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

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).

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Key information

Conditions

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

Age range

6 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

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

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Group A (HVs) Major Inclusion Criteria:

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.

Group A (HVs) Major Exclusion Criteria:

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.

Group B (PH1 and PH2 patients) Major Inclusion Criteria:

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.
If taking Vitamin B6 (pyridoxine), must have been on stable regimen for at least 4 weeks.

Group B (PH1 and PH2 patients) Major Exclusion Criteria:

Prior renal and/or hepatic transplantation.
Currently receiving dialysis.
Participation in any clinical study where they received an investigational agent within 4 months before enrollment.
Presence of any medical condition, including but not limited to: Severe intercurrent illness, known causes of active liver disease.
Liver function test (LFT) abnormalities.
History of reactions to an oligonucleotide-based therapy.

Treatment and study plan

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.

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.

Primary outcomes

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

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

Sponsors and collaborators

Lead sponsor

Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Industry

Registry information

Official study title

A Placebo-Controlled, Single-Blind, Single-Center Phase 1 Study in Normal Healthy Volunteers and Open-Label Multi-Center Study in Patients With Primary Hyperoxaluria to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Doses of DCR-PHXC Solution for Injection (Subcutaneous Use)

Important dates

Study start: 2017
Primary completion: 2019
Study completion: 2019
First posted: Jan 8, 2018
Registry last updated: Sep 19, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed