 
Between 24 and 72 hours after the insertion of the second film, a member of the study team will 
contact the study participant via telephone or SMS to assess experiences with the second vaginal 
film in situ. Participants who prefer to complete these procedures in-person may elect to do so. 
The staff member will ask the participant about sensation with the film in place, any experiences 
of leakage, and any other concerns. If conducted as a phone conversation, this is anticipated to 
be less than 5 minutes. If conducted as an SMS exchange, this is anticipated to be less than 5 
text messages from each party. If participants raise any concerns that require more in-depth 
discussion, the staff member will assess the proper follow-up method. 
 
Table 6:  Phone check-in (24-72 hours after 2nd insertion) – Visit 7 
Phone check-in (24-72 hours after 2nd insertion) – Visit 7 
Component 
Procedures 
Administrative and Regulatory 
• Provide reimbursement 
Behavioral/Counseling 
• Brief behavioral assessment (concerns and comfort with film use) 
 
7.3.5 6-week Telephone Contact – Visit 8 (14 days after Visit 6) 
 
Approximately two weeks after the second film insertion at Visit 6, the study team will contact 
the study participant via telephone or SMS to assess participant wellness, comfort with the film, 
and any concerns. Participants who prefer to complete these procedures in-person may elect to 
do so. Participants who report AEs or otherwise express concerns may be asked to come in for 
an Interim Visit, if willing, to conduct additional counseling and/or testing as needed. 
 

 
 
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Table 7: 6-week Telephone Contact – Visit 8 (14 days after Visit 6) 
6-week Telephone Contact – Visit 8 (14 days after Visit 6)  
Component 
Procedures 
Administrative and Regulatory 
 
• Review/update locator information 
• Provide reimbursement 
• Schedule next visit/contact 
Behavioral/Counseling 
• Brief behavioral assessment (concerns and comfort with film use) 
• Protocol counseling* 
Clinical 
• Review/update medical and menstrual history  
• Review/update concomitant medications 
• AE assessment 
• Provide available test results 
*If indicated and/or per local standard of care 
 
7.3.6 8-week Visit – Visit 9 (28 days after Visit 6) 
 
At least four weeks after the second film insertion at Visit 6, participants will come to the clinic 
for acceptability and safety evaluation for the second film, and the clinician will remove any visible 
film. Participants will be asked to provide a urine sample for a UPT, undergo HIV/STI testing and 
a pelvic examination, and complete an interviewer-administered acceptability questionnaire about 
the film and a social harms and benefits assessment. This visit will constitute the Early 
Termination Visit. 
 
Table 8: 8-week Visit – Visit 9 (28 days after Visit 6) 
8-week Visit – Visit 9 (28 days after Visit 6)  
Component 
Procedures 
Administrative and Regulatory 
 
• Review/update locator information 
• Provide reimbursement 
• Confirm permission to contact sexual partner for IDI (subset) and 
invite per site Sexual Partner Contact SOP 
• Schedule next visit/contact 
Behavioral/Counseling 
• HIV pre- and post-test counseling 
• HIV/STI risk reduction counseling 
• Protocol counseling 
• Follow-up behavioral questionnaire (acceptability and product use 
experiences; intravaginal practices and sexual activity) 
• Social harms and benefits assessment 
• Conduct participant IDI (subset)a 
Clinical 
• Review/update medical and menstrual history  
• Review/update concomitant medications 
• Perform targeted physical examination* 
• Perform pelvic examination with speculum 
• AE assessment 
• Treat or prescribe treatment for RTI/UTI/STIs* 
• Provide available test results 
Laboratory 
Saliva 
• HIV test(s) (only at sites with CLIA certification) 
Urine 
• Urine pregnancy test 
• Urine dipstick/culture* 

 
 
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8-week Visit – Visit 9 (28 days after Visit 6)  
Component 
Procedures 
Blood 
• HIV test(s) (not required for sites that conduct saliva testing) 
• CBC 
• Serum creatinine 
• AST/ALT 
Pelvic 
• NAAT for GC/CT/TV 
• Saline/KOH wet mount for candidiasis and/or BV* 
• Vaginal Gram stain 
• Vaginal swab(s) for microbiota 
• Vaginal pH 
Study Product/Supplies 
• Offer male condoms 
*If indicated and/or per local standard of care; a At or after Visit 9, before Visit 10 
 
A subset of up to 35 participants will be purposively selected to complete a single explanatory IDI 
to provide further insight on their experiences using the placebo film and behaviors relevant to 
the study endpoints. The IDI Visit may occur on the same day as Visit 9 if agreed upon by the 
participant(s) and the study staff or may be scheduled up until Visit 10. Participants selected for 
the sexual partner subset IDI will be asked to confirm permission to contact their sexual partner 
and – if confirmed – the sexual partner will be invited per site Sexual Partner Contact SOP. 
 
7.3.7 Final Telephone Contact/Study Exit Visit – Visit 10 (7 days after Visit 9) 
 
The Final Telephone Contact will occur approximately one week after study product use has 
ended. The study team will contact the study participant via telephone or SMS to assess 
participant wellness and any concerns. Participants who prefer to complete these procedures in-
person may elect to do so. This visit constitutes the Study Exit Visit (SEV) and will serve as a final 
safety assessment. 
 
Table 9: Final Contact/SEV – Visit 10 (7 days after Visit 9) 
Final Contact/SEV – Visit 10 (7 days after Visit 9) 
Component 
Procedures 
Administrative and Regulatory 
• Review/update locator information 
• Provide reimbursement 
Clinical 
• Review/update medical and menstrual history  
• Review/update concomitant medications 
• AE assessment 
• Provide available test results 
 
7.3.8 Sexual Partners – IDI Visit 
 
Up to 30 sexual partners will be screened and enrolled to take part in a single IDI within one 
month of their participant partner’s Visit 9. Members of the protocol team and site teams will 
collaboratively determine which sexual partners to contact from among those that participants 
have given written permission for the study team to contact. Permission to contact sexual partners 
will be confirmed at Visit 9, and – if confirmed – sites will contact sexual partners according to 
site SOP and/or local IRB/IEC guidelines. Participants may change their decision about their sexual 
partners’ involvement at any time during the study. Selection of sexual partners to invite for an 

 
 
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IDI will be purposive so that characteristics/experiences of the enrolled study participant, use of 
film A or B, study site, and a breadth of perspectives and experiences are represented. Selection 
criteria and procedures will be further described in the MATRIX-002 SSP Manual. The IDI will 
include the following topics: 
• 
Disclosure/knowledge/understanding of clinical study, participant’s involvement in 
MATRIX-002, protocol restrictions on sexual activity in Month 1, and study product. 
• 
Experiences of sex with clinical study participant during the time they were using study 
product. 
• 
Perspectives and attitudes regarding monthly vaginal film use for HIV prevention. 
 
Table 10: IDI Visit with Sexual Partner Subset 
IDI Visit with Sexual Partner Subset – Screening and Enrollment Procedures 
Component 
Procedures 
Administrative and Regulatory 
  
• Confirm eligibility  
• Obtain written informed consent 
• Assign a unique PTID Number 
• Collect demographic data 
• Collect locator information 
• Provide reimbursement for study visit 
Behavioral 
• Administer brief behavioral questionnaire  
• Conduct sexual partner IDI b 
 b Within one month of participant Visit 9 
 
Multiple visits may be conducted to complete all required procedures, if necessary. 
 
7.4 Follow-up Procedures for Participants Who Permanently Discontinue Study 
Product 
 
7.4.1 Participants Who Become Infected with HIV 
 
If a participant tests positive for HIV after the Enrollment Visit, the participant will be referred to 
local care and treatment services and may return to the research clinic for additional counseling 
and other support services, as needed. Continued study participation would be of no added 
benefit to the participant, thus follow-up visits and procedures will be discontinued, study product 
use will cease, and the participant will be considered terminated from the study. An Early 
Termination Visit will be conducted, if the participant is willing (see Section 7.3.6). Please 
reference the MATRIX-002 SSP Manual for additional details. 
 
7.4.2 Participants Who Become Pregnant 
 
If a participant becomes pregnant after the Enrollment Visit, the participant will be referred to 
local health care services and may return to the research clinic for additional counseling, as 
needed. Continued study participation would be of no added benefit to the participant, thus study 
product use will cease, follow-up visits and procedures will be discontinued, and the participant 
will be considered terminated from the study. An Early Termination Visit will be conducted, if the 
participant is willing (see Section 7.3.6). Please reference the MATRIX-002 SSP Manual for 
additional details. 
 

 
 
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7.4.3 Participants Who Permanently Discontinue Study Product Use  
 
Participants who permanently discontinue study product use for any clinician-initiated reason 
other than HIV infection or pregnancy may, after consultation with the PSRT and MATRIX-002 
Management Team, have their remaining study follow-up visits and procedures discontinued. 
Participants will, however, be asked to complete an Early Termination Visit, if willing (see Section 
7.3.6). In the event study follow-up is continued, participants will have the protocol-specified 
visits through SEV. Sites should contact the PSRT and management team to determine whether 
the participant should be followed on study and what study procedures should be completed.  
 
Participants who permanently discontinue study product use due to an adverse event (AE) should 
continue to be followed in the study, if willing, until resolution (return to baseline) or stabilization 
of the AE is documented. 
 
7.5 Interim Visits/Contacts 
 
Interim visits/contacts (i.e., between regularly scheduled visits) may be performed as needed 
(e.g., participant reports an AE or social harm) at any time during the study, and any visit/contact 
procedures may be conducted as indicated. All interim contacts and visits will be documented in 
participants' study records. Refer to the MATRIX-002 SSP Manual for additional details. 
 
7.6 Behavioral Evaluations 
 
The study will address questions related to the primary, secondary, and exploratory objectives of 
acceptability, usability, and social harms and benefits, and both participants’ and sexual partners’ 
attitudes towards and experiences with the vaginal film. The study will assess film use facilitators 
and challenges experienced by participants, from the perspectives of both the participants and a 
subset of sexual partners. The study will also explore participants’ and sexual partners’ views on 
acceptable approaches to support study product adherence. These questions will be assessed via 
behavioral questionnaires and IDIs conducted by trained interviewers/facilitators. In addition, the 
study aims to gain further insight on: 
 
• 
Product insertion 
• 
Attitudes towards and experiences with using the vaginal film 
• 
Perspectives on any changes in vaginal environment 
• 
Comparisons between the two study products and comparisons to existing HIV prevention 
options 
• 
Factors related to future willingness to use/recommend the vaginal film 
• 
Sexual partner attitudes towards and experiences with the vaginal film, and their 
perspective of participant’s attitudes and experiences 
 
Additional questions and probes will be designed to delve further into the social and cultural 
norms that may play a role more broadly in product use. SMS or a phone call 24-72 hours after 
Visit 2 and Visit 6 will be employed as a measure to obtain information about initial experiences 
with vaginal film after insertion at the clinic. If a participant reports sexual activity, douching, or 
use of an intravaginal product, the site staff will record these behaviors on the appropriate CRF. 
 

 
 
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7.6.1 Quantitative Behavioral Assessments 
 
Participant attitudes and behaviors will be assessed throughout the study period using multiple 
data collection methods. Behavioral questionnaires at enrollment and during follow-up will 
measure key dimensions of acceptability pertinent to the vaginal film in its current phase of 
development alongside women’s experiences in using the film during the study. In addition, 
behavioral questionnaires will measure vaginal practices, contraceptive use, HIV prevention 
behaviors, sexual behavior and relationship factors. These questionnaires will be used to assess 
factors correlated with placebo vaginal film acceptability and use experiences. Additionally, 
quantitative questionnaire data will be complemented by data captured through structured SMS 
and phone visits, and through IDIs with subsets of participants and sexual partners. 
 
Table 11 outlines a summary of the assessment methods that will be used and the specific 
components of acceptability that will be assessed, informed by previous work and the Theoretical 
Framework of Acceptability as presented in Ortblad et. al.19  
 
 Table 11: Summary of behavioral assessments  
Assessments and Timepoints 
 Acceptability components measured 
Baseline assessment 
(Visit 2) 
Affective attitude, burden, opportunity costs, 
barriers/benefits 
Follow-up phone/SMS contacts 
(Visits 3-5, 7-8) 
Concerns and comfort with film use 
Follow-up assessments  
(Visits 6 and 9) 
Affective attitude, burden, opportunity costs, 
overall satisfaction, usability, appropriateness, 
preferences, perceived barriers/benefits 
Social harms and benefits assessment 
(Visit 9) 
N/A 
Participant IDI 
(At or after Visit 9, before Visit 10) 
Affective attitude, burden, satisfaction, usability, 
appropriateness, perceived barriers/benefits 
Sexual partner IDI 
(Within one month of Visit 9) 
Affective attitude, burden, satisfaction, usability, 
appropriateness, perceived barriers/benefits 
 
7.6.2 Qualitative Behavioral Assessments 
 
Two sets of IDI will be completed. The first will be conducted with a subset of participant film 
users who will be purposively selected and invited to complete an IDI after their second one-
month period of film use. The IDI will take place at Visit 9 or scheduled after the visit and before 
study exit (Visit 10). Additionally, a subset of sexual partners of participants will be purposively 
selected to participate in an IDI, which will take place within approximately one month of Visit 9. 
We will explore participant experiences using the vaginal film, acceptability of shape and 
dependent attributes such as tactile quality of the films, and social factors influential to attitudes 
toward the vaginal film as a future HIV prevention option. We will also explore sexual partner 
views on the vaginal film and their perceptions of and experience with the film during sexual 
activity. IDIs will be conducted separately with participants and their sexual partners to assess 
these topics. IDIs will include, but not be limited to, the following topics: 
 

 
 
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• 
Descriptions of film insertion practices  
• 
Main challenge(s) encountered with film use, especially during sex 
• 
Potential changes to the film 
• 
Other factors (e.g., situational, relationship, trial-specific, social/cultural/economic, sex 
and menstruation related, vaginal practices) influencing film acceptability and use 
experience 
• 
Sexual partner attitudes towards and experiences with the vaginal film, and their 
perspective of participant’s attitudes and experiences 
 
Semi-structured IDI guides will be developed by qualified social scientists and administered by 
qualified interviewers. Guides will contain key research questions relating to the main topics of 
interest and suggested probes. Interviews and discussion sessions will be audio-recorded and 
transcribed. 
 
7.7 Protocol Adherence Counseling 
 
Participants will receive protocol counseling upon enrollment into the study (Visit 2) and at Visit 
6 as appropriate to the visit. Study staff will document administration of study product and that 
the counseling was provided. Contraception counseling will be provided to participants of 
childbearing potential at all clinic visits beginning at Screening. Protocol adherence counseling will 
be provided at all clinic visits beginning at Screening, except SEV. Counseling will be provided by 
different site staff than those conducting the behavioral assessments when feasible, in accordance 
with standard study methods and as specified in site SOPs. Counseling also will include reminders 
regarding concomitant medication, sexual activity, intravaginal product use and practices, and 
behavioral restrictions during study participation as specified in Section 6.7. 
 
7.8 Clinical Evaluations and Procedures 
 
Physical Examination and Medical History 
The full physical examination will include the following assessments: 
• 
Vital signs 
o Blood pressure 
• 
Measurements of weight and height 
• 
General appearance 
• 
Cardiac exam 
• 
Respiratory exam 
• 
Abdomen  
 
Participants will be asked about medications/therapies at every visit, including Screening. Study 
staff will ask about adverse events at all visits beginning at Enrollment. A full physical examination 
will be completed by a clinician at Screening. Thereafter, a targeted physical examination will be 
performed to assess any complaints or symptoms with which the participant presents at the 
follow-up visits as clinically indicated. 
 
