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Posted On: 01/19/2021 3:58:06 PM
Post# of 148899
700mg was proven better back in 2010 when Lalazari and the docs from progenics were running trials and writing papers on it.
Phase 2a Study of the CCR5 Monoclonal Antibody PRO 140 Administered Intravenously to HIV-Infected Adults
Jeffrey M. Jacobson, Jacob P. Lalezari, Melanie A. Thompson, Carl J. Fichtenbaum, Michael S. Saag, Barry S. Zingman, Paul D'Ambrosio, Nancy Stambler, Yakov Rotshteyn, Andre J. Marozsan, Paul J. Maddon, Stephen A. Morris, William C. Olson
DOI: 10.1128/AAC.00086-10
ArticleFigures & DataInfo & MetricsPDF
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/μl, 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 log10 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.
In this study, PRO 140 demonstrated potent, rapid, and prolonged antiretroviral activity when it was administered as single 5-mg/kg or 10-mg/kg intravenous infusions to individuals infected with CCR5-tropic HIV-1. The mean maximum decrease in viral load was 1.8 log10 units at each dose level, and this value compares favorably to the reductions observed in prior studies of PRO 140 (6, 7) and with small-molecule CCR5 antagonists (4, 10, 16, 19). Overall, single doses of 5 mg/kg or 10 mg/kg were generally well tolerated when they were administered as short-term monotherapy. Notably, we observed that 10 mg/kg, the highest dose tested to date, did not demonstrate any dose-dependent pattern of adverse events relative to placebo or to the 5-mg/kg dose. The present study adds to our understanding of the pharmacologic, pharmacokinetic, and safety profiles of this agent.......
There was a striking consistency in the antiviral effects observed in the present study and a prior study of intravenous PRO 140 (6). Remarkably, the mean maximum reduction in the HIV-1 RNA level was 1.8 log10 units for doses of 5 mg/kg or higher in each study. The consistency of outcomes underscores the robustness of the single-dose activity observed for intravenous PRO 140. The median reduction in viral load was slightly higher in the 10-mg/kg group, and more subjects in the 10-mg/kg group achieved a ≥2-log10-unit reduction in HIV-1 RNA levels.
Phase 2a Study of the CCR5 Monoclonal Antibody PRO 140 Administered Intravenously to HIV-Infected Adults
Jeffrey M. Jacobson, Jacob P. Lalezari, Melanie A. Thompson, Carl J. Fichtenbaum, Michael S. Saag, Barry S. Zingman, Paul D'Ambrosio, Nancy Stambler, Yakov Rotshteyn, Andre J. Marozsan, Paul J. Maddon, Stephen A. Morris, William C. Olson
DOI: 10.1128/AAC.00086-10
ArticleFigures & DataInfo & MetricsPDF
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/μl, 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 log10 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.
In this study, PRO 140 demonstrated potent, rapid, and prolonged antiretroviral activity when it was administered as single 5-mg/kg or 10-mg/kg intravenous infusions to individuals infected with CCR5-tropic HIV-1. The mean maximum decrease in viral load was 1.8 log10 units at each dose level, and this value compares favorably to the reductions observed in prior studies of PRO 140 (6, 7) and with small-molecule CCR5 antagonists (4, 10, 16, 19). Overall, single doses of 5 mg/kg or 10 mg/kg were generally well tolerated when they were administered as short-term monotherapy. Notably, we observed that 10 mg/kg, the highest dose tested to date, did not demonstrate any dose-dependent pattern of adverse events relative to placebo or to the 5-mg/kg dose. The present study adds to our understanding of the pharmacologic, pharmacokinetic, and safety profiles of this agent.......
There was a striking consistency in the antiviral effects observed in the present study and a prior study of intravenous PRO 140 (6). Remarkably, the mean maximum reduction in the HIV-1 RNA level was 1.8 log10 units for doses of 5 mg/kg or higher in each study. The consistency of outcomes underscores the robustness of the single-dose activity observed for intravenous PRO 140. The median reduction in viral load was slightly higher in the 10-mg/kg group, and more subjects in the 10-mg/kg group achieved a ≥2-log10-unit reduction in HIV-1 RNA levels.
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