 |
|
|
| |
Weekly and Biweekly Subcutaneous PRO 140 Demonstrates Potent, Sustained Antiviral Activity: 2-week study
|
| |
| |
Reported by Jules Levin
CROI Feb 8-12 2009, Montreal
Melanie Thompson*1, J Lalezari2, M Saag2, J Jacobson3, B Zingman4, N Stambler5, P D'Ambrosio5, P Maddon5, W Olson5, and S Morris5
1AIDS Res Consortium of Atlanta, GA, US; 2Quest Clinical Res, San Francisco, CA, US; 3Drexel Univ Coll of Med, Philadelphia, PA, US; 4Montefiore Med Ctr, Bronx, NY, US; and 5Progenics Pharmaceuticals, Tarrytown, NY, US
Background: PRO 140 is a humanized CCR5 monoclonal antibody that potently inhibits CCR5-tropic (R5) HIV-1 in vitro. Previous clinical studies established PRO 140 as a well-tolerated and potent antiretroviral agent with extended activity following a single intravenous dose.The present phase 2a study is the first to evaluate subcutaneous (SC) administration (subcutaneous infusions) of PRO 140 in HIV-1-infected subjects.
Methods: Entry criteria included HIV-1 RNA >5000 copies/mL, only R5 virus detectable, CD4 >300/μL, and no ART within 12 weeks. Subjects (n = 44) were randomized to 1 of 4 groups: placebo subcutaneously on days 1, 8, and 15; weekly PRO 140 162 mg subcutaneously on days 1, 8, and 15; biweekly PRO 140 324 mg subcutaneously on days 1 and 15 and placebo on day 8; weekly PRO 140 324 mg subcutaneously on days 1, 8, and 15. Subjects were followed for a total of 58 days for safety and antiviral effects.
Results: Baseline demographics were equally distributed across the 4 groups. Baseline log10 HIV-1 RNA values and CD4 counts ranged from 3.61 to 6.68 and from 307 to 911/μL, respectively, and were similar for the 4 groups. Maximum log10 changes in HIV-1 RNA are shown in the table. All doses of PRO 140 were well tolerated, with no dose-related adverse events. Administration-site reactions were absent or mild in all subjects.
Conclusions: SC PRO 140 demonstrated potent and prolonged antiretroviral activity without significant local or systemic toxicity. The findings support further exploration of infrequent subcutaneously dosing with PRO 140 as a long-acting approach to HIV-1 therapy.
|
| |
|
|
|
|
|
