Anti-HIV-1 activity of weekly or biweekly treatment with subcutaneous PRO 140, a CCR5 monoclonal antibody

Abstract

Background: PRO 140 is a humanized CCR5 monoclonal antibody that has demonstrated potent antiviral activity when it is administered intravenously to adults infected with CCR5-tropic (R5) human immunodeficiency virus type 1 (HIV-1). This study is the first to evaluate subcutaneous administration.

Methods: A randomized, double-blind, placebo-controlled study was conducted among 44 subjects with HIV-1 RNA levels of >5000 copies/mL, CD4(+) cell counts of >300 cells/microL, no receipt of antiretroviral therapy for >or=12 weeks, and only R5 HIV-1 detectable. Subjects received placebo, 162 mg of PRO 140, or 324 mg of PRO 140 weekly for 3 weeks or 324 mg of PRO 140 every other week for 2 doses by means of subcutaneous infusion. Subjects were monitored for 58 days for safety, antiviral effects, and PRO 140 serum concentrations.

Results: Subcutaneous PRO 140 demonstrated potent and prolonged antiretroviral activity. Mean log(10) reductions in HIV-1 RNA level were 0.23, 0.99 (P=.009), 1.37 (P<.001), and 1.65 (P<.001) for the placebo, 162 mg weekly, 324 mg biweekly, and 324 mg weekly dose groups, respectively. Viral loads remained suppressed between successive doses. Treatment was generally well tolerated.

Conclusions: This trial demonstrates proof of concept for a monoclonal antibody administered subcutaneously in HIV-1 infected individuals. Subcutaneous PRO 140 offers the potential for significant dose-dependent HIV-1 RNA suppression and infrequent patient self-administration.

Trial registration: ClinicalTrials.gov identifier: NCT00642707 .

Conflict of interest statement

Potential conflict of interest:

PD, NS, YR, AJM, PJM, SAM and WCO are current or past employees of Progenics Pharmaceuticals and may hold stock or stock options in the company. Progenics has a proprietary commercial interest in PRO 140.

Figures

Figure 1. Mean log10 change from baseline in HIV-1 RNA over time for the different treatment groups

The arrows indicate days that study drug was administered (Days 1, 8 and 15).

Figure 2. Mean serum concentrations of PRO 140 following a 162mg or 324mg SC dose

The error bars depict standard deviations. The curve for 324mg includes data for the 324mg weekly and biweekly treatment groups.