NEDOSIRAN for Primary hyperoxaluria type 1

Inclusion criteria

• {"criterion_text":"- Four age groups of participants will be enrolled: a. adults and adolescents (aged ≥ 12 years); b. children 6 to 11 years of age c. children 2 to 5 years of age and d. infants and newborns from birth to < 2 years of age.\n- 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.\n- For children younger than 12 years of age, assent will be based on local regulations.\n- Affiliated with or is a beneficiary of a health insurance system (if applicable per national regulations).\n- Documented diagnosis of PH1 confirmed by genotyping (historically available genotype information is acceptable for study eligibility).\n- Estimated GFR at Screening < 30 mL/min normalized to 1.73 m2 BSA. For infants aged less than 12 months, serum creatinine above the 97.5th percentile of a healthy population.\n- Mean of 2 plasma oxalate values > 20 μmol/L during Screening.\n- For participants receiving hemodialysis or peritoneal dialysis, total duration of hemodialysis or peritoneal dialysis must be less than or equal to 24 months and hemodialysis or peritoneal dialysis regimen must have been stable for at least 2 weeks prior to Screening.\n- Male or female.\n- A male participant with a female partner of childbearing potential must agree to use contraception, as detailed in Section 10.5.2, 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.\n- 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 in Section 10.5.2.2 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.\n- 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."}

Exclusion criteria

• {"criterion_text":"- Prior hepatic transplantation; or scheduled transplantation within 6 months of Day 1. Renal transplantation planned in the 6 months from Day 1. Prior renal transplantation is allowed.\n- Inability or unwillingness to comply with the specified study procedures, including the lifestyle considerations detailed in Section 5.3.\n- Documented evidence of clinical manifestations of severe systemic oxalosis (including preexisting retinal, heart, or skin calcifications, or history of severe bone pain, pathological fractures, or bone deformations).\n- Presence of any condition or comorbidities that would interfere with study compliance or data interpretation or potentially impact patient safety.\n- Use of an RNAi drug, other than DCR-PHXC, within the last 6 months.\n- History of one or more of the following reactions to an oligonucleotide-based therapy.\n- 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.\n- Liver function test abnormalities: ALT and/or AST >1.5 × ULN for age and gender.\n- Positive anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibody test at Screening.\n- Known hypersensitivity to DCR-PHXC or any of its ingredients."}

Primary endpoints

• {"endpoint_text":"- The absolute and percent change in Pox from Baseline to Day 180.","definition_or_measurement_approach":"Change in plasma oxalate (Pox) measured as absolute and percent change comparing Baseline Pox to Pox measured on Day 180."}

Secondary endpoints

• {"endpoint_text":"- Absolute and percent change in Pox from Baseline to maximum reduction through Day 180.","definition_or_measurement_approach":"Change in plasma oxalate (Pox) measured as absolute and percent change from Baseline to the timepoint of maximum reduction up to Day 180."}
• {"endpoint_text":"- Change in the hemodialysis or peritoneal dialysis regimen.","definition_or_measurement_approach":"Documented changes to participants' hemodialysis or peritoneal dialysis regimen (e.g., frequency, duration, modality) assessed from Baseline through study visits up to Day 180."}
• {"endpoint_text":"- Change in stone burden identified via ultrasound from Baseline to Day 180.","definition_or_measurement_approach":"Renal stone burden assessed by ultrasound at Baseline and at Day 180; change in stone burden recorded."}
• {"endpoint_text":"- Change in nephrocalcinosis score.","definition_or_measurement_approach":"Nephrocalcinosis scored using the trial-specified nephrocalcinosis scoring method at Baseline and follow-up visits; change recorded (method details in protocol)."}
• {"endpoint_text":"- Change in cardiac oxalosis.","definition_or_measurement_approach":"Assessment of cardiac oxalosis by protocol-specified clinical/imaging assessments; change from Baseline recorded (specific imaging modality/method not detailed in available metadata)."}

Germany

Latest Decision Or Authorization Date

20-02-2026

Number Of Sites

2

Number Of Participants

2

Italy

Latest Decision Or Authorization Date

04-11-2024

Number Of Sites

1

Number Of Participants

2

Spain

Latest Decision Or Authorization Date

20-02-2026

Number Of Sites

1

Number Of Participants

2

Primary sponsor

Full Name

Dicerna Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Premier Research

Responsibilities

Multiple sponsor duties including eTMF and Medical Monitoring (sponsorDuties codes listed in record)

Name

PPD Development LP

Responsibilities

sponsorDuties codes: 4

Name

Icon (Lr) Limited

Responsibilities

sponsorDuties codes: 4

Third parties

• {"country":"United States","full_name":"Premier Research","duties_or_roles":"sponsorDuties codes: 1,10,11,12,2,3,5,6,7; includes: eTMF and Medical Monitoring","organisation_type":"Industry"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Novo Nordisk A/S","duties_or_roles":"sponsorDuties codes: 8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Elligo Health Research Inc.","duties_or_roles":"Patient travel reimbursement","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Centogene GmbH","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"The Doctors Laboratory Limited","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Axolabs GmbH","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon (Lr) Limited","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Cardiabase","duties_or_roles":"ECG analysis and review","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Mde Services Group Limited","duties_or_roles":"Home nursing","organisation_type":"Non-Pharmaceutical company"}