The Protocol (Protocol Amendment 1, dated 26 September 2016) was revised to Protocol Amendment 2, dated 01 November 2016 in response to a Food and Drug Administration (FDA) request to add measures pertinent to the progressive multifocal encephalopathy (PML) monitoring plan in the trial following review of the PTG-100 Investigational New Drug application. The revisions included: 1. Clarification that a complete neurological examination would be conducted at Screening and subjects with abnormal neurological findings would be excluded. 2. Addition of a phone follow-up 6 months after the end of study treatment to assess signs and symptoms of PML, and incorporation of features to enhance the completeness of follow up. 3. Modification of the protocol’s monitoring program for PML such that it included education of site personnel and subjects about the signs and symptoms of PML and advised subjects to report to designated personnel if they experienced any of these signs or symptoms. Clarification of the conditions in which a neurologist would be consulted for the follow-up PML assessments. 4. Creation of a specific algorithm/action plan for all subjects suspected of having PML and referencing of this plan in the protocol, including details indicating which portions of the algorithm could be conducted by the Investigator or a consulting neurologist, and the conditions whereby a case would be referred to an outside panel of PML experts (with at least one neurologist) for final determination of whether or not the subject had PML. 5. Modification of Appendix D to include both a subjective and objective PML assessment checklist for screening and evaluation of suspected PML, to add further information regarding PML assessment.

The Protocol Amendment 2 was revised to Protocol Amendment 3, dated 16 November 2017 in order to include the following changes: 1. Extension of the Screening window by 1 week, although sites were still encouraged to complete Screening as soon as possible. 2. Allowing for the option to have a combined Screening visit that included endoscopy. 3. Clarification of Inclusion Criteria #5d and addition of #5e, regarding contraception requirements that applied to sexual activity with a non-sterile male partner. 4. Clarification of the Exclusion Criteria #4 for Clostridium difficile to be based on the toxin result and not the PCR result. In addition, clarified that subjects with prior HCV infection who were successfully treated could be enrolled. 5. Clarification added to the synopsis that PD samples were to be collected at selected sites only (in line with the main body of the protocol). 6. Removal of the statement that all visit procedures needed to be performed prior to the final dose on Day 84. 7. Clarification of the resting time needed prior to ECG assessments. 8. Inclusion of a statement to clarify that if there was a delay to the IP shipment for Day 0 dosing, that would not be considered a protocol deviation. 9. Updating of the Sponsor’s Medical Director’s name and title. 10. Clarification that the 6-month phone call could occur before this date if the subject terminated early from the study. 11. Clarification for which subjects would be considered in the Interim Analysis. 12. Removal of references to dipstick in the protocol as all subjects had a macro analysis performed instead. 13. Clarification that subject numbering would be assigned by an Interactive Web Response System and not by the clinical site staff. 14. Inclusion of language to clarify how Mayo scores for rectal bleeding and stool frequency were to be calculated if the Screening visit was combined. 15. Removal of text regarding the addition of an additional dose arm (not tested in Stage 1