Study of DCR-PHXC-101 in Normal Healthy Volunteers and Patients With Primary Hyperoxaluria

NCT03392896 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: DCR-PHXC-101
• Study Type: interventional
• Target: 43
• Locations: 5 countries
• Sites: 7

Brief Summary

This is a double-blind, placebo-controlled, dose escalation trial of DCR-PHXC in Healthy Volunteers (HVs) and patients with Primary Hyperoxaluria (PH). Once safety has been established in HV, PH patients with a confirmed diagnosis of PH1 and PH2 will be enrolled across multiple dosing cohorts. The study design will allow enrollment of PH patient cohorts at a given dose level once safety has been demonstrated in HV at that dose level. The study will be conducted in two parts: Part A: Single ascending dose (SAD) in HV; Part B: SAD in patients with PH1 and PH2 (lagging Part A by 1 dose level cohort).

Conditions

Primary Hyperoxaluria

Outcome Measures

Primary Outcomes (1)

• Number of patients with Treatment-Related Adverse Events (TEAEs)

  Part A (SAD in HVs) screening through Day 29; Part B (SAD in PH patients) screening through Day 57

Study Arms (3)

Group A Active (DCR-PHXC)

EXPERIMENTAL

HVs, single ascending doses of DCR-PHXC.

Drug: DCR-PHXC

Group A Placebo

PLACEBO COMPARATOR

HVs, normal saline 0.9% injection to match active doses.

Drug: Placebo

Group B Active (DCR-PHXC)

EXPERIMENTAL

PH1 and PH2 patients, open label, single ascending doses of DCR-PHXC.

Drug: DCR-PHXC

Interventions

DCR-PHXC DRUG

DCR-PHXC is a novel, potent, and long-acting small interference ribonucleic acid (siRNA) molecule conjugated to N-acteylgalactosamine (GalNAc) that is designed to decrease liver oxalate production. DCR-PHXC is delivered via subcutaneous (SC) injection.

Group A Active (DCR-PHXC); Group B Active (DCR-PHXC)

Placebo DRUG

Single SC administration of placebo, which will be a sterile, preservative-free normal saline 0.9% solution for SC injection, which is of similar osmolality to the DCR-PHXC formulation.

Group A Placebo

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide informed consent and comply with study requirements.
• Male or female subjects between 18 and 55 years of age, inclusive.
• Subject must have a body mass index (BMI) 19.0 to 32 kg/m2, inclusive.
• Non-smokers, at least 1-month tobacco free, and willing to remain tobacco free through end of study (EOS).
• Women of child bearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception.

You may not qualify if:

• Presence of any medical condition, including but not limited to: Severe intercurrent illness, known causes of active liver disease.
• Routine or chronic use of more than 3 grams of acetaminophen (Tylenol) daily.
• History of kidney stones.
• Use of any investigational agent within 90 days before the first dose of study medication.
• History of donation of more than 450 mL of blood within 90 days prior to dosing in the clinical research center or planned donation less than 30 days after receiving Investigational Medicinal Product (IMP).
• Plasma or platelet donation within 7 days of dosing and through EOS.
• History of reactions to an oligonucleotide-based therapy.
• Males with female partners who are planning to attempt to become pregnant during this study or within 90 days after last dosing of IMP.
• Plasma or platelet donation within 7 days of dosing and through EOS.
• Willing and able to provide informed consent and comply with study requirements.
• Male or female, at least 6 years of age.
• Minimum body weight of 25 kg.
• Genetic confirmation of PH1 and PH2 disease.
• Meet the 24 hour urine oxalate excretion requirements.
• Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2.

Sponsors & Collaborators

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

Study Sites (7)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Centre d'Investigation Clinique - CIC 1407 - Hospices Civils de Lyon

Bron, 69677, France

Location

Universitätsklinikum Bonn-Institut für Klinische Chemie und Klinische Pharmakologie

Bonn, 53127, Germany

Location

University of Amsterdam

Amsterdam, 1012 WX, Netherlands

Location

Queen Elizabeth Hospital Birmingham

Birmingham, B15 2GW, United Kingdom

Location

Birmingham Children's Hospital NHS Trust

Birmingham, B4 6NH, United Kingdom

Location

Clinical Trial Site

Wales, CF484DR, United Kingdom

Location

Related Publications (1)

• Zhang S, Gamallo P, Rawson V. Population Pharmacokinetic and Pharmacodynamic Modelling and Simulation for Nedosiran Clinical Development and Dose Guidance in Pediatric Patients with Primary Hyperoxaluria Type 1. Clin Pharmacokinet. 2025 Sep;64(9):1395-1411. doi: 10.1007/s40262-025-01540-1. Epub 2025 Jul 2.

  PMID: 40601241 DERIVED

MeSH Terms

Conditions

Hyperoxaluria, Primary

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 Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: SAD period in HV is single-blind (unblinded clinical site staff member who is not a member of study team administers dose). SAD period in Group B (PH1 and PH2 patients) is open-label.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two-arm (active and placebo), single-blind, SAD period (Group A, HVs) followed by open-label, SAD period (Group B, PH1 and PH2 patients).

Study Record Dates

• First Submitted: December 21, 2017
• First Posted: January 8, 2018
• Study Start: December 6, 2017
• Primary Completion: November 19, 2019
• Study Completion: November 19, 2019
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

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