A Phase 2a Study to Evaluate the Safety, Tolerability, and Immunogenicity of One Dose of NDV-3A Vaccine in Patients With STAT3-Mutated Hyper-IgE Syndrome NIAID Protocol Number: 17-I-0017 Version Number: 3.0 Date: August 13, 2018 Investigational New Drug (IND) Number: 17230 IND Sponsor: Office of Clinical Research Policy and Regulatory Operations (OCRPRO) Division of Clinical Research (DCR) National Institute of Allergy and Infectious Diseases (NIAID) National Institutes of Health (NIH) Sponsor Medical Monitor: H. Preston Holley, MD, FIDSA Medical Monitor Leidos Biomedical Research 5705 Industry Lane Frederick, MD 21701 Phone: 301 228-4005 Email: [email protected] Pharmaceutical Support Provided by: NovaDigm Therapeutics, Inc. 4201 JaMes Ray Drive Technology Transfer Building Grand Forks, ND 58202 OHRP Assurance: FWA00011288 Principal Investigator: Alexandra FreeMan, MD Laboratory of Clinical IMMunology and Microbiology (LCIM) Building 10 Room 11N234 10 Center Drive Bethesda, MD 20814 Phone: 301-594-9045 Email: [email protected] Conducted by: LCIM, NIAID, NIH NDV-3A Vaccine Study Protocol Version 3.0 August 13, 2018 Study Staff Roster Associate Investigators: Lisa Barnhart, RN, MSN PaMela Welch, RN, BSN LCIM/NIAID Leidos Biomedical Research, Inc Phone: (301) 496-5270 LCIM/NIAID Email: [email protected] Phone: (301) 402-0449 Email: [email protected] Angelique Biancotto, PhD Center for Human ImMunology AutoiMMunity, and InflaMMation External Collaborators: (CHI)/National Heart, Lung and Blood John P. Hennessey, Jr, PhD Institute (NHLBI) NovaDigm Therapeutics, Inc. Phone: (301) 594-0060 4201 JaMes Ray Drive Email: [email protected] Technology Transfer Building Grand Forks, ND 58202 Jinguo Chen, MD Phone: (267) 640-5189 CHI/NHLBI Email: [email protected] Phone: (301) 594-4636 Dr. Hennessey will supply the vaccine from Email: [email protected] NovaDigm. He will also perform the serologic assays, including anti-rAls3 IgG Elise Ferré, PA-C, MPH and IgA1 responses, at baseline and to the LCIM/NIAID vaccine on the de-identified saMples. He Phone: (301) 496-8985 will also assist in the data analysis of the Email: [email protected] cytokine responses to the vaccination. Steven Holland, MD LCIM/NIAID Phone: (301) 402-7684 Email: [email protected] External Collaborators (Cont.): Jack E. Edwards, Jr, MD Sally Hunsberger, PhD Los Angeles Biomedical Research Institute Biostatistics Research Branch/NIAID Harbor-UCLA Medical Center Phone: (240) 669-5257 Division of Infectious Diseases (RB2) Email: [email protected] 1124 W. Carson Street Torrance, CA 90502 Michail Lionakis, MD Phone: (310) 222-3813 LCIM/NIAID Email: [email protected] Phone: (301) 443-5089 Dr. Edwards will assist in the interpretation Email: [email protected] of the serologic and cytokine responses to the vaccines on de-identified saMples. AManda Urban, CRNP Leidos Biomedical Research, Inc LCIM/NIAID Phone: (301) 451-3191 Email: [email protected] Page 2 of 47 NDV-3A Vaccine Study Protocol Version 3.0 August 13, 2018 Study Site: Institutional Review Board (IRB): NIH Clinical Center (CC) NIAID IRB 10 Center Drive 5601 Fishers Lane Bethesda, MD 20814 Bethesda, MD 20892 Page 3 of 47 NDV-3A Vaccine Study Protocol Version 3.0 August 13, 2018 Table of Contents Study Staff Roster ............................................................................................................................ 2 Table of Contents ............................................................................................................................ 4 List of Abbreviations ....................................................................................................................... 7 Protocol SumMary ........................................................................................................................... 8 Précis ............................................................................................................................................. 10 1 Background Information and Scientific Rationale ................................................................ 11 Background Information ............................................................................................... 11 Description of the Study Agent ............................................................................. 11 SumMary of Preclinical Studies of NDV-3 and NDV-3A .................................... 11 SumMary of Relevant Clinical Studies of NDV-3 and NDV-3A .......................... 13 SumMary of Relevant Clinical Studies of Other Vaccines ................................... 14 Rationale ........................................................................................................................ 15 2 Study Objectives .................................................................................................................... 16 PriMary Objective .......................................................................................................... 16 Secondary Objectives .................................................................................................... 16 Exploratory Objectives .................................................................................................. 16 3 Study Design .......................................................................................................................... 17 Description of the Study Design .................................................................................... 17 Study Endpoints ............................................................................................................ 17 PriMary Endpoint ................................................................................................... 17 Secondary Endpoints ............................................................................................. 17 Exploratory Endpoints ........................................................................................... 17 4 Study Population .................................................................................................................... 18 RecruitMent Plan ........................................................................................................... 18 Subject Inclusion Criteria .............................................................................................. 19 Subject Exclusion Criteria ............................................................................................. 19 Justification for Exclusion of Special Populations ........................................................ 21 Exclusion of women .............................................................................................. 21 Exclusion of minors ............................................................................................... 21 5 Study Agent/Interventions ..................................................................................................... 21 Disposition and Dispensation ........................................................................................ 21 Formulation, Packaging, and Labeling .................................................................. 21 Study Agent Storage and Stability ................................................................................ 22 Preparation, Administration, and Dosage of Study Agent ............................................ 22 Study Product Accountability Procedures ..................................................................... 22 AssessMent of Subject Compliance with Study Agent ................................................. 22 Concomitant Medications and Procedures .................................................................... 22 Prohibited Medications and Procedures ........................................................................ 23 6 Study Schedule and Procedures ............................................................................................. 23 Screening (Day −28 to baseline) ................................................................................... 23 Baseline Visits (Days –3 to 0) ....................................................................................... 24 Visit for Vaccination (Days 0 to 2) ............................................................................... 24 Follow-up Visits ............................................................................................................ 25 Early Termination Visit ................................................................................................. 26 Pregnancy and Follow-up Visit ..................................................................................... 26 Page 4 of 47 NDV-3A Vaccine Study Protocol Version 3.0 August 13, 2018 7 Potential Risks and Benefits .................................................................................................. 26 Potential Risks ............................................................................................................... 26 Potential Benefits ........................................................................................................... 28 8 Research Use of Stored Human SaMples, SpeciMens, or Data ............................................. 28 9 Data Sharing Plan .................................................................................................................. 29 10 ReMuneration Plan for Participants ......................................................................................