MHRP VSV Consortium Overview and key questions being addressed in Phase 1 Trials Nelson L. Michael, M.D., Ph.D Colonel, Medical Corps, U.S. Army US Military HIV Research Program Walter Reed Army Institute of Research WHO Consultation: EVD Vaccines Geneva, Switzerland 29 September 2014 The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army or the Department of Defense.
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VSV Consortium Overview and key questions being addressed in Phase 1 Trials Nelson L. Michael, M.D., Ph.D
Colonel, Medical Corps, U.S. Army
US Military HIV Research Program
Walter Reed Army Institute of Research
WHO Consultation: EVD Vaccines
Geneva, Switzerland
29 September 2014
The views expressed are those of the authors and should not be construed to
represent the positions of the U.S. Army or the Department of Defense.
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Preclinical rVSV vaccine development
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BioProtection
Systems
•Deletion of fusogenic VSV-G protein
•Substitution of Ebolavirus Zaire-strain Kikwit envelope protein
• 1-2 log reduction in titer relative to wild-type
• Eliminates VSV-G toxicity
•This vaccine vector is the PHAC construct that has been published previously
(i.e., Nature Med 2005, PLoS Pathogens 2007, Vaccine 2008,…)
• EBOV-specific antibody and cellular response (exploratory, subset)
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NIAID Div of Clinical Research (Lane)
Phase 1 Trial
WRAIR design + day 28 boost
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Drug Manufacture and Supplies
• GMP-compliant MSV and MCB are available and large enough to sustain manufacturing activity for several years
• Manufacturing process successfully executed at 10 L scale
• Multiple manufacturing runs at 30L scale scheduled through December with goal to reach 50 - 100,000 vials at 108 pfu/ml to be released from Q4 through Q1 2015
• Process development underway to increase to 250 L scale representing roughly 50,000 vials per lot
• Phase 1 studies include dose finding to determine available doses. Dose-sparing studies also pending in October 2014
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Phase 1 Trials under discussion
VEBCON Proposed Trial 1 Hamburg-Marburg
Group Dose N Vaccination Rx-AE-SAE Immunology time points
A 2 x 10 ^7 10 Day 0 14d-28d-180d Lab 0,1,2,7,56,84,180
0,7, 14, 28, 56,84, 180 B 5 x 10 ^7 10 Day 0
Sequential dose escalation Viremia, shedding days 1-7,14,28,56
VEBCON Proposed Trial 2 Lambarene Gabon and Kilifi Kenya
Group Dose N Vaccination Rx-AE-SAE Immunology time points
A 2 x 10 ^7 50 Day 0 14d-28d-6 mo Daily 7 days Lab 0,1,2,7,28, 56,84,180
0,7, 14, 28, 56, 84, 180
B 5 x 10 ^7 50 Day 0
Sequential dose escalation Viremia, shedding days 0,1,6,14
VEBCON Proposed Trial 3 Geneva
Group Dose N Vaccination Rx-AE-SAE Immunology time points
A 2 x 10 ^7 50 Day 0 14d-28d-6 mo 0,7, 14, 28, 90, 180, (356) B 5 x 10 ^7 50 Day 0
Randomized dose comparison Viremia, shedding days 0,1,3,7