Ensayos clínicos

Inclusion Criteria:

• Participant must be at least 6 years of age, at the time of signing the informed consent/assent.
• 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:
  • 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;
  • Siblings must:
  • be younger than 18 years of age;
  • meet all other eligibility criteria (including genotyping) iii. have two 24-hour Uox values ≥ 0.7 mmol (adjusted per 1.73 m^2 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:
  • 0.44 mol/mol in participants < 6 months;
  • 0.34 mol/mol in participants from 6 months to < 12 months;
  • 0.26 mol/mol in participants 12 months to < 2 years;
  • 0.20 mol/mol in participants from 2 to < 3 years; and
  • 016 mol/mol in participants from 3 to 5 years.
• 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 m^2 BSA, calculated using the CKD-EPI equation in participants aged ≥ 18 years (Levey & Stevens, 2010), or the 2012 multivariate equation by Schwartz in participants aged 6 to 17 years (Schwartz et al., 2012). In Japan, the equation by Uemura et al. will be used for participants aged 6 to 17 years and the equation by Matsuo et al. will be used in participants aged ≥ 18 years (Uemura et al., 2014; Matsuo et al., 2009).
  • Note: For participants rolling over from a 6-month multidose study of DCR-PHXC, the eGFR value from either the Day 150 or Day 180 (EOS) visit may be used for screening.
• Body weight ≥ 10.25 kg for participants rolling over from a previous study of DCR-PHXC OR body weight ≥ 12.75 kg for pediatric siblings.
• A male participant with a female partner of childbearing potential must agree to use contraception, 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.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) 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 clinical studies.
• Participant (and/or participant’s parent or legal guardian if participant is a minor [defined as patient < 18 years of age, or younger than the age of majority, according to local regulations]) is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol:
  • Adolescents (12 to < 18 years of age, or older than 12 years but younger than the age of majority, according to local regulations) must be able to provide written assent for participation;
  • For children younger than 12 years of age, assent will be based on local regulations.

Exclusion Criteria:

• Prior renal or hepatic transplantation; or planned transplantation within the study period;
• Currently receiving dialysis.
• Documented evidence of clinical manifestations of systemic oxalosis (including preexisting 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 5. History of one or more of the following reactions to an oligonucleotide-based therapy:
  • severe thrombocytopenia (platelet count ≤ 100,000/µL);
  • 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);
  • severe flu-like symptoms leading to discontinuation of therapy;
  • localized skin reaction from the injection (graded severe) leading to discontinuation of therapy;
  • 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 before Screening:
  • 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.
• Known hypersensitivity to DCR-PHXC or any of its ingredients.
• Inability or unwillingness to comply with the specified study procedures, including collection of 24-hour urine samples, and the lifestyle considerations.

Eligibility last updated 5/4/22. Questions regarding updates should be directed to the study team contact.