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MIV-150/Zinc Acetate/Carrageenan Gel) Administered Rectally to HIV-1 Seronegative Adults

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MIV-150/Zinc Acetate/Carrageenan Gel) Administered Rectally to HIV-1 Seronegative Adults MTN-037 A Phase 1 Safety and Pharmacokinetic Study of PC-1005 (MIV-150/Zinc Acetate/Carrageenan Gel) Administered Rectally to HIV-1 Seronegative Adults Microbicide Trials Network Funding Agencies: Division of AIDS, US National Institute of Allergy and Infectious Diseases US Eunice Kennedy Shriver National Institute of Child Health and Human Development US National Institute of Mental Health US National Institutes of Health Grant Numbers: UM1AI068633, UM1AI068615, UM1AI106707 DAIDS Protocol ID: 35122 IND Sponsor: DAIDS IND #TBD Protocol Chair: Craig Hendrix, MD Version 1.0 November 9, 2017 MTN-037 A Phase 1 Safety and Pharmacokinetic Study of PC-1005 (MIV-150/Zinc Acetate/Carrageenan Gel) Administered Rectally to HIV-1 Seronegative Adults TABLE OF CONTENTS LIST OF ABBREVIATIONS AND ACRONYMS ..................................................................... 6 PROTOCOL TEAM ROSTER ............................................................................................. 11 PROTOCOL SUMMARY ..................................................................................................... 20 1 KEY ROLES .................................................................................................................. 23 1.1 Protocol Identification ............................................................................................ 23 1.2 Funding Agencies, Sponsor and Monitor Identification ......................................... 23 1.3 Medical Officer ...................................................................................................... 24 1.4 Laboratory Centers ............................................................................................... 24 1.5 Data Center ........................................................................................................... 24 1.6 Study Implementation ........................................................................................... 24 2 INTRODUCTION ........................................................................................................... 25 2.1 Background of Rectal Microbicide Research and Study Rationale ....................... 25 2.2 PC-1005 Gel ......................................................................................................... 26 2.3 Non-Clinical Studies of PC-1005 Gel .................................................................... 28 2.4 Animal Studies ...................................................................................................... 32 2.5 Clinical Studies ..................................................................................................... 37 2.6 Study Hypotheses and Rationale for Study Design .............................................. 41 3 OBJECTIVES ................................................................................................................ 43 3.1 Primary Objectives ................................................................................................ 43 3.2 Secondary Objectives ........................................................................................... 43 3.3 Exploratory Objectives .......................................................................................... 43 4 STUDY DESIGN ............................................................................................................ 44 4.1 Identification of Study Design ................................................................................ 44 4.2 Summary of Major Endpoints ................................................................................ 44 4.3 Description of Study Population ............................................................................ 45 4.4 Time to Complete Accrual ..................................................................................... 45 4.5 Study Groups ........................................................................................................ 45 4.6 Expected Duration of Participation ........................................................................ 45 4.7 Sites ...................................................................................................................... 45 5 STUDY POPULATION ................................................................................................... 45 5.1 Selection of the Study Population ......................................................................... 45 5.2 Inclusion Criteria ................................................................................................... 46 5.3 Exclusion Criteria .................................................................................................. 46 5.4 Co-enrollment Guidelines...................................................................................... 48 6 STUDY PRODUCT ........................................................................................................ 49 6.1 Regimen................................................................................................................ 49 6.2 Administration ....................................................................................................... 49 6.3 Study Product Formulation.................................................................................... 49 6.4 Study Applicator .................................................................................................... 49 MTN-037, Version 1.0 2 November 9, 2017 6.5 Study Product Supply and Accountability ............................................................. 49 6.6 Study Product Dispensing ..................................................................................... 50 6.7 Ancillary Study Supplies ....................................................................................... 50 6.8 Concomitant Medications and Practices ............................................................... 50 7 STUDY PROCEDURES ................................................................................................ 52 7.1 Pre-screening ........................................................................................................ 52 7.2 Screening .............................................................................................................. 53 7.3 Enrollment (Day 0) ................................................................................................ 54 7.4 Follow-up Visits ..................................................................................................... 55 7.5 Follow-up Procedures for Participants Who Permanently Discontinue Study Product ................................................................................................................. 61 7.6 Interim Visits ......................................................................................................... 62 7.7 Protocol Counseling: Adherence and Contraception Counseling ......................... 62 7.8 Clinical Evaluations and Procedures ..................................................................... 62 7.9 Behavioral Assessments ....................................................................................... 64 7.10 Pharmacokinetics, Pharmacodynamics and Biomarkers of Mucosal Safety ......... 64 7.11 Laboratory Evaluations ......................................................................................... 65 7.12 Specimen Management ........................................................................................ 66 7.13 DAIDS Laboratory Oversight ................................................................................. 67 7.14 Biohazard Containment ........................................................................................ 67 8 ASSESSMENT OF SAFETY ......................................................................................... 67 8.1 Safety Monitoring .................................................................................................. 67 8.2 Clinical Data and Safety Review ........................................................................... 68 8.3 Adverse Events Definitions and Reporting Requirements .................................... 69 8.4 Adverse Event Reporting Requirements ............................................................... 71 8.5 Pregnancy and Infant Outcomes ........................................................................... 72 8.6 Regulatory Requirements ..................................................................................... 72 8.7 Social Harms Reporting ........................................................................................ 72 9 CLINICAL MANAGEMENT ............................................................................................ 72 9.1 Grading System .................................................................................................... 73 9.2 Dose Modification Instructions .............................................................................. 73 9.3 General Criteria for Permanent Discontinuation of Study Product ........................ 73 9.4 Follow-up in Response to Observed Adverse Events ........................................... 73 9.5 HIV-1 Infection ...................................................................................................... 74 9.6 Pregnancy ............................................................................................................. 74 9.7 Criteria for Early Termination of Study Participation ............................................
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