Gane 2010

Methods	Randomised clinical trial
Participants	71 participants Sex: 54 men, 17 women Mean age: 47.6 years Inclusion criteria: treatment‐naive and treatment‐experienced adults aged 18–65 years, who were chronically infected with HCV genotype 1 but did not have cirrhosis, and who had a minimum HCV RNA of 10⁵ IU/mL. Participants were required to have normal renal and hepatic function and no clinically significant comorbidities. Exclusion criteria: co‐infection with hepatitis B or HIV, concurrent medical or psychiatric disorder (or history of such), history of any neoplastic disease, history of clinically significant cardiovascular or cerebrovascular disease, use of growth factors, or anticipated use or need for significant concomitant medical treatment.
Interventions	Experimental group: Arm B: 500 mg RG7128 twice daily and 100 mg danoprevir every 8 h (treatment‐naive) Arm C1: 500 mg RG7128 twice daily and 200 mg danoprevir every 8 h (treatment‐naive) Arm C2 1000 mg RG7128 twice daily and 100 mg danoprevir every 8 h (treatment‐naive) Arm D: 1000 mg RG7128 twice daily and 200 mg danoprevir every 8 h (treatment‐naive) Arm E: 1000 mg RG7128 twice daily and 600 mg danoprevir twice a day (non‐null responders) Arm F: 1000 mg RG7128 twice daily and 900 mg danoprevir twice a day (null responders) Arm G: 1000 mg RG7128 twice daily and 900 mg danoprevir twice a day (treatment‐naive) Control group: placebo RG7128 and Placebo Danoprevir Co‐intervention: standard of care treatment (180 μg/week peg‐IFN α‐2a, and RBV at 1000 mg/day for participants weighing < 75 kg or 1200 mg/day for those weighing ≥ 75 kg)
Outcomes	Safety, pharmacokinetics, antiviral activity
Notes	We emailed Gane and colleagues on 06 June 2016 for additional information on SVR24 but reply not received yet.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The random allocation sequence was computer‐generated
Allocation concealment (selection bias)	Low risk	Randomly assigned by interactive voice or web response system to active treatment or placebo
Blinding of participants and personnel (performance bias) All outcomes	High risk	Investigators, personnel at the study centre, and participants were masked to treatment allocation. Study drugs and placebo were identical in colour, size, shape, and taste but "(...) apart from patients in cohort F, who were unmasked after the last assessment was completed"
Blinding of outcome assessment (detection bias) All outcomes	High risk	The pharmacist who prepared the doses, personnel involved in pharmacokinetic sample analyses, statisticians who prepared data summaries, and the clinical pharmacologists who reviewed the data before deciding to initiate dosing in the next cohort were not masked to treatment allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	There was under 5% dropouts (only 2 dropouts)
Selective reporting (reporting bias)	Low risk	The outcomes stated in the protocol were reported on (NCT00801255)
Vested‐interest bias	High risk	The trial was funded by a company that might have an interest in a given result (Hoffmann‐La Roche)
Other bias	Low risk	The trial appeared to be free of other components that could put it at risk of bias