Primary HyperoxaluriaPhase 2PHYOX8NCT05001269
Nedosiran in Pediatric Patients From Birth to 11 Years of Age With PH and Relatively Intact Renal Function
A Phase 2 study testing nedosiran in people with Primary Hyperoxaluria and Primary Hyperoxaluria Type 1, run by Dicerna Pharmaceuticals, Inc., a Novo Nordisk company at 13 sites in 11 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 11 years
- Conditions the study is for
- Primary Hyperoxaluria, Primary Hyperoxaluria Type 1, Primary Hyperoxaluria Type 2
- What is being tested?
- nedosiran
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 13 sitesin 11 countries
- Study dates
- 22 Feb 2022to 5 Feb 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 11 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
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- > 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:
- Not a woman of childbearing potential (WOCBP) as defined in Section 10.5.1 OR A WOCBP who agrees to follow the contraceptive guidance in Section 10.5.2 during the treatment period and for at least 12 weeks after the last dose of study intervention.
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Note: If the childbearing potential changes after start of the study (e.g., a premenarchal female participant experiences menarche) or the risk of pregnancy changes (e.g., a female participant who is not heterosexually active becomes active), the participant must discuss this with the Investigator, who should determine if a female participant must begin a highly effective method of contraception or a male participant must use a condom. If reproductive status is questionable, additional evaluation should be considered.
- Participant's parent or legal guardian is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
- For children younger than 12 years of age, assent will be based on local regulation. If assent is required, participant must be able to provide written assent for participation.
- A legal guardian or primary caregiver must be available to help the study-site personnel ensure follow up; accompany the participant to the study site on each assessment day according to the SoA (e.g., able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures); consistently and consecutively be available to provide information on the participant using the rating scales during the scheduled study visits; accurately and reliably dispense study intervention as directed.
- Affiliated with or is a beneficiary of a health insurance system (if applicable per national regulations)
Who cannot join
- 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
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- 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
- Coagulopathy/clinically significant prolongation of clotting time
- Participation in any clinical study in which they received an IMP within 4 months or 5 times the half-life of the drug (whichever is longer) before Screening
- For IMPs with the potential to reduce urine and/or plasma oxalate concentrations, these concentrations must have returned to historical baseline levels prior to Screening
- Liver function test (LFT) abnormalities: ALT and/or AST > 1.5 × ULN for age and gender
- Known hypersensitivity to nedosiran, or any of its ingredients
- Inability or unwillingness to comply with the specified study procedures, including the lifestyle considerations detailed in Section 5.3.
Trial locations and contacts
13 sites in 11 countries.
13 sites in 11 countries
Germany2 sites
Clinical Trial Site
Bonn, 53127
Clinical Research Site
Heidelberg, 69120
Japan2 sites
Clinical Research Site
Fukuoka, 830-0011
Clinical Research Site
Nagoya, 467-8602
Turkey (Türkiye)1 site
Clinical Research Site
Yenimahalle, Ankara, 06506
About this study
Official title: A Phase 2 Open-Label Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Nedosiran in Pediatric Patients From Birth to 11Years of Age With Primary Hyperoxaluria and Relatively Intact Renal Function
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.
Read the detailed description
This is an open-label, repeat-dose, Phase 2 study of nedosiran in participants 11 years of age or younger who have PH1, PH2 or PH 3 and relatively intact renal function.
Following the up-to-35- day screening period, participants will return to the clinic for monthly dosing visits through Day 180.
The total duration of this study is approximately 15 months from first participant, first visit, until last participant, last visit.
- Conditions
- Primary Hyperoxaluria, Primary Hyperoxaluria Type 1, Primary Hyperoxaluria Type 2, Primary Hyperoxaluria Type 3
- Being tested
- nedosiran
- Keywords
- PH1, PH2, PH3, pediatric
- Medical subject headings
- Hyperoxaluria, Primary, Primary hyperoxaluria type 1, Primary hyperoxaluria type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nedosiranDrug
Also called DCR-PHXC
Monthly subcutaneous dosing throughout study period
| Study group | Role | What they receive |
|---|---|---|
| Open-Label DCR-PHXC | Experimental | Open-Label monthly subcutaneous injection of DCR-PHXC based on age and weight. Receives: Drug: nedosiran |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline (Week 0), Month 6
Secondary outcomes (58)
Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
This outcome measure reported number of incidents of TEAEs and SAEs. An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, and medical events. An AE will be defined as treatment emergent if they have an onset or worsen in severity after a participant receives the study intervention.
