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

NCT04555486 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: DCR-PHXC-104
• Study Type: interventional
• Target: 6
• Locations: 4 countries
• Sites: 6

Brief Summary

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.

Conditions

Primary Hyperoxaluria Type 3

Keywords

primary hyperoxaluria; primary hyperoxaluria type 3; primary hyperoxaluria 3; PH; PH type 3; PH3; RNAi; RNAi therapeutic; LDHA; LDH; GalNAc; siRNA; nedosiran; DCR-PHXC

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Plasma pharmacokinetics (PK) of a single dose of DCR-PHXC in PH3 patients

  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

  After screening, 24-hour Uox will be measured at Days 29, 43, 57, and 85.

Study Arms (2)

DCR-PHXC

EXPERIMENTAL

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

Sterile Normal Saline (0.9% NaCl)

PLACEBO COMPARATOR

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)

Interventions

DCR-PHXC DRUG

Intervention, drug, DCR-PHXC

Also known as: Nedosiran

DCR-PHXC

Sterile Normal Saline (0.9% NaCl) DRUG

Placebo comparator

Sterile Normal Saline (0.9% NaCl)

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Genetically confirmed PH3
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Dicerna Pharmaceuticals, Inc., a Novo Nordisk company: lead

Study Sites (6)

Clinical Trial Site

Boston, Massachusetts, 02115, United States

Location

Clinical Trial Site

Rochester, Minnesota, 55905, United States

Location

Clinical Trial Site

New York, New York, 10016, United States

Location

Clinical Trial Site

Bonn, 53127, Germany

Location

Clinical Trial Site

Amsterdam, 1105 AZ, Netherlands

Location

Clinical Trial Site

London, NW3 2QG, United Kingdom

Location

MeSH Terms

Conditions

Hyperoxaluria, Primary

Interventions

nedosiran

Condition Hierarchy (Ancestors)

Hyperoxaluria; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Alexandra Haagensen, MD, MBA

  Dicerna Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants are randomly assigned to one of two interventions: the study drug DCR-PHXC (also known as nedosiran) or the placebo comparator Sterile Normal Saline. For every 2 participants that receive DCR-PHXC, 1 participant will receive placebo. Thus, 4 participants are expected to receive DCR-PHXC, and 2 participants are expected to receive placebo.

Study Record Dates

• First Submitted: September 2, 2020
• First Posted: September 18, 2020
• Study Start: September 14, 2020
• Primary Completion: September 7, 2021
• Study Completion: September 7, 2021
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

GB (1); NL (1); DE (1); US (3)