Primary Hyperoxaluria Type 3 MedDRA version: 20.1 Level: PT Classification code 10020703 Term: Hyperoxaluria System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Name: DCR-PHXC
Pharmaceutical Form: Solution for injection
INN or Proposed INN: nedosiran
CAS Number: 2247026-22-6
Current Sponsor code: DCR-PHXC
Other descriptive name: DCR-L1360
Concentratio
Sponsors
Dicerna Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age 1. At least 6 years of age at the time of signing the informed consent/assent Type of Participant and Disease Characteristics 2. Documented diagnosis of PH3, confirmed by genotyping (historically available genotype information is acceptable for study eligibility) 3. 24-hour Uox excretion = 0.7 mmol (adjusted per 1.73 m2 BSA in participants =65 years) yes F.1.3.1 Number of subjec
Exclusion criteria
Exclusion criteria: Medical Conditions 1. Prior renal or hepatic transplantation; or planned transplantation within the study period 2. Currently receiving dialysis or anticipating requirement for dialysis during the study period 3. Plasma oxalate > 30 µmol/L 4. Documented evidence of clinical manifestations of systemic oxalosis (including pre-existing retinal, heart, or skin calcifications, or history of severe bone pain, pathological fractures, or bone deformations) 5. Presence of any condition or comorbidities that would interfere with study compliance or data interpretation or potentially impact patient safety including, but not restricted to: a. Severe intercurrent illness b. Known causes of active liver disease/injury or transaminase elevation (e.g., alcoholic liver disease, nonalcoholic fatty liver disease/steatohepatitis) c. Physician concerns about intake of drugs of abuse or excessive alcohol intake, or history of excessive alcohol intake in the 2 years prior to enrollment (defined as = 21 units of alcohol per week in men and = 14 units of alcohol per week in women; where a “unit” of alcohol is equivalent to a 12-ounce beer, 4-ounce glass of wine, or 1 ounce shot of hard liquor) d. history of serious mental illness that includes, but is not limited to, schizophrenia, bipolar disorder, or severe depression requiring hospitalization or pharmacological intervention e. clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, hematological, lymphatic, neurological, musculoskeletal, genitourinary, immunological diseases, including dermatological including rash, severe eczema or dermatitis, or connective tissue diseases or disorders Prior/Concomitant Therapy 6. Use of an RNAi drug within the last 6 months 7. History of one or more of the following reactions to an oligonucleotide-based therapy: a. Severe thrombocytopenia (platelet count = 100,000/µL) b. Hepatotoxicity, defined as alanine transaminase (ALT) or aspartate transaminase (AST) > 3 times the upper limit of normal (ULN) and total bilirubin > 2 × ULN or international normalized ratio (INR) >1.5 c. Severe flu-like symptoms leading to discontinuation of therapy d. Localized skin reaction from the injection (graded severe) leading to discontinuation of therapy e. Coagulopathy/clinically significant prolongation of clotting time Prior/Concurrent Clinical Study Experience 8. Participation in any clinical study in which they received an investigational medicinal product (IMP) within 4 months or 5 times the half-life of the drug (whichever is longer) before Screening Diagnostic Assessments 9. Liver function test abnormalities: ALT and/or AST >1.5 × ULN for age and gender 10. Positive screening for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibodies, or anti-human immunodeficiency virus (HIV) 1 and 2 antibodies. If participant has been tested in the past 3 months, medical record documentation of this testing can be used for screening. 11. Positive anti-dsDNA test at Screening Other Exclusions 12. Known hypersensitivity to DCR-PHXC or any of its ingredients 13. Inability or unwillingness to comply with the specified study procedures, including the lifestyle considerations detailed in Section 5.3.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of a single dose of DCR-PHXC in patients with PH3;Secondary Objective: 1. To characterize the plasma PK of a single dose of DCR-PHXC in patients with PH3 2. To assess the efficacy of a single dose of DCR PHXC in reducing oxalate burden in patients with PH3;Primary end point(s): • Incidence and severity of treatment-emergent AEs, SAEs, and AESI • Changes from baseline in clinical laboratory test results, including hematology, serum chemistry, and urinalysis • Changes from baseline in vital signs measurements • Changes from baseline in 12-lead ECG findings • Incidence and nature of treatment-emergent clinically significant physical examination findings;Timepoint(s) of evaluation of this end point: All the primary end points will be evaluated from baseline to end of study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Plasma PK parameters of DCR-PHXC and its metabolites, including Cmax, AUC(0-t), and AUC(0-inf), if estimable 2. The proportion of participants achieving a > 30% decrease from baseline in 24-hour Uox on 2 consecutive visits;Timepoint(s) of evaluation of this end point: 1. Plasma PK parameters will be evaluated until Day 29. 2. Decrease in 24-hour Uox will be evaluated from Baseline until End of Study. | — |
Countries
France, Germany, Netherlands, United Kingdom, United States
Contacts
Public ContactKerry Russell
Dicerna Pharmaceuticals, Inc.
Outcome results
None listed