Pelvic Examination 
Pelvic exams will be performed using visual inspection of external genitalia and using a speculum 
for examination of the cervix and vagina, assessment of film persistence, and insertion of film (if 

 
 
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participant fails first two attempts). Bimanual exam may be performed as needed (required at 
Screening Visit). Pelvic exams will be conducted at Screening, Enrollment, and Visits 6 and 9 for 
vaginal microenvironment specimen collection and as indicated based on participant reports. 
Cervicovaginal fluid (CVF) will be collected using swabs. 
 
Additional clinical assessments/procedures may be performed at the discretion of the examining 
clinician in response to symptoms or illnesses present at the time of the exam/procedure. 
 
7.9 Laboratory Evaluations 
 
Local Laboratory 
• 
Saliva (only at sites with CLIA certification) 
o HIV test(s) 
 
• 
Urine 
o Urine pregnancy test 
o Urine dipstick/culture (as indicated, per local standard of care) 
 
• 
Blood 
o HIV test(s) (not required for sites that conduct saliva testing) 
o CBC 
o Serum creatinine 
o AST/ALT 
o Syphilis serology 
 
• 
Pelvic 
o NAAT for GC/CT/TV 
o Pap test (if indicated [if participant is unable to provide documentation of a normal 
Pap test within 3 years prior to enrollment]) 
o KOH wet mount for candidiasis and/or BV (if indicated) 
o Vaginal pH 
 
Designated Laboratory 
• 
Blood 
o Plasma for archive 
 
• 
CVF 
o Gram Stain for Nugent Scoring 
o Microbiota 
 
Only Local Laboratory test results will be provided to the participant. Once all required study 
analyses of collected specimens are complete, any remaining samples may be shipped to 
Pitt/MWRIF for use in study-related quality assurance and quality control testing. If study samples 
will be used for assay validation or proficiency testing that is not study related, all participant 
identifiers (PTID) will be removed from the samples prior to use. Specimens obtained from 
participants who do not consent to long term storage will not be used for assay validation or 
proficiency testing purposes and will be destroyed when all protocol-specified testing has been 
completed. 

 
 
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7.10 Specimen Management  
 
Study sites will adhere to the standards of good clinical laboratory practice, in accordance with 
the MATRIX-002 SSP Manual and site SOP for proper collection, processing, labeling, transport, 
and storage of specimens. Specimen collection, testing, and storage at the site laboratories will 
be documented when applicable using the Laboratory Data Management System (LDMS). In cases 
where laboratory results are not available due to administrative or laboratory error, or out of 
range and the site IoR/designee determines reasonable to repeat, the site is permitted to re-draw 
specimens. No genetic testing (limited or genome-wide) is planned on leftover samples that are 
stored for the purposes of future research. 
 
7.11 Laboratory Oversight 
 
All laboratories participating in this study will adhere to MATRIX’s Laboratory Policy 
(www.matrix4prevention.org). 
 
7.12 Biohazard Containment 
 
As the acquisition 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 US Centers for Disease Control and Prevention 
(CDC), National Institutes of Health (NIH), and other applicable national regulatory authorities. 
All biological specimens will be transported using packaging mandated by Code of Federal 
Regulations (CFR) 42 Part 72. All dangerous goods materials, including diagnostic specimens and 
infectious substances, must be transported according to instructions detailed in the International 
Air Transport Association (IATA) Dangerous Goods Regulations. Biohazardous waste will be 
contained according to institutional, transportation/carrier, and all other applicable regulations. 
 
 
8 
ASSESSMENT OF SAFETY 
 
8.1 Safety Monitoring 
 
Site IoRs/designees 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 Co-Chairs, Protocol Safety Physician, Clinical Research 
Manager(s) (CRM), and Pitt/MWRIF representatives will serve as the PSRT. The Clinical Data 
Manager(s) (CDM) prepares routine AE and clinical data reports for review by the PSRT, which 
meets via conference call approximately once per month or more frequently as needed 
throughout the period of study implementation to review safety data, discuss product use 
management, and address any potential safety concerns. 
 

 
 
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8.2 Clinical Data and Safety Review 
 
A multi-tiered safety review process will be followed for the duration of this study. The site 
IoRs/designees are responsible for the initial evaluation and reporting of safety information at the 
participant level and for alerting the PSRT if unexpected concerns arise. Participant safety is also 
monitored through a series of routine reviews conducted by the PSRT and (if applicable) study 
sponsors. Additional reviews may be conducted at each of these levels as dictated by the 
occurrence of certain events.  
 
The CDM(s) will review incoming safety data on an ongoing basis. Events identified as 
questionable, inconsistent, or unexplained will be queried for verification. To ensure prompt 
review of AEs of concern (e.g., serious adverse events [SAE] and Related Grade 3+ AEs), such 
AE reports submitted in the clinical database will be forwarded to the PSRT for review within 72 
hours of entry. 
 
The PSRT will meet approximately every month, or as needed, via conference call to review 
clinical data reports generated by the CDM(s). The content, format and frequency of the clinical 
data reports will be agreed upon by the PSRT and the CDM(s) in advance of study implementation. 
In addition to the routine safety data reviews, the PSRT will convene on an ad hoc basis to make 
decisions regarding the handling of any significant safety concerns. If necessary, experts external 
to MATRIX representing expertise in the fields of microbicides, biostatistics, HIV acquisition and 
medical ethics may be invited to join the PSRT safety review. A recommendation to pause or stop 
the trial may be made by the PSRT at this time or at any such time that the team agrees that an 
unacceptable type and/or frequency of AEs has been observed. 
 
The Independent Safety Physician (ISP) will review participant safety data as part of their regular 
reviews (see Section 10.6.1), since no Data and Safety Monitoring Board (DSMB) oversight is 
planned for MATRIX-002. These reviews will take place approximately every 3 months, or as 
needed. The ISP will be an independent investigator(s) with no interest (financial or otherwise) 
in the outcomes of this study. At the time of these reviews, or at any other time, the ISP or PSRT 
may convene a panel (composed of the ISP, PSRT and protocol statistician[s]) to review study 
findings. This panel may recommend that the study proceed as designed, proceed with design 
modifications, or be discontinued. If at any time a decision is made to discontinue enrollment 
and/or study product use in all participants, Pitt/MWRIF will notify USAID and (as necessary) 
relevant regulatory autorities, and Site IoRs/designees will notify the responsible IRBs/IECs 
expeditiously per local guidelines. 
 
8.3 Adverse Events Definitions and Reporting Requirements 
 
8.3.1 Adverse Events  
 
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 study participants and is applied beginning at the time of 

 
 
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enrollment (i.e., once a participant is randomized). The term “investigational products” for this 
study refers to the two placebo vaginal films A and B. 
 
Study participants will be provided instructions for contacting the study site to report any 
untoward medical occurrences they may experience. In cases of potentially life-threatening 
events, participants will be instructed to seek immediate emergency care. Where feasible and 
medically appropriate, participants will be encouraged to seek evaluation where a study clinician 
is based, and to request that the clinician be contacted upon their arrival. With appropriate 
permission of the participant, whenever possible, records from all non-study medical providers 
related to untoward medical occurrences may be obtained and required data elements will be 
recorded on study CRF. All participants reporting an untoward medical occurrence should be 
followed clinically until the occurrence resolves (returns to baseline) or stabilizes. 
 
Study site staff will document in source documents and in the study database all AEs reported by 
or observed in enrolled study participants regardless of severity and presumed relationship to 
study product. AE severity will be graded per the DAIDS Table for Grading Adult and Pediatric 
Adverse Events, Corrected Version 2.1, July 2017 and/or Addenda 1 (Female Genital Grading 
Table for Use in Microbicide Studies [Dated November 2007]). 
 
Asymptomatic BV and asymptomatic candidiasis will not be reportable AEs but will be captured 
on the appropriate study CRF. Bleeding at the time of speculum insertion/removal and/or 
cervicovaginal specimen collection that is judged by the clinician to be within the range of 
normally anticipated for that procedure, will not be reportable as an AE. Bleeding that is judged 
by the clinician to be due to contraception use will also not be reportable as an AE. 
 
For any SAEs that are continuing at a participant’s study exit visit, the IoR/designee must establish 
a clinically appropriate follow-up plan for the AE. At a minimum, the SAE must be re-assessed by 
study staff 30 days after the participant’s study exit visit; additional evaluations also may take 
place at the discretion of the IoR/designee.  
 
The same approach must be taken for any AEs that are found to have increased in severity to 
Grade 3 or higher at the study exit visit. For those AEs requiring re-assessment, if the AE has not 
resolved or stabilized at the time of re-assessment, study staff should continue to re-assess the 
participant at least once per month while the study is ongoing. After the study has ended, all AEs 
requiring re-assessment should be re-assessed at least once within the 30 days after the study 
end date.  
 
Grade 1 and Grade 2 AEs classified as “related” to study product or procedures still ongoing at 
study exit require follow up by the study team at least once within 30 days of study exit. 
 
The PSRT may advise study staff as to whether any additional follow-up may be indicated on a 
case-by-case basis. For AEs that are re-assessed after study exit, information on the status of the 
AE at the time of re-assessment will be recorded in source documents only — no updates should 
be made to AE CRFs based on the re-assessments. 
 

 
 
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8.3.2 Serious Adverse Events  
 
As per the International Council for Harmonization of Technical Requirements for Pharmaceuticals 
for Human Use Good Clinical Practice Guidance (ICH E6; https://www.ich.org/page/efficacy-
guidelines), SAEs are defined as AEs occurring at any dose that: 
 
• 
Results in death 
• 
Is life-threatening  
• 
Results in persistent or significant disability/incapacity  
• 
Is a congenital anomaly/birth defect 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization 
 
NOTE: Per ICH SAE definition, hospitalization itself is not an AE, but is an outcome of the 
event. Thus, hospitalization in the absence of an AE is not regarded as an AE. The 
following are examples of hospitalization that are not considered to be AEs: 
o Protocol-specified admission (e.g., for procedure required by study protocol) 
o Admission for treatment of target disease of the study, or for pre-existing condition 
(unless it is worsening or increases in frequency of hospital admissions as judged 
by the clinical investigator) 
o Diagnostic admission (e.g., for a work-up of an existing condition such as 
persistent pretreatment lab abnormality) 
o Administrative admission (e.g., for annual physical) 
o Social admission (e.g., placement for lack of place to sleep) 
o Elective admission (e.g., for elective surgery) 
 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon 
appropriate medical judgment, they may jeopardize the participant and may require medical or 
surgical intervention to prevent one of the outcomes listed above. 
 
8.3.3 Adverse Event Relationship to Study Product 
 
Relatedness is an assessment made by a study clinician of whether or not the event is related to 
the study agent. 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) 
 
8.4 Pregnancy and Infant Outcomes 
 
Pregnant women are excluded from this study. A participant who becomes pregnant during the 
study will have study product discontinued and will be terminated from the study. Please see 
Section 9.7 for additional details. 
 

 
 
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8.5 Regulatory Requirements 
 
AEs reported on CRFs will be included in reports to the applicable national drug regulatory 
authorities (DRA) in accordance with DRA requirements. Site IoRs/designees also will submit AE 
information and any other relevant safety information to their IRB/IEC in accordance with IRB/IEC 
requirements. 
 
8.6 Social Harms Reporting 
 
Although study sites will 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. For example, participants could be treated unfairly, or could have problems 
being accepted by their families, partners and/or communities. Social harms that are judged by 
the IoR/designee to be serious or unexpected will be reported to the PSRT and responsible site 
IRB/IEC according to their individual 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. 
While maintaining participant confidentiality, study sites may engage their community advisory 
boards (CABs) in exploring the social context surrounding instances of social harm. To mitigate 
one possible source of social harms, each site will carefully explain to eligible participants the 
potential consequences of enrolling their sexual partner (e.g., disclosure of study involvement 
and/or film use) prior to contacting the partner. 
 
 
9 
CLINICAL MANAGEMENT 
 
Guidelines for clinical management and permanent discontinuation of study product are outlined 
in this section. Permanent discontinuation of study product will be defined as not having the 
second film inserted at Visit 6. In general, the IoR/designee has the discretion to hold study 
product at any time if s/he feels that continued product use would be harmful to the participant 
or interfere with treatment deemed clinically necessary. Unless otherwise specified below, the 
IoR/designee should immediately consult the PSRT for further guidance on resuming study 
product during second month of product use (if product discontinuation occurs during first month 
of product use) or progressing to permanent discontinuation of study product and early study 
termination. The IoR/designee will document all permanent discontinuations on applicable CRFs. 
 
9.1 Grading System 
 
AE severity grading is described in Section 8.3.1. 
 
9.2 Dose Modification Instructions 
 
No dose modifications will be undertaken in this study. 
 

 
 
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9.3 General Criteria for Permanent Discontinuation of Study Product 
 
A participant will be permanently discontinued from product use by the IoR/designee for any of 
the following reasons: 
• 
A reactive rapid HIV test. 
• 
Pregnancy or breastfeeding. 
• 
Allergic reaction to the study product(s)/drug(s). 
• 
Reported use of or need for PrEP or PEP. Participants who experience a known or potential 
HIV exposure during study participation or have a recognized risk of exposure and thus 
need PEP or PrEP will have study product permanently discontinued and will be referred 
for PEP or PrEP initiation. Those who need PEP will be encouraged to start it as quickly as 
possible and within 72 hours of potential exposure. Since continued study follow-up would 
be of no benefit following permanent discontinuation of study product use, these 
participants will be exited from the study. 
• 
Non-therapeutic injection drug use. 
• 
Participant develops a Grade 3 Related or Grade 4 AE. 
• 
Participant is unable or unwilling to comply with required study procedures, or otherwise 
might be put at undue risk to their safety and well-being by continuing product use, 
according to the judgment of the IoR/designee. 
 
The IoR/designee must consult the PSRT on all discontinuations instituted at their discretion for 
further guidance on resuming product use during second month of product use (if product 
discontinuation occurs during first month of product use) or progressing to permanent 
discontinuation of study product and early study termination. 
 
9.4 Permanent Discontinuation in Response to Observed Adverse Events 
 
Grade 1, Grade 2 and Grade 3 Unrelated 
Unless specifically addressed in Section 9.5 below, a participant who develops a Grade 1 or 2 AE, 
regardless of relationship to study product, may continue product use. Participants who develop 
a Grade 3 AE that is judged by the IoR/designee to be unrelated to study product may also 
continue product use. If the IoR/designee opts to discontinue study product, the PSRT must be 
notified.  
 
 
Grade 3 Related and Grade 4 
Study product must be permanently discontinued and the PSRT notified for participants who 
develop a Grade 3 Related AE or a Grade 4 AE. 
 
9.5 Other Clinical Findings 
 
A thorough evaluation of genital complaints is expected in the context of this study; however, 
syndromic management of genital symptoms is acceptable while awaiting laboratory results if 
such practice is in line with the local standards of care. Observed single dose treatment should 
be provided whenever possible, per clinician discretion. When clinically appropriate, investigators 
should use oral or parenteral medications when at all possible. 
 
Product use need not be held in the event of an STI/RTI requiring treatment, unless other 
permanent discontinuation guidelines apply. Should the IoR/designee determine that a 

 
 
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permanent discontinuation is warranted due to an STI or RTI, consultation with the PSRT is 
required. The IoR/designee should manage STI/RTI per local guidelines or current WHO 
guidelines, available at http://www.who.int/en/. Test for cure is not required after treatment of 
asymptomatic STIs. 
 
If a suspected finding is reported by the participant between scheduled visits, an interim visit may 
be scheduled at the discretion of the site investigator. 
 
