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

• ClinicalTrials.gov Identifier: NCT03392896
• Recruitment Status: Completed
• First Posted: January 8, 2018
• Last Update Posted: January 22, 2020
• Sponsor: Dicerna Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Dicerna Pharmaceuticals, Inc.

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Primary Hyperoxaluria	Drug: DCR-PHXC; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Two-arm (active and placebo), single-blind, SAD period (Group A, HVs) followed by open-label, SAD period (Group B, PH1 and PH2 patients).
• Masking: Double (Participant, Investigator)
• Masking Description: 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.
• Primary Purpose: Treatment
• Official 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)
• Actual Study Start Date: December 6, 2017
• Actual Primary Completion Date: November 19, 2019
• Actual Study Completion Date: November 19, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group A Active (DCR-PHXC); HVs, single ascending doses of DCR-PHXC.	Drug: DCR-PHXC; 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 Comparator: Group A Placebo; HVs, normal saline 0.9% injection to match active doses.	Drug: Placebo; 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.
Experimental: Group B Active (DCR-PHXC); PH1 and PH2 patients, open label, single ascending doses of DCR-PHXC.	Drug: DCR-PHXC; 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.

Outcome Measures

Primary Outcome Measures :

1. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 6 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Massachusetts

Boston Children's Hospital

Boston, Massachusetts, United States, 02115

France

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

Bron, France, 69677

Germany

Universitätsklinikum Bonn-Institut für Klinische Chemie und Klinische Pharmakologie

Bonn, Germany, 53127

Netherlands

University of Amsterdam

Amsterdam, Netherlands, 1012 WX

United Kingdom

Queen Elizabeth Hospital Birmingham

Birmingham, United Kingdom, B15 2GW

Birmingham Children's Hospital NHS Trust

Birmingham, United Kingdom, B4 6NH

Clinical Trial Site

Wales, United Kingdom, CF484DR

Sponsors and Collaborators

Dicerna Pharmaceuticals, Inc.

More Information

• Responsible Party: Dicerna Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03392896
• Other Study ID Numbers: DCR-PHXC-101
• First Posted: January 8, 2018
• Last Update Posted: January 22, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Hyperoxaluria, Primary; Hyperoxaluria; Kidney Diseases; Urologic Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases