JUMP‐C 2013

Methods	Phase IIb, randomised, double‐blind, parallel‐group study in treatment‐naive participants with HCV genotype 1 or 4 infection (ClinicalTrials.gov NCT01057667)
Participants	168 participants were randomised Sex: 118 men, 48 women Mean age: experimental group: 49.7 years/control group: 48.2 years Countries: 25 sites in the USA and Canada. Inclusion criteria: eligible participants were treatment‐niıve adults 18‐70 years of age with chronic hepatitis C of at least 6 months’ duration, a serum HCV RNA titer of at least 50,000 IU/mL (COBAS AmpliPrep/ COBAS TaqMan HCV Test; lower limit of detection ¼ 15 IU/mL), and HCV genotype 1 or 4 infection were eligible for the study. Participants were required to have had a liver biopsy within the previous 24 months (36 months in participants with cirrhosis/bridging fibrosis). Participants with compensated cirrhosis (Child‐Pugh grade A) or transition to cirrhosis were required to have had an abdominal ultrasound, computerised tomography scan, magnetic resonance imaging scan demonstrating the absence of evidence of HCC (within 2 months before randomisation), and a serum alpha‐fetoprotein level < 100 ng/mL. Exclusion criteria: infection with hepatitis A or B viruses or HIV; previous treatment with IFN‐based therapy or any investigational anti‐HCV agent; systemic antiviral therapy within the previous 3 months; history or evidence of medical condition associated with chronic liver disease other than HCV; absolute neutrophil count < 1.5 x 109 cells/L; platelet count < 90 x 109 cells/L; haemoglobin concentration < 12 g/dL in women (< 13 g/dL in men); history of renal disease, serum creatinine > 1.5 times the ULN, an estimated creatinine clearance ≤ 70 mL/min or microproteinuria.
Interventions	Participants were randomised in a 1:1 ratio. 166 participants received at least 1 dose. Experimental group: oral mericitabine (Genentech, San Francisco, CA) 1000 mg twice a day for 24 weeks in participants with eRVR (defined as undetectable HCV RNA from week 4 through 22) or for 48 in participants without eRVR. Control group: placebo twice a day. Co‐intervention: peg‐IFN α‐2a (40 kD) (Pegasys; Roche, Basel,Switzerland) 180 lg subcutaneously once‐weekly and oral RBV (Copegus; Roche) at a dosage of 1000 (body weight: < 75 kg) or 1200 mg/day (body weight: > 75 kg) in 2 divided doses for 24 or 48 weeks.
Outcomes	Proportion of participants with undetectable plasma HCV RNA 24 weeks after the end of treatment (SVR24), with SAE, AEs, mortality.
Notes	We emailed Pockros and colleagues on 06 June 2016 for additional information but reply not received yet.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	A computer‐generated randomisation list was maintained by the sponsor, and neither study personnel nor investigators had access to the list
Allocation concealment (selection bias)	Low risk	Participants were randomised by an interactive voice‐response system. A computer‐generated randomisation list was maintained by the sponsor, and neither study personnel nor investigators had access to the list
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Double‐blinding was achieved through the use of matching placebo tablets. Investigators were advised byinteractive voice‐response system at week 24 as to whether a participant was to stop treatment (mericitabine‐treated participants with an eRVR) or continue to week 48 (mericitabine‐treated participants without an eRVR and all placebo‐treated participants). JF: "I guess that all participants were not blinded to maximum‐follow up then? Since it would be obvious that the ones who stopped treatment after 24 weeks, received the study drug?"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	The trial authors reported that only 55 participants in the experimental group completed 24 weeks of follow‐up. It seems like there are 81 participants in the included analysis of SVR24. The trial authors do not account for how they imputed the participants with missing data
Selective reporting (reporting bias)	Low risk	All outcomes in the protocol were reported on
Vested‐interest bias	Unclear risk	This research was funded by F. Hoffmann‐La Roche Ltd.
Other bias	Low risk	The trial appeared to be free of other components that could put it at risk of bias