The Journal of infectious diseases · 2017
Antiviral Activity of Pocapavir in a Randomized, Blinded, Placebo-Controlled Human Oral Poliovirus Vaccine Challenge Model.
СтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Collett Marc S, Hincks Jeffrey R, Benschop Kimberley, Duizer Erwin, van der Avoort Harrie, Rhoden Eric, Liu Hongmei, Oberste M Steven, McKinlay Mark A, Hartford Marianne
Аннотация
BACKGROUND: Immunodeficient individuals who excrete vaccine-derived polioviruses threaten polio eradication. Antivirals address this threat.
METHODS: In a randomized, blinded, placebo-controlled study, adults were challenged with monovalent oral poliovirus type 1 vaccine (mOPV1) and subsequently treated with capsid inhibitor pocapavir or placebo. The time to virus negativity in stool was determined.
RESULTS: A total of 144 participants were enrolled; 98% became infected upon OPV challenge. Pocapavir-treated subjects (n = 93) cleared virus a median duration of 10 days after challenge, compared with 13 days for placebo recipients (n = 48; P = .0019). Fifty-two of 93 pocapavir-treated subjects (56%) cleared virus in 2-18 days with no evidence of drug resistance, while 41 of 93 (44%) treated subjects experienced infection with resistant virus while in the isolation facility, 3 (3%) of whom were infected at baseline, before treatment initiation. Resistant virus was also observed in 5 placebo recipients (10%). Excluding those with resistant virus, the median time to virus negativity was 5.5 days in pocapavir recipients, compared with 13 days in placebo recipients (P < .0001). There were no serious adverse events and no withdrawals from the study.
CONCLUSIONS: Treatment with pocapavir was safe and significantly accelerated virus clearance. Emergence of resistant virus and transmission of virus were seen in the context of a clinical isolation facility.
CLINICAL TRIALS REGISTRATION: EudraCT 2011-004804-38.
METHODS: In a randomized, blinded, placebo-controlled study, adults were challenged with monovalent oral poliovirus type 1 vaccine (mOPV1) and subsequently treated with capsid inhibitor pocapavir or placebo. The time to virus negativity in stool was determined.
RESULTS: A total of 144 participants were enrolled; 98% became infected upon OPV challenge. Pocapavir-treated subjects (n = 93) cleared virus a median duration of 10 days after challenge, compared with 13 days for placebo recipients (n = 48; P = .0019). Fifty-two of 93 pocapavir-treated subjects (56%) cleared virus in 2-18 days with no evidence of drug resistance, while 41 of 93 (44%) treated subjects experienced infection with resistant virus while in the isolation facility, 3 (3%) of whom were infected at baseline, before treatment initiation. Resistant virus was also observed in 5 placebo recipients (10%). Excluding those with resistant virus, the median time to virus negativity was 5.5 days in pocapavir recipients, compared with 13 days in placebo recipients (P < .0001). There were no serious adverse events and no withdrawals from the study.
CONCLUSIONS: Treatment with pocapavir was safe and significantly accelerated virus clearance. Emergence of resistant virus and transmission of virus were seen in the context of a clinical isolation facility.
CLINICAL TRIALS REGISTRATION: EudraCT 2011-004804-38.