26 4.1 Contraception and Pregnancy Testing ............................................................................................ 26 4.2 Screening, Study Visits and Procedures ........................................................................................... 26 4.2.1 Screening Visits and Procedures ................................................................................................ 26 4.2.2 Study Visits and Procedures ................................................................................................... 27 4.2.3 Final Study Visit .................................................................................................................. 29 4.2.4 Post-Study Follow-up .......................................................................................................... 29 4.2.5 Discontinuation Visit .......................................................................................................... 30 5.0 STUDY MATERIALS AND PROCEDURES ........................................................................................... 30 5.1 Products........................................................................................................................................... 30 5.1.1 TAPA- Pulsed Dendritic Cells (DCs) ........................................................................................... 30 5.2 Storage and Drug Accountability ................................................................................................ 31 5.2.1 TAPA- Pulsed Dendritic Cells (DCs) ...................................................................................... 31 6.0 TREATMENT .................................................................................................................................... 31 6.1 Selection of TAPA- Pulsed DC Dose Level ......................................................................................... 31 6.1.1 Rationale ..................................................................................................................................... 31 6.1.2 TAPA-Pulsed DC Vaccination ............................................................................................ 31 DCs per Vaccination ............................................................................................................................. 32 6.1.3. Imiquimod Treatment .......................................................................................................... 32 6 .2 Study Drug Administration .......................................................................................................... 32 6.2.1 Cyclophosphamide (CYP) ........................................................................................................ 32 6.2.2 TAPA- Pulsed Dendritic Cells (DC) .................................................................................... 32 6.3 Study Drug Quality and Safety Measures ................................................................................... 33 6.3.1 TAPA- Pulsed Dendritic Cells (DCs) ...................................................................................... 33 6.4 Specific Restrictions and Requirements ...................................................................................... 33 6.4.2 Compliance with Therapy ................................................................................................... 34 7.0 SAMPL E SIZE AND STATISTICAL METHODS ..................................................................................... 34 7.1 Determination of Sample Size ......................................................................................................... 34 7.1.1 Sample Size for Safety Evaluation .............................................................................................. 34 7.1.2 Sample Size for Evaluation of Immune Efficacy ................................................................. 34 7.2 Statistical Methods ................................................................................................................. 34 7.2.1 Safety and Toxicity .............................................................................................................. 34 KIROVAX 003 Date: August 22, 2018- Version 00 7 CONFIDENTIAL Page 6 of 47 7.2.2 Immune Efficacy (IE) .......................................................................................................... 34 8.0 ETHICAL CONSIDERATIO NS ............................................................................................................. 35 8.1 Protection of Patients from Unnecessary Harm .............................................................................. 35 8.2 Privacy and Confidentiality ......................................................................................................... 35 8.3 Informed Consent ....................................................................................................................... 35 8.4 IRB Approval ................................................................................................................................ 35 9.0 SAFETY CONSIDERATION S ............................................................................................................... 36 9.1 TAPA -Pulsed DC Vaccination ........................................................................................................... 36 9.2 Adverse Immune Responses Against TAPA -Pulsed DC Vaccinations .......................................... 36 9.3 Regulatory Aspects ..................................................................................................................... 36 10.0 FINANCIAL CONSIDERAT IONS ......................................................................................................... 36 11.0 POTENTIAL CONFLICT O F INTEREST ................................................................................................ 36 12.0 QUALITY CONTROL AND QUALITY ASSURANCE .............................................................................. 37 13.0 PUBLICATION POLICY ...................................................................................................................... 37 14.0 DIRECT ACCESS TO SOU RCE DATA AND DOCUMEN TS, DATA HANDLING, AND RECORD KEEPING AND RETENTION OF STU DY DOCUMENTS .................................................................................................. 37 APPENDIX 1: STUDY CALENDAR ................................................................................................................... 38 APPENDIX 2: KARNOFSKY PERFORMANCE STATUS SCALE .......................................................................... 39 APPENDIX 3: RESPONSE CRITERIA ............................................................................................................... 40 APPENDIX 4: NCI CTCAE V4.0 ...................................................................................................................... 42 APPENDIX 5: ADVERSE EVENT LOG .............................................................................................................. 43 15.0 REFERENCES ................................................................................................