Primary Hyperoxaluria MedDRA version: 20.1 Level: PT Classification code 10020703 Term: Hyperoxaluria System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Sponsors
Dicerna Pharmaceuticals Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, an individual must meet all of the following criteria: Age 1. Four age groups of participants will be enrolled, in sequence: a. adults and adolescents (aged = 12 years; 6 participants) b. children 6 to 11 years of age (2 participants) c. children 2 to 5 years of age (2 participants) and d. infants and newborns from birth to 30 µmol/L 5. For participants receiving hemodialysis or peritoneal dialysis, total duration of hemodialysis or peritoneal dialysis must be less than 18 months. Sex 6. Male or female Male participants: A male participant with a female partner of childbearing potential must agree to use contraception, as detailed in Section 10.4.2, during the treatment period and for at least 12 weeks after the last dose of study intervention and refrain from donating sperm during this period. Female participants: A female participant is eligible to participate if she is not pregnant (see Section 10.4.3), not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) as defined in Section 10.4.1.1. OR A WOCBP who agrees to follow the contraceptive guidance in Section 10.4.2.2 for the 4 weeks prior to randomization, during the treatment period, and for at least 12 weeks after the last dose of study intervention and agrees to refrain from harvesting/freezing eggs during this period. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Informed Consent/Assent 7. Participant (and/or participant’s parent or legal guardian if participant is a minor [defined as patient =65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: An individual who meets any of the following criteria will be excluded from participation in this study: Medical Conditions 1. Prior hepatic transplantation; or scheduled transplantation within 6 months of Day 1. Prior renal transplantation is allowed. 2. Documented evidence of severe systemic oxalosis, defined as overt signs of bone oxalate deposition in a plain x-ray of the left hand, as evidenced by large diffuse metaphyseal bands 3. 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 (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) Prior/Concomitant Therapy 4. Routine or chronic use of more than 3 grams of acetaminophen/paracetamol daily 5. Use of an RNAi drug, other than DCR-PHXC, within the last 6 months 6. 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 7. Participation in any clinical study in which they received an investigational medicinal product (IMP) other than DCR-PHXC within 4 months before Screening. Diagnostic Assessments 8. Liver function test abnormalities: ALT and/or AST >1.5 × ULN for age and gender 9. Positive anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibody test at Screening Other Exclusions 10. Known hypersensitivity to DCR-PHXC or any of its ingredients 11. 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 characterize the safety of DCR-PHXC in participants with PH1 or PH2 and severe renal impairment, with or without hemodialysis or peritoneal dialysis;Secondary Objective: 1. To assess the efficacy of DCR-PHXC in lowering Pox in participants with PH1 or PH2 and severe renal impairment, with or without hemodialysis or peritoneal dialysis 2. To assess the multiple dose PK of DCR-PHXC and its metabolites in participants with PH1 or PH2 and severe renal impairment, with or without hemodialysis or peritoneal dialysis 3. To assess the effect of DCR-PHXC on the hemodialysis or peritoneal dialysis regimen of participants with PH1 or PH2 undergoing hemodialysis or peritoneal dialysis ;Primary end point(s): Incidence and severity of TEAEs and SAEs, and the change from Baseline in 12-lead ECG, physical examination findings, vital signs, and clinical laboratory tests;Timepoint(s) of evaluation of this end point: The primary endpoint is safety and will be evaluated during the whole study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change from Baseline in Pox 2. Plasma PK parameters for DCR-PHXC and its metabolites (e.g., Cmax and AUC, based on NCA or POP-PK analysis) 3. The change in the duration and number of weekly hemodialysis or peritoneal dialysis sessions from Baseline to Month 12 and quarterly thereafter in the long-term extension;Timepoint(s) of evaluation of this end point: The secondary endpoints evaluation will be based on: - Change in Pox from Baseline to Day 180 - Change in the duration and number of weekly hemodialysis or peritoneal dialysis sessions | — |
Countries
Australia, France, Germany, Italy, Japan, Romania, Spain, United Kingdom, United States
Contacts
Public ContactRalf Rosskamp
Dicerna Pharmaceuticals Inc
Outcome results
None listed