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Protocol HVTN 107 Are Described Below

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Protocol HVTN 107 Are Described Below PROTOCOL HVTN 107 A Phase 1/2a partially double-blinded, randomized clinical trial to characterize the safety and immunogenicity of clade C ALVAC-HIV (vCP2438) and Bivalent Subtype C gp120 alone, with MF59® adjuvant, and with alum adjuvant in healthy, HIV- uninfected adult participants DAIDS DOCUMENT ID 12006 CLINICAL TRIAL SPONSORED BY Division of AIDS (DAIDS) National Institute of Allergy and Infectious Diseases (NIAID) National Institutes of Health (NIH) Department of Health and Human Services (DHHS) Bethesda, Maryland, USA STUDY PRODUCT(S) PROVIDED BY Sanofi Pasteur Swiftwater, Pennsylvania, USA GlaxoSmithKline Biologicals, S.A. Rixensart, Belgium NIH, NIAID, Vaccine Research Center (VRC) Bethesda, Maryland, USA May 4, 2017 HVTN 107 Version 3.0 HVTN 107 Version 3.0 / May 4, 2017 Contents 1 Ethical considerations .............................................................................................. 5 2 IRB/EC review considerations ................................................................................. 7 2.1 Minimized risks to participants ..................................................................... 7 2.2 Reasonable risk/benefit balance .................................................................... 8 2.3 Equitable subject selection ............................................................................ 8 2.4 Appropriate informed consent ....................................................................... 8 2.5 Adequate safety monitoring ........................................................................... 8 2.6 Protect privacy/confidentiality ....................................................................... 9 3 Overview ................................................................................................................ 10 3.1 Protocol Team .............................................................................................. 14 4 Background ............................................................................................................ 15 4.1 Rationale for trial concept ........................................................................... 15 4.2 ALVAC-HIV (vCP2438)............................................................................. 19 4.3 Bivalent Subtype C gp120 ........................................................................... 21 4.4 MF59® adjuvant ........................................................................................... 22 4.5 Aluminum Hydroxide Suspension ............................................................... 23 4.6 Bivalent Subtype C gp120/MF59® for injection .......................................... 23 4.7 Bivalent Subtype C gp120 admixed with Aluminum Hydroxide Suspension for injection ................................................................................................. 24 4.8 Trial design rationale ................................................................................... 24 4.9 Plans for future product development and testing ....................................... 27 4.10 Preclinical safety studies .............................................................................. 27 4.11 Clinical studies ............................................................................................ 30 4.12 Potential risks of study products and administration ................................... 46 5 Objectives and endpoints ....................................................................................... 48 5.1 Primary objectives and endpoints ................................................................ 48 5.2 Secondary objectives and endpoints ............................................................ 49 5.3 Exploratory objectives ................................................................................. 49 6 Statistical considerations ........................................................................................ 51 6.1 Accrual and sample size calculations .......................................................... 51 6.2 Randomization ............................................................................................. 54 6.3 Blinding ....................................................................................................... 54 6.4 Statistical analysis ........................................................................................ 55 7 Selection and withdrawal of participants ............................................................... 60 7.1 Inclusion criteria .......................................................................................... 60 7.2 Exclusion criteria ......................................................................................... 62 7.3 Participant departure from vaccination schedule or withdrawal .................. 65 8 Study product preparation and administration ....................................................... 68 8.1 Vaccine regimen .......................................................................................... 68 8.2 Study product formulation ........................................................................... 69 8.3 Preparation of study products ...................................................................... 70 8.4 Administration ............................................................................................. 72 8.5 Acquisition of study products ...................................................................... 73 8.6 Pharmacy records......................................................................................... 73 8.7 Final disposition of study products .............................................................. 73 HVTN107_v3.0_FINAL.docx / Page 2 of 155 HVTN 107 Version 3.0 / May 4, 2017 9 Clinical procedures ................................................................................................ 74 9.1 Informed consent ......................................................................................... 74 9.2 Pre-enrollment procedures ........................................................................... 76 9.3 Enrollment and vaccination visits ................................................................ 77 9.4 Follow-up visits ........................................................................................... 79 9.5 Innate immunity and mucosal sampling ...................................................... 80 9.6 Stool sampling ............................................................................................. 81 9.7 HIV counseling and testing ......................................................................... 82 9.8 Contraception status..................................................................................... 83 9.9 Urinalysis ..................................................................................................... 84 9.10 Assessments of reactogenicity ..................................................................... 84 9.11 Visit windows and missed visits .................................................................. 85 9.12 Early termination visit ................................................................................. 86 9.13 Pregnancy .................................................................................................... 86 10 Laboratory .............................................................................................................. 87 10.1 HVTN CRS laboratory procedures .............................................................. 87 10.2 Total blood volume ...................................................................................... 87 10.3 Primary immunogenicity timepoint ............................................................. 87 10.4 Endpoint assays: humoral ............................................................................ 87 10.5 Endpoint assays: cellular ............................................................................. 88 10.6 Innate immunity assays................................................................................ 88 10.7 Genotyping .................................................................................................. 88 10.8 Lab assay algorithm ..................................................................................... 89 10.9 Exploratory studies ...................................................................................... 89 10.10 Other use of stored specimens ..................................................................... 89 10.11 Biohazard containment ................................................................................ 90 11 Safety monitoring and safety review ..................................................................... 91 11.1 Safety monitoring and oversight .................................................................. 91 11.2 Safety reporting ........................................................................................... 92 11.3 Safety pause and prompt PSRT AE review ................................................. 95 11.4 Review of cumulative safety data ................................................................ 96 11.5 Study termination......................................................................................... 96 12 Protocol conduct .................................................................................................... 98 12.1 Social impacts .............................................................................................
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