9.6 HIV Infection 
 
HIV testing will be performed at designated study visits. Potential participants who test positive 
for HIV during Screening or Enrollment will not be enrolled in the study but will be referred to 
HIV care and management. Enrolled participants who test positive for HIV will have study product 
and all follow-up visits discontinued, and will be considered terminated from the study as per 
Section 7.4.1. Participants identified as infected with HIV are managed or referred for 
management according to the local standard of care. Guidance regarding management and 
referral for participants confirmed to be HIV-positive can be found in Section 13.10. Sites will not 
be responsible for paying for HIV-related care. 
 
9.7 Pregnancy 
 
Pregnancy testing will be performed at designated study visits and participants will be encouraged 
to report all signs or symptoms of pregnancy to study staff. The IoR/designee will counsel any 
participant who becomes pregnant according to site SOPs. The IoR/designee also will refer the 
participant to all applicable services; however, sites will not be responsible for paying for 
pregnancy-related care. A participant who becomes pregnant during the course of the study will 
have study product and all follow-up visits discontinued, and will be considered terminated from 
the study as per Section 7.4.2. 
 
9.8 Criteria for Early Termination of Study Participation  
 
Participants may voluntarily withdraw from the study for any reason at any time. IoRs/designees 
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. Sites must notify the PSRT immediately of 
any such instances. Participants also may be withdrawn if Pitt/MWRIF, USAID, MATRIX, 
government or regulatory authorities, including the Office for Human Research Protections 
(OHRP), or site IRB/IEC/DRA 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 (see details regarding the Early Termination Visit in 
Section 7.3.6). Study staff members will record the reason(s) for all withdrawals in participants’ 
study records. 
 
 

 
 
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10 
STATISTICAL CONSIDERATIONS 
 
10.1 Overview and Summary of Design 
 
MATRIX-002 is a two-arm, randomized, multi-center trial to assess acceptability, safety and 
usability of two placebo prototype films when administered vaginally once monthly for two 
months. The primary objective of MATRIX-002 is to assess the acceptability of two placebo film 
types (A and B) administered vaginally once monthly for two months, with the overall goal of 
drawing on findings across primary, secondary and exploratory endpoints to inform design of 
drug-loaded vaginal film. 
 
10.2 Study Endpoints 
 
Primary endpoints 
 
Acceptability 
• 
Participant ratings of overall satisfaction with using the placebo vaginal films. 
 
Secondary endpoints 
 
Safety 
• 
Proportion of participants with genitourinary Grade 2 or higher Adverse Events deemed 
related to study product. 
 
Usability 
• 
Proportion of participants with clinically assessed proper insertion (more than half of the 
vaginal film proximal to introitus). 
 
Exploratory endpoints 
 
Participant acceptability, attitudes and experiences 
• 
Participant responses to quantitative acceptability assessments and IDI questions. Multiple 
dimensions will be explored, including: 
o Vaginal film attributes, including acceptability (e.g., ease of insertion, burden, 
perceived effectiveness of film as delivery form) and preferences 
o Experience and comfort with inserted vaginal film (e.g., expulsions, leakage, 
awareness of film during daily activities) 
o Experience during sex and menses 
o Vaginal practices and concomitant vaginal product use while using vaginal film 
o Perception of sexual partners’ attitudes towards vaginal film 
o Perceived benefits and concerns/challenges with the vaginal film as a future HIV 
prevention option 
o Interest in using vaginal film as a future HIV prevention option 
 
Sexual partner attitudes and experiences 
• 
Sexual partner responses during IDI related to: 
o Vaginal film attributes, including acceptability and preferences 
o Perception of participant’s experience using the vaginal film during the study 

 
 
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o Physical sensation of the participant’s vaginal film use during sex (as relevant) 
o Perceived benefits and concerns/challenges with the vaginal film as a future HIV 
prevention option 
 
Vaginal microenvironment 
• 
Change from baseline in vaginal pH following film use during the two study phases (i.e., 
with and without sexual abstinence requirement). 
• 
Change from baseline in quantity of selected vaginal microbiota following film use during 
the two study phases (i.e., with and without sexual abstinence requirement). 
• 
Change from baseline in Nugent score following film use during the two study phases (i.e., 
with and without sexual abstinence requirement). 
 
Social harms and social benefits 
• 
Participant self-report of social harms (i.e., non-clinical adverse consequences of study 
participation or product use that may manifest in social, psychological or physical ways). 
• 
Participant and sexual partner self-report of social benefits (e.g., positive consequences 
of product use disclosure such as self-confidence, improved communication with intimate 
partner) resulting from vaginal film use and/or study participation. 
 
10.3 Sample Size and Power Calculations 
 
MATRIX-002 will enroll approximately 100 evaluable participants (i.e., participants who complete 
Visit 6), with approximately 20 participants per site. Participants will be randomized to the 2 study 
arms in a 1:1 ratio, allocating 50 women per arm.  In light of the short study duration and the 
teams’ previous experiences conducting similar research with the study’s target population, we 
anticipate 5% LTFU. Therefore, we expect approximately 95 participants (45-48 per arm) will 
complete the study. A subset of up to 35 study participants will complete an IDI after the 2nd 
period of film use. We will enroll up to 30 sexual partners to complete an IDI after the participant 
completes the 2nd period of film use. 
 
Note: Replacement participants will be considered in consultation with study leadership if LTFU 
is higher than expected. 
 
Table 12 presents the range of potential detectable effect sizes reflecting differences in primary, 
secondary and exploratory endpoints of the two study products assuming 80% power, two-sided 
α=0.05, varying standard deviations or marginal probabilities, a sample size of 100, and 5% 
LTFU.  
 
The primary acceptability endpoint will be measured at Visits 6 and 9. Secondary endpoints will 
be assessed cumulatively to calculate an overall proportion experiencing the outcome (e.g., AE). 
The usability of the vaginal film will be determined by clinician-observed and participant-reported 
measures (e.g., ease of insertion, number of attempts). Exploratory acceptability endpoints will 
be collected at Visits 6 and 9. In addition, interim data on experience using the placebo vaginal 
film will be collected 24-72 hours after each film insertion and again 1 week (1st use period only) 
and 2 weeks after each film insertion via SMS or telephone. 
 

 
 
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Table 12: Range of potential effect sizes for each endpoint 
 
Continuous outcomes: effect size is difference in means 
Endpoint 
Endpoint type 
Standard deviation 
Minimum detectable 
difference 
Overall satisfaction  
(Likert scale 1-10) 
Primary: Acceptability 
0.5 – 3.0 
0.29 – 1.75 
Likelihood of future use 
(Likert scale 1-4) 
Exploratory: Acceptability 
0.4 – 1.0 
0.23 – 0.59 
Binary outcomes: effect size is risk difference 
Endpoint 
Endpoint type 
Marginal probabilities 
Minimum detectable 
difference 
Adverse events 
Safety 
0.10 – 0.30 
0.24 – 0.29 
 
Qualitative data collection 
Participant experiences: Up to 35 study participants will be purposively selected and invited to 
complete an IDI at Visit 9 or before study exit. 
 
Sexual partner attitudes and experiences: Up to 30 sexual partners will be invited to provide 
insights into their attitudes and experiences through IDIs.  
 
An overall sample of 30 IDIs per group is estimated to provide sufficient opportunity to reach 
saturation in the qualitative data on key topics. An estimated 6 IDIs per site per group is expected 
to provide sufficient opportunity for any variation on key topics based on geographic location. 
Participants will be purposively selected for invitation to an IDI based on vaginal film assignment 
(A or B) and other characteristics or experiences while using the study product. Sexual partners 
will be purposively selected for invitation to the IDI based on permission provided by the clinical 
study participant, key experiences reported by the clinical study participant, and partner 
interest/availability.  
 
10.4 Randomization Procedures 
 
Participants will be randomized in a 1:1 ratio to the two study arms (Film A or Film B), stratified 
by study site. The randomization scheme and procedures will be generated and maintained by 
the MWRI statistical team that will conduct and coordinate the randomization procedures. 
 
10.5 Participant Accrual, Follow-up and Retention 
 
We anticipate participant accrual to take place over a period of approximately 3-6 months. Each 
participant enrolled will be followed for a period of approximately 2 months. 
 
10.6 Data and Safety Monitoring and Analysis 
 
10.6.1 Study Monitoring 
 
No DSMB oversight is planned for this study. The MATRIX Clinical Trials Hub will conduct interim 
reviews of study progress, including rates of participant accrual, retention, completion of primary 
and secondary endpoint assessments, and study or laboratory issues. The ISP will conduct interim 
review of incident AEs. These reviews will take place approximately every three months, or as 
needed. At the time of these reviews, or at any other time, the ISP or PSRT may convene a panel 

 
 
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(composed of the ISP, PSRT and protocol statistician[s]) to review study findings. This panel may 
recommend that the study proceed as designed, proceed with design modifications, or be 
discontinued. Safety monitoring will be done by the PSRT. 
 
10.6.2 Primary Analysis(es) 
 
All participants randomized into the study who complete Visit 6 will be included in the primary 
analysis.  
 
When the use of descriptive statistics to assess group characteristics or differences is required, 
the following methods will be used: for categorical variables, the number and percent in each 
category; for continuous variables, the mean, median, standard deviation, quartiles and range 
(minimum, maximum). Overall and within-treatment group assessment of the change from the 
baseline measurement to a follow-up measurement will be analyzed using McNemar’s test (for 
categorical response variables) or the paired t-test or Wilcoxon signed-ranks test (for continuous 
variables). When using formal testing to assess endpoint differences between users of Film A or 
Film B, the following methods will be used: for binomial response variables, chi-square tests and 
logistic regression (or exact testing methods); for continuous variables, t-tests and linear 
regression or nonparametric methods if data are non-Normal. 
 
To assess the adequacy of the randomization, participants in each arm will be compared for 
baseline characteristics including demographics and laboratory measurements using descriptive 
statistics. Due to the small sample size, formal comparisons will not be done. 
 
We will calculate overall estimates for mean satisfaction rating at Visit 9 (Likert 10-point scale) 
and by study arm to permit comparisons between Film A and Film B. We will test for difference 
in mean overall satisfaction rating at Visits 6 and 9 (Likert 10-point scale) between Film A and 
Film B using a two-sided t-test (primary endpoint). A nonparametric test will be used if normality 
assumptions are not met. Analyses will examine sociodemographic and behavioral correlates of 
acceptability rating (i.e., satisfaction) using linear regression models with robust standard errors. 
 
10.6.3 Secondary and Exploratory Analyses 
 
Safety 
All visits in which participants have been exposed to the study products will be included in the 
analysis of safety. Secondary intent to treat analyses may also be performed. To assess 
genitourinary safety, the number and percentages of participants experiencing each safety 
endpoint (see Section 10.2) will be tabulated by study arm as well as the total number of safety 
endpoints experienced in each arm. Each participant will contribute once in each category (i.e., 
only for the highest severity AE for each participant) for the calculation of event rates. Exact 
binomial confidence intervals will be calculated for each safety endpoint for each arm. 
 
Usability 
Usability, participants' ability to insert the film correctly, will be examined by calculating the 
proportion of participants who correctly inserted the film on the first attempt (and after two 
attempts). This will be examined by study arm and overall. Changes in ability to insert the film 
correctly will examine this measure at V6 and V9, by study arm and overall. 
 

 
 
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38 
Exploratory Acceptability Assessment 
In addressing the exploratory acceptability objective, we will compare ratings of acceptability 
measures reflecting distinct components of the acceptability framework and related dimensions 
by study arm. Acceptability endpoints will be summarized by assessment time point (Visits 2, 6, 
and 9) using descriptive statistics (e.g., frequencies, means), as appropriate. For example, we 
will examine the level of interest in future use of the film as an HIV prevention option overall and 
by study arm. We will also examine responses over time (e.g., ratings of anticipated comfort prior 
to initial film insertion, after first month of film use, and after second month of film use), assessing 
whether they changed with increased experience with product insertion. In addition, analyses will 
examine sociodemographic and behavioral correlates of acceptability endpoints using linear 
regression models with robust standard errors (for rating outcomes) and using multivariable 
logistic regression for dichotomous outcomes such as willingness to use (e.g., disinterest in future 
use). 
 
Participant and Sexual Partner Attitudes and Experiences  
Qualitative data will be audio-recorded, processed, and coded for qualitative analyses, using 
Dedoose or a similar qualitative software. Data coding will be used as a primary analytical 
approach for data reduction, that is, to summarize, extract meaning, and condense the data.21,22 
Transcripts will be coded first through descriptive coding for key themes and topics, using a 
preliminary codebook.23 Additional codes will be identified through an iterative process of reading 
the textual data to identify emergent themes, and the codebook will be modified accordingly. In 
addition to descriptive codes, inductive codes, which achieve a greater level of abstraction, will 
be used to start linking themes and topics together in order to explore the relationship between 
socio-contextual factors and product use experiences.22 Whenever possible, we will also compare 
study sites and explore differences or similarities due to different socioeconomic, cultural and 
geographical contexts. The analysis will be done by the investigative team, working interactively 
through emails, and regular phone or face-to-face meetings. The findings and interpretations of 
the data will be critically discussed until there is group consensus on the dominant themes and 
meanings contained in the data.24 
 
10.6.4 Missing Data 
 
In any situation with missing data, appropriate secondary analyses will be performed to adjust 
for variables that may be related to the missingness mechanism. If missing data rates are higher 
than 10%, covariates that are related to missingness in likelihood-based regression models will 
be included. Sensitivity analyses to assess the potential impact of the missing data will also be 
performed. These analyses will include imputing the data under the most extreme scenarios of 
information missingness, such as assuming everyone missing has an extreme value of the missing 
variable, and less informative imputation approaches. 
 
 
11 
DATA HANDLING AND RECORDKEEPING 
 
11.1 Data Management Responsibilities 
 
Data collection tools will be developed by the CDM(s) in conjunction with the protocol team. 
Quality control and data integrity are managed manually and systematically with reports and 

 
 
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queries routinely generated and provided by the CDM(s) to the study sites for verification and 
resolution. As part of the study activation process, each study site will identify all CRFs to be used 
as source documents. Study CRF data will be entered and managed using REDCap, a data 
management system compliant with the International Council on Harmonization (ICH) Good 
Clinical Practices (GCP) and US CFR guidelines for electronic data capture. 
 
Transcriptions of interviews will be generated in the field and electronically transferred to RTI 
International using a secure File Transfer Protocol site, where they will be uploaded and managed 
using a qualitative software package. RTI International will act as a hub and manage all qualitative 
data for the study. A convention for file naming will be developed, and all data will be labeled 
according to this process. RTI International will save all versions of all files on a secure, password-
protected server in the US. 
 
11.2 Source Documents and Access to Source Data/Documents 
 
All study sites will maintain source data/documents in accordance with MATRIX’s Good 
Documentation Practice (GDP) guidelines (www.matrix4prevention.org). 
 
Each IoR/designee will maintain, and store securely, complete, accurate and current study records 
throughout the study. In accordance with U.S. regulations, IoRs/designees will maintain all study 
documentation for at least three years after completion of the study. 
 
Study records must be maintained on site for the entire period of study implementation.  
Thereafter, instructions for record storage will be provided by Pitt/MWRIF. No study records may 
be moved to an off-site location or destroyed prior to receiving approval from Pitt/MWRIF. 
 
11.3 Quality Control and Quality Assurance 
 
Study sites will conduct quality control and quality assurance procedures in accordance with 
MATRIX’s Quality Management Plan (www.matrix4prevention.org). 
 
