Primary Hyperoxaluria Type 1 MedDRA version: 18.0 Level: PT Classification code 10020703 Term: Hyperoxaluria System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Name: DCR-PH1
Pharmaceutical Form: Concentrate for solution for injection
INN or Proposed INN: Not Yet Assigned
CAS Number: NA
C
Sponsors
Dicerna Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, at least 12 years of age at the time of obtaining informed consent. 2. Diagnosis of PH1, confirmed by genotyping for homozygosity or compound heterozygosity in the AGXT gene (historically available genotype information is acceptable for study eligibility). 3. 24-hour urine oxalate excretion = 0.7 mmol per 1.73 m2 BSA. 4. eGFR = 40 mL/min normalized to 1.73 m2 BSA calculated using the Modification of Diet in Renal Disease (MDRD) formula in adults (age = 18 years), or the formula by Schwartz in patients 12 to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Prior renal and/or hepatic transplantation. 2. History of clinical signs and symptoms of systemic oxalosis other than nephrolithiasis or nephrocalcinosis. 3. Participation in any clinical study involving administration of any investigational drug within the 30 days before enrollment (NOTE: participation in PHYOS observational study is allowed). 4. Pregnancy or lactation at the time of screening or enrollment. 5. Sexually active females of childbearing potential (FOCBP) who are not using a highly effective contraception method and men with a fertile FOCBP partner who are unable or unwilling to use a highly effective contraception method (see Section 8.4). 6. Patients with a known history of human immunodeficiency virus (HIV), or active infection with hepatitis B virus or hepatitis C virus. 7. Moderate or severe hepatic impairment (Child-Pugh class B or C) 8. Liver function test abnormalities: alanine transaminase (ALT) and/or aspartate transaminase (AST) > 2 times upper limit of normal (ULN). 9. Active alcohol or substance abuse within 60 days prior to enrollment. 10. Prolonged QTc = 450 msec for males or QTc = 470 msec for females, at baseline as assessed by either Bazett’s or Fredericia’s correction methods. 11. Clinically significant prior cardio-respiratory disease, such as myocardial infarction within 6 months due to obstructive coronary artery disease, third degree atrioventricular block or uncontrolled rhythm disturbances, active cardiomyopathy (i.e., symptomatic left ventricular dysfunction), or chronic heart failure (CHF) New York Heart Association (NYHA) Class =III, or documented moderate or more severe chronic obstructive pulmonary disease (COPD) (ie forced expiratory volume in during the first second [FEV1] < 80% predicted). 12. Major surgery or interventional procedure within 30 days prior to study entry, or patients with an inadequate recovery from any surgical or interventional procedure. 13. History of severe reaction to a liposomal product or a known hypersensitivity to lipid products. For Part B (MAD portion), patients with a Grade 3 or higher adverse reaction during Part A (SAD portion) will not be eligible to participate. 14. Unable to collect 24-hour urine samples or follow other study procedures. 15. Any disorder or alteration in mental status that would preclude understanding of the informed consent process and/or completion of the study-related evaluations. 16. Any significant illness, organ system dysfunction, or other condition that, in the opinion of the Investigator, would interfere with the patient’s ability to comply with the protocol requirements, including the ability to attend all visits and undergo all assessments.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the safety and tolerability of DCR-PH1 administered via IV infusion to patients with PH1.; Secondary Objective: To study the pharmacokinetics of DCR-PH1 To study the pharmacodynamic effects of DCR-PH1 including, but not limited to changes in plasma and urine oxalate and glycolate levels ; Primary end point(s): Safety and tolerability as determined by number of subjects with adverse events ; Timepoint(s) of evaluation of this end point: SAD: Adverse events to be collected from Day 1 through EOS or Day 29 (±1 day). MAD: Adverse events to be collected from Day 1 through EOS or Day 85 (±1 day). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Determination of pharmacokinetics parameters 2) Change in plasma levels from baseline (BL) to each time point of oxalate and glycolate 3) Change in urine levels from baseline (BL) of oxalate, oxalate to creatinine ratio and glycolate ; Timepoint(s) of evaluation of this end point: 1) Plasma samples to be collected: SAD: Before DCR-PH1 administration on Day 1, and at ca. 60 min after the start of infusion, at the end of infusion; at 30, 120, 240, 360 and 480 min after end of infusion; at Days 2, 3, 8 (±1 day), 15 (±1 d), 22 (±1 d), 29 (±1 d) MAD: Before DCR-PH1 administration and at ca. 60 min after the start of infusion, at the end of infusion; at 30, 120, 240, 360 and 480 min after end of infusion on Day 1; on Days 2, 3, 8 (±1 day), 22 (±1 d), 29 (±1 d), 57 (±1 d) 2) Plasma samples to be collected: SAD: Days 1 (BL), 15 (±1 day), 22 (±1 d), 29 (±1 d) MAD: Days 1 (BL), 22(±1 day), 29 (±1 d), 57(±1 d), 85 (±1 d) 3) Urine samples to be collected: SAD: Scr (BL), days 8(±1 day), 15(±1 d), 22 (±1 d) MAD: Scr(BL), days 22(±1 day), 29(±1 d), 57(±1 d), 78(±1 d) | — |
Countries
France, Germany, Israel, Netherlands, United Kingdom, United States
Contacts
Public ContactClinical Operations
Dicerna Pharmaceuticals, Inc.
Outcome results
None listed