Phase IIB/III clinical trials into Pfizer’s investigational CCR5 inhibitor, maraviroc, should be allowed to continue, the study’s independent Data Safety Monitoring Board (DSMB) has concluded.
Clinical studies examining the safety and efficacy of once- and twice-daily doses of maraviroc in combination with AZT (zidovudine, Retrovir) and 3TC (lamivudine, Epivir) involving individuals with previous experience of HIV treatment are to be allowed to continue as originally designed.
However, the trial into once-daily maraviroc treatment involving people who had never taken HIV therapy before, is to be stopped early. An analysis of the first 205 patients given 300mg of maraviroc once daily in combination with AZT and 3TC found that, after 16 weeks of treatment, the combination did not prove itself to be “non-inferior” to efavirenz, AZT and 3TC, a recognised standard of HIV care.
A study comparing twice-daily maraviroc and AZT with 3TC against efavirenz (Sustiva) with AZT and 3TC is to be allowed to continue, and individuals randomised to the once-daily treatment arm are to be offered the option of switching to the twice-daily dose of maraviroc.
So far over 1,400 patients have been enrolled in maraviroc studies. Late in 2005, a treatment-naïve patient enrolled in the maraviroc study experienced severe liver toxicities. The DSMB concluded that these were probably due to other medications she was taking that are known to cause liver problems, but they did not rule out the possible involvement of maraviroc. In September 2005, GlaxoSmithKline terminated a Phase IIB study involving treatment-naïve patients into its CCR5 inhibitor aplaviroc after reports of severe liver toxicities. Last year Schering Plough terminated a study of its chemokine antagonist, vircriviroc, in treatment-naive patients because of a higher failure rate in the vicriviroc group when compared to the AZT/3TC/efavirenz control group.