Natural History of Patients With PH3 and a History of Stone Events

The relationship between the level of Uox and the incidence of kidney stones and/or nephrocalcinosis in patients with PH3 has not been established. The goal of this study is to record 24-hour Uox levels and the incidence of new stone formation and/or the degree of nephrocalcinosis in patients with PH3 over time.

Potential participants are screened over an up-to-7 week period according to the eligibility criteria and will then be followed every 6 months over an up-to-2-year period to determine the annualized new stone formation rate (number of new stones being formed per year) and the change in the degree of nephrocalcinosis (if applicable).

New stone formation is defined as occurrence of any of the following:

• Spontaneous stone passage in the absence of pre-existing stones
• Stone passage occurring without change in the number of pre-existing stones detected by renal ultrasound
• Appearance of new stones on renal ultrasound or 100% or more growth of a pre-existing stone (estimated area)
• Surgical removal of newly formed stones Note: Spontaneous passage or surgical removal of pre-existing stones does not meet the criteria for new stone formation.

This is a non-interventional study that will last up to 2 years.

Key inclusion criteria

• Genetically confirmed PH3
• For participants at least 2 years of age, history of stone events (defined as presence of calcifications in the urinary tract and/or kidney, their relative location, and the number and size of stones) during the last 3 years and/or presence of pre-existing stones detected by renal ultrasound at Screening
• Uox ≥ 0.7 mmol/24 hours (adjusted per 1.73 m2 BSA in participants < 18 years of age) OR if not able to collect 24-hour urine, average spot Uox to creatinine ratio at Screening above the 95th percentile for age:

• > 220 mmol/mol in participants < 6 months
• > 170 mmol/mol in participants from 6 months to < 12 months
• > 130 mmol/mol in participants 12 months to < 2 years
• > 100 mmol/mol in participants from 2 to < 3 years and
• > 80 mmol/mol in participants from 3 to 5 years
• eGFR at Screening ≥ 30 mL/min or for infants aged less than 12 months, serum creatinine below the 97th percentile of a healthy population

Key Exclusion Criteria:

• Prior or planned liver transplant within study period
• Currently receiving dialysis or anticipating dialysis during study period
• Unwillingness to comply with study procedures