H-1269a. Antiviral Activity and Tolerability of 5 mg/kg and 10 mg/kg Doses of PRO 140, a Humanized Monoclonal Antibody to CCR5
Session: Poster Session: Antiretroviral Therapy: New Agents
Sunday, October 26, 2008: 12:00 AM
Room: Hall C
Background: PRO 140 potently inhibits CCR5-tropic (R5) HIV in vitro. In a prior study, single 5mg/kg IV doses reduced HIV RNA by 1.83 log10 in subjects with early-stage disease and R5 virus only. The present study compared 5mg/kg and 10mg/kg IV doses for antiviral activity and tolerability. Methods: Entry criteria included HIV RNA >5,000 copies/mL, R5 virus only, CD4 >300/μL, and no antiretroviral therapy for 12 weeks. Subjects were randomized to receive placebo, 5mg/kg PRO 140 or 10mg/kg PRO 140. They were followed for 58 days post-treatment. An interim analysis was performed on data from the first 15 subjects. Results: Interim enrollment was equally distributed across the treatment groups. Baseline HIV RNA and CD4 averaged 35,480 cps/mL and 403/μL, respectively. Mean maximum log10 reductions in HIV RNA were 0.48 (range 0.15-0.73) for placebo, 1.90 (range 1.44-2.17, p<0.0001) for 5mg/kg PRO 140 and 2.17 (range 2.09-2.26, p<0.0001) for 10mg/kg PRO 140. At Day 12, mean log10 changes in HIV RNA were +0.06, -1.88 (p<0.0001), and -2.01 (p<0.0001) for placebo, 5mg/kg and 10mg/kg, respectively. The mean viral load reduction was >1.5 log10 through Day 22 at 10mg/kg. PRO 140 was generally well tolerated. Trial enrollment has completed, and updated data will be presented. Conclusions: The data confirm the antiviral activity reported previously for 5mg/kg PRO 140. A 10mg/kg dose increased the duration of antiviral effect. The findings indicate the potential for infrequent IV dosing. SC dosing regimens are also being evaluated.
Barry Zingman, MD1, Carl Fichtenbaum, MD2, Daniel Berger, MD3, Jacob Lalezari, MD4, Jeffrey Jacobson, MD5, Margaret Fischl6, Marti Michael7, Melanie Thompson, MD8, Michael Saag, MD9, Nancy Stambler7, Paul Maddon, MD, PhD10, Paul D'Ambrosio, PhD7, Ralph Liporace11, Stephen Morris, PhD12, William Olson, PhD10, Yakov Rotshteyn7 and  J. M. Jacobson,
Drexel University College of Medicine Role(s): Employee, Received: Salary., (1)Einstein-Montefiore Center for AIDS Research, Bronx, NY, (2)University of Cincinnati Medical Center, Cincinnati, OH, (3)North Star Medical Center, Chicago, IL, (4)Quest Clinical Research, San Francisco, CA, (5)Drexel University College of Medicine, Philadelphia, PA, (6)U. Miami, (7)Progenics Pharmaceuticals, (8)ARCA, (9)University of Alabama at Birmingham, Birmingham, AL, (10)Progenics Pharmaceuticals, Inc., Tarrytown, NY, (11)Albany Med. Ctr., (12)Brunel University

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