 
12 
CLINICAL SITE MONITORING 
 
Study monitoring will be carried out by the African Clinical Research Organisation (ACRO) for the 
African sites and by the University of Pittsburgh Education and Compliance Support for Human 
Subject Research (ECS-HSR) for the US site. Study monitors will do the following: 
 
• 
Review informed consent forms, procedures, and documentation. 
• 
Assess compliance with the study protocol, Good Clinical Practices (GCP) guidelines, and 
applicable regulatory requirements (US and non-US), including US Code of Federal 
Regulations (CFR) Title 45 Part 46 and Title 2 Parts 200 and 225. 
• 
Perform source document verification to ensure the accuracy and completeness of study 
data. 
• 
Verify proper collection and storage of biological specimens. 
• 
Verify proper storage, dispensing, and accountability of investigational study products. 

 
 
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• 
Assess implementation and documentation of internal site quality management 
procedures. 
 
Monitoring visits may be conducted on-site or remotely. Remote visits may include remote source 
document verification using methods specified for this purpose. Remote monitoring visits may be 
performed in place of or in addition to onsite visits to ensure the safety of study participants and 
data integrity. 
 
For on-site visits, the IoR/designee will allow study monitors to inspect study facilities and 
documentation (e.g., informed consent forms, clinic and laboratory records, other source 
documents, CRFs), as well as observe the performance of study procedures. The IoR/designee 
also will allow inspection of all study-related documentation by authorized representatives of 
MATRIX, Pitt/MWRIF, USAID, OHRP, IRB/IEC and other local, US, or international regulatory 
authorities. A site visit log will be maintained at the study site to document all visits. 
 
 
13 
HUMAN SUBJECTS PROTECTIONS 
 
Site investigators will make efforts to minimize risks to participants. Participants and study staff 
members will take part in a thorough informed consent process. Before beginning the study, 
IoRs/designees will have obtained IRB/IEC approval. IoRs/designees will permit audits by USAID, 
OHRP, MATRIX, IRB/IEC, and other local, US, or international regulatory authorities or any of 
their appointed agents. 
 
Changes to this protocol may be implemented by investigators prior to IRB/IEC approval, if those 
changes are required to eliminate apparent immediate hazards to the study participant; see 45 
CFR 46.108(a)(3)(iii) under the 2018 Requirements (https://www.ecfr.gov). These changes must 
be documented as Protocol Deviations and reported to the Protocol Team and IRB/IEC as soon 
as possible; see ICH E6(R2), Good Clinical Practice, Section 4.5.4 (https://www.fda.gov/science-
research/clinical-trials-and-human-subject-protection/ich-guidance-documents). In the event of a 
public health emergency, investigators should adhere to the recommendations of their local 
institutions, IRB/IEC and local health departments. When conflicts exist between local directives, 
MATRIX, Protocol Team and/or USAID policies or guidance, sites should follow the requirement 
that is most protective of study participants and site staff. 
 
13.1 Institutional Review Boards/Ethics Committees 
 
Each participating institution will be responsible for assuring that this protocol, the associated 
site-specific informed consent forms (ICF), and study-related documents (such as participant 
education and recruitment materials) are reviewed by the IRB/IEC responsible for oversight of 
research conducted at their study site and by applicable national DRA. Any amendments to the 
protocol must be approved by the responsible IRBs/IECs and (if applicable) national DRA prior to 
implementation. 
 
Subsequent to the initial review and approval, the responsible IRBs/IECs must review the study 
at least annually. Each IoR/designee will make safety and progress reports to their IRB/IEC and 
(if applicable) to their national DRA at least annually and within three months after study 

 
 
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termination or completion. These reports will include the total number of participants enrolled in 
the study, the number of participants who completed the study, all changes in the research 
activity, and all unanticipated problems involving risks to human subjects or others. In addition, 
the results of all safety reviews of the study will be provided to the IRBs/IECs and (if applicable) 
national DRA. 
 
13.2 Protocol Implementation 
 
Prior to implementation of this protocol, and any subsequent full version amendments, each site 
must have the protocol and the protocol consent forms approved, as appropriate, by their local 
IRB/IEC and any other applicable regulatory entities. Upon receiving final approval, sites will 
submit copies of all relevant protocol/amendment documents (i.e., IRB/IEC approval letters with 
a detailed list of approved documents, approved ICF documents, etc.) to the MATRIX Clinical 
Trials Hub Regulatory team. 
 
The MATRIX CRM(s) will review the submitted document packet to ensure receipt of all required 
protocol/amendment documents prior to study activation at the sites. Sites will receive a Study 
Activation Notification from the MATRIX CRM(s) that indicates successful completion of the 
protocol readiness process. A copy of the Study Activation Notification should be retained in the 
site's regulatory files. 
 
Upon receiving final IRB/IEC and any other applicable approval(s) for an amendment, activated 
sites should implement the amendment immediately but are still required to submit copies of all 
relevant amendment documents to the MATRIX Clinical Trials Hub Regulatory team. 
 
13.3 Study Coordination 
 
Study implementation will be directed by this protocol, which may not be amended without prior 
written approval from the Protocol Co-Chairs and Protocol Team representatives from MATRIX, 
Pitt/MWIF and USAID. Study implementation will also be guided by a common SSP Manual that 
provides further instructions and operational guidance on conducting study visits; data and forms 
processing; specimen collection, processing, and shipping; AE assessment, management and 
reporting; dispensing study products and documenting product accountability; and other study 
operations. Standardized study-specific training will be provided to sites by the MATRIX CRM(s) 
and other designated members of the Protocol Team.  
 
Close coordination between protocol team members is necessary to track study progress, respond 
to queries about proper study implementation, and address other issues in a timely manner. The 
PSRT will address issues related to study eligibility and AE management and reporting as needed 
to assure consistent case management, documentation, and information-sharing across sites. 
Rates of accrual, adherence, follow-up, and AE incidence will be monitored closely by the team 
as well as the ISP and the MATRIX Clinical Trials Hub. 
 

 
 
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13.4 Risk Benefit Statement 
 
13.4.1 
Risks 
 
General 
HIV and STI testing may make the participant feel anxious regardless of the test results.  
Counseling and testing for HIV and other STIs may cause worry and discomfort by learning more 
about risk for those conditions. A participant may become worried, sad or depressed after finding 
out that they have HIV or an STI. Trained study staff will be available to help participants deal 
with these feelings. 
 
Finding out their HIV status could also cause problems between participants and their partners,  
family, or friends. Participants also could have problems in their partner relationships associated 
with study-required abstinence. The study staff will provide counselling and referral for support 
and/or care where required. 
 
Participation in clinical research includes the risk of loss of confidentiality and discomfort with the 
personal nature of questions when discussing sexual behaviors. Study staff will make every effort 
to protect participant privacy and confidentiality during the study visits. Visits will take place in 
private, however, it is possible that others may learn of an individual’s study participation and, 
because of this, may treat them unfairly or discriminate against them. 
 
Phlebotomy 
Participants may feel discomfort or pain when their blood is drawn. They may feel dizzy or faint 
or develop a bruise, swelling, small clot, or in rare cases, an infection where the needle goes into 
their arm. 
 
Pelvic Examination and Procedures 
Participants may feel discomfort, pain or pressure during the exam and when specimens are 
collected. They may have a small amount of vaginal bleeding or spotting which should stop shortly 
after the exam. 
 
CVF Collection 
Collection of CVF may cause discomfort or pressure in the vagina or genital area. 
 
Risks Associated with Vaginal Films 
Participants may feel discomfort, itching, irritation, and vaginal discharge during film use. Based 
on previous film studies, these experiences are not prevalent. 
 
Risks Associated with Placebo Excipients 
All the excipients used in both films are generally regarded as safe (GRAS) and/or have a history 
of pharmaceutical use. 
 
Social Harms  
Although study sites will make every effort to protect participant privacy and confidentiality, it is 
possible that involvement in the study could become known to others and that social harms – 

 
 
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non-medical adverse consequences – may result. For example, participants could be treated 
unfairly, or could have problems being accepted by their families, partners and/or communities.  
 
13.4.2 
Benefits 
 
Participants in this study may experience no direct benefit. Participants and others may benefit 
in the future from information learned from this study. Specifically, information learned in this 
study may lead to the development of safe and effective interventions to prevent HIV acquisition 
and transmission. Participants also may appreciate the opportunity to contribute to the field of 
HIV prevention. 
 
Participants will receive HIV/STI risk reduction counseling, HIV and STI testing, and physical and 
pelvic exams. Participants will be provided STI treatment free of charge, and referrals may be 
provided if needed. For other medical conditions identified as part of the study screening and/or 
follow-up procedures, participants will be referred to other sources of care available in their 
community. Some participants may have the opportunity to access expedient treatment and 
decreased morbidity due to early diagnosis and treatment of abnormalities identified during tests, 
examinations and referrals. 
 
13.5 Informed Consent Process 
 
Written informed consent will be obtained from each study participant prior to screening. Written 
informed consent also will be obtained for long-term specimen storage and possible future testing, 
although consent for specimen storage is not required for study participation. In obtaining and 
documenting informed consent, the IoR and their designees will comply with applicable local and 
US regulatory requirements and will adhere to GCP and to the ethical principles that have their 
origin in the Declaration of Helsinki. Study staff must document the informed consent process in 
accordance with MATRIX’s GDP guidelines (www.matrix4prevention.org). Participants will be 
provided with copies of the ICF if they are willing to receive them.   
 
In addition to the ICF, the Protocol Team will work with study staff and community representatives 
to develop appropriate materials about the study and a standardized approach to the informed 
consent process to be implemented at study sites, which will be detailed in the MATRIX-002 SSP 
Manual.  
 
The informed consent process will cover all elements of informed consent required by research 
regulations. In addition, the process specifically will address the following topics of importance to 
this study: 
 
• 
The need to practice safer sex behaviors. 
• 
Both study products are placebos that provide no protection against HIV acquisition, STIs, 
or pregnancy. 
• 
The importance of adherence to the study visit and procedures schedule. 
• 
The potential medical risks of study participation (and what to do if such risks are 
experienced). 
• 
The potential social harms associated with study participation (and what to do if such 
harms are experienced). 
• 
The limited benefits of study participation. 

 
 
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• 
The distinction between research and clinical care. 
• 
The right to withdraw from the study at any time. 
 
Furthermore, participants who agree to have their sexual partner contacted while in MATRIX-002 
will be asked to read and sign an additional “Permission to Contact” form before the partner is 
invited to enroll. This form will explain that the participant gives the study staff permission to 
contact their sexual partner with the understanding that the partner will be invited to discuss their 
views on the film and its attributes and the participant’s experiences using the vaginal film. This 
means the sexual partner will be aware of the participant’s study involvement and use of the 
vaginal film. Sites will contact sexual partners according to site SOP and/or local IRB/IEC 
guidelines. Sexual partners who agree to enroll in the study will provide written informed consent 
prior to completing the IDI. 
 
13.6 Participant Confidentiality 
 
All study procedures will be conducted in private, and every effort will be made to protect 
participant privacy and confidentiality to the extent possible. Study sites will implement 
confidentiality protections that reflect the local study implementation plan and the input of study 
staff and community representatives to identify potential confidentiality issues and strategies to 
address them.  
 
All study-related information will be stored securely at the study site. All participant information 
will be stored in locked areas with access limited to study staff. All laboratory specimens, study 
data collection, and administrative forms will be identified by coded participant number only to 
maintain participant confidentiality. All records that contain names or other personal identifiers, 
such as locator forms and ICFs, will be stored separately from study records identified by code 
number. All local databases will be secured with password protected access systems. Forms, lists, 
logbooks, appointment books, and any other listings that link participants’ ID numbers to 
identifying information will be stored in a separate, locked file in an area with limited access. 
Participants’ study information will not be released without their written permission, except as 
necessary for review, monitoring, and/or auditing by the following: 
 
• 
Representatives of the US Federal Government, including the US OHRP, USAID, and/or 
contractors of USAID, and other local, US, or international regulatory authorities 
• 
ACRO and ECS-HSR 
• 
Representatives of Pitt/MWRIF 
• 
MATRIX designees/representatives 
• 
Study staff  
• 
Site IRBs/IECs 
 
13.7 Special Populations 
 
13.7.1 
Pregnant Women 
 
Women who test positive for pregnancy at the Screening or Enrollment Visit will not be eligible 
to participate in this study. Should a participant test positive for pregnancy after Enrollment, a 
product discontinuation will be implemented. Follow-up visits and procedures will be discontinued, 
and the participant will be considered terminated from the study. An Early Termination Visit may 

 
 
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be completed and data collected per Section 7.4.2. During the informed consent process, 
participants will be informed that the placebo vaginal film is not a method of contraception and 
the effects of the placebo vaginal film on a developing human fetus are unknown. 
 
13.7.2 
Children 
 
The US NIH has mandated that children, defined as younger than 18 years old, be included in 
research trials when appropriate. This study meets “Justifications for Exclusion” criteria for 
younger children as set forth by the NIH (specifically, “insufficient data are available in adults to 
judge potential risk in children” and “children should not be the initial group to be involved in 
research studies”). As such, this study does not plan to enroll children. 
 
13.8 Compensation 
 
Pending IRB/IEC approval, participants will be compensated for time and effort in this study, 
and/or be reimbursed for travel to study visits and time away from work. Site-specific 
reimbursement amounts will be determined per local IRB/IEC/DRA guidelines and will be specified 
in the study ICFs of each individual site. 
 
If a participant becomes ill or injured as a result of participation in this trial, medical treatment 
for the adverse reaction or injury will be provided appropriately. The site staff will refer the 
participant for ongoing treatment for the injury, if needed. Where required, clinical trial insurance 
purchased by sites will be responsible for compensating the study participant for appropriate 
medical expenses for treatment of any such illness or injury. An HIV infection that occurs during 
the course of the trial will not be considered an injury or illness caused by trial participation. 
 
13.9 Reporting 
 
13.9.1 
Communicable Disease Reporting 
 
Study staff will comply with local requirements to report communicable diseases including HIV 
identified among study participants to health authorities. Participants will be made aware of 
reporting requirements during the informed consent process. 
 
13.9.2 
Other Reporting 
 
Study staff will comply with local requirements to report cases of sexual assault or of sexual 
activity involving a person below the age of consent identified in the study. 
 
13.10 Access to HIV-related Care 
 
13.10.1 
HIV Counseling and Testing 
 
HIV test-related counseling will be provided to all potential study participants who consent to 
undergo HIV screening to determine their eligibility for this study, and to all enrolled participants 
at each follow-up HIV testing time point. Testing will be performed in accordance with the 
algorithms in Appendix II. Counseling will be provided in accordance with standard HIV counseling 
policies and methods at each site and additionally will emphasize the unknown efficacy of the 

 
 
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study products in preventing HIV infection. Participants must receive their HIV test results to take 
part in this study. Condoms will be available to participants as part of standard risk reduction 
counseling. 
 
13.10.2 
Care for Participants Identified as HIV-Positive 
 
An individual who has been identified as infected with HIV will be referred for management 
according to the local standard of care. Should a participant test positive for HIV after Enrollment 
Visit, follow-up procedures will be performed as per Section 7.4.1. 
 
13.11 Study Discontinuation 
 
This study may be discontinued at any time by USAID, MATRIX, Pitt/MWRIF, the OHRP, other 
local, US or international regulatory authorities, or site IRB/IEC. 
 
 
14 
PUBLICATION POLICY 
 
USAID and MATRIX policies will govern publication of the results of this study. Any presentation, 
abstract, or manuscript will be submitted by the investigator to USAID, MATRIX and Pitt/MWRIF 
for review prior to submission. 
 
