Safety & Efficacy of DCR-PHXC in Patients With PH1 and ESRD

Safety: Incidence of Events

To assess the efficacy of DCR-PHXC in lowering Pox in participants with PH1 and severe renal impairment, with or without hemodialysis or peritoneal dialysis.

Safety: Incidence of Events

Characterize the safety of DCR-PHXC in participants with PH1 and severe renal impairment, with or without dialysis.

Change from Baseline in Plasma Oxalate Concentration

To evaluate the effect of DCR-PHXC on Plasma Oxalate concentration from Baseline to day 180

To characterize the PK of DCR PHXC in patients with PH by observing secondary parameters of the area under the curve.

Population and individual pharmacokinetic (PK) parameters for DCR PHXC, including secondary parameters of area under the curve (AUC)

To characterize the PK of DCR PHXC in patients with PH by observing maximum observed concentration (Cmax).

Population and individual pharmacokinetic (PK) parameters for DCR PHXC, including maximum observed concentration (Cmax)

To characterize the PK of DCR PHXC in patients with PH by observing minimum concentration (Cmin).

Population and individual pharmacokinetic (PK) parameters for DCR PHXC, including minimum observed concentration (Cmin)

Change from Baseline in the Short Form (36) Health Survey (SF-36®) in adults

To evaluate the effect of DCR-PHXC on Quality of Life (QoL) assessments in patients with PH. The SF 36 is a set of generic, coherent, and easily administered quality-of-life measures that taps 8 health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. It also includes a single item that provides an indication of perceived change in health. The 36 items are identical to the MOS SF 36 described in Ware and Sherbourne (1992). Participants respond to each item on a categorical scale. Categorical answers are transformed to a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. All items are scored so that a high score defines a more favorable health state

Change from Baseline in the EQ-5D-5L™ in adults

To evaluate the effect of DCR-PHXC on Quality of Life (QoL) assessments in patients with PH. The EQ-5D-5L consists of the EQ 5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system has 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The digits for the 5 dimensions can be combined into a 5-digit number that describes the participant's health state. The EQ VAS records the participant's self-rated health on a 20-cm vertical VAS, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine.' Participants are asked to place an "X" on the line that represents their health on that day.

Change from Baseline in the Pediatric Quality of Life Inventory (PedsQL™) in children

To evaluate the effect of DCR-PHXC on Quality of Life (QoL) assessments in patients with PH. The 23-item PedsQL is comprised of 5 items in the Emotional, Social, and School Functioning dimensions (Psychosocial Health) and 8 items in the Physical Functioning (Physical Health) dimension. Items are reverse-scored on a 0 to 4 Likert scale and linearly transformed to a 0 to 100 scale, so that higher scores indicate better functioning and HRQOL. Scale Scores are the sum of the items in each dimension, divided by the number of items answered.

Changes from Baseline number of kidney stones

Evaluate the effect of DCR-PHXC on stone burden in participants with PH1 and severe renal impairment through Kidney Ultrasound