Study to Evaluate Safety, Tolerability, PK and PD of DCR-PHXC in PH Type 3 Patients (PHYOX4)

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.

Study Overview

• Status: Completed
• Conditions: Primary Hyperoxaluria Type 3
• Intervention / Treatment: Drug: DCR-PHXC; Drug: Sterile Normal Saline (0.9% NaCl)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Bonn, Germany, 53127
    • Clinical Trial Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Clinical Trial Site
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • Clinical Trial Site
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Clinical Trial Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Clinical Trial Site
  • New York
    • New York, New York, United States, 10016
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DCR-PHXC; Participants that are at least 12 years old will receive a single dose of 3 mg/kg DCR-PHXC (or nedosiran) via subcutaneous (SC) injection. Participants that are 6-11 years old will receive a single dose of 3.5 mg/kg DCR-PHXC (nedosiran) via SC injection.	Drug: DCR-PHXC; Intervention, drug, DCR-PHXC; Other Names: Nedosiran
Placebo Comparator: Sterile Normal Saline (0.9% NaCl); Participants will receive a single dose of Sterile Normal Saline (0.9% NaCl) for subcutaneous (SC) injection, administered at same injection volume as DCR-PHXC, to serve as placebo.	Drug: Sterile Normal Saline (0.9% NaCl); Placebo comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety profile of a single dose of DCR-PHXC in PH3 Patients	Number of patients with abnormalities in clinically significant laboratory results, vital signs, and 12-lead ECG findings	Screening through Day 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma pharmacokinetics (PK) of a single dose of DCR-PHXC in PH3 patients	Measure maximum plasma concentration of DCR-PHXC	Day 1 (dosing) through Day 29
The proportion of participants achieving a > 30% decrease from baseline in 24-hour Urine Oxalate (Uox) on 2 consecutive visits	Participants must maintain at least a 30% decrease from the average of 2 screening 24-hour Uox values to be considered "responders" to treatment. The proportion of responders to non-responders will be utilize to assess the efficacy of a single dose of DCR-PHXC in PH3 patients.	After screening, 24-hour Uox will be measured at Days 29, 43, 57, and 85.

Collaborators and Investigators

• Sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
• Investigators: Study Director: Alexandra Haagensen, MD, MBA, Dicerna Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2020
• Primary Completion (Actual): September 7, 2021
• Study Completion (Actual): September 7, 2021

Study Registration Dates

• First Submitted: September 2, 2020
• First Submitted That Met QC Criteria: September 14, 2020
• First Posted (Actual): September 18, 2020

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 11, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: RNAi therapeutic; siRNA; PH; RNAi; GalNAc; LDH; primary hyperoxaluria; PH type 3; PH3; primary hyperoxaluria type 3; primary hyperoxaluria 3; LDHA; nedosiran; DCR-PHXC
• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Hyperoxaluria; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hyperoxaluria, Primary
• Other Study ID Numbers: DCR-PHXC-104

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No