03-BMT-148: A Phase I/II, Randomized, Placebo-Controlled Trial to Assess the Safety and Efficacy of IV Immunoglobulin G Containing High Anti-West Nile Virus Antibody Titers in Patients with, or at High-Risk

1. Provide clinical leadership (for adult and pediatric studies), scientific and medical advice and judgment regarding research options, for the development and implementation of protocols conducted under this contract. 2. Within 90 days of initiation of this contract, and yearly thereafter, the Contractor shall, in consultation and conjunction with the Project Officer (PO) and NIAID staff, convene an ad hoc group ofleading experts (including, but not limited to, infectious disease experts), that shall report directly DMID, to identify important potential studies relevant to the development of optimal therapies for herpesvims infections and other medically significant, non-HIV, viral infections in special populations. The panel of experts shall: a) identify and address critical gaps in the existing knowledge oftherapeutic status and discuss the types of studies described in this proposal that will address some of these gaps. b) review progress made on planning and implementing studies to address the identified gaps after the first year. c) shall identify required resources and address feasibility issues based on target enrollment projections. The panel will be convened annually to discuss new directions and to identify and recommend solutions to encountered problems. The Contractor shall provide funding for all costs incurred to convene the group of experts. In response to the recommendations from the panel, the Contractor shall develop a plan to delineate the mechanism by which new studies will be developed and prioritized. The plan will also address the mechanism for any reprioritization of studies based on resources or in response to NIAID-directed studies for Bio-defense. The plan shall be updated annually, following the panel meeting, and submitted for review and approval by the PO. Public health needs and scientific opportunities may arise which will require revision of the research agenda before the annual submission. Any revisions must be submitted to the PO for review and approval prior to implementation. 3. At the direction of the PO, develop and conduct rigorously designed single-center and multi-center controlled clinical trials to evaluate the safety and efficacy oftherapies for herpesvims infections and other serious non-HIV viral diseases in special populations (as recommended by the expert panel or NIAID). 4. At the direction of the PO, develop and conduct strategic, non-therapeutic, studies to support future therapeutic or medical management studies of herpesvirus infections or other medically important, rare viral diseases in special populations (as recommended by the expert panel or NIAID). These studies may include, but are not limited to, natural history/pathogenesis studies including immunologic responses of patients to infections, determination of resistance to antiviral therapies, development/testing of rapid viral diagnostic tests where these are needed, and identification of prognosticators/surrogate markers for outcome of therapy. 5. Provide clinical pharmacology expertise for the development and analysis of phalmacokilletic (exposure) studies and pharmacodynamic (exposure-response) studies for adult and pediatric populations. 6. Develop and conduct, safety, exposure and/or exposure-response studies to support the development of therapeutics for emerging viral diseases and Bio-defense, as directed by the DMID PO.