Primary Hyperoxaluria
Conditions
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).
Interventions
DRUGDCR-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.
DRUGPlacebo
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.
Sponsors
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, 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.
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).
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
Yes
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
Countries
France, Germany, Netherlands, United Kingdom, United States
Outcome results
None listed