Journal Article

A Randomized, Double-Blind Placebo Controlled Trial of Balapiravir, a Polymerase Inhibitor, in Adult Dengue Patients

Nguyen, Quyen Than Ha, Hoang, Long Truong, Javanbakht, Hassan, Petric, Rosemary, Nagarajan, Niranjan, Hammond, Janet, Tran, Hien Tinh, Nguyen, Chinh Tran, Simmons, Cameron P., Duong, Kien Thi Hue, le Anh Huynh, Huy, Nguyen, Truong Thanh, Phung, Lam Khanh, Hibberd, Martin L., Wolbers, Marcel, Klumpp, Klaus, Pham, Mai Phuong, Farrar, Jeremy, Merson, Laura, Aw, Pauline P. K., Nguyen, Nguyet Minh, Wilm, Andreas, Tran, Chau Nguyen Bich, Van Vinh Nguyen, Chau, Nguyen, Dung Thi

2013

Overview

Background. Dengue is the most common arboviral infection of humans. There are currently no specific treatments for dengue. Balapiravir is a prodrug of a nucleoside analogue (called R1479) and an inhibitor of hepatitis C virus replication in vivo. Methods. We conducted in vitro experiments to determine the potency of balapiravir against dengue viruses and then an exploratory, dose-escalating, randomized placebo-controlled trial in adult male patients with dengue with <48 hours of fever. Results. The clinical and laboratory adverse event profile in patients receiving balapiravir at doses of 1500 mg (n = 10) or 3000 mg (n = 22) orally for 5 days was similar to that of patients receiving placebo (n = 32), indicating balapiravir was well tolerated. However, twice daily assessment of viremia and daily assessment of NS1 antigenemia indicated balapiravir did not measurably alter the kinetics of these virological markers, nor did it reduce the fever clearance time. The kinetics of plasma cytokine concentrations and the whole blood transcriptional profile were also not attenuated by balapiravir treatment. Conclusions. Although this trial, the first of its kind in dengue, does not support balapiravir as a candidate drug, it does establish a framework for antiviral treatment trials in dengue and provides the field with a clinically evaluated benchmark molecule. Clinical Trials Registration. NCT01096576.

• Publisher: Oxford University Press
• Subject: Administration, Oral / Adult / Antigens, Viral - blood / Antiviral Agents - administration & dosage / Antiviral Agents - adverse effects / Antivirals / Arboviroses / Biological and medical sciences / Blood plasma / Dengue / Dengue - drug therapy / Dengue - pathology / Dengue - virology / Dengue fevers / Dengue Virus - isolation & purification / Dosage / Double-Blind Method / Fever - drug therapy / Fundamental and applied biological sciences. Psychology / Hepatitis C virus / Human viral diseases / Humans / Infections / Infectious diseases / Major and Brief Reports / Male / Medical sciences / Microbiology / Nucleosides - administration & dosage / Nucleosides - adverse effects / Placebos / Placebos - administration & dosage / Statistical median / Treatment Outcome / Tropical viral diseases / Viral diseases / Viral Load / Viremia / Viremia - drug therapy / Virology / Viruses / Young Adult