Table 4.

Clinical stage development of iminosugars for the treatment of Flaviviridae infections.

Compound	Indication/Virus	Study Details	Study Endpoint/Readouts	Results	References
Celgosivir	HCV (genotype 1)	Phase 2a randomized, dose-ranging trial; 43 adult participants, ages 18–65 with chronic HCV infections who were IFN-intolerant or never treated with IFN; 200 or 400 mg once daily or 200 mg twice daily for 12 weeks	Safety and efficacy (viral load reduction)	Viral load reduction observed for 2 of the 35 patients who completed the full treatment course. Well tolerated but no measurable therapeutic benefit.	NCT00157534; Durantel 2009; Yoshida et al. (2006)
	DENV	Phase 1 randomized, double-blind, placebo-controlled study; 50 adult participants, ages 21–60 with uncomplicated DENV fever (fever ≥38 °C for less than 48 h); 24 participants received celgosivir (400 mg loading dose, 200 mg maintenance dose every 12 h for a total of 9 doses) and 26 participants received placebo control	Safety, pharmacokinetics, and efficacy (primary: viral load reduction and fever reduction; secondary: NS1 and NS1 clearance)	Celgosivir was well tolerated by patients; no measurable reduction in viral load or fever burden.	NCT01619969; Low et al. (2014)
Phase 2 double-blind, placebo-controlled study; Adult participants ages 21–65 with acute febrile illness with fever >37.5 °C for less than 48 h); celgosivir arm: 150 mg every 6 h for a total of 20 doses	Safety and efficacy (primary: viral load reduction, AUC; secondary: fever clearance time, duration of illness, time to NSI clearance)	NA/not yet recruiting	NCT02569827
Celgosivir ± standard care (PEGylated IFN-α2b + Ribavirin)	HCV (genotype 1)	Phase 2 randomized, active controlled study; 50 adult participants, ages 18–65 with chronic HCV infections who were not previously treated with IFN; 400 mg or 600 mg celgosivir qd plus standard care, or standard care alone, for 12 weeks	Safety, tolerability, pharmacokinetics, efficacy (viral load reduction)	NA	NCT00332176
Celgosivir + PEGylated IFN-α2b +/− Ribavirin	HCV (genotype 1)	Phase 2 randomized, active controlled study; 60 participants ages 18–65 with chronic HCV infections who did not respond or only partially responded to prior treatment with PEGylated IFN-α2b; Study arms not indicated, 12-week treatment	Safety and efficacy (viral load reduction)	Non-responders treated with the triple drug combination had an increased average early viral response (42%) when compared to patients that received the standard treatment of PEGylated IFN-α2b and ribavirin (10%), and a greater reduction in viral load (−1.6310) compared to the control group receiving the standard treatment (−0.92 log10).	NCT00217139
HCV (genotype 1)	Phase 2 (extension of clinical trial NCT00217139); allow patients to switch and/or continue celgosivir (plus IFN or IFN and ribavirin) treatment for an additional 36 weeks	Safety and efficacy (viral load reduction)	N/A	NCT00292084
UV-4B	DENV	Phase 1 randomized, double-blind, placebo-controlled, single-ascending dose study; 64 participants, healthy subjects received placebo control or up to 1,000 mg UV-4B (single dose)	Safety, tolerability, and pharmacokinetics	No serious adverse events.	NCT02061358; Spurgers et al., unpublished data
Phase 1 randomized, double-blind, placebo-controlled, multiple ascending dose study; healthy adult subjects, ages 18–45; placebo or UV-4B TID treatment (ascending doses) for 7 days	Safety, tolerability, and pharmacokinetics	Terminated early before DENV-infected patients were dosed; product development ceased for business reasons.	NCT02696291

Abbreviations: BID, twice daily; DENV, dengue virus; h, hours; HCV, hepatitis C virus; IFN, interferon; NA, not available; NS1, non-structural protein 1; qd, once daily; RT-PCR, reverse transcription polymerase chain reaction; TID, three times daily; WNV, West Nile virus.