 
15 
APPENDICES 
 
 

 
 
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APPENDIX I:  SCHEDULE OF STUDY VISITS AND EVALUATIONS 
SCR   
Visit 1    
ENR      
Visit 2 
(Day 0) 
24-72 hr 
Contacts 
Visits 3&7 
(1-3 days 
after V2&V6) 
1- & 2-wk 
Contacts 
Visits 4-5 
(7&14 days 
after V2) 
4-wk Visit 
Visit 6 
(28 days 
after V2) 
6-wk 
Contact 
Visit 8 
(14 days 
after V6) 
8-wk 
Visit 
Visit 9 
(28 days 
after V6) 
Final 
Contact 
Visit 10 
(7 days 
after V9) 
ADMINISTRATIVE AND REGULATORY 
Obtain/review informed 
consent for screening &/or 
enrollment (sites may split 
screening and enrollment 
consent if requested/ 
required by IRB/IEC) 
X 
X 
 
 
 
 
 
 
Assign a unique PTID 
X 
 
 
 
 
 
 
 
Collect demographic and 
background information 
X 
 
 
 
 
 
 
 
Assess/confirm eligibility 
X 
X 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
Confirm permission to 
contact sexual partner for 
IDI (subset) 
 
 
 
 
 
 
X 
 
Collect/update/review 
contact/locator information 
X 
X 
 
X 
X 
X 
X 
X 
Provide reimbursement 
X 
X 
X 
X 
X 
X 
X 
X 
Schedule next visit/contact 
* 
* 
 
X 
X 
X 
X 
 
COUNSELING 
HIV pre- and post-test 
counseling 
X 
X 
 
 
X 
 
X 
 
HIV/STI risk reduction 
counseling 
X 
X 
 
 
X 
 
X 
 
Protocol counseling 
X 
X 
 
* 
X 
* 
X 
 
BEHAVIORAL 
Review instructional 
materials 
 
X 
 
 
X 
 
 
 
Behavioral questionnaire(s) 
 
X  
(pre & post 
insertion) 
 
 
X 
 
X 
 
Brief behavioral 
assessment (concerns and 
comfort with film use) 
 
 
X 
X 
 
X 
 
 
Social harms and benefits 
assessment 
 
 
 
 
 
 
X 
 
IDI – subset of participants 
 
 
 
 
 
 
Xa 
 
IDI – sexual partners 
 
 
 
 
 
 
Xb 
 
CLINICAL 
Collect/update/review 
medical and menstrual 
history 
X 
X 
 
X 
X 
X 
X 
X 
Collect/update/review 
concomitant medications 
X 
X 
 
X 
X 
X 
X 
X 
Physical exam (targeted 
after Screening) 
X 
* 
 
 
* 
 
* 
 

 
 
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SCR   
Visit 1    
ENR      
Visit 2 
(Day 0) 
24-72 hr 
Contacts 
Visits 3&7 
(1-3 days 
after V2&V6) 
1- & 2-wk 
Contacts 
Visits 4-5 
(7&14 days 
after V2) 
4-wk Visit 
Visit 6 
(28 days 
after V2) 
6-wk 
Contact 
Visit 8 
(14 days 
after V6) 
8-wk 
Visit 
Visit 9 
(28 days 
after V6) 
Final 
Contact 
Visit 10 
(7 days 
after V9) 
Pelvic exam with speculum 
(including bimanual exam 
at Screening) 
X 
X 
 
 
X 
 
X 
 
Visual examination by 
clinician to check vaginal 
film placement 
 
X 
 
 
X 
 
 
 
Film insertion assessment 
 
X 
 
 
X 
 
 
 
Provide available test 
results 
X 
X 
 
X 
X 
X 
X 
X 
AE assessment 
 
X 
 
X 
X 
X 
X 
X 
Treat or prescribe 
treatment for RTI/UTI/STIs 
* 
* 
 
 
* 
 
* 
 
LABORATORY 
SALIVA 
HIV test(s) (only at 
sites with CLIA 
certification) 
X 
X 
 
 
X 
 
X 
 
URINE 
Urine pregnancy test 
X 
X 
 
 
X 
 
X 
 
Urine dipstick/culture 
* 
* 
 
 
* 
 
* 
 
BLOOD 
HIV test(s) (not 
necessary for sites that 
perform saliva testing) 
X 
X 
 
 
X 
 
X 
 
Plasma for archive 
 
X 
 
 
 
 
 
 
CBC 
X 
* 
 
 
* 
 
X 
 
Serum creatinine 
X 
* 
 
 
* 
 
X 
 
AST/ALT 
X 
* 
 
 
* 
 
X 
 
Syphilis serology 
X 
 
 
 
 
 
 
 
PELVIC  
Pap test 
^ 
 
 
 
 
 
 
 
KOH wet mount for 
candidiasis and/or BV 
* 
* 
 
 
* 
 
* 
 
Vaginal Gram Stain 
 
X 
 
 
X 
 
X 
 
Vaginal swab(s) for 
microbiota 
 
X 
 
 
X 
 
X 
 
Vaginal pH 
 
X 
 
 
X 
 
X 
 
NAAT for GC/CT/TV 
X 
X 
 
 
X 
 
X 
 
STUDY PRODUCT SUPPLY 
Provide vaginal film for 
self-insertion at clinic 
 
X 
 
 
X 
 
 
 
Clinician insertion of vaginal 
film at clinic (only if 
participant fails two 
attempts) 
 
X 
 
 
X 
 
 
 
Offer male condoms 
 
 
 
 
X 
 
X 
 
   X Required 
   *If indicated and/or per local standard of care 
   ^ if indicated (if participant is unable to provide documentation of a normal Pap test within 3 years prior to enrollment)  
     a At or after Visit 9, before Visit 10 
     b Within one month of participant Visit 9 
 
 

 
 
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APPENDIX II:  ALGORITHM FOR HIV TESTING – 
SCREENING/ENROLLING/FOLLOW-UP 
 
START 
2 different  
rapid tests* 
Is this a 
Screening
Participant
? 
- / - 
+ / + or + / - or Indeterminate 
+ 
Yes 
HIV Confirmation 
Test 
- or Indeterminate 
No
Report as 
HIV Uninfected 
Not eligible for 
enrollment 
 *CLIA certified labs may perform 1 rapid test   
Report as HIV 
Infected 
Consult 
Protocol 
Team 

 
 
 
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APPENDIX III:  SAMPLE INFORMED CONSENT FORM (SCREENING, 
ENROLLMENT, LONG-TERM STORAGE AND FUTURE TESTING) 
 
SAMPLE INFORMED CONSENT FORM 
 
MATRIX-002 
Trial to Assess Acceptability and Safety of Two Placebo Prototype Vaginal 
Films 
 
USAID 
 
Version 1.0 
24 May 2023 
 
PRINCIPAL INVESTIGATOR: [SITES TO INSERT] 
INSTITUTION: [SITES TO INSERT] 
AFTER HOURS CONTACT DETAILS: [SITES TO INSERT] 
STUDY SITE CONTACT DETAILS: [SITES TO INSERT] 
SHORT TITLE: VALUE Placebo Film Study 
 
INFORMED CONSENT 
[SITES TO INSERT APPROPRIATE GREETING] You are being invited to take part in this research 
study because you are an 18-45-year-old woman in good health. Approximately 100 women will 
take part in this study across sites in the United States (US), Kenya, South Africa, and Zimbabwe. 
This study is looking at two placebo vaginal films. 
 
This study is sponsored by the US Agency for International Development (USAID) and conducted 
by the University of Pittsburgh/Magee-Womens Research Institute and Foundation (Pitt/MWRIF) 
as part of MATRIX: A USAID Project to Advance the Research and Development of Innovative 
HIV Prevention Products for Women. The placebo vaginal films are supplied by Pitt/MWRIF. At 
this site, the person in charge of this study is [SITES TO INSERT]. 
 
KEY INFORMATION 
• 
The study will assess the acceptability and safety of the two placebo vaginal films. The placebo 
films do not contain any active medication; the films do not prevent HIV.  
• 
You would be randomly assigned to one of the two films and asked to use (self-insert) the 
assigned film two times (approximately one month apart). The study involves answering 
questions, undergoing pelvic examinations, and collecting blood and vaginal fluid samples.   
• 
You would be in the study for approximately 9 weeks once you are enrolled. 
• 
The study involves a total of 10 visits/contacts, including in person visits and telephone calls.  
• 
There may be no benefit to participating. 
• 
You cannot join this research study if you are living with HIV, pregnant, breastfeeding, or are 
already taking part in another research study involving drugs, medical devices, vaginal 
products, or vaccines. 
• 
Taking part in this research study is voluntary. You do not have to participate, and you can 
stop your participation in the study at any time. 

 
 
 
MATRIX-002, Version 1.0 
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Please take the time to read this entire form and ask questions before deciding to join the study. 
If you are willing to take part in the study, you will sign this form. A copy of this form will be 
offered to you. Signing this form does not mean you will be able to join the study. You must first 
complete the screening tests and exams to see if you are eligible. It is important to know that 
your participation in this research study is your decision and taking part in this study is completely 
voluntary (see Your Rights as a Research Participant/Volunteer for more information). 
 
WHY IS THIS RESEARCH BEING DONE? 
Investigators are studying products that women can use for HIV prevention. Vaginal films are 
being evaluated as one potential way to deliver anti-HIV drugs into the vagina (in future studies).   
 
This study will allow participants to use one of the placebo vaginal films twice during their 
participation. The study will evaluate safety and will collect information on acceptability and use.   
 
Both vaginal films being used in this study are 2 x 2 inch placebo vaginal films (contain no 
medication). They are “prototype” films for future studies and will be referred to as Film A and 
Film B. They differ by shape. The components of the placebo films being used in this study have 
been used in other products and/or have been generally regarded as safe.  
 
WHO WILL BE IN THIS RESEARCH STUDY? 
Approximately 100 women who are 18-45 years old will be enrolled in the study across sites in the 
United States (US), Kenya, South Africa, and Zimbabwe. 
 
DO I HAVE TO BE IN THIS STUDY? 
You do not have to be in this study. You can still get the care you need even if you do not join 
the study. If you join today, you can change your mind later. 
 
WHAT WILL I BE ASKED TO DO IF I JOIN THIS RESEARCH STUDY?   
You will undergo a screening visit to be sure you are eligible and interested. If you are eligible 
and decide to enroll in this study, you will be asked to use (self-insert) one of two placebo vaginal 
films, approximately one month apart. Neither you nor investigators can choose the film you will 
use.  Both placebo films are important to the study.  
 
You must be using an effective method of birth control for at least two weeks before screening 
and agree to continue to use the method throughout the duration of the study to qualify. 
 
At the Enrollment Visit (V2) you will be asked to insert the first vaginal film, undergo evaluations, 
and provide feedback about your experience. During the first month after film insertion, you will 
be asked to abstain from sex and not use anything in the vagina. For example, this means no 
sex, fingers, tampons, menstrual cups, toys, douches, vaginal medications. If you do not think 
you can agree to this, you should not participate.   
 
Approximately a month later (V6) you will be asked to insert a second film (the same assigned 
film), undergo evaluations, and provide feedback about your experience. During the month 
following this 2nd film insertion, you will be permitted to have sex and use vaginal products if you 
choose.   
 

 
 
 
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You will have scheduled follow-up clinic visits and telephone contacts as detailed below. 
 
WHAT WILL HAPPEN DURING THE STUDY VISITS? 
The study includes a total of ten (10) clinic visits or telephone contacts, including the Screening 
Visit today. All in-person visits will take place at this clinic. Telephone contacts may be done 
through a phone call or via text message. Participants who prefer to complete the telephone 
contacts in-person may elect to do so. 
 
Study Visit Schedule: 
 
 
 
 
 
 
Screening Visit (Visit 1) Procedures: 
The procedures done at this visit will let us know if you can join this study and will take about 
[SITES TO SPECIFY TIMEFRAME].  
 
At the Screening Visit, you will: 
• 
Answer questions related to 
o Demographics: date of birth, race, contact information, etc. 
o Medical and menstrual history:  review of any medical problems you may have 
o Medication use: review any medication you take, including start date, dose, etc. 
o Birth control method: you must be using and agree to continue to use an acceptable, 
reliable method throughout the study to qualify  
o Visit questionnaire 
• 
Undergo counseling 
o HIV/STI (sexually transmitted infection) counseling and how to reduce your risk 
o Abstinence (no sex and no vaginal product) counseling will be reviewed. This would 
be for the first month, starting at the Enrollment Visit. 
 
It is important that you know if you are not currently using an 
acceptable method of contraception, or if you do not think you can 
abstain from vaginal intercourse or use of vaginal products for the first 
month of film use, you will not be eligible to participate in this study. 
Scr
V1
Enr 
V2
24-72 hr 
Phone 
check
V3
Wk 1 
Phone 
check
V4
Wk 2
Phone 
check
V5
Wk 
3
Wk 4 
Clinic 
follow 
up
V6
24-72hr 
Phone 
check
V7
Wk 
5
Wk 6 
Phone 
check
V8
Wk 
7
Wk 8 
Clinic 
follow 
up
V9
Wk 9 
Final 
phone 
contact
V10
No sex or vaginal product use permitted 
 No restrictions on sex or vaginal product use 
≤45 days 
2nd Film 
1st Film 
Note: phone check visits may be converted to other remote contact method (e.g., SMS) or in-person as needed and preferred by sites and individual 
participants and in accordance with local regulatory requirements 

 
 
 
MATRIX-002, Version 1.0 
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• 
Have examinations 
o Physical exam 
o Pelvic exam: a speculum (device inserted into the vagina) will be used to look at the 
vagina and cervix      
• 
Have baseline testing: 
o Urine pregnancy test:  If you are pregnant, you will not be able to join 
o HIV test:  [SITES TO INSERT TYPE OF HIV TEST and LOCAL REQUIRED LANGUAGE] 
o Blood test: Approximately [SITES TO INSERT VOLUME] will be collected to look at the 
general health of your blood, basic kidney and liver function, and to screen for syphilis  
o STI test for gonorrhea, chlamydia and trichomonas by collecting a Q-tip like swab 
o Pap smear:  If you have not had a normal result within the required period and/or the 
report is not available, you will have a Pap smear performed by using a soft brush to 
collect a sample from your cervix [SITES TO MODIFY/ADD AS NEEDED: to screen for 
cervical cancer]  
o Additional tests may be done if you are having symptoms and as clinically indicated:  
urine dip stick/culture and/or microscope exam of vaginal fluid to check for infections 
• 
Receive test results 
o Results of the tests listed above will be reviewed with you once available. Some tests 
results may be available while you are at today’s visit (urine pregnancy test) while 
others may take up to a week to result (STI testing). The results of these tests will 
help to determine if you are eligible to participate.  
o If you are diagnosed with a urinary, vaginal (i.e., yeast or BV) or an STI at Screening, 
you will be offered/prescribed treatment   
o If there are other clinically significant findings, for example on your blood test or Pap 
smear, you will be referred for additional evaluations and treatment as needed   
• 
In addition 
o Be provided reimbursement 
o May be tentatively scheduled for an Enrollment Visit within 45 days of Screening  
 
Your menstrual cycle will be considered when scheduling your in-person visits 
because, ideally, no bleeding should occur around those visits 
 
It may be necessary to conduct more than one clinic visit to complete all required screening 
procedures or if a test needs to be repeated. 
 
If you do not join the study, blood and other samples collected at the Screening visit will not be 
kept or used for any tests other than those listed above. 
 
