Pharmacy and Poisons Board: Applications

List Applications

Protocol No:

ECCT/15/10/01

Date of Protocol:

29-04-2015

Study Title:	Safety and Virologic Effect Of A Human Monoclonal Antibody, VRC-HIVmAb060-00-Ab (VRCOl), With Broad HIV-1 Neutralizing Activity, Administered Intravenously to Adults During Early Acute HIV Infection.
	The summary of changes is provided as an attachment, with the sections ammended highlighted.
Study Objectives:	PRIMARY OBJECTIVES 1. Safety of VRC01 in acutely HIV-infected viremic individuals 2. Impact of VRC01 on plasma viremia in each mAb arm compared to the ART plus placebo control at day 7 (+/- 1 day) 3.2 SECONDARY OBJECTIVES 1. Impact of VRC01 on viral dynamics in plasma over the course of 24 weeks. 2. Impact of VRC01 on HIV reservoir measures in peripheral blood mononuclear cells and plasma 3. Impact of VRC01 on clinical outcomes/characteristics of AHI 4. Impact of VRC01 on CD4 + T cell count 5. Pharmacokinetics of VRC01 in AHI in peripheral blood 3.3 EXPLORATORY OBJECTIVES 1. Impact of VRC01 on reservoir measures in CSF, mucosal, and tissue compartments 2. Comparison of peripheral blood reservoir measures to those in the CSF, mucosal and tissue compartments 3. Impact of VRC01 on reservoir measures in T cell subsets 4. Pharmacokinetics of VRC01 in CSF and mucosal compartments 5. Anti-VRC01 antibody detection 6. Impact of VRC01 on immune responses and activation 7. Effect of VRC01 on viral sequence, phenotype, and evolution 8. Predictors of favorable viral dynamics, immune responses, and reservoir seeding 9. Impact of VRC01 on neuropsychological testing outcomes
Laymans Summary:	The Human Immunodeficiency Virus (HIV) epidemic presents the most serious infectious disease threat worldwide. The global incidence of new human immunodeficiency virus (HIV) infections peaked in the mid-1990s, and a reduction in this incidence has been observed. In 2012 there were 2.3 million new cases, down from 3.4 million in 2001. The reduction of HIV incidence is due to multiple factors that include prevention and treatment programs. The wider availability of antiretroviral therapy (ART), prevention of mother-to-child transmission programs, and a diverse array of other interventions have all contributed to turning the tide of the epidemic. Long-term use of antiretroviral therapy (ART) in HIV-positive persons may be challenged by the need for high-level life long adherence to a daily regimen, development of drug resistance and cross-resistance, short and long-term toxicities, and cost. Administration of broadly neutralizing monoclonal antibodies has the potential to treat HIV infection by preventing viral spread, by facilitating clearance of virus particles and mediating destruction of virusproducing cells. This may decrease the viral reservoir and limit chronic immune activation. This is a multi-centre, double-blinded, placebo-controlled study of the safety and impact of broadly neutralizing monoclonal antibody therapy with VRC01 on viremia in acute HIV infection, alone or in combination with antiretroviral therapy (ART). A total of twenty four participants will be enrolled, with Kericho site enrolling about six participants. Participants will be randomized to three groups; 1, 2 and 3. Group 1 will receive immediate ART only (n=8), Group 2 will receive immediate ART and mAb therapy (n=8) and Group 3 will receive immediate mAb therapy and subsequent ART from day 7 (n=8). Other sites participating include Uganda, Tanzania and Thailand. Participants from the RV217 High Risk Cohort study who become acutely infected with HIV will be screened and enrolled into this study. The study duration is 25 weeks. Results obtained from this study may inform considerations for the development of broadly neutralizing monoclonal antibodies for use in therapeutic settings.
1	The protocol was amended as a result of the changes that occurred in the parent protocol. The parent protocol ended, hence this protocol could no longer enroll at the Kericho site, but will continue enrolling in Thailand where a similar parent cohort is ongoing.
Abstract of Study:	The Human Immunodeficiency Virus (HIV) epidemic presents the most serious infectious disease threat worldwide. The global incidence of new human immunodeficiency virus (HIV) infections peaked in the mid-1990s, and a reduction in this incidence has been observed. In 2012 there were 2.3 million new cases, down from 3.4 million in 2001. The reduction of HIV incidence is due to multiple factors that include prevention and treatment programs. The wider availability of antiretroviral therapy (ART), prevention of mother-to-child transmission programs, and a diverse array of other interventions have all contributed to turning the tide of the epidemic. Long-term use of antiretroviral therapy (ART) in HIV-positive persons may be challenged by the need for high-level life long adherence to a daily regimen, development of drug resistance and cross-resistance, short and long-term toxicities, and cost. Administration of broadly neutralizing monoclonal antibodies has the potential to treat HIV infection by preventing viral spread, by facilitating clearance of virus particles and mediating destruction of virusproducing cells. This may decrease the viral reservoir and limit chronic immune activation. This is a multi-centre, double-blinded, placebo-controlled study of the safety and impact of broadly neutralizing monoclonal antibody therapy with VRC01 on viremia in acute HIV infection, alone or in combination with antiretroviral therapy (ART). A total of twenty four participants will be enrolled, with Kericho site enrolling about six participants. Participants will be randomized to three groups; 1, 2 and 3. Group 1 will receive immediate ART only (n=8), Group 2 will receive immediate ART and mAb therapy (n=8) and Group 3 will receive immediate mAb therapy and subsequent ART from day 7 (n=8). Other sites participating include Uganda, Tanzania and Thailand. Participants from the RV217 High Risk Cohort study who become acutely infected with HIV will be screened and enrolled into this study. The study duration is 25 weeks. Results obtained from this study may inform considerations for the development of broadly neutralizing monoclonal antibodies for use in therapeutic settings.
1	None