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Journal article
Phase 2a Study of the CCR5 Monoclonal Antibody PRO 140 Administered Intravenously to HIV-Infected Adults
Antimicrobial agents and chemotherapy, v 54(10), pp 4137-4142
01 Oct 2010
PMID: 20660677
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The anti-CCR5 antibody PRO 140 has shown potent and prolonged antiretroviral activity in subjects infected with CCR5-tropic (R5) HIV-1. Prior studies have examined single intravenous doses ranging up to 5 mg/kg of body weight or up to three subcutaneous doses ranging up to 324 mg. Here we report the results of a randomized, double-blind, placebo-controlled trial that examined the antiviral activity, tolerability, and pharmacokinetics of single 5-mg/kg and 10-mg/kg intravenous infusions of PRO 140 in 31 treated subjects. Eligibility criteria included HIV-1 RNA levels of >5,000 copies/ml, CD4(+) cell counts of >300/mu l, no antiretroviral therapy for >= 12 weeks, and detection of only R5 HIV-1 in the original Trofile assay. Following poststudy testing with an enhanced-sensitivity Trofile assay, one subject treated with 10 mg/kg was reclassified as having dual/mixed-tropic virus at screening, and the data for that subject were censored from efficacy analyses. The mean maximum reduction of the HIV-1 RNA level from the baseline level was 1.8 log(10) units for both the 5-mg/kg and 10-mg/kg doses (P < 0.0001 relative to placebo). Viral loads reached their nadir at day 12 posttreatment and remained significantly (P < 0.01) reduced through day 29 for both PRO 140 dose groups. Treatment was generally well tolerated, with no dose-limiting toxicity being observed. Peak serum concentrations and overall exposures increased proportionally with dose. In summary, single 5-mg/kg and 10-mg/kg doses of PRO 140 exhibited potent, long-lived antiviral activity and were generally well tolerated. The findings further delineate the safety and antiviral properties of this novel, long-acting antiretroviral agent.
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Details
- Title
- Phase 2a Study of the CCR5 Monoclonal Antibody PRO 140 Administered Intravenously to HIV-Infected Adults
- Creators
- Jeffrey M. Jacobson - Drexel UniversityJacob P. Lalezari - Quest Clinical ResearchMelanie A. Thompson - AIDS Research Consortium of AtlantaCarl J. Fichtenbaum - University of CincinnatiMichael S. Saag - University of Alabama at BirminghamBarry S. Zingman - Montefiore Medical CenterPaul D'Ambrosio - Progenics PharmaceuticalsNancy Stambler - Progenics PharmaceuticalsYakov Rotshteyn - Progenics PharmaceuticalsAndre J. Marozsan - Progenics PharmaceuticalsPaul J. Maddon - Progenics PharmaceuticalsStephen A. Morris - Progenics PharmaceuticalsWilliam C. Olson - Progenics PharmaceuticalsMarla A Thompson - College of Engineering (1970-)
- Publication Details
- Antimicrobial agents and chemotherapy, v 54(10), pp 4137-4142
- Publisher
- Amer Soc Microbiology
- Number of pages
- 6
- Grant note
- AI066329 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Engineering
- Web of Science ID
- WOS:000281907200014
- Scopus ID
- 2-s2.0-77957349209
- Other Identifier
- 991019168973004721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Microbiology
- Pharmacology & Pharmacy