A randomized, double-blind placebo controlled trial of balapiravir, a polymerase inhibitor, in adult dengue patients.
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.


BACKGROUND
NCT01096576.
Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
Nguyet Minh
NM
Nguyen
Chau Nguyen Bich
CN
Tran
Lam Khanh
LK
Phung
Kien Thi Hue
KT
Duong
Huy le Anh
Hle A
Huynh
Jeremy
J
Farrar
Quyen Than Ha
QT
Nguyen
Hien Tinh
HT
Tran
Chau Van Vinh
CV
Nguyen
Laura
L
Merson
Long Truong
LT
Hoang
Martin L
ML
Hibberd
Pauline P K
PP
Aw
Andreas
A
Wilm
Niranjan
N
Nagarajan
Dung Thi
DT
Nguyen
Mai Phuong
MP
Pham
Truong Thanh
TT
Nguyen
Hassan
H
Javanbakht
Klaus
K
Klumpp
Janet
J
Hammond
Rosemary
R
Petric
Marcel
M
Wolbers
Chinh Tran
CT
Nguyen
Cameron P
CP
Simmons
D000284:Administration, Oral; D000328:Adult; D000956:Antigens, Viral / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003715:Dengue / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D003716:Dengue Virus / Q000302:isolation & purification; D004311:Double-Blind Method; D005334:Fever / Q000188:drug therapy; D006801:Humans; D008297:Male; D009705:Nucleosides / Q000008:administration & dosage* / Q000009:adverse effects; D010919:Placebos / Q000008:administration & dosage; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy; D055815:Young Adult
D000956:Antigens, Viral; D000998:Antiviral Agents; D009705:Nucleosides; D010919:Placebos; C530825:balapiravir