If you are eligible and decide to enroll in the study, there are common study procedures that will 
happen at every in-person visit (V2, V6, V9), including:  
• 
Review/update your contact information, including address and phone number* 
• 
Review/update your medical and menstrual history* 
• 
Review/update any medications you are taking/using* 
• 
Review/update any sexual activity or intravaginal product use 
• 
Have HIV/STI testing and counseling [SITES TO MODIFY/ADD BELOW LANGUAGE AS 
NEEDED] 
o You will be told your test results as soon as they are available. You will talk with 
the study staff about the meaning of your results, how you feel about them, and 
learn about ways to prevent HIV and other STIs. Sometimes HIV tests are not 

 
 
 
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clearly positive, but also not clearly negative. In that case, we will do more tests 
until we are sure of your status. To participate in the study, you must receive the 
results of your HIV test. If the test shows you have HIV, you cannot join the study. 
We will refer you to available sources of medical care and other services you may 
need. 
• 
Review of any new complaints or side effects once you start using the film* 
• 
Targeted physical exam, as clinically indicated based on symptoms/complaints 
• 
Have a urine pregnancy test 
• 
Have pelvic exam with collection of Q-tip swabs to look at the bacteria in the vagina 
• 
As needed tests:   
o Repeat blood tests (general health of blood, kidney and liver function) 
o Microscope exam of vaginal fluid to look for yeast or bacteria 
o Urine dip/culture 
• 
Review of test results* 
• 
Treatment or referral for abnormal test results as needed 
• 
Undergo protocol counseling, including HIV/STI risk reduction and contraceptive 
counseling, as needed* 
• 
Reimbursement for the study visit/contact* 
• 
Schedule next visit/contacts* 
 
*These procedures will also be done at the scheduled Telephone Contacts (V4, V5, V8, V10) 
 
Enrollment Visit (Visit 2) Procedures: 
Your Enrollment Visit (the visit where you enter the study) will take about [SITES TO SPECIFY 
TIMEFRAME]. You will be randomized to one of two vaginal placebo films at this visit. You will 
receive either placebo film A or B at this visit, to be self-inserted at the clinic. 
 
The Enrollment Visit will take place up to 45 days after your Screening Visit.  
 
In addition to the common study procedures listed above, at the Enrollment Visit, you will: 
• 
Answer questions 
o About the vaginal film 
o About sexual behaviors and risk factors 
o Additional questions about the vaginal film following insertion 
• 
Undergo counseling 
o Abstinence (refrain from sex and vaginal products) counseling 
• 
Have examinations 
o Pelvic exam prior to inserting film 
o Visual external (outside) genital exam after insertion of film to check placement 
• 
Take a blood sample [SITES TO INSERT AMOUNT]. This blood sample will be stored in 
case there is a question about your test results at a later time. 
• 
Be randomized to use Film A or B as described above 
• 
Review instructional materials 
o You will be provided with vaginal film instruction materials to review prior to inserting 
the film. Study staff will be available to answer any questions you may have. 
• 
Self-insert the assigned vaginal film (A or B) 
o You will have two attempts to insert the vaginal film 

 
 
 
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o If after two attempts, you are having difficulty, a clinician will insert the film using a 
speculum 
 
24-72-hour Phone Check-in (Visit 3) Procedures: 
This contact will take place between 24-72 hours after insertion of the first film and will take 
approximately 5 minutes to complete. 
 
You will be asked if you are having any issues or concerns with the film. You will be reimbursed 
for this contact. 
 
1-week and 2-week Telephone Contacts (Visits 4 and 5) Procedures: 
Your 1-week and 2-week follow-up contacts will take place approximately 7 and 14 days (one 
and two weeks) following the Enrollment Visit. These telephone contacts will take approximately 
[SITES TO SPECIFY TIMEFRAME] to complete. 
 
In addition to the common study procedures with Telephone Contacts listed earlier, you will be 
asked about concerns and comfort with film use. 
 
4-week Visit (Visit 6) Procedures: 
This clinic visit will occur approximately 28 days (4 weeks) after the Enrollment Visit and will take 
between [SITES TO SPECIFY TIMEFRAME] to complete. 
 
In addition to the common study procedures listed earlier, at this visit you will: 
• 
Answer questions 
o About your experiences using the vaginal film 
o About sexual behaviors and use of vaginal products 
o Additional questions about the vaginal film following insertion 
• 
Undergo protocol instructions/counseling 
o Reminder there are no restrictions on sex or vaginal product use  
o Explanation of (optional) sexual partner interview component 
 
You will be given information to share with your partner to see if your partner 
would be comfortable participating in an interview 
 
This is optional; if you don’t feel comfortable including or asking your partner to 
participate, you will not be disqualified 
 
Your partner would need to sign a separate consent 
o Offer male condoms 
• 
Have examinations 
o Pelvic exam with removal of any visible film from the first insertion  
o Visual external (outside) genital exam after insertion of second film to check placement 
• 
Review instructional materials 
o You will be provided with vaginal film instruction materials to review prior to inserting 
the film. Study staff will be available to answer any questions you may have.  
• 
Self-insert second vaginal film (A or B) 
o You will be provided with your previously assigned vaginal film 
o You will have two attempts to insert the vaginal film 
o If after two attempts, you are having difficulty, a clinician will insert the film using a 
speculum 
 

 
 
 
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24-72-hour Phone Check-in (Visit 7) Procedures: 
This contact will take place between 24-72 hours after insertion of the second film and will take 
approximately 5 minutes to complete. 
 
You will be asked if you are having any issues or concerns with the film. You will be reimbursed 
for this contact. 
 
6-week Telephone Contact (Visit 8) Procedures: 
Your 6-week follow-up contact will take place approximately 14 days (2 weeks) after Visit 6. This 
telephone contact will take between [SITES TO SPECIFY TIMEFRAME] to complete. 
 
In addition to the common study procedures with Telephone Contacts listed earlier, you will be 
asked about concerns and comfort with film use. 
 
8-week Visit (Visit 9) Procedures: 
This clinic visit will occur approximately 28 days (4 weeks) after Visit 6 and will take between 
[SITES TO SPECIFY TIMEFRAME] to complete. 
 
In addition to the common study procedures listed earlier, at this visit you will: 
• 
Answer questions 
o About your experiences using the vaginal film 
o About sexual behaviors and use of vaginal products 
o A subset of participants (up to 35 total) will be chosen to do an in-depth interview 
 
If chosen, the interview will be performed [SITES TO SPECIFY MECHANISM: in 
the presence of one or two MATRIX-002 research staff members / remotely by a 
behavioral researcher]  
 
Study staff will make every effort to ensure your privacy and confidentiality, and 
information you provide during the interview will not be shared with your partner  
 
The interviewer may take notes, and interviews will be audio-recorded to make 
sure we record your words exactly how you said them 
 
The interview will be focused on your experiences using the film and behaviors 
during the study and could take up to an hour to complete 
 
The interview may occur during V9 or after up until V10 
• 
Have examinations 
o Pelvic exam and removal of any visible film 
• 
Blood test: Approximately [SITES TO INSERT VOLUME] will be collected to look at the 
general health of your blood and basic kidney and liver function 
• 
Offer male condoms 
• 
In addition 
o Investigators will ask if you are willing to have your partner contacted to participate 
in an in-depth interview about your partner’s experience while you were in the study.  
This is optional and you should only agree if you (and your partner) feel comfortable.  
o If you agree, you will be asked to [SITES TO SPECIFY CONTACT METHOD: provide 
your partner’s current contact information at this time / provide our contact 
information to your partner so they can call us if interested in participating] 
 

 
 
 
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Final Telephone Contact – Study Exit Visit (Visit 10) Procedures: 
Your Final Telephone Contact will take place approximately 7 days (one week) following Visit 9. 
This telephone contact will take approximately [SITES TO SPECIFY TIMEFRAME] to complete. 
 
In addition to the common procedures with Telephone Contacts listed above, you will be asked 
about your wellness and any concerns.  This will end your participation in the study. 
 
Additional Visits and Procedures 
In addition to the procedures listed above, it is possible that study clinicians may need to perform 
additional exams or tests, if necessary. For example, you may be asked to make additional clinic 
visits to perform these exams/tests if you report having symptoms and/or other issues, if there 
are abnormal test results, or due to mistakes during the collection, processing and/or shipping of 
your samples. These exams/tests might include the following: 
• 
Physical and/or pelvic exam 
• 
Test genital samples for STIs 
• 
Test your urine for STIs or other infections 
• 
Test your blood for STIs 
• 
Test your blood to check the health of your blood, liver and kidneys 
• 
Give you treatment or refer you for treatment of STIs or other issues, if needed. 
 
It is important for you to complete every study visit/contact. If you cannot make a scheduled 
visit/contact, please tell the study staff as soon as possible so that the visit/contact can be 
rescheduled.  
 
It is important that you remember that at any time during the study, study staff can answer any 
questions you may have about the procedures mentioned above or any other aspect of this study. 
 
WHAT IF I BECOME INFECTED WITH HIV? 
The placebo vaginal films do not contain medications and will not prevent HIV infection. Persons 
living with HIV will not be included in this study. Being in this study will not cause HIV infection. 
However, there is always a chance that you can get HIV through sex or other activities. If you 
become HIV-positive, you will stop using the study product and will stop taking part in this study. 
The study staff will refer you for medical care and other available services. The study does not 
pay for this care. [SITES TO INCLUDE/AMMEND THE FOLLOWING IF APPLICABLE: If you are 
interested, study staff will inform you of other available research studies you may be eligible for.]  
 
Depending on local and national health requirements, the study staff may need to report certain 
diseases, including HIV. The reportable diseases at this site are [SITES TO INSERT]. We must 
inform the following [SITES TO INSERT MORE DETAILED INFORMATION REGARDING WHO WILL 
BE INFORMED OF THE REPORTABLE DISEASES].  [SITES TO INCLUDE/AMMEND THE 
FOLLOWING]: Outreach workers from the [LOCAL HEALTH AUTHORITY] may then contact you 
about informing your partner/s, since they also should be tested. If you do not want to inform 
your partner/s yourself, the outreach workers may contact them, according to the confidentiality 
guidelines of the [LOCAL HEALTH AUTHORITY]. 
 
WHAT IF I BECOME PREGNANT? 
The placebo vaginal films are not family planning methods and will not prevent pregnancy. We 
do not know what effect the study product(s) have on pregnancy, including any effect on the 

 
 
 
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unborn babies. Because of this, pregnant women may not join this study. Also, you must use an 
effective family planning method (e.g., birth control pills, hormonal-based methods, intrauterine 
device [IUD], the patch) other than a vaginal ring for at least two weeks before screening and 
for the study duration.   
 
If you become pregnant during the study, study staff will refer you to available medical care and 
other services. The study does not pay for this care. You will stop using the study product and 
will stop taking part in this study. [SITES TO INCLUDE/AMMEND THE FOLLOWING IF 
APPLICABLE: If you are interested, study staff will inform you of other available research studies 
you may be eligible for.] 
 
RISKS AND/OR DISCOMFORTS 
 
Risks of Blood Draws  
You may feel discomfort or pain when your blood is drawn. You may feel dizzy or faint. You may 
have a bruise, swelling, small clot, or infection where the needle goes into your hand or arm. 
 
Risks of Pelvic Exams  
You may feel discomfort or pressure during the pelvic exam and collection of genital samples. 
You may have a small amount of vaginal bleeding or spotting which should stop shortly after the 
exam. 
 
Risks of Vaginal Films 
You may feel discomfort, itching, irritation, and vaginal discharge during film use. 
 
Risks of Placebo Excipients 
All the materials used in both films are generally regarded as safe and/or have a history of 
pharmaceutical use. 
 
Risks of HIV and Sexually Transmitted Infection (STI) Testing 
HIV and STI testing may make you feel anxious regardless of the test results. Finding out your 
HIV status may also cause problems with your family, friends, or partner. 
 
Other Possible Risks 
You may feel embarrassed and/or worried when talking about sexual activities (if you are 
currently sexually active), your living situation, ways to protect against HIV and STIs, and your 
test results. You can choose not to answer questions at any time. Trained study staff will help 
you with any feelings or questions you have. 
 
We will make every effort to protect your privacy and confidentiality during the study visits. Your 
visits will take place in private. Reports via computer will be stored in computers that are 
password-protected and will not include personal information that could identify or link 
information to you; only your study ID number will be recorded. However, it is possible that 
others may learn of your participation in this study, and because of this, may treat you unfairly 
or discriminate against you. If you have any problems, study staff will talk with you and try to 
help you. 
 

 
 
 
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The in-depth interviews with study staff may be performed [SITES TO SPECIFY MECHANISM: at 
the clinic / remotely]. The interviews will be audio recorded and questions of a personal nature 
may be asked. Responding to these questions may make you uncomfortable. The audio files will 
be put into writing by the person conducting the interview or by another person who does not 
know you and does not have your personal information. You should NOT identify anyone in the 
interviews and any names that might be mentioned on the recording will only be noted in the 
transcript using a generic description. The audio files will be stored in computers that are 
password protected. 
 
BENEFITS 
Though you may not experience any direct benefit from participation in this study, information 
learned from this study may help us learn ways to prevent the spread of HIV in the future. Your 
opinions about the film are important to scientists working to develop this new prevention option. 
You will receive medical exams and counseling and testing for HIV and STIs. You will also have 
tests to check your overall health. 
 
This study cannot give you general medical care, but study staff will refer you to another medical 
provider for care, if needed. Male condoms will be available at no cost, if you need them. If you 
are diagnosed with an STI during the study, you will receive medicine and/or a referral, if you 
need it.   
 
NEW INFORMATION 
You will be told about any new information learned during this study that may affect your 
willingness to stay in the study. For example, we will let you know if we learn that the study 
product may be causing bad side-effects. 
 
WHY YOU MAY STOP USING THE STUDY PRODUCT EARLY OR BE ASKED TO LEAVE 
THE STUDY 
You may need to leave the study early without your permission if: 
• 
The study is cancelled by USAID, Pitt/MWRIF, the US Office for Human Research 
Protections (OHRP), MATRIX, the local government or regulatory agency, or the 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC). An IRB/IEC is a 
committee that watches over the safety and rights of study participants. 
• 
You are not able to keep appointments. 
• 
Other reasons that may prevent you from completing the study successfully. 
 
The study doctor will ask you to stop using the study products if: 
• 
You acquire an HIV infection (see “If You Become Infected With HIV” section). 
• 
You become pregnant or are breastfeeding (see “If You Become Pregnant” section).  
• 
You use drugs for HIV prevention or to prevent infection after HIV exposure. 
• 
You use injectable drugs for reasons other than treating disease. 
• 
You experience a serious adverse event while on study. 
• 
You fail to follow study requirements in a manner judged by the study doctor to 
significantly put you at risk of an adverse reaction or otherwise affect study outcomes. 
• 
A study clinician decides that using the study product would be harmful to you, for 
example, you have a bad reaction to the vaginal film(s). 
 

 
 
 
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If a study doctor asks you to stop using study product, we will ask you to come in for an interim 
visit during which some/all of the procedures scheduled to occur on Visit 9 will be completed. You 
will then be exited from the study, unless otherwise informed by study staff. 
 
ALTERNATIVES TO BEING IN THE STUDY 
This is a placebo study enrolling healthy, adult women. You can choose not to participate in this 
study without affecting your care at this or other facilities or your ability to participate in other 
studies. 
 
[SITES TO INCLUDE/AMEND THE FOLLOWING, IF APPLICABLE: You may be able to join other 
studies here or in the community. There may be other places where you can go for HIV counseling 
and testing and family planning. We will tell you about those studies and those places if you 
wish.] 
 
COSTS TO YOU 
[SITES TO COMPLETE ACCORDING TO SITE CAPACITY] There is no cost to you for study visits, 
study products, physical/clinical exams, laboratory tests or other procedures.  We can give you 
treatments for STIs (other than HIV) at no cost while you are in the study, or we can refer you 
for available treatment. 
 
