SP01A: The Study of an Oral Entry Inhibitor in Treatment-Experienced HIV Patients

Currently approved antiretroviral medications target either the HIV viral reverse transcriptase (RT), (Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)) or the viral protease, (Protease Inhibitors (PIs)) or inhibit viral fusion with target cells (Fusion Inhibitors). A regimen using a combination of these agents is considered the standard of care and, when effective, results in suppression of the virus below the detection limits. However, the long-term use of antiretroviral therapy is sometimes hampered by poor compliance due to pill burden, food restrictions, and major side effects that impact Quality of Life. Furthermore, one of the major reasons for therapy failure is the emergence of resistant virus against one or more of the anti-HIV medications or, to some extent, an entire class of drug (cross resistance). Enfuvirtide (Fuzeon™) was recently approved as an HIV-1 fusion/entry inhibitor, a new class of treatment that prevents fusion of the HIV-1 virus to the CD4+ cell membrane by preventing the conformational changes required for this fusion. Since the mechanism of action of Enfuvirtide is different from other classes of anti-HIV medication, it is effective in patients who have failed other therapies due to emergence of resistant virus. However, a recent study demonstrated the emergence of resistance to Enfuvirtide due to a mutation in viral gp41. The rapid rate of mutation of HIV-1 and conferred resistance of the virus to current therapies continues to necessitate a need for additional therapeutic agents. To that end, a hypothesis has been suggested regarding the immuno-modulating and anti-viral effects of SP01A in the treatment of HIV infection. SP01A may affect cholesterol binding, which is directly implicated in the pathogenesis of HIV. Several observations have also established that inhibitors of cholesterol synthesis inhibit cell fusion formation induced by HIV-l and that drugs extracting cholesterol from the cellular membrane exert an anti-HIV-1 effect in-vitro. Taken together, these data may suggest that procaine hydrochloride and SP01A reduces HIV-1 virus replication by modifying the cholesterol content of the cell membrane, rendering it much more difficult for the virus to enter and infect the cell. There is an urgent need to develop improved new therapeutic agents. SP01A, which targets different viral or cellular components with a new mechanism of action, is being developed and tested by Samaritan Pharmaceuticals, Inc. as a new anti-viral therapeutic agent. This multi-center, double-blind, randomized, placebo-controlled study of orally administered SP01A as monotherapy in HIV-infected patients with evidence of resistance to currently available antiretroviral therapy was designed to further evaluate the dose response, efficacy, and safety of SP01A. HIV-positive patients will be evaluated during the pre-study period. Following a 2-week washout period (if required), patients will be randomized into one of four study arms and all arms will initiate the 28-day monotherapy study. The first arm will receive 200 mg of SP01A QID. Arm Two will receive 200 mg bid. The third arm will orally administer 400 mg bid. Finally, the fourth arm will receive placebo twice daily. During the treatment period, patients will make five scheduled visits to the treatment facility on or about Days 1, 8, 15, 22, and 29. During these visits patients will be monitored for viral load and general health parameters. At the conclusion of the 28-day monotherapy study, patients will have optimized viral testing for further treatment. On Day 43, patients will make their final visit to the treatment facility for post-study evaluation.