Study for patients with Primary Hyperoxaluria to evaluate the Long-Term Safety and Efficacy of DCR-PHXC Solution for Injectio
- Conditions
- Primary HyperoxaluriaMedDRA version: 20.1Level: PTClassification code: 10020703Term: Hyperoxaluria Class: 100000004857Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- CTIS2024-512260-54-00
- Lead Sponsor
- Dicerna Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 68
Participants starting at birth are eligible for this study, Documented diagnosis of PH, confirmed by genotyping (historically available genotype information is acceptable for study eligibility), Participant successfully completed a Dicerna Pharmaceuticals, Inc. study of DCR PHXC, or is the sibling of a participant who either successfully completed a Dicerna Pharmaceuticals, Inc. study of DCR PHXC or completed 24 weeks of participation in Study DCR-PHXC-204. a. For participants rolling over from a multidose study of DCR-PHXC, enrollment should occur within a window of 25 to 75 days from the last dose of study intervention. In order to minimize any gap in administration of DCR-PHXC, every effort should be made to enroll participants as soon as all assessments from the previous study have been completed. It should be noted if the participant was required to repeat the end-of-study (EOS) 24-hour Uox collection for violation of completeness criteria. b. Siblings must i. be younger than 18 years of age ii. meet all other eligibility criteria (including genotyping) iii. have two 24-hour Uox values = 0.7 mmol (adjusted per 1.73 m2 BSA) at Screening OR for siblings aged 0 to 5 years old, average spot Uox-to-creatinine ratio at Screening above 2 times the 95th percentile for age based on Matos et al, 1999: 1. 0.44 mol/mol in participants < 6 months 2. 0.34 mol/mol in participants from 6 months to <12 months 3. 0.26 mol/mol in participants 12 months to < 2 years 4. 0.20 mol/mol in participants from 2 to < 3 years and 5. 0.16 mol/mol in participants from 3 to 5 years iv. Participants who perform 24-hour collections must have less than 20% variation between the two 24-hour urinary creatinine excretion values obtained in the screening period. Individuals who do not achieve < 20% variation between the 2 screening values may undergo a second round of urine collection. An extra 7 calendar days may be added to the screening window for participants to complete a second round of urine collection. Should potential participants again fail to achieve the within- 20% variation, they will be excluded from participation, Estimated GFR at screening = 30 mL/min normalized to 1.73 m2 BSA, calculated using the equations found in Section 8.2.4.1. For infants aged less than 12 months, serum creatinine below the 97.5th percentile of a healthy population (Boer et al., 2010). Note: For participants rolling over from a 6-month multidose study of DCR-PHXC, the eGFR/serum creatinine value from either the Day 150 or Day 180 (EOS) visit may be used for screening., Body weight = 12.75 kg for pediatric siblings, 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 10.4.1), 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 OR A WOCBP who agrees to follow the contraceptive guidance in Section 10.4.2 during the treatment period and for at least 12 weeks after the last dose of study intervention. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clin
Prior renal or hepatic transplantation; or planned transplantation within the study period, Known hypersensitivity to DCR-PHXC or any of its ingredients, In Germany, when deciding whether this study is suitable for a particular patient, the Investigator should consider the availability and appropriateness of lumasiran or other approved treatment options for PH prior to screening patients into this study. Patients who are suitable for and have access to an approved PH1 treatment should be excluded from the study. If the eGFR value for a participant declines to < 30 mL/min/1.73m2, the Investigator should contact the Medical Monitor for advice regarding study intervention, Inability or unwillingness to comply with the specified study procedures, including collection of 24-hour urine samples, and the lifestyle considerations detailed in Section 5.3, Currently receiving dialysis, 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), Use of an RNAi drug (other than DCR-PHXC) within the last 6 months, 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 aminotransferase [ALT] or aspartate aminotransferase [AST] > 3 × 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, Participants receiving pyridoxine (vitamin B6) must have been at a stable dose for at least 4 weeks prior to Day 1 and must be willing to remain on the same stable dose throughout the study, Participation in any clinical study in which they received an investigational medicinal product (IMP) other than DCR-PHXC within 4 months or 5 times the half-life of the drug (whichever is longer) before Screening. a. For IMPs (other than DCR-PHXC) with the potential to reduce urine and/or plasma oxalate concentrations, these concentrations must have returned to historical baseline levels prior to Screening, Plasma oxalate > 30 µmol/L Note: For participants = 18 years of age rolling over from a 6-month multidose study of DCR-PHXC, the plasma oxalate value from either the Day 150 or Day 180 (EOS) visit may be used for screening. If the previous study is blinded at the time of entry in DCR-PHXC-301, plasma oxalate values will be reviewed by the unblinded Medical Monitor. For participants < 18 years of age rolling over from a 6-month multidose study of DCR-PHXC, the plasma oxalate value from Screening in the previous study will be used
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method