TY - JOUR
TI - 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
AU - Deng, Y.
AU - Campbell, F.
AU - Han, K.
AU - Theodore, D.
AU - Deeg, M.
AU - Huang, M.
AU - Hamatake, R.
AU - Lahiri, S.
AU - Chen, S.
AU - Horvath, G.
AU - Manolakopoulos, S.
AU - Dalekos, G.N.
AU - Papatheodoridis, G.
AU - Goulis, I.
AU - Banyai, T.
AU - Jilma, B.
AU - Leivers, M.
JO - Journal of Viral Hepatitis
PY - 2020
VL - 27
TODO - 7
SP - 699-708
PB - Wiley-Blackwell Publishing Ltd
SN - 1352-0504, 1365-2893
TODO - 10.1111/jvh.13282
TODO - 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
TODO - 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
ER -