Presentation Abstract

Session: 143-HIV
Monday, Sep 14, 2009, 8:30 AM -11:00 AM
Presentation Title: H-1229 - Phase 2a Study of PRO 140 in HIV-Infected Adults
Location: Room 301
Presentation Number: H-1229
Pres. Time: Monday, Sep 14, 2009, 9:45 AM -10:00 AM
Category: H
Keywords: PRO 140; CCR5; HIV co-receptor
Author(s): J. JACOBSON1, M. THOMPSON 2, M. FISCHL 3, M. SAAG 4, B. ZINGMAN 5, R. LIPORACE 6, J. LALEZARI 7, C. FICHTENBAUM 8, D. BERGER 9, N. STAMBLER 10, Y. ROTSHTEYN 10, P. D'AMBROSIO 10, S. MORRIS 10, P. MADDON 10, W. OLSON 10;
1Drexel Univ. Coll. of Med., Philadelphia, PA, 2ARCA, Atlanta, GA, 3U. Miami, Miami, FL, 4UAB, Birmingham, AL, 5Montefiore Med. Ctr., Bronx, NY, 6Albany Med. Ctr., Albany, NY, 7Quest Clin. Res., San Francisco, CA, 8U. Cincinnati, Cincinnati, OH, 9NorthStar Med. Ctr., Chicago, IL, 10Progenics Pharmaceuticals, Tarrytown, NY.
Financial Disclosures:  J. Jacobson,
Cytheris Role(s): Other, Data and Safety Monitoring Board, Received: Consulting Fee.
Pfizer Role(s): Other, Data and Safety Monitoring Board, Received: Consulting Fee.
Sangamo Biosciences Role(s): Other, Data and Safety Monitoring Board, Received: Consulting Fee.
Glaxo Smith Klein Role(s): Research Relationship, Received: Research Grant.
Abstract: Background: PRO 140 is a humanized CCR5 monoclonal antibody. Prior studies examined single intravenous (IV) doses and up to three weekly subcutaneous (SC) doses. In a prior IV study, the mean maximum reduction in HIV RNA was 1.83 log10 at 5 mg/kg. Here we evaluated 5 and 10 mg/kg single IV doses for antiviral activity and tolerability. Methods: Entry criteria included HIV RNA ≥ 5,000 copies/mL, only R5 virus in the original Trofile assay, CD4 ≥ 300/μL, and no antiretroviral therapy within 12 weeks. Subjects received placebo (PBO), 5 mg/kg or 10 mg/kg PRO 140. Subjects were followed for 58 days. Results: Median baseline HIV RNA values and CD4 counts were 33,300 copies/mL and 382/μL. All PRO 140 subjects had a >1 log10 reduction in HIV RNA except for one 10 mg/kg subject with dual/mixed virus pre-treatment in the Enhanced Sensitivity Trofile assay. This subject was excluded from efficacy analyses. Mean maximum log10 reductions in HIV RNA were 1.83 for both PRO 140 groups and 0.32 for PBO. At Day 12, mean log10 changes in HIV RNA were -1.69 (p<0.0001) and -1.73 (p<0.0001) for 5 and 10 mg/kg v. +0.02 for PBO. Mean log10 changes at Day 22 were -0.92 (p=0.0002) for 5 mg/kg, -1.30 (p<0.0001) for 10 mg/kg, and -0.01 for PBO. Conclusions: PRO 140 demonstrated potent and prolonged antiviral effects. Results for 5 mg/kg were consistent with those of a prior study. The 10 mg/kg dose showed high-level activity without apparent increase in toxicity. PRO 140 has shown favorable activity and was generally well tolerated when given IV and SC. The SC route was selected for further development in part because it offers the potential for self-administration.



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