3 LIST OF ABBREVIATION S AND DEFINITION OF TERMS .......................................... 7 1.0 BACKGROUND AND RATIO NALE ................................................................... 16 1.1 Rationale .................................................................................................. 16 1.2 Background .............................................................................................. 16 1.3 Placebo Rationale .................................................................................... 21 1.4 Summary of Findings from Human Clinical Studies ................................. 22 1.5 Safety of Poxviral Vectors ........................................................................ 24 1.6 Potential Benefits and Risks to Human Subjects ..................................... 27 1.7 Rationale for Double- Blinding .................................................................. 28 2.0 NAME AND DESCRIPTION OF STUDY AGENTS ............................................ 29 2.1 Formulation, Packaging, and Labeling ..................................................... 29 2.2 Investigational Drug Product (PROSTVAC -V/F) ...................................... 29 2.3 GM-CSF ................................................................................................... 30 2.4 PROSTVAC -V/F Placebo: Empty fowlpox vector ................................... 31 2.5 GM-CSF Placebo ..................................................................................... 31 3.0 STUDY OBJECTIVES AND ENDPO INTS ......................................................... 32 3.1 Study Objectives ...................................................................................... 32 3.2 Study Endpoints ....................................................................................... 33 4.0 INVESTIGATIONAL PLAN ................................................................................ 34 4.1 Study Design ........................................................................................... 34 4.2 Sample S ize ............................................................................................. 34 4.3 Selection of Study Population .................................................................. 34 4.4 Targeted Enrollment of Minorities ............................................................ 35 4.5 Method of Assigning Subjects to Treatment Groups ................................ 35 4.6 Inclusion Criteria ...................................................................................... 35 4.7 Exclusion Criteria ..................................................................................... 36 5.0 SAFETY MONITORING ..................................................................................... 38 5.1 Data Monitoring Committee (DMC) .......................................................... 38 5.2 Dose -limiting Toxicities and Trial Stopping Rules .................................... 38 5.3 Emergency Unblinding Of Treatment Assignment (If Applicable) ............ 39 5.4 Removal of Subjects from Therapy or Assessment ................................. 39 5.5 Replacement Policy ................................................................................. 40 Protocol BNIT -PRV- 301; Amendment 7 PROSTVAC -V/F Version 2.7, 08 February 2017 CONFIDENTIAL AND RESTRICTED 4 Amend 7 Disclosure requires written consent from Bavarian Nordic , Inc. 6.0 STUDY TREATMENTS ......................................................................................