A Phase 2, Randomized Study to Assess the Safety and Anti-Cytomegalovirus (CMV) Activity of Different Doses of Maribavir for Treatment of CMV Infections that are Resistant or Refractory to Treatment with Ganciclovir/Valganciclovir or Foscarnet in Transplant Recipients
There is no consensus regarding the appropriate treatment regimen for resistant/refractory CMV. Currently available systemic anti-CMV agents include IV or oral ganciclovir, oral valganciclovir, IV foscarnet, and IV cidofovir. While these agents are considered effective, their use is limited by their respective toxicities, most notably bone marrow suppression caused by ganciclovir/valganciclovir and renal impairment caused by foscarnet or cidofovir. Maribavir is a potent and selective, orally bioavailable antiviral drug. Current anti-CMV agents inhibit CMV DNA polymerase. Maribavir inhibits viral DNA assembly as well as egress of viral capsids from the nucleus of infected cells. In vitro assays show 3- to 20-fold more activity than ganciclovir and cidofovir, and at least 100-fold more activity than foscarnet. Maribavir is active in vitro against strains of CMV that are resistant to ganciclovir, foscarnet, or cidofovir. Maribavir was safe and well tolerated across the range of doses tested in Phase 1 (up to 2400 mg/day for 28 days). Taste disturbance, nausea, and diarrhea were the most common drug-related AE. In a Phase 2 study of 82 subjects, prophylaxis with maribavir at all doses studied reduced the rate of CMV reactivation compared to the placebo.
1.â?¥ 12 years of age 2.Be a recipient of stem cell or solid organ transplantation 3.Have documented CMV infection in blood or plasma 4.Have a current CMV infection that is resistant or refractory to treatment: a.One or more CMV genetic mutations associated with resistance b.Failure to achieve greater than 1 log decrease in CMV DNA after 2 or more weeks of treatment with IV ganciclovir, oral valganciclovir, or IV foscarnet 5.Be able to swallow tablets, or receive crushed tablets via a nasogastric or orogastric tube
Treatment Groups 1. 400 mg BID Maribavir or placebo 2. 800 mg BID Maribavir or placebo 3. 1200 mg BID Maribavir
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