Long Term Extension Study in Patients With Primary Hyperoxaluria

NCT04042402 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: DCR-PHXC-301
• Study Type: interventional
• Target: 75
• Locations: 13 countries
• Sites: 23

Brief Summary

The proposed study is designed to provide patients previously enrolled in Phase 1 and 2 studies of DCR-PHXC and their siblings (\<18 years old) long-term access to DCR-PHXC, and to evaluate the long-term safety and efficacy of DCR-PHXC in patients with PH.

Conditions

Primary Hyperoxaluria Type 1 (PH1); Primary Hyperoxaluria Type 2 (PH2); Kidney Diseases; Urologic Diseases; Genetic Disease; Primary Hyperoxaluria Type 3 (PH3)

Keywords

Primary Hyperoxaluria; PH1; PH2; RNAi; GalNAc; LDHA; LDH; siRNA; PH3

Outcome Measures

Primary Outcomes (1)

• The annual rate of decline in eGFR in participants with PH1

  To evaluate the effect of DCR PHXC on estimated glomerular filtration rate (eGFR) in participants with PH1

  Annual change from baseline

Secondary Outcomes (16)

• The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal 12 lead electrocardiogram (ECG) readings

  TEAEs and SAEs are evaluated monthly for 6 years

• The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal physical examination findings

  TEAEs and SAEs are evaluated monthly for 6 years

• The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal vital signs

  TEAEs and SAEs are evaluated monthly for 6 years

• The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs related to abnormal clinical laboratory tests (hematology, chemistry, coagulation parameters, and urinalysis)

  TEAEs and SAEs are evaluated monthly for 6 years

• To identify the proportion of participants with normalized or near-normalized 24 hour urinary oxalate (Uox)

  24 hour urine collections (if applicable) are performed monthly for 6 months (or quarterly for PH1 multidose rollovers), quarterly for 2 1/2 years (or monthly for PH2/PH3 multidose rollovers until Month 12), and every 6 months for 3 years after that.

Other Outcomes (8)

• To evaluate the effect of DCR PHXC on eGFR in participants with PH2 and PH3

  Annual change from baseline

• To characterize the PK of DCR PHXC in patients with PH by observing minimum concentration (Cmin).

  Participants rolling from a single dose study will be analyzed at Day 1, Day 2, Day 30, Day 31, Day 150, and Day 180; multidose rollovers will just collect Day 1 and 180. Then there will be analyses every 6 months for 2.5 years, and annually for 3 years.

• To characterize the PK of DCR PHXC in patients with PH by observing maximum concentration (Tmax).

  Participants rolling from a single dose study will be analyzed at Day 1, Day 2, Day 30, Day 31, Day 150, and Day 180; multidose rollovers will just collect Day 1 and 180. Then there will be analyses every 6 months for 2.5 years, and annually for 3 years.

Study Arms (1)

Open Label

EXPERIMENTAL

Open label, monthly subcutaneous injection

Drug: DCR-PHXC

Interventions

DCR-PHXC DRUG

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

Also known as: Nedosiran

Open Label

Eligibility Criteria

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

You may qualify if:

• Participant successfully completed a Dicerna Pharmaceuticals, Inc. study of DCR PHXC.
• OR Participant is the sibling of a participant who successfully completed a Dicerna Pharmaceuticals, Inc. study of DCR PHXC. Siblings must be younger than 18 years of age and must have genetically confirmed PH.
• For participants rolling over from a multidose study of DCR-PHXC, enrollment should occur within a window of 25 to 75 days from the last dose of study intervention.
• Estimated GFR at screening ≥ 30 mL/min normalized to 1.73 m2 body surface area (BSA), calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) formula in participants aged ≥ 18 years, or the multivariate equation by Schwartz in participants aged 12 months to 17 years. In Japan, the cystatin C-based Uemura formula will be used for participants aged 12 months to \<2 years, the creatinine-based Uemura formula by will be used for participants aged 2 to 17 years, and the equation by Matsuo will be used in participants aged ≥ 18 years.

You may not qualify if:

• Renal or hepatic transplantation (prior or planned within the study period)
• Plasma oxalate \> 30 µmol/L
• Currently on dialysis
• Documented evidence of clinical manifestations of systemic oxalosis

Sponsors & Collaborators

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

Study Sites (23)

Clinical Research 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 Research Site

Herston, Queensland, 4029, Australia

Location

Clinical Trial Site

Melbourne, 3052, Australia

Location

Clinical Research Site

Hamilton, Ontario, L8S 4K1, Canada

Location

Clinical Trial Site

Bron, 69500, France

Location

Clinical Trial Site

Paris, 75019, France

Location

Clinical Trial Site

Bonn, 53127, Germany

Location

Clinical Trial Site

Heidelberg, 69120, Germany

Location

Clinical Research Site

Roma, 00165, Italy

Location

Clinical Trial Site

Fukuoka, 830-0011, Japan

Location

Clinical Trial Site

Nagoya, 467-8601, Japan

Location

Clinical Trial Site

Tokyo, 183-8561, Japan

Location

Clinical Trial Site

Beirut, Lebanon

Location

Clinical Trial Site

Amsterdam, 1105AZ, Netherlands

Location

Clinical Trial Site

Tromsø, 9019, Norway

Location

Clinical Research Site

Barcelona, 08035, Spain

Location

Clinical Trial Site

Barcelona, 08035, Spain

Location

Clinical Trial Site

Ankara, 06560, Turkey (Türkiye)

Location

Clinical Trial Site

Hampstead, London, United Kingdom

Location

Clinical Trial Site

Birmingham, 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

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

Study Officials

• Verity Rawson, MB.CHB

  Dicerna, A Novo Nordisk Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2019
• First Posted: August 2, 2019
• Study Start: July 9, 2019
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2030
• Last Updated: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); JP (3); DE (2); NO (1); LE (1); NL (1); TU (1); AU (2); ES (2); CA (1); FR (2); IT (1); US (4)