The first amendment included change of primary efficacy endpoint SVR24 for ongoing and future SMV Phase 3 trials, to SVR12. Evaluation and updating the sustained virologic response definition and specific toxicities section. Additional tests for the urine dipstick analysis were listed. Upper age limit of 70 years for all participants was added, exclusion criteria 10 was revised. It was clarified that a liver biopsy was the required method for all subjects without a contraindication for this procedure. Clarifications were made to the disallowed concomitant medication section by adjusting the wording. Female subjects of male participants did not have to perform a pregnancy test. In the initial Clinical Trial Protocol HPC3001, it was previously required that female partners performed pregnancy tests regularly. An additional Skindex-16 questionnaire was added at the first unscheduled visit for rash management for subjects who presented with any rash. Comparison of treatments on severity and impact of rash in subjects who experienced rash was a secondary objective instead of an exploratory objective.

In the second amendment CTPA-GEN-II,criterion related to the liver biopsy requirement (inclusion criterion 2) was updated and provided clarification about when and which alternative non-invasive methods were to be used. The definition of viral breakthrough and the on-treatment failure definition were clarified. Removal of erythropoiesis-stimulating agents from the list of disallowed medications to treat treatment-emergent anemia. Reduction in HCV RNA from baseline of <2 log10 IU/mL assessed after Week 12 until Week 24 was considered adequate for the identification of subjects with prior null response. The eligibility cut-off for alpha-fetoprotein (AFP) was increased from 50 to 100 ng/mL. A CT or MRI examination was mandatory for inclusion of cirrhotics with elevated AFP levels. Clarifications in the Pre study and Concomitant Therapy section, the Safety Evaluation section and the Study Medication Withdrawal section. Revision of the overall sampling schedule for pharmacokinetics evaluations following analysis of recent Phase 2 trials. Further recommendations were added related to female partners of male subjects who do not have to perform a pregnancy test because of privacy protection regulations. The Roche Cobas TaqMan HCV Test v2.0, for use with the High Pure System was used as the assay to determine HCV RNA levels. On request of Health Authorities, the key performance characteristics were added and the assay performance and validation documents were added to the reference list. The statistical methods were updated based on Health Authorities feedback regarding the primary endpoint, resulting in an update of the secondary endpoints. In addition, PROs were updated.