Phase 2a study of the CCR5 monoclonal antibody PRO 140 administered intravenously to HIV-infected adults.
Antimicrob Agents Chemother
; 54(10): 4137-42, 2010 Oct.
Article
in En
| MEDLINE
| ID: mdl-20660677
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 log(10) 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
HIV Antibodies
/
HIV Infections
/
CCR5 Receptor Antagonists
/
Antibodies, Monoclonal
Type of study:
Clinical_trials
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Antimicrob Agents Chemother
Year:
2010
Type:
Article
Affiliation country:
United States