A Study to Evaluate DCR-PHXC in Children and Adults With Primary Hyperoxaluria Type 1 and Primary Hyperoxaluria Type 2

NCT03847909 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: DCR-PHXC-201
• Study Type: interventional
• Target: 35
• Locations: 15 countries
• Sites: 28

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of DCR-PHXC in Children and Adults with Primary Hyperoxaluria Type 1 (PH1) and Primary Hyperoxaluria Type 2 (PH2)

Conditions

Primary Hyperoxaluria Type 1 (PH1); Primary Hyperoxaluria Type 2 (PH2); Kidney Diseases; Urologic Diseases; Genetic Disease

Keywords

PH1; PH2; Primary Hyperoxaluria; RNAi; RNAi therapeutic; GalNAc; LDHA gene; LDH; siRNA

Outcome Measures

Primary Outcomes (1)

• AUC From Day 90 To Day 180, Based on Percent Change From Baseline in 24-Hour Uox

  The AUC of 24-hour urinary oxalate (Uox) from Day 90 to Day 180, based on percent change from baseline, was compared between the active treatment group and placebo group. A multiple imputation approach was used to handle missing Uox data and then calculate the AUC.

  From Day 90 to 180

Secondary Outcomes (36)

• Percentage of Participants Whose 24-hour Uox Values Normalized or Near-normalized on at Least 2 Consecutive Visits

  From Day 90 to 180

• Percent Change From Baseline to Day 180 in the Summed Surface Area of Kidney Stones

  Baseline, Day 180

• Percent Change From Baseline to Day 180 in the Number of Kidney Stones

  Baseline, Day 180

• Percent Change From Baseline to Day 180 in Plasma Oxalate (For Adults Only)

  Baseline, Day 180

• Rate of Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Day 180

  Baseline, Day 180

Study Arms (2)

DCR-PHXC

EXPERIMENTAL

Intervention, drug, DCR-PHXC

Drug: DCR-PHXC

Placebo - Sterile Normal Saline (0.9% NaCl)

PLACEBO COMPARATOR

Placebo, sterile normal saline (0.9% NaCl) for subcutaneous (SC) injection

Drug: Sterile Normal Saline (0.9% NaCl)

Interventions

DCR-PHXC DRUG

Multiple fixed doses of DCR-PHXC by subcutaneous (SC) injection

Also known as: nedosiran

DCR-PHXC

Sterile Normal Saline (0.9% NaCl) DRUG

Sterile Normal Saline (0.9% NaCl) for subcutaneous (SC) injection, administered at same injection volume as DCR-PHXC, to serve as placebo

Placebo - Sterile Normal Saline (0.9% NaCl)

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable and willing to provide written informed consent or assent
• Documented diagnosis of PH1 or PH2, confirmed by genotyping
• Must meet the 24 hour urine oxalate excretion requirements
• Less than 20% variation between the two 24-hour urinary creatinine excretion values derived from the two 24-hour urine collections in the screening period
• Estimated GFR at screening ≥ 30 mL/min normalized to 1.73 m2 BSA

You may not qualify if:

• Renal or hepatic transplantation (prior or planned within the study period)
• Currently on dialysis or anticipated 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)
• Use of an RNA interference (RNAi) drug within the last 6 months
• Participation in any clinical study in which you received an investigational medicinal product (IMP) within 4 months before Screening
• Liver function test (LFT) abnormalities: Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>1.5 times upper limit of normal (ULN) for age and gender
• Inability or unwillingness to comply with study procedures

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (28)

Clinical Trial Site

San Francisco, California, 94143, United States

Location

Clinical Trial Site

Boston, Massachusetts, 02115, United States

Location

Clinical Trial Site

Rochester, Minnesota, 55905, United States

Location

Clinical Trial Site

New York, New York, 10016, United States

Location

Clinical Trial Site

Pittsburgh, Pennsylvania, 15224, United States

Location

Clinical Trial Site

Herston, 4029, Australia

Location

Clinical Trial Site

Parkville, 3052, Australia

Location

Clinical Trial Site

Hamilton, Canada

Location

Clinical Trial Site

Bron, France

Location

Clinical Trial Site

Paris, 75019, France

Location

Clinical Trial Site

Bonn, 53127, Germany

Location

Clinical Trial Site

Heidelberg, 69120, Germany

Location

Clinical Trial Site

Jerusalem, 9103102, Israel

Location

Clinical Trial Site

Roma, 00165, Italy

Location

Clinical Trial Site

Nagoya, 467-8601, Japan

Location

Clinical Trial Site

Tochigi, 329-0431, Japan

Location

Clinical Trial Site

Tokyo, 183-8561, Japan

Location

Clinical Trial Site

Beirut, 2807, Lebanon

Location

Clinical Trial Site

Beirut, Lebanon

Location

Clinical Trial Site

Amsterdam, 1105 AZ, Netherlands

Location

Clinical Trial Site

Auckland, New Zealand

Location

Clinical Trial Site

Bialystok, Poland

Location

Clinical Trial Site

Bucharest, Romania

Location

Clinical Trial Site

Barcelona, 08035, Spain

Location

Clinical Trial Site

Santa Cruz, 38320, Spain

Location

Clinical Trial Site

Birmingham, United Kingdom

Location

Clinical Trial Site

London, WCIN 3JH, United Kingdom

Location

Clinical Trial Site

London, United Kingdom

Location

Related Publications (3)

• 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

• Baum MA, Langman C, Cochat P, Lieske JC, Moochhala SH, Hamamoto S, Satoh H, Mourani C, Ariceta G, Torres A, Wolley M, Belostotsky V, Forbes TA, Groothoff J, Hayes W, Tonshoff B, Takayama T, Rosskamp R, Russell K, Zhou J, Amrite A, Hoppe B; PHYOX2 study investigators. PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2. Kidney Int. 2023 Jan;103(1):207-217. doi: 10.1016/j.kint.2022.07.025. Epub 2022 Aug 22.

  PMID: 36007597 DERIVED

MeSH Terms

Conditions

Primary hyperoxaluria type 1; Primary hyperoxaluria type 2; Kidney Diseases; Urologic Diseases; Genetic Diseases, Inborn; Hyperoxaluria, Primary

Interventions

nedosiran

Condition Hierarchy (Ancestors)

Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperoxaluria; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; 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

• Clinical Transparency (dept. 1452)

  Novo Nordisk A/S

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2019
• First Posted: February 20, 2019
• Study Start: October 28, 2019
• Primary Completion: June 21, 2021
• Study Completion: June 29, 2021
• Last Updated: May 22, 2024
• Results First Posted: May 22, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

JP (3); DE (2); CA (1); LE (2); IL (1); IT (1); PL (1); RO (1); US (5); AU (2); NL (1); FR (2); NZ (1); ES (2); GB (3)