REIMBURSEMENT 
[SITES TO INSERT INFORMATION ABOUT LOCAL REIMBURSEMENT:] You will receive [SITES TO 
INSERT AMOUNT $XX] for your time, effort, and travel to and from the clinic for each scheduled 
study visit. You may receive [SITES TO INSERT AMOUNT $XX] for any extra study visits. For 
responding to phone calls and text messages, you will receive up to [SITES TO INSERT AMOUNT 
$XX]. If you are selected and agree to take part in the in-depth interview, you will receive [SITES 
TO INSERT AMOUNT $XX]. 
 
CONFIDENTIALITY 
We will make every effort to keep your information private and confidential. But we cannot 
guarantee it. 
 
Study visits will take place in private. We will keep the information about your study visits in a 
secure place that only certain people can access for the purposes of this study. We will only enter 
your information into computers protected by passwords and will not include information that 
could identify you. Your identity on these records will be indicated by a number rather than by 
your name, and the information linking these numbers with your name will be kept separate from 
the research records. You can choose not to answer questions at any time. We will keep the audio 
recordings and materials from all interviews and discussions confidential and will only use study 
numbers or fake names. We will store the original records, including the audio recordings, for at 
least three years after completion of the study. These records will be stored in a secure, locked 
location. 
 
Your personal information may be disclosed if required by law. For example, if we learn something 
that would immediately put you or others in danger, the study staff must take steps to keep you 
and others safe. This means that we have to share any information with the authorities (hospital, 
police, or social services) that tells us you may be in danger. For example, if you tell us that you 

 
 
 
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plan to hurt or kill yourself, hurt or kill someone else, or if you tell us that someone is abusing or 
neglecting you. 
 
The study staff may use your personal information to verify that you are not in any other research 
studies. This study will not use your name or identify you personally in any publication. 
 
[SITES TO INSERT INFORMATION ABOUT SYSTEMS CURRENTLY IN PLACE TO ENSURE 
PARTICIPANTS ARE NOT PART OF OTHER CONFLICTING STUDIES, INCLUDING BIOMETRIC 
IDENTIFICATION SYSTEMS; SEE EXAMPLE BELOW FOR SOUTH AFRICAN SITES: 
 
In clinical studies where study products or other medical devices are being assessed, it is 
important that volunteers are enrolled in only one clinical study at a time. Using more than one 
study product may lead to drug interactions and side effects that could potentially be harmful to 
your health. In addition to compromising the health of the study participant, this can affect the 
outcome of the study.  
 
The Biometric Co-Enrollment Prevention System (BCEPS) is a web-based system developed by 
the South African Medical Research Council IT (Information Technology) department, for the 
prevention of co-enrolment (being enrolled in more than one study at a time). It is a secure 
system that is used to ensure participant safety and study integrity, in studies where co-enrolment 
could impact both. 
 
Authorized study staff enters the South African Identify number (SA ID) or SA/foreign Passport 
Number of the participant into the system to check if they are enrolled in any study within any of 
the organizations using BCEPS in South Africa. During screening for a study at an Aurum Institute 
clinic/site, the SA ID number or SA/foreign Passport Number and all fingerprints are captured 
onto the system. At every study follow-up visit thereafter, their SA ID number or SA/foreign 
Passport Number and fingerprints will be checked. 
 
In the long term, after study completion, it is important that study staff can verify what studies a 
participant has volunteered in, in order to ensure that the participant’s safety is not compromised 
in future study participation. The SA ID number or SA/foreign Passport Number and fingerprints 
will remain in the database on an ongoing basis for a period of up to 15 years after the end of a 
study. If the participant has not participated in any additional studies for the 15-year period, their 
SA ID number or SA/foreign Passport Number and fingerprints will be removed from the system.  
  
If a participant refuses for the system to be used at the initial visit or requests to be removed 
from the system while using a study product, the study investigator will decide if it is safe for the 
participant to be enrolled into the study or if it is safe to continue using study product without 
regularly checking for co-enrolment. The study that the potential participant is screening for may 
also prohibit co-enrolment in which case we will not be able to screen you.] 
 
Your records may be reviewed by: 
• 
Representatives of the US Federal Government, including US OHRP, USAID and/or USAID 
contractors, and other US, local or international regulatory authorities 
• 
[SITES TO INSERT APPLICABLE LOCAL AND NATIONAL AUTHORITIES] 
• 
Representatives of Pitt/MWRIF 
• 
MATRIX representatives 

 
 
 
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• 
Study monitors 
• 
Site IRB/IEC 
• 
Study staff 
 
[US SITE TO INCLUDE/AMEND THE FOLLOWING: Federal and state laws and the federal medical 
Privacy Rule also protect your privacy. By signing this form, you provide your authorization for 
the use and disclosure of information protected by the Health Insurance Portability and 
Accountability Act (HIPAA) Privacy Rule. This includes things learned from the procedures 
described in this consent form. Study staff may also collect other information including your name, 
address, date of birth, and information from your medical records.]  
 
[NON-US SITES TO INCLUDE/AMEND THE FOLLOWING: As part of your participation in this 
research study, your personal information may be sent to the United States for analysis or 
storage. This includes things learned from the procedures described in this consent form. Study 
staff may also collect other information including your name, address, date of birth, and 
information from your medical records. There are laws in the U.S. to protect your personal 
information when in that country.] 
 
[SOUTH AFRICA SITES TO INCLUDE/AMEND THE FOLLOWING: The Protection of Personal 
Information Act (POPIA) ensures that all South African institutions collect, process, store, and 
share your personal information in a responsible manner and that they will be held accountable 
should they abuse or compromise your personal information.] 
 
People outside the study team may need to see or receive your information for this study, such 
as those listed above. We cannot do this study without your authorization to use and give out 
your information to them. You do not have to give us this authorization. If you do not, then you 
may not join this study. 
 
The use and disclosure of your information has no time limit. You may cancel your authorization 
to use and disclose your information at any time by notifying the Principal Investigator of this 
study in writing. If you do cancel your authorization to use and disclose your information, your 
part in this study will end and no further information about you will be collected. Your cancellation 
would not affect information already collected in the study, or information we disclosed before 
you wrote to the Principal Investigator to cancel your authorization. 
 
RESEARCH-RELATED INJURY 
[SITES TO INCLUDE/AMMEND PER THEIR INSTITUTIONAL POLICY: It is unlikely that you will be 
injured by being in this study. If you are injured or get sick from being in this study, please tell 
study staff immediately. 
 
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. If you become ill or injured 
as a result of participation in this study, medical treatment for the adverse reaction or injury will 
be provided appropriately. The site staff will refer you for ongoing treatment for the injury, if 
needed. Clinical trial insurance purchased by the site will be responsible for compensating you for 
appropriate medical expenses for treatment of any such illness or injury. An HIV infection that 
occurs during the course of the trial will not be considered an injury or illness caused by trial 

 
 
 
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participation. The research center or sponsor is not responsible for any loss, injuries and/or 
damages that are caused by any of the following things: 
• 
Any injury that happens because you used other medicine during the study that you did 
not tell us about. 
• 
Any injury that happens because you did not follow instructions given by the study doctor 
or nurse. 
• 
Any injury that happens because of negligence on your part.] 
 
[SITES TO SPECIFY ANY ADDITIONAL POLICY RELATED TO EMERGENCY MEDICAL ATTENTION]  
 
[US SITE TO INCLUDE/AMEND THE FOLLOWING: To pay these medical expenses, Pitt/MWRIF 
will need to know some information about you, like your name, date of birth, and social security 
number or Medicare Health Insurance Claim Number. This is because they have to check to see 
if you receive Medicare and if you do, report the payment it makes to Medicare.] 
 
You are not giving up any legal rights by signing this form. 
 
CLINICALTRIALS.GOV 
A description of this research study will be available on https://www.ClinicalTrials.gov, as required 
by U.S. law. 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. 
 
[SOUTH AFRICA SITES TO INCLUDE LANGUAGE RELATED TO SOUTH AFRICAN NATIONAL 
CLINICAL TRIALS REGISTER] 
 
YOUR RIGHTS AS A RESEARCH PARTICIPANT/VOLUNTEER 
[SITES TO SPECIFY INSTITUTIONAL POLICY:] Being in this study is completely voluntary. You 
may choose not to join this study or leave this study at any time. If you choose not to join or to 
leave the study, you can still join other studies and you can still access non-study services you 
would normally get at this or another clinic. If you leave the study, your specimens will be 
destroyed when all protocol-specified testing has been completed and your study records may be 
kept for at least three years after study completion. If you want the results of the study after it 
is over, let the study staff members know. 
 
PROBLEMS OR QUESTIONS 
If you ever have any questions about the study, or if you have a research-related injury, you 
should contact [INSERT NAME OF THE INVESTIGATOR OR OTHER STUDY STAFF] at [INSERT 
TELEPHONE NUMBER AND/OR PHYSICAL ADDRESS]. 
 
If you have questions about your rights as a research participant, you should contact [INSERT 
NAME OR TITLE OF PERSON ON THE IRB/EC OR OTHER ORGANIZATION APPROPRIATE FOR 
THE SITE] at [INSERT PHYSICAL ADDRESS AND TELEPHONE NUMBER]. 
 
 

 
 
 
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[SITES TO OMIT THE FOLLOWING IF A SEPARATE CONSENT FOR STORAGE AND FUTURE 
TESTING OF SPECIMENS IS REQUIRED] 
 
CONSENT FOR LONG-TERM STORAGE AND FUTURE TESTING OF SPECIMENS and 
RELATED HEALTH INFORMATION 
 
There might be a small amount of blood or genital samples left over after we have done all of 
the study-related testing. We would like to ask your permission to store these leftover samples 
and related health information for use in future studies, such as future research to fight HIV and 
other related diseases. This health information may include personal facts about you such as your 
race, ethnicity, sex, medical conditions and your age range. This health information will not 
include your name or any personal identifying information. The samples will be stored by your 
participant number only. 
 
If you enroll in the study and agree, your samples and related health data will be stored safely 
and securely at facilities that are designed so that only approved researchers will have access to 
the samples. Some employees of the facilities will need to have access to your samples to store 
them and keep track of where they are, but these people will not have information that directly 
identifies you.   
 
There is no time limit on how long your samples will be stored. Your samples may be shipped 
and/or stored outside of the country. The type of testing planned for your leftover specimens is 
not yet known. However, samples may be used by Pitt/MWRIF to complete additional quality 
assurance testing, ensuring that the tests work correctly and supply accurate data. No genetic 
testing on either a limited set or the full set of genes is planned for leftover samples that are 
stored for the purposes of future research. It is important that you know that any future testing 
or studies planned for these specimens must be approved by an Institutional Review Board before 
they can be done. You will not receive the results from any future testing of these specimens.  
 
You can still enroll in this study if you decide not to have leftover samples stored for 
future studies.  If you do not want the leftover samples stored, we will destroy them 
when all protocol-specified testing has been completed. You can withdraw your 
consent for the storage and future testing of specimens at any time by providing your 
request in writing to the person in charge of this study. However, researchers will not 
be able to destroy samples or information from research that is already underway. 
 
 
 
_______________ 
I DO agree to allow my biological specimens and health data to be  
Initials and Date          stored and used in future research studies. I understand my biological 
  specimens may be shipped and stored outside of the country. 
 
 
_______________ 
I DO NOT agree to allow my biological specimens and health data  
Initials and Date          to be stored and used in future research studies.  
 
 
 

 
 
 
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[SITES TO OMIT THE FOLLOWING IF A SEPARATE CONSENT IS REQUIRED FOR PARTICIPANT 
IDI] 
 
CONSENT TO PARTICIPATE IN AN IN-DEPTH INTERVIEW 
 
We would like to ask your permission to participate in a conversation-style interview (in-depth 
interview or IDI) at the end of the study to gather more feedback about the placebo vaginal film. 
If you agree and are selected to participate in the IDI, trained study staff will ask you questions 
about your experiences using the product, about product design, packaging and delivery, and 
other topics related to product use. Information you provide during the IDI will not be shared 
with your partner. The IDI may be conducted at the study site, over a secure digital platform, or 
an agreed upon location. 
 
The IDI is anticipated to last approximately 45-60 minutes. Study staff will take notes and record 
the interview. You can choose not to answer questions at any time. We will keep the audio 
recordings and materials from all interviews and discussions confidential and will only use study 
numbers or fake names to identify them. These materials will be stored in a secure, locked 
location for at least three years after completion of the study. 
 
We will reconfirm the decision you make today at later study visits should you change your mind 
about participating in the IDI. 
 
You can still enroll in this study if you decide not to participate in the IDI. You can 
withdraw your consent to participate in the IDI at any time. 
 
 
 
_______________ 
I DO agree to participate in an in-depth interview. I understand the  
Initials and Date 
interview will be recorded and notes will be taken. 
 
 
_______________ 
I DO NOT agree to participate in an in-depth interview.  
Initials and Date 
 
 
 

 
 
 
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[SITES TO OMIT THE FOLLOWING IF A SEPARATE CONSENT IS REQUIRED FOR PERMISSION 
TO CONTACT SEXUAL PARTNER] 
 
PERMISSION TO CONTACT SEXUAL PARTNER 
 
We would like to ask your permission to contact your sexual partner to participate in a 
conversation-style interview (in-depth interview or IDI) at the end of the study to gather more 
feedback about the vaginal film.  
 
If both of you agree and your partner is selected to participate in the IDI, trained study staff will 
ask your partner questions about their views on the vaginal film and its characteristics and about 
your experiences using the vaginal film. This means that your partner will be aware of your 
participation in this study and your use of the vaginal film but no other information will be shared 
with your partner.  
 
If you give us permission to talk to your sexual partner, you will be asked to [SITES TO SPECIFY 
CONTACT METHOD: provide their current contact information at this time / provide our contact 
information to your partner so they can call us if interested in participating]. 
 
We will reconfirm the decision you make today at later study visits should you change your mind 
about us contacting your sexual partner. 
 
You can still enroll in this study if you decide not to give us permission to contact your 
sexual partner. You can withdraw your permission for us to contact your sexual 
partner at any time. 
 
 
 
_______________ 
I DO give permission for study staff to talk to my sexual partner. I agree 
Initials and Date 
to [SITES TO SPECIFY CONTACT METHOD: provide current contact 
information for my sexual partner / provide my partner with your contact 
information so they can call you for more information]. 
 
 
_______________ 
I DO NOT give permission for study staff to talk to my sexual partner.  
Initials and Date 
 
 
 

 
 
 
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[SITES TO OMIT THE FOLLOWING IF NOT APPLICABLE] 
 
CONSENT FOR OFF-SITE VISITS 
 
If the site determines that an off-site visit is appropriate and with your permission, members of 
the research team at this clinic may be able to schedule off-site visits with you at your home or 
at another location as part of the study. Some of the scheduled study visits and some of the study 
procedures may take place at your home or other location outside of the research clinic. For 
example, if you need to receive study product or to have a urine or blood sample collected but 
you are unable to come into the clinic. The study personnel will explain in greater detail the 
requirements of these visits (like the conditions of the place, the type of visit and the time it will 
take) and the procedures in-place to maintain your information in a confidential manner. 
However, it is important that you know that off-site visits may eventually affect your 
confidentiality even if the study staff take precautions not to disclose the purpose of the visits. 
 
We will only conduct visits outside of the clinic if you give us permission to do so. Please read 
carefully the following statement and initial and date one option. Choosing not to have study visit 
procedures outside of the study clinic will not affect your participation in this study. Even if you 
agree today, you can withdraw your consent for off-site visits at any time by providing your 
request in writing to the person in charge of this study. In addition, before each off-site visit, we 
will confirm with you that you still agree and remember today’s discussion.  
 
 
PARTICIPANT INITIALS 
 
_____________________________ 
Initials                            Date   
 
I DO agree to have study visit procedures at a location 
other than the study clinic by clinic staff, when 
necessary. 
 
