Efficacy and safety of celgosivir in patients with dengue fever (CELADEN): a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial

• Published in: The Lancet infectious diseases Vol. 14; no. 8; pp. 706 - 715
• Main Authors: Low, Jenny G, MPH, Sung, Cynthia, PhD, Wijaya, Limin, MRCP, Wei, Yuan, MSc, Rathore, Abhay P S, MSc, Watanabe, Satoru, PhD, Tan, Boon Hian, BSc, Toh, Liying, BSc, Chua, Lian Tee, BSc, Hou, Yan'an, BSc, Chow, Angelia, Dip Sc, Howe, Shiqin, BSc, Chan, Wing Ki, BSc, Tan, Kah Hin, BSc, Chung, Jasmine S, MRCP, Cherng, Benjamin P, MRCP, Lye, David C, FRACP, Tambayah, Paul A, Prof, Ng, Lee Ching, PhD, Connolly, John, PhD, Hibberd, Martin L, Prof, Leo, Yee Sin, FRCP, Cheung, Yin Bun, Prof, Ooi, Eng Eong, FRCPath, Vasudevan, Subhash G, Prof
• Format: Journal Article
• Language: English
• Published: London Lancet Publishing Group 01-08-2014; Elsevier Limited
• Subjects: Adult; Aged; Analgesics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - adverse effects; Antiviral Agents - therapeutic use; Arboviroses; Biological and medical sciences; Blood; Dengue - drug therapy; Dengue fever; Dengue fevers; Double-Blind Method; Drug dosages; Drug therapy; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - pathology; Enzymes; Female; Fever; Hospitals; Human viral diseases; Humans; Indolizines - adverse effects; Indolizines - therapeutic use; Infections; Infectious Disease; Infectious diseases; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Placebos - administration & dosage; Singapore; Substance abuse treatment; Treatment Outcome; Tropical viral diseases; Vaccines; Vector-borne diseases; Viral diseases; Viral Load; Young Adult; Singapore; ISEW, Singapore; Infection; Human; Alkaloid; Viral disease; Dengue; Arbovirus disease; Antiviral; Celgosivir
• ISSN: 1473-3099; 1474-4457
• DOI: 10.1016/S1473-3099(14)70730-3

Summary Background Dengue infection is the most common mosquito-borne viral disease worldwide, but no suitable antiviral drugs are available. We tested the α-glucosidase inhibitor celgosivir as a treatment for acute dengue fever. Methods To establish eligibility for inclusion in a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial, individuals aged 21–65 years who had had a fever (≥38°C) for less than 48 h, met at least two criteria indicating probable dengue infection, and had a positive result on a dengue point-of-care test kit or PCR assay were referred for screening at a centre in Singapore between July 30, 2012, and March 4, 2013. Using a web-based system, we randomly assigned patients who met full inclusion criteria after screening (1:1; random permuted block length four) to celgosivir (initial 400 mg loading dose within 6 h of randomisation, followed by 200 mg every 12 h for a total of nine doses) or matched placebo. Patients and the entire study team were masked to group assignment. The primary endpoints were mean virological log reduction (VLR) from baseline for days 2, 3, and 4, and area under the fever curve (AUC) for a temperature above 37°C from 0 h to 96 h. Efficacy analyses were by intention to treat. This study is registered with ClinicalTrials.gov , number NCT01619969. Findings We screened 69 patients and randomly assigned 50 (24 to celgosivir, 26 to placebo). Mean VLR was greater in the celgosivir group (–1·86, SD 1·07) than in the placebo group (–1·64, 0·75), but the difference was non-significant (–0·22, 90% CI −0·65 to 0·22; one-sided p=0·203). The mean AUC was also higher in the celgosivir group (54·92, SD 31·04) than in the placebo group (40·72, 18·69), but again the difference was non-significant (14·20, 90% CI 2·16–26·25; one-sided p=0·973). We noted similar incidences of adverse events between groups. Interpretation Although generally safe and well tolerated, celgosivir does not seem to reduce viral load or fever burden in patients with dengue. Funding STOP Dengue Translational Clinical Research.