Study to Evaluate Safety, Tolerability, PK and PD of DCR-PHXC in PH Type 3 Patients

A Phase 1 Placebo-Controlled, Double-Blind, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Dose of DCR-PHXC in Patients With Primary Hyperoxaluria Type 3

The DCR-PHXC-104 study is designed to assess the safety, tolerability, and pharmacological parameters of a single dose of DCR-PHXC in Primary Hyperoxaluria Type 3 (PH3). Participants should have had at least one stone event within 12 months of screening and intact renal function.

Potential participants are screened over an up-to-35-day period (with an extra 7-day period for participants who are required to repeat screening 24-hour urine collections or initially unanalyzable screening laboratory assessment samples) prior to randomization. Eligible participants will receive a single dose of DCR-PHXC or placebo on Day 1.

In order to maintain the treatment blind, 24-hour urine oxalate (Uox) results that could unblind the study will not be reported to investigative sites or other blinded personnel until the study has been unblinded.

It is expected that approximately 10 participants will be screened in order to randomize 6 participants (2:1 randomization; 4 nedosiran:2 placebo) to the study.

Following the up-to-6-week screening period, participants will return to the clinic for interim visits up to Day 85. Visits occurring between the Day 1 and the Day 85 visit may be conducted as at-home telemedicine visits at the discretion of the Investigator. The total time on study for each participant is approximately 18 weeks.

Key Inclusion Criteria:

• Genetically confirmed PH3

• 24-hour Uox excretion ≥ 0.7 mmol (adjusted per 1.73 m^2 body surface area [BSA] in participants < 18 years of age) on both assessments conducted in the screening period

• Less than 20% variation between the two 24-hour urinary creatinine excretion values (mmol/kg/24 hours) in the screening period

• Estimated glomerular filtration rate (eGFR) at screening ≥ 30 mL/min, normalized to 1.73 m^2 BSA

• History of at least one stone event within the last 12 months. Stone events are defined as any of the following:

  • renal stone requiring medical intervention, e.g., outpatient procedures such as lithotripsy, or hospitalization or inpatient surgical intervention for confirmed stone-related pain and/or complications;
  • stone passage with or without hematuria; or
  • renal colic requiring medication.

Key Exclusion Criteria:

• Documented evidence of clinical manifestations of systemic oxalosis (including pre-existing retinal, heart, or skin calcifications, or history of severe bone pain, pathological fractures, or bone deformations)
• Plasma oxalate > 30 μmol/L