_____________________________ 
Initials                             Date 
 
I DO NOT agree to have study visit procedures at a 
location other than the study clinic by clinic staff, 
when necessary. 
 
 

 
 
 
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SIGNATURE PAGE 
 
[INSERT SIGNATURE BLOCKS AS REQUIRED BY THE LOCAL IRB/IEC:] 
All of the above has been explained to me and all of my current questions have been answered. 
I understand that I can ask questions about any aspect of this research study during the course 
of this study, and that future questions will be answered by the researchers listed on the first 
page of this form or their representatives. 
 
Any questions I have about my rights as a research participant will be answered by [INSERT 
LOCAL IRB/IEC INFORMATION]. 
 
I voluntarily agree to be in this research study. A copy of this permission form will be given to 
me.  
 
 
 
________________________________ 
      
Participant’s Name (Print)   
 
 
  
 
 
________________________________  
______________  
Participant’s Signature  
 
 
Date  
 
 
 
________________________________ 
            
Study Staff’s Name Conducting  
Consent Discussion (Print) 
 
 
  
 
________________________________  
______________  
Study Staff Conducting  
 
 
Date 
Consent Discussion (Signature) 
 
 
 
________________________________ 
      
Witness Name (Print)   
 
 
  
 
 
________________________________  
______________  
Witness Signature  
 
 
 
Date  
 
 
 
 

 
 
 
MATRIX-002, Version 1.0 
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APPENDIX IV:  SAMPLE INFORMED CONSENT FORM (SEXUAL PARTNER 
SUBSET) 
 
SAMPLE INFORMED CONSENT FORM 
 
MATRIX-002 
Trial to Assess Acceptability and Safety of Two Placebo Prototype Vaginal 
Films 
 
USAID 
 
Version 1.0 
24 May 2023 
 
PRINCIPAL INVESTIGATOR: [SITES TO INSERT] 
INSTITUTION: [SITES TO INSERT] 
AFTER HOURS CONTACT DETAILS: [SITES TO INSERT] 
STUDY SITE CONTACT DETAILS: [SITES TO INSERT] 
SHORT TITLE: VALUE Placebo Film Study 
 
INFORMED CONSENT 
[SITES TO INSERT APPROPRIATE GREETING] You are being invited to take part in this research 
study because you were identified by a MATRIX-002 study participant as their sexual partner. 
MATRIX-002 is looking at two placebo vaginal films. Up to 30 sexual partners of MATRIX-002 
participants like you will take part in this study across sites in the United States (US), Kenya, South 
Africa, and Zimbabwe. 
 
This study is sponsored by the US Agency for International Development (USAID) and conducted 
by the University of Pittsburgh/Magee-Womens Research Institute and Foundation (Pitt/MWRIF) 
as part of MATRIX: A USAID Project to Advance the Research and Development of Innovative 
HIV Prevention Products for Women. At this site, the person in charge of this study is [SITES TO 
INSERT]. 
 
KEY INFORMATION 
• 
There are no study products (investigational drugs or other products) for you to use in this 
research study.  
• 
The purpose of including sexual partners in this study is to better understand your views 
about the vaginal film and its characteristics, and your views on your partner’s experiences 
using the vaginal film. 
• 
If you qualify and choose to participate, you will be enrolled in the study and asked to 
complete one conversation-style interview (in-depth interview) with trained study staff. The 
total length of your participation in the study will be one visit of approximately [SITES TO 
SPECIFY TIMEFRAME].   
• 
Some risks or discomforts from participating in this study include:  
o Feeling uncomfortable with some of the questions study staff may ask about your sexual 
behaviors and relationships. 

 
 
 
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o Risk of conflict in your relationship if you or your partner are upset by discussions of sex, 
contraceptive choice, or HIV prevention. 
• 
There may be no benefit to participating. 
• 
Taking part in this research study is voluntary. You do not have to participate, and you can 
stop your participation in the study at any time. 
 
Please take the time to read this entire form and ask questions before deciding to join the study. 
If you are willing to take part in the study, you will sign this form. A copy of this form will be 
offered to you. Signing this form does not mean you will be able to join the study. You must first 
complete the screening assessment to see if you are eligible. It is important to know that your 
participation in this research study is your decision and taking part in this study is completely 
voluntary (see Your Rights as a Research Participant/Volunteer for more information). 
 
WHY IS THIS RESEARCH BEING DONE? 
Investigators are studying products that women can use for HIV prevention. Vaginal films are 
being evaluated as one potential way to deliver anti-HIV drugs into the vagina (in future studies). 
The MATRIX-002 study involves two placebo vaginal films (containing no medication). The 
components of both placebo films used in this study have been used in other products and/or 
have been generally regarded as safe. 
 
The main goal of including sexual partners like you in this study is to better understand your 
views about the vaginal film and its characteristics, and your views on your partner’s experiences 
using the vaginal film during the study. 
 
WHO WILL BE IN THIS RESEARCH STUDY? 
Up to 30 sexual partners of MATRIX-002 participants will be enrolled in the study across various sites 
in the United States (US), Kenya, South Africa, and Zimbabwe. 
 
DO I HAVE TO BE IN THIS STUDY? 
You do not have to be in this study. You can still get the care you need even if you do not join 
the study. 
 
WHAT WILL I BE ASKED TO DO IF I JOIN THIS RESEARCH STUDY?   
You will be asked to participate in an in-depth interview (IDI) with trained study staff. You will 
be asked about your attitudes towards and experiences with the vaginal film, and your perspective 
of your partner’s attitudes and experiences with the vaginal film. 
 
WHAT WILL HAPPEN DURING THE STUDY VISIT? 
The study consists of one study visit, which will take place after you sign this informed consent 
form. If you agree and are eligible to participate, the IDI may take place today. If scheduling 
does not allow, it may take place on a different day that is convenient for you. Additional visit(s) 
may be conducted to complete all required procedures, if necessary. The visit will take place at a 
place agreed upon by you and the study staff, which may be the study clinic, your home, or 
another convenient location [SITE TO INCLUDE ALTERNATE LOCATION]. 
 
The procedures done at this visit will take about [SITES TO SPECIFY TIMEFRAME].  
• 
Study staff will ask you where you live and other questions about you, and your 
understanding of the study requirements. 

 
 
 
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• 
In the IDI, you will be asked questions about: 
o Your age, education level, health, relationship status, and employment status. 
o Your views about HIV risk and prevention, sexual history, existing prevention methods, 
and aspects of your relationship. 
o Your views about the vaginal film and your partner’s experiences using the vaginal 
film. 
• 
The IDI will be performed [SITES TO SPECIFY MECHANISM: in the presence of one or 
two MATRIX-002 research staff members / remotely by a behavioral researcher]. The IDI 
will take approximately [SITES TO SPECIFY TIMEFRAME].  
o Study staff will make every effort to ensure your privacy and confidentiality. 
Information you provide during the IDI will not be shared with your partner. 
o During the IDI, the interviewer may take notes. Interviews will be audio-recorded to 
make sure we record your words exactly how you said them. 
• 
In addition, study staff will: 
o Reimburse you for your visit. 
o Inform you about other available health and social services, if needed. 
o Schedule your next visit, if necessary. 
 
RISKS AND/OR DISCOMFORTS 
You may feel embarrassed and/or worried when talking about sexual activities, your living 
situation, or your opinions about HIV prevention strategies. You can choose not to answer 
questions at any time. Trained study staff will help you with any feelings or questions you have. 
 
We will make every effort to protect your privacy and confidentiality during the study visit. Your 
visit will take place in private. Reports via computer will be stored in computers that are password-
protected and will not include personal information that could identify or link information to you; 
only your study ID number will be recorded. However, it is possible that others may learn of your 
participation in this study, and because of this, may treat you unfairly or discriminate against you. 
If you have any problems, study staff will talk with you and try to help you. 
 
The interviews with study staff will be audio recorded and questions of a personal nature may be 
asked. Responding to these questions may make you uncomfortable. The audio files will be put 
into writing by the person conducting the interview or by another person who does not know you 
and does not have your personal information. You should NOT identify anyone in the interviews 
and any names that might be mentioned on the recording will only be noted in the transcript 
using a generic description. The audio files will be stored in computers that are password 
protected. 
 
BENEFITS 
Though you may not experience any direct benefit from participation in this study, information 
learned from this study may help us learn ways to prevent the spread of HIV in the future. Your 
opinions about the film are important to scientists working to develop this new prevention option. 
 
Medical care for HIV infection and other health conditions will not be part of this study. This study 
cannot provide you with general medical care, but study staff will refer you to other available 
sources of care, if needed.   
 

 
 
 
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NEW INFORMATION 
You will be told when study results may be available, and how to learn about them. 
 
COSTS TO YOU 
There is no cost to you for study-related visits. 
 
REIMBURSEMENT 
[SITES TO INSERT INFORMATION ABOUT LOCAL REIMBURSEMENT:] You will receive [SITES TO 
INSERT AMOUNT $XX] for your time, effort, and travel to and from the clinic to take part in the 
in-depth interview. 
 
CONFIDENTIALITY 
We will make every effort to keep your information private and confidential. But we cannot 
guarantee it. 
 
The study visit will take place in private. We will keep the information about your study visit in a 
secure place that only certain people can access for the purposes of this study. We will only enter 
your information into computers protected by passwords and will not include information that 
could identify you. Your identity on these records will be indicated by a number rather than by 
your name, and the information linking these numbers with your name will be kept separate from 
the research records. You can choose not to answer questions at any time. We will keep the audio 
recordings and materials from all interviews and discussions confidential and will only use study 
numbers or fake names. We will store the original records, including the audio recordings, for at 
least three years after completion of the study. These records will be stored in a secure, locked 
location. 
 
Your personal information may be disclosed if required by law. For example, if we learn something 
that would immediately put you or others in danger, the study staff must take steps to keep you 
and others safe. This means that we have to share any information with the authorities (hospital, 
police, or social services) that tells us you may be in danger. For example, if you tell us that you 
plan to hurt or kill yourself, hurt or kill someone else, or if you tell us that someone is abusing or 
neglecting you. 
 
This study will not use your name or identify you personally in any publication. 
 
Your records may be reviewed by: 
• 
Representatives of the US Federal Government, including US OHRP, USAID and/or USAID 
contractors, and other US, local or international regulatory authorities 
• 
[SITES TO INSERT APPLICABLE LOCAL AND NATIONAL AUTHORITIES] 
• 
Representatives of Pitt/MWRIF 
• 
MATRIX representatives 
• 
Study monitors 
• 
Site IRB/IEC 
• 
Study staff 
 
[US SITE TO INCLUDE/AMEND THE FOLLOWING: Federal and state laws and the federal medical 
Privacy Rule also protect your privacy. By signing this form, you provide your authorization for 
the use and disclosure of information protected by the Health Insurance Portability and 

 
 
 
MATRIX-002, Version 1.0 
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73 
Accountability Act (HIPAA) Privacy Rule. This includes things learned from the procedures 
described in this consent form. Study staff may also collect other information including your name, 
address, date of birth, and information from your medical records.]  
 
[NON-US SITES TO INCLUDE/AMEND THE FOLLOWING: As part of your participation in this 
research study, your personal information may be sent to the United States for analysis or 
storage. This includes things learned from the procedures described in this consent form. Study 
staff may also collect other information including your name, address, date of birth, and 
information from your medical records. There are laws in the U.S. to protect your personal 
information when in that country.] 
 
[SOUTH AFRICA SITES TO INCLUDE/AMEND THE FOLLOWING: The Protection of Personal 
Information Act (POPIA) ensures that all South African institutions collect, process, store, and 
share your personal information in a responsible manner and that they will be held accountable 
should they abuse or compromise your personal information.] 
 
People outside the study team may need to see or receive your information for this study, such 
as those listed above. We cannot do this study without your authorization to use and give out 
your information to them. You do not have to give us this authorization. If you do not, then you 
may not join this study. 
 
The use and disclosure of your information has no time limit. You may cancel your authorization 
to use and disclose your information at any time by notifying the Principal Investigator of this 
study in writing. If you do cancel your authorization to use and disclose your information, your 
part in this study will end and no further information about you will be collected. Your cancellation 
would not affect information already collected in the study, or information we disclosed before 
you wrote to the Principal Investigator to cancel your authorization. 
 
RESEARCH-RELATED INJURY 
[SITES TO INCLUDE/AMMEND PER THEIR INSTITUTIONAL POLICY: It is unlikely that you will be 
injured by being in this study. If you are injured or get sick from being in this study, please tell 
study staff immediately. 
 
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. If you become ill or injured 
as a result of participation in this study, medical treatment for the adverse reaction or injury will 
be provided appropriately. The site staff will refer you for ongoing treatment for the injury, if 
needed. Clinical trial insurance purchased by the site will be responsible for compensating you for 
appropriate medical expenses for treatment of any such illness or injury. An HIV infection that 
occurs during the course of the trial will not be considered an injury or illness caused by trial 
participation. The research center or sponsor is not responsible for any loss, injuries and/or 
damages that are caused by any of the following things: 
• 
Any injury that happens because you used other medicine during the study that you did 
not tell us about. 
• 
Any injury that happens because you did not follow instructions given by the study doctor 
or nurse. 
• 
Any injury that happens because of negligence on your part.] 
 

 
 
 
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[SITES TO SPECIFY ANY ADDITIONAL POLICY RELATED TO EMERGENCY MEDICAL ATTENTION]  
 
[US SITE TO INCLUDE/AMEND THE FOLLOWING: To pay these medical expenses, Pitt/MWRIF 
will need to know some information about you, like your name, date of birth, and social security 
number or Medicare Health Insurance Claim Number. This is because they have to check to see 
if you receive Medicare and if you do, report the payment it makes to Medicare.] 
 
You are not giving up any legal rights by signing this form. 
 
CLINICALTRIALS.GOV 
A description of this research study will be available on https://www.ClinicalTrials.gov, as required 
by U.S. law. 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. 
 
[SOUTH AFRICA SITES TO INCLUDE LANGUAGE RELATED TO SOUTH AFRICAN NATIONAL 
CLINICAL TRIALS REGISTER] 
 
YOUR RIGHTS AS A RESEARCH PARTICIPANT/VOLUNTEER 
[SITES TO SPECIFY INSTITUTIONAL POLICY:] Being in this study is completely voluntary. You 
may choose not to join this study or leave this study at any time. If you choose not to join or to 
leave the study, you can still join other studies and you can still access non-study services you 
would normally get at this clinic. If you leave the study, your study records may be kept for at 
least three years after study completion. If you want the results of the study after it is over, let 
the study staff members know. 
 
PROBLEMS OR QUESTIONS 
If you ever have any questions about the study, or if you have a research-related injury, you 
should contact [INSERT NAME OF THE INVESTIGATOR OR OTHER STUDY STAFF] at [INSERT 
TELEPHONE NUMBER AND/OR PHYSICAL ADDRESS]. 
 
If you have questions about your rights as a research participant, you should contact [INSERT 
NAME OR TITLE OF PERSON ON THE IRB/EC OR OTHER ORGANIZATION APPROPRIATE FOR 
THE SITE] at [INSERT PHYSICAL ADDRESS AND TELEPHONE NUMBER]. 
 
 
 

 
 
 
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SIGNATURE PAGE 
 
[INSERT SIGNATURE BLOCKS AS REQUIRED BY THE LOCAL IRB/IEC:] 
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of this study, and that future questions will be answered by the researchers listed on the first 
page of this form or their representatives. 
 
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LOCAL IRB/IEC INFORMATION]. 
 
I voluntarily agree to be in this research study. A copy of this permission form will be given to 
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