A Phase II Randomized, Double-Blinded, Controlled Study in ...

1 A Phase II Randomized, Double-Blinded, Controlled Study in Healthy Adults to Assess the Safety, Reactogenicity, and Immunogenicity of a Monovalent Influenza A/H7N9 Virus Vaccine Administered at Different Dosages Given With and Without MF59 AdjuvantDMID Protocol Number: 13-0032 DMID Funding Mechanism:Vaccine Treatment and Evaluation UnitsPharmaceutical Support:sanofi pasteurNovartis Vaccines and DiagnosticsIND Sponsor:Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLead Principal Investigator:Mark J. Mulligan, MD, FIDSADMID Clinical Project Manager: Wendy L.

2 Buchanan, BSN, MSDMID Medical Monitor:Soju Chang, MD, MPHDMID Medical Officer: Valerie Riddle, MD, FACPDMID Scientific Lead: Linda Lambert, 30, 2013 Downloaded From: on 08/05/2020 DMID Protocol 13-0032 Version Mix and Match with MF59 in Healthy AdultsSeptember 30, 2013_____iSTATEMENT OF COMPLIANCEThe trial will be carried out in accordance with Good Clinical Practices (GCP) as required by the following: United States Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part 46; 21 CFR Part 50, 21 CFR Part 54, 21 CFR Part 56, and 21 CFR Part 312); International Conference on Harmonization (ICH) E6; 62 Federal Register 25691 (1997).

3 National Institutes of Health (NIH) Clinical Terms of Award, as with these standards provides public assurance that the rights, safety and well-being of Study subjects are protected, consistent with the principles that have their origin in the Declaration of key personnel (all individuals responsible for the design and conduct of this trial) have completed Human Subjects Protection From: on 08/05/2020 DMID Protocol 13-0032 Version Mix and Match with MF59 in Healthy AdultsSeptember 30, 2013_____iiSIGNATURE PAGEThe signature below constitutes the approval of this protocol and the attachments, and provides the necessary assurances that this trial will be conducted according to all stipulations of the protocol, including all statements regarding confidentiality, and according to local legal and regulatory requirements and applicable United States of America (US) federal regulations and ICH Principal Investigator:Name/Title (Print)Signature:Date: _____Downloaded From.

4 On 08/05/2020 DMID Protocol 13-0032 Version Mix and Match with MF59 in Healthy AdultsSeptember 30, 2013_____iiiTABLE OF CONTENTSPageSTATEMENT OF COMPLIANCE ..i SIGNATURE PAGE .. ii TABLE OF CONTENTS .. iii LIST OF vii PROTOCOL 1 Key 2 Background Information and Scientific Background Public Readiness and Emergency Preparedness Scientific Rationale ..7 Potential Risks and Benefits ..8 Potential Risks ..8 Known Potential 3 Study Objectives and Outcome Study Study Outcome Measures ..14 4 Study Sub 5 Study Enrollment and Subject Inclusion Criteria ..20 Subject Exclusion Criteria.

5 21 Treatment Assignment Enrollment and Randomization Masking Reasons for Withdrawal and Discontinuation of Treatment ..26 Handling of Withdrawals and Discontinuation of Termination of Study ..28 6 Study Intervention/Investigational Study Product Formulation, Storage, Packaging, and Labeling ..30 Study Product Storage and Stability Dosage, Preparation, and Administration of Study Intervention/Investigational Modification of Study Intervention/Investigational Product for a Accountability Procedures for the Study Intervention/Investigational Product(s) ..32 Assessment of Subject Compliance with Study Investigational Concomitant Medications/Treatments.

6 33 7 Study Procedures and Clinical Downloaded From: on 08/05/2020 DMID Protocol 13-0032 Version Mix and Match with MF59 in Healthy AdultsSeptember 30, Laboratory Evaluations ..35 Clinical Laboratory Special Assays or Specimen Preparation, Handling, and Shipping ..38 8 Study Enrollment/Baseline Visit ..39 Visit 01, Day 0, Dose 1, Clinic Follow-up Visit 01A, Day 2, Phone Visit 02, Day 8, Clinic Visit 03, Day 21, Dose 2, Clinic Visit 03A, Day 23, Phone Call ..43 Visit 04, Day 29, Clinic Visit 05, Day 42, Clinic Visit 06, Day 81, Follow-up Phone Visit 07, Day 141, Follow-up Phone Visit 08, Day 201, Follow-up Phone Final Visit.

7 45 Visit 09, Day 386, Follow-up Phone Early Termination Visit (if needed)..45 Unscheduled Visit (if needed)..45 9 Assessment of Specification of Safety Parameters ..47 Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters ..47 Adverse Events ..47 Additional Adverse Event Severity Serious Adverse Events ..51 Procedures to be Followed in the Event of Abnormal Laboratory Test Values or Abnormal Clinical Reporting Procedures ..53 Serious Adverse Events ..53 Regulatory Reporting for Studies Conducted Under DMID-Sponsored Reporting of Type and Duration of Follow-up of Subjects after Adverse Halting Rules.

8 55 Safety Oversight ..56 Independent Safety Monitor (ISM) ..56 Data and Safety Monitoring Board (DSMB) ..57 10 Clinical Monitoring ..58 Site Monitoring Downloaded From: on 08/05/2020 DMID Protocol 13-0032 Version Mix and Match with MF59 in Healthy AdultsSeptember 30, 2013_____v11 Statistical Considerations ..59 Study Study Outcome Measures ..59 Sample Size Considerations ..62 Study Study Population ..63 Subject Enrollment and Follow-up ..64 Sample Size ..64 Planned Interim Analyses ..65 Interim Safety Review ..65 Interim Immunogenicity Final Analysis Plan.

9 66 Analysis Safety Data ..67 Immunogenicity Data (HAI and Neut) ..67 Exploratory Immunogenicity Missing Values and Outliers ..69 12 Data Collection Forms and Access to Source Data/Documents ..70 13 Quality Control and Quality Assurance ..71 14 Ethics/Protection of Human Ethical Institutional Review Board ..72 Informed Consent Process ..72 Informed Exclusion of Women, Minorities, and Children (Special Populations)..73 Subject Confidentiality ..74 Study Costs, Subject Compensation, and Research Related Future Use of Stored Specimens ..75 15 Data Handling and Record Data Management Data Capture Types of Data.

10 78 Timing/Reports ..78 Study Records Retention ..78 Protocol Deviations ..78 16 Publication Policy ..80 17 Literature References ..82 Appendix A: Schedule of Procedures and Appendix B: Preparation, Labeling, Storage, and Administration of Study Vaccine for Group 1 ..91 Downloaded From: on 08/05/2020 DMID Protocol 13-0032 Version Mix and Match with MF59 in Healthy AdultsSeptember 30, 2013_____viAppendix C: Preparation, Labeling, Storage, and Administration of Study Vaccine for Group 2 ..94 Appendix D: Preparation, Labeling, Storage, and Administration of Study Vaccine for Group 3 ..97 Appendix E: Preparation, Labeling, Storage, and Administration of Study Vaccine for Group 4.