Protocol amendment 1: (UK and EU) Substantial changes made to the protocol were to: limit propylene glycol exposure to within the recommended limits; modify testing requirements for monitoring the liver chemistry test; and add evaluations in the event of a confirmed elevation in ALT or total bilirubin level. (US) In addition to the changes noted for the UK and EU amendment, substantial changes were made to clarify the frequency for the evaluation of MRX plasma levels.

Protocol amendment 2: Substantial changes made to the protocol were to: modify inclusion and exclusion criteria regarding serum bile acid levels, surgical procedures, and prohibited medications; increase the number of evaluable participants; increase the number of clinic visits and duration of treatment from 48 weeks to 72 weeks. A second interim analysis was added when all enrolled subjects reached the 48-week visit.

Protocol amendment 3: Substantial changes made to the protocol were to: add an Optional Follow-up Treatment Period (After Week 72) that allowed eligible participants treated in the LUM001-501 study to continue on treatment after Week 72 until the first of the following occurred: (i) up to 52 weeks of additional treatment (Week 124), or (ii) in the event that a new study opened to enrollment; and added an objective to obtain safety and efficacy data in participants treated long term on MRX including genotyping characteristics

Protocol amendment 4: Substantial changes made to the protocol were to: - allow continued participation in the Optional Follow-Up Treatment Period - clarify that study treatment in the Optional Follow-up Treatment Period could continue until the first of the following occurred: (i) the participants were eligible to enter another MRX study or (ii) MRX was available commercially - clarify that eligible participants who had previously discontinued from the study could re-enter and receive study treatment in the Optional Follow-up Treatment Period (after Week 72) - describe objectives and assessments of the Optional Follow-up Treatment Period, including the following: exploration of a BID dosing regimen and higher daily dosing of MRX; identification of genetic indicators of treatment response, including use of exome sequencing; assessment of AFP levels; assessment of the palatability of the MRX formulation in all patients; addition of an exploratory objective to allow the possibility of analysis of serum markers of treatment response using metabolomic and proteomic analysis on previously collected serum samples. A higher maximum dosing level was selected for the Optional Follow-up Treatment Period because of the findings in healthy volunteers (Study SHP625-101) of higher fecal bile acid (fBA) excretion on higher maralixibat doses and BID dosing regimen up to 100 mg QD and 50 mg BID with a comparable safety profile across the tested dose range. During the BID dosing regimen, the dose was to be taken at least 30 minutes prior to the main morning and evening meal in order to cover the luminal bile acid release associated with meals. Participants with sBA levels above the ULN and/or ItchRO score ≥1.5 were eligible to start BID dosing. If a participant experienced intolerance at any time during the study, the physician Investigator in consultation with the Medical Monitor may have lowered the dose for the remainder of the study.

Protocol amendment 4.1: Substantial changes made to the protocol were to reflect the change of sponsorship from Lumena Pharmaceuticals LLC to Mirum Pharmaceuticals, Inc; document the change in Medical Monitor; and reduce the interval that new medications used to treat pruritus were prohibited to between Baseline until Week 13 (time point for primary analysis).