Vaxfectin (TVDV) Study

GLP TOXICITY STUDY FOR Vaxfectin (TVDV) VACCINE The contractor will perform a GLP toxicity study in New Zealand White rabbits as described below. The following requirements must be met: 1. The contractor must have a facility size that can accommodate up to 52 rabbits at one time. 2. The contractor must have experience with GLP toxicity studies to support Investigational New Drug submissions to the FDA. 3. The contractor must be an - Assured Institution by the National Institute of Health Office of Lab Animal Welfare (OLAW) and be certified by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC). 4. The contractor must be able to initiate the study by 1 October 2009 and earlier starts are preferable. Proposed starting dates must accompany the proposal. 5. The study performance site must be within reasonable driving distance of the NMRC facility to allow easy coordination, training, and movement of the vaccine test articles from the WRAIR GMP storage site. 6. The contractor will provide weekly updates to the principle investigator at NMRC on the interim results of the study. Such information includes graphs, charts and direct communication by phone and email. The contractor will provide an audited report within 12 weeks of study conclusion. The study report will include a summary and detailed charts, figures and supporting information to report on the elements described below. 7. The contractor will submit a bid to conduct the required toxicity study (group 1, 2, and 3) in Figure 1 and will also submit a bid to conduct the optional study (group 4) in Figure 2. Toxicity Study: Test articles: supplied as single dose kits, designed as single vial Group 1, three vials Group 2, two vials Group 3, and two vials Group 4, storage at -30 - C. Formulation SOPs and on-site training (or training video) to be provided by sponsor, however in brief multi-vial kits require 5 min vortex step (hands-free) and should take ~10 min to complete. - Species: New Zealand White rabbits, 3.0-3.5 kg. - Groups and dosing: o Group 1: PBS (two 1 mL doses bilateral IM) for a total dose of 2 ml per immunization; and o Group 2: TVDV (two 1 ml doses bilateral IM) for a total dose of 2 ml per immunization. o Group 3: Vaxfectin (1 ml dose unilateral IM) for a total dose of 1 ml one time. o Group 4: TVDV without vaxfectin or misformulation (two 1 ml doses bilateral IM) for a total dose of 2 ml per immunization. - Group size: Group 1: PBS at N=12 (equally divided between sexes); Group 2: TVDV at N=16 (equally divided between sexes); Group 3: Vaxfectin at N=12 (equally divided between sexes); Group 4: TVDV without Vaxfectin at N= 12. - Dosing schedule: Groups 1, 2 and 4 days 0, 30, 60 and 90. Group 3 day 0. - Scheduled euthanasia time-points: Groups 1, 2 and 4 50% of animals on D92 (acute toxicity animals), 50% on D120 (recovery animals). Group 3 50% of animals on D2 (acute toxicity animals), 50% on D30 (recovery animals) - Endpoints: o Mortality o Clinical pathology with hematology/coagulation/clinical chemistry: standard panels plus C-reactive protein and fibrinogen (see Figure 1): pre-dose and Days 2, 30 (pre-dose (pre-euthanasia Group 3)), 60 (pre-dose), 90 (pre-dose), 92, and 120. Serum sample to be returned frozen to sponsor for assays after each blood draw. Provide reference values for clinical chemistry endpoints based on the historical experience at your laboratory. The reference values should include the average value and standard deviations or 75% quartiles values. o Clinical observations: pre-study and weekly thereafter o Food consumption: pre-study and daily o Weight: pre-study, 48 hours post each injection, weekly on study and at euthanasia o Body Temperature: pre-study, 24 hours post injection, weekly on study and at euthanasia. o Ophthalmological exams: pre-study and prior to scheduled euthanasia (up to 48 hr prior) o Dermal observations (Draize scoring): pre-study and daily after vaccination until normal (assume 5 days for estimating purposes). Report eschar, abscess, and other non-draize measured abnormalities in a manner consistent with FDA recommendations. o Gross pathology with organ weights and ratio and full histopathology at scheduled euthanasia. BM smear to be prepared at take-downs for subsequent evaluations if warranted (pending histopathology report). (Contact primary point of contact for tables that would not copy into this announcement properly)