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

Phase 1

Completed

• Conditions: Primary Hyperoxaluria
• Interventions: Drug: DCR-PHXC; Drug: Placebo

• Registration Number: NCT03392896
• Lead Sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2017-12-06
• Study First Submitted: 2017-12-21
• Study First Submitted QC: 2018-01-02
• Study First Posted: 2018-01-08
• Primary Completion: 2019-11-19
• Study Completion: 2019-11-19
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-10
• Last Update Posted: 2024-07-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 43

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A Active (DCR-PHXC)	DCR-PHXC	HVs, single ascending doses of DCR-PHXC.
Group A Placebo	Placebo	HVs, normal saline 0.9% injection to match active doses.
Group B Active (DCR-PHXC)	DCR-PHXC	PH1 and PH2 patients, open label, single ascending doses of DCR-PHXC.

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (7)

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States

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

Universitätsklinikum Bonn-Institut für Klinische Chemie und Klinische Pharmakologie; 🇩🇪 Bonn, Germany

University of Amsterdam; 🇳🇱 Amsterdam, Netherlands

Queen Elizabeth Hospital Birmingham; 🇬🇧 Birmingham, United Kingdom

Birmingham Children's Hospital NHS Trust; 🇬🇧 Birmingham, United Kingdom

Clinical Trial Site; 🇬🇧 Wales, United Kingdom