Nedosiran in Pediatric Patients From Birth to 11 Years of Age With PH and Relatively Intact Renal Function

NCT05001269 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: DCR-PHXC-203
• Study Type: interventional
• Target: 27
• Locations: 11 countries
• Sites: 13

Brief Summary

The aim of this study is to evaluate nedosiran in participants 11 years of age and younger who have Primary Hyperoxaluria with relatively intact renal function.

Conditions

Primary Hyperoxaluria; Primary Hyperoxaluria Type 1; Primary Hyperoxaluria Type 2; Primary Hyperoxaluria Type 3

Keywords

PH1; PH2; PH3; pediatric

Outcome Measures

Primary Outcomes (2)

• Percent Change From Baseline to Month 6 in Spot Urinary Oxalate-to-creatinine Ratio in PH1, PH2, or PH3 Participant Subgroups

  This outcome measure reported percent change from baseline to Month 6 in spot urinary oxalate-to-creatinine ratio in pediatric participants (birth to 11 years of age) with genetically confirmed primary hyperoxaluria type 1 (PH1), primary hyperoxaluria type 2 (PH2), or primary hyperoxaluria type 3 (PH3) subgroups.

  Baseline (Week 0), Month 6

• Absolute Change From Baseline to Month 6 in Spot Urinary Oxalate-to-creatinine Ratio in PH1, PH2, or PH3 Participant Subgroups

  This outcome measure reported absolute change from baseline to Month 6 in spot urinary oxalate-to-creatinine ratio in pediatric participants (birth to 11 years of age) with genetically confirmed PH1, PH2, or PH3 subgroups.

  Baseline (Week 0), Month 6

Secondary Outcomes (58)

• Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  From baseline (Week 0) up to Month 6

• Number of Treatment Emergent Adverse Events and Serious Adverse Events-Nature

  From baseline (Week 0) up to Month 6

• Change From Baseline in 12-lead Electrocardiogram (ECG)- ECG Mean Heart Rate

  Baseline (Week 0), Month 6

• Change From Baseline in 12-lead ECG- RR Interval

  Baseline (Week 0), Month 6

• Change From Baseline in 12-lead ECG-PR Interval, Aggregate

  Baseline (Week 0), Month 6

Study Arms (1)

Open-Label DCR-PHXC

EXPERIMENTAL

Open-Label monthly subcutaneous injection of DCR-PHXC based on age and weight.

Drug: nedosiran

Interventions

nedosiran DRUG

Monthly subcutaneous dosing throughout study period

Also known as: DCR-PHXC

Open-Label DCR-PHXC

Eligibility Criteria

• Age: Up to 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Birth to 11 years of age inclusive, at the time of signing the informed consent.
• Documented diagnosis of PH1 or PH2 or PH3 confirmed by genotyping (historically available genotype information is acceptable for study eligibility).
• Average spot Uox to creatinine ratio at Screening above 2 times the 95th percentile for age (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
• \> 0.16 mol/mol in participants from 3 to \< 5 years \> 0.14 mol/mol in participants from 5 to \<7 years \> 0.12 mol/mol in participants from 7 to 11 years
• Estimated GFR at Screening ≥ 30 mL/min normalized to 1.73 m2 BSA. See Section 8.2.6.1 for equations. For infants aged less than 12 months, serum creatinine below the 97th percentile of a healthy population (Boer et al., 2010).
• Participants must have been on a stable treatment regimen for PH for 3 months prior to Day 1 and parent(s)/legal guardian should be willing to ensure participant remains on the same stable treatment regimen during the study. Dose adjustments for interval weight gain are acceptable.
• Male or Female
• Male participants:
• A male participant with a female partner of childbearing potential must agree to use contraception, as detailed in Section 10.5.2, 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.
• Female participants:
• A female participant is eligible to participate if she is not pregnant (see Section 10.5.1), not breastfeeding, and at least 1 of the following conditions applies:

You may not qualify if:

• 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 (Pox) \> 30 μmol/L at Screening
• 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)
• Presence of any condition or comorbidities that would interfere with study compliance or data interpretation or potentially impact participant's 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 \[NAFLD/NASH\])
• 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
• Use of an RNAi drug within the last 6 months
• History of 1 or more of the following reactions to an oligonucleotide-based therapy:
• Severe thrombocytopenia (platelet count ≤ 100,000/µL)
• Hepatotoxicity, defined as ALT or AST \> 3 times the upper ULN and total bilirubin \> 2 × ULN or 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

Sponsors & Collaborators

• Dicerna Pharmaceuticals, Inc., a Novo Nordisk company: lead

Study Sites (13)

Clinical Research Site

Rochester, Minnesota, 55905, United States

Location

Clinical Research Site

Hamilton, Ontario, L8S 4K1, Canada

Location

Clinical Trial Site

Bonn, 53127, Germany

Location

Clinical Research Site

Heidelberg, 69120, Germany

Location

Clinical Trial Site

Roma, 00165, Italy

Location

Clinical Research Site

Fukuoka, 830-0011, Japan

Location

Clinical Research Site

Nagoya, 467-8602, Japan

Location

Clinical Research Site

Beirut, 1100, Lebanon

Location

Clinical Research Site

Bialystok, 15-274, Poland

Location

Clinical Research Site

Barcelona, 08035, Spain

Location

Clinical Research Site

Yenimahalle, Ankara, 06506, Turkey (Türkiye)

Location

Clinical Trial Site

Dubai, +971, United Arab Emirates

Location

Clinical Trial Site

London, WC1N 3JH, United Kingdom

Location

Related Publications (2)

• Zhang S, Gamallo P, Rawson V. Population Pharmacokinetic and Pharmacodynamic Modelling and Simulation for Nedosiran Clinical Development and Dose Guidance in Pediatric Patients with Primary Hyperoxaluria Type 1. Clin Pharmacokinet. 2025 Sep;64(9):1395-1411. doi: 10.1007/s40262-025-01540-1. Epub 2025 Jul 2.

  PMID: 40601241 DERIVED

• Cox JH, Boily MO, Caron A, Sheng T, Wu J, Ding J, Gaudreault S, Chong O, Surendradoss J, Gomez R, Lester J, Dumais V, Li X, Gumpena R, Hall MD, Waterson AG, Stott G, Flint AJ, Moore WJ, Lowther WT, Knight J, Percival MD, Tong V, Oballa R, Powell DA, King AJ. Characterization of CHK-336, A First-in-Class, Liver-Targeted, Small-Molecule Lactate Dehydrogenase Inhibitor for Hyperoxaluria Treatment. J Am Soc Nephrol. 2025 Apr 7;36(8):1535-1547. doi: 10.1681/ASN.0000000690.

  PMID: 40193200 DERIVED

MeSH Terms

Conditions

Hyperoxaluria, Primary; Primary hyperoxaluria type 1; Primary hyperoxaluria type 2

Interventions

nedosiran

Condition Hierarchy (Ancestors)

Hyperoxaluria; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Clinical Reporting Office (2834)
• Organization: Novo Nordisk A/S

clinicaltrials@novonordisk.com

(+1) 866-867-7178

Study Officials

• Sarb Shergill, PhD

  Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Children 2-11 years of age will begin enrolling prior to the under 2 year old age group's open.

Study Record Dates

• First Submitted: June 30, 2021
• First Posted: August 11, 2021
• Study Start: February 22, 2022
• Primary Completion: February 5, 2025
• Study Completion: February 5, 2025
• Last Updated: April 16, 2026
• Results First Posted: April 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

LE (1); DE (2); JP (2); US (1); ES (1); AE (1); PL (1); GB (1); CA (1); TU (1); IT (1)