Τίτλος:
Randomized clinical trials towards a single-visit cure for chronic hepatitis C: Oral GSK2878175 and injectable RG-101 in chronic hepatitis C patients and long-acting injectable GSK2878175 in healthy participants
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Single-visit cures for chronic hepatitis C are lacking. We conducted two clinical studies towards the goal of developing a regimen for single-visit cure. In a randomized, open-label, Phase 2 study (RG101-04), investigators enrolled 26 adult chronic hepatitis C patients to evaluate safety and efficacy of single subcutaneous injection of RG-101 (4 mg/kg) and daily oral tablets of GSK2878175 (20 mg) for 6, 9 or 12 weeks. In another randomized, double-blind, single dose Phase 1 study (RG101-06), investigators enrolled 18 healthy men to assess safety and PK of GSK2878175 long-acting injectable at 100, 200 or 400 mg. In RG101-04, SVR48 rates were 50%, 56% and 89%, for the 6, 9 and 12 weeks treatment arms, respectively. All AEs were mild or moderate in severity (≤Grade 2). In RG101-06 at 400 mg, the mean duration of GSK2878175 plasma levels above in vitro therapeutic concentrations for GT1b was 41 days. All AEs were Grade 2 or less. In conclusion, single injection of RG-101 combined with 12 weeks of GSK2878175 oral tablets was generally well tolerated and resulted in high SVR rates in chronic hepatitis C patients. Single injections of GSK2878175 long-acting injectable were also well tolerated; however, higher doses would be required if used in combination with RG-101 to achieve the SVR rates observed in the oral combination study to enable a single-visit curative regimen. © 2020 John Wiley & Sons Ltd
Συγγραφείς:
Deng, Y.
Campbell, F.
Han, K.
Theodore, D.
Deeg, M.
Huang, M.
Hamatake, R.
Lahiri, S.
Chen, S.
Horvath, G.
Manolakopoulos, S.
Dalekos, G.N.
Papatheodoridis, G.
Goulis, I.
Banyai, T.
Jilma, B.
Leivers, M.
Περιοδικό:
Journal of Viral Hepatitis
Εκδότης:
Wiley-Blackwell Publishing Ltd
Λέξεις-κλειδιά:
antivirus agent; gsk 2878175; long acting drug; placebo; rg 10104; rg 10106; temavirsen; unclassified drug; antivirus agent, adult; aged; area under the curve; Article; bronchitis; cholestasis; chronic hepatitis C; clinical article; clinical study; combination chemotherapy; concentration response; controlled clinical trial; controlled study; disease severity; double blind procedure; drug absorption; drug distribution; drug efficacy; drug elimination; drug half life; drug metabolism; drug safety; drug screening; drug tolerability; fatigue; female; flu like syndrome; follow up; hematologic disease; human; in vitro study; injection site reaction; kidney disease; male; maximum concentration; open study; patient compliance; phase 1 clinical trial; phase 2 clinical trial; priority journal; randomized controlled trial; relapse; rhabdomyolysis; single drug dose; survival rate; sustained virologic response; time to maximum plasma concentration; treatment duration; treatment failure; upper respiratory tract infection; clinical trial; normal human; treatment outcome, Adult; Antiviral Agents; Double-Blind Method; Healthy Volunteers; Hepatitis C, Chronic; Humans; Male; Treatment Outcome
