Clinical Trials

Inclusion Criteria:

• At least 6 years of age at the time of signing the informed consent/assent.
• Documented diagnosis of PH3, confirmed by genotyping (historically available genotype information is acceptable for study eligibility).
• 24-hour Uox excretion ≥ 0.7 mmol (adjusted per 1.73 m^2 BSA in participants < 18 years of age) in both collections performed in the screening period.
• Less than 20% variation between the two 24-hour urinary creatinine measurements 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 (Chronic Kidney Disease Epidemiology Collaboration) formula in participants aged ≥ 18 years (Levey & Stevens, 2010) or the multivariate formula by Schwartz in participants aged 6 to 17 years (Schwartz et al., 2012).
• History of at least one stone event within the last 12 months. Stone events are defined as any of the following:
  • Renal stone requiring medical intervention; e.g., outpatient procedures such as lithotripsy, or hospitalization or inpatient surgical intervention for confirmed stone-related pain and/or complications;
  • Stone passage with or without hematuria;
  • Renal colic requiring medication.
• 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, not breastfeeding, and at least 1 of the following conditions applies:
      • Not a woman of childbearing potential (WOCBP);
      • A WOCBP who agrees to follow the contraceptive guidance for at least 12 weeks after the last dose of study intervention.
• 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 or anticipating requirement for dialysis during the study period.
• Plasma oxalate > 30 μmol/L.
• 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).
• 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:
  • Severe intercurrent illness;
  • Known causes of active liver disease/injury or transaminase elevation (e.g., alcoholic liver disease, nonalcoholic fatty liver disease/steatohepatitis);
  • 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);
  • History of serious mental illness that includes, but is not limited to, schizophrenia, bipolar disorder, or severe depression requiring hospitalization or pharmacological intervention;
  • 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.
• Routine or chronic use of more than 3 grams of acetaminophen/paracetamol daily
• Use of an RNAi drug within the last 6 months
• 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 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;
  • 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.
• Participation in any clinical study in which they received an investigational medicinal product (IMP) within 4 months before Screening.
• Liver function test abnormalities: ALT and/or AST >1.5 × ULN for age and gender.
• 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.
• Positive urine drug screen (to include at minimum: amphetamines, barbiturates, cocaine, opiates, and benzodiazepines). Urine drug screening is not required for participants ≤ 12 years of age. Exclusion for a positive test is at the Investigator’s discretion.
• Positive anti-dsDNA test at Screening.
• Known hypersensitivity to DCR-PHXC or any of its ingredients.
• Inability or unwillingness to comply with the specified study procedures, including the lifestyle considerations.