Measured: From baseline (Week 0) up to Month 6
Number of Treatment Emergent Adverse Events and Serious Adverse Events-Nature
This outcome measure reported nature of TEAEs and SAEs. An AE is any untoward medical occurrence in clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent disability/incapacity, is a congenital anomaly/birth defect, and medical events. An AE is treatment emergent if they have an onset or worsen in severity after a participant receives the study intervention. TEAEs are considered as leading to discontinuation if the action taken is marked as "drug withdrawn" on the case report form. TEAEs of special interest include injection site reactions, muscle pain and weakness, and kidney stone events.
Measured: From baseline (Week 0) up to Month 6
Change From Baseline in 12-lead Electrocardiogram (ECG)- ECG Mean Heart Rate
This outcome measure reported change from baseline to Month 6 in ECG mean heart rate.
Measured: Baseline (Week 0), Month 6
Change From Baseline in 12-lead ECG- RR Interval
This outcome measure reported change from baseline to Month 6 in RR Interval.
Measured: Baseline (Week 0), Month 6
Change From Baseline in 12-lead ECG-PR Interval, Aggregate
This outcome measure reported change from baseline to Month 6 in aggregate PR Interval.
Measured: Baseline (Week 0), Month 6
Change From Baseline in 12-lead ECG-QRS Duration, Aggregate
This outcome measure reported change from baseline to Month 6 in aggregate QRS Interval.
Measured: Baseline (Week 0), Month 6
Change From Baseline in 12-lead ECG-QT Interval, Aggregate
This outcome measure reported change from baseline to Month 6 in aggregate QT Interval.
Measured: Baseline (Week 0), Month 6
Change From Baseline in 12-lead ECG-QTcF Interval, Aggregate
This outcome measure reported change from baseline to Month 6 in aggregate QTcF Interval.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Participants With Significant Findings- Physical Examination
This outcome measure reported change from baseline to Month 6 in number of participants with significant findings (physical examination). Change from baseline was calculated using formula: value at current time point - baseline value.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Vital Sign Assessment- Height
This outcome measure reported change from baseline to Month 6 in participants heights.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Vital Sign Assessment-Weight
This outcome measure reported change from baseline to Month 6 in participants weights.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Vital Sign Assessment-Body Mass Index (BMI)
This outcome measure reported change from baseline to Month 6 in participants BMI.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Vital Sign Assessment-Oral Body Temperature
This outcome measure reported change from baseline to Month 6 in participants oral body temperature.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Vital Sign Assessment-Respiratory Rate
This outcome measure reported change from baseline to Month 6 in participants respiratory rate.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Vital Sign Assessment-Heart Rate
This outcome measure reported change from baseline to Month 6 in participants heart rate.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Vital Sign Assessment-Systolic Blood Pressure and Diastolic Blood Pressure
This outcome measure reported change from baseline to Month 6 in participants systolic and diastolic blood pressure.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Erythrocytes
This outcome measure reported change from baseline to Month 6 in participants erythrocytes.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Hemoglobin
This outcome measure reported change from baseline to Month 6 in participants hemoglobin.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Hematocrit
This outcome measure reported change from baseline to Month 6 in participants hematocrit.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Erythrocytes Mean Corpuscular Volume
This outcome measure reported change from baseline to Month 6 in participants erythrocytes mean corpuscular volume.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Erythrocytes Mean Corpuscular Hemoglobin
This outcome measure reported change from baseline to Month 6 in participants erythrocytes mean corpuscular hemoglobin.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Erythrocytes Mean Corpuscular Hemoglobin Concentration
This outcome measure reported change from baseline to Month 6 in participant's erythrocytes mean corpuscular hemoglobin concentration.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Reticulocytes
This outcome measure reported change from baseline to Month 6 in participants reticulocytes.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Haematology Assessment: Platelets
This outcome measure reported change from baseline to Month 6 in participants platelets.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Mean Platelet Volume
This outcome measure reported change from baseline to Month 6 in participants mean platelet volume.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Leukocytes
This outcome measure reported change from baseline to Month 6 in participants leukocytes.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Lymphocytes
This outcome measure reported change from baseline to Month 6 in participants lymphocytes.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Monocytes
This outcome measure reported change from baseline to Month 6 in participants monocytes.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Eosinophils
This outcome measure reported change from baseline to Month 6 in