Abstract

The overall goal of this program is to combine ReProtect's BufferGel technology with Starpharma's dendrimer technology in order to develop combination topical microbicide candidates with a dual mode of action against the sexually transmission of HIV. Subproject 0001 will seek to combine Starpharma's established microbicide candidate SPL7013 with ReProtect's BufferGel technology. Subproject 0002 will seek to combine ReProtect's BufferGel technology with a second generation dendrimer based microbicide microbicide with enhanced efficacy relative to SPL7013. Subproject 0003 will assess the safety of the combination microbicide candidates developed in Subprojects 0001 and 0002 in pilot Phase I clinical trials and develop optical coherence tomography as a new cervicovaginal imaging technique in microbicide clinical research. This Core will contribute to each of these projects and the overall goal of the program through the development of prototype formulations of SPL7013 and BufferGel (Subproject 0001) and second generation dendrimer based microbicide candidates and BufferGel (Subproject 0002). Selected protoptypes arising from both Subprojects 0001 and 0002 will be maunfactured to support preliminary aminal safety and efficacy studies. Final prototypes will be maunfactured to support macaque and GLP pre-clinical studies. Clinical trial material will also be maunfactured to supply the clinical trial site (Subproject 0003). As a result this Core has four Specific Aims:
Specific Aim 1 (Year 1 and 2): Develop optimal formulations based on a combination of BufferGel and SPL7013, and to formulate second generation dendrimers as they are identified.
Specific Aim 2 (Years 1-4): Provide well-characterized vaginal gel formulations to support animal efficacy and toxicity studies in the Program Project Grant.
Specific Aim 3 (Year 1 and 3): Complete scale-up of final gel prototypes and GMP manufacturing at the CPST to support preclinical GLP Safety/Toxicity Studies.
Specific Aim 4 (Year 2 and 4): Complete GMP Manufacturing and Formal ICH Stability Studies at the CPST to support human clinical trials.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI060598-03
Application #
7286249
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
3
Fiscal Year
2006
Total Cost
$161,953
Indirect Cost

  Institution

Name
Starpharma, Ltd
Department
Type
DUNS #
748902798
City
Melbourne
State
Country
Australia
Zip Code
VIC 3-004

  Publications

O'Hanlon, Deirdre E; Moench, Thomas R; Cone, Richard A (2013) Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota. PLoS One 8:e80074
Vincent, Kathleen Listiak; Vargas, Gracie; Bourne, Nigel et al. (2013) Image-based noninvasive evaluation of colorectal mucosal injury in sheep after topical application of microbicides. Sex Transm Dis 40:854-9
Vincent, Kathleen L; Vargas, Gracie; Wei, Jingna et al. (2013) Monitoring vaginal epithelial thickness changes noninvasively in sheep using optical coherence tomography. Am J Obstet Gynecol 208:282.e1-7
Aldunate, Muriel; Tyssen, David; Johnson, Adam et al. (2013) Vaginal concentrations of lactic acid potently inactivate HIV. J Antimicrob Chemother 68:2015-25
Radecki Breitkopf, Carmen; Loza, Melissa; Vincent, Kathleen et al. (2012) Acceptability of optical coherence tomography and abstinence requirements among women participating in microbicide safety trials. Sex Transm Dis 39:28-31
Breitkopf, Carmen Radecki; Loza, Melissa; Vincent, Kathleen et al. (2011) Perceptions of reimbursement for clinical trial participation. J Empir Res Hum Res Ethics 6:31-8
Vincent, Kathleen L; Stanberry, Lawrence R; Moench, Thomas R et al. (2011) Optical coherence tomography compared with colposcopy for assessment of vaginal epithelial damage: a randomized controlled trial. Obstet Gynecol 118:1354-61
Telwatte, Sushama; Moore, Katie; Johnson, Adam et al. (2011) Virucidal activity of the dendrimer microbicide SPL7013 against HIV-1. Antiviral Res 90:195-9
O'Hanlon, Deirdre E; Moench, Thomas R; Cone, Richard A (2011) In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide. BMC Infect Dis 11:200
Tyssen, David; Henderson, Scott A; Johnson, Adam et al. (2010) Structure activity relationship of dendrimer microbicides with dual action antiviral activity. PLoS One 5:e12309

Showing the most recent 10 out of 19 publications