A Study To Evaluate The Safety And Effectiveness Of DCR-PHXC To Treat Patients With Primary Hyperoxaluria Type 1 Or 2 And Severe Renal Impairment

Overview

About this study

The purpose of this study is to evaluate DCR-PHXC in patients with primary hyperoxaluria type 1 (PH1) and severe renal impairment, with or without dialysis.

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Adults and adolescents (aged ≥ 12 years; 6 participants).
  • Children 6 to 11 years of age (2 participants).
  • Children 2 to 5 years of age (2 participants).
  • Infants and newborns from birth to < 2 years of age (2 participants).
  • Documented diagnosis of PH1 or PH2, confirmed by genotyping (historically available genotype information is acceptable for study eligibility).
  • Estimated GFR at Screening < 30 mL/min normalized to 1.73 m^2 BSA. For infants aged less than 12 months, serum creatinine above the 97th percentile of a healthy population (Boer et al., 2010).
  • Plasma oxalate > 30 μmol/L.
  • For participants receiving hemodialysis or peritoneal dialysis, total duration of hemodialysis or peritoneal dialysis must be less than 18 months.
  • Male or female.
  • Male participants:
    • 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.
  • Female participants:
    • 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); OR
      • A WOCBP who agrees to follow the contraceptive guidance 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.
  • 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: 
    • 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 hepatic transplantation; or scheduled transplantation within 6 months of Day 1. Prior renal transplantation is allowed.
  • 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.
  • Presence of anycondition or comorbidities that would interferewith 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 (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 ≥ 21units 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).
  • Routine or chronic use of more than 3 grams ofacetaminophen/paracetamol daily.
  • Use of an RNAidrug,other than DCR-PHXC,within the last 6 months.
  • History of one or more of the following reactions to an oligonucleotide-basedtherapy:
    • Severe thrombocytopenia (platelet count ≤ 100,000/μL);
    • Hepatotoxicity, defined asalanine transaminase (ALT) or aspartate transaminase (AST) > 3 times the upper limit of normal (ULN)andtotal 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)other than DCR-PHXCwithin 4months before Screening.
  • Liver function test abnormalities: ALT and/or AST >1.5 × ULNfor age and gender.
  • Positive anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibody testat 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.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

John Lieske, M.D.

Closed for enrollment

Contact information:

Leah Knoke

(800) 270-4637

knoke.leah@mayo.edu

More information

Publications

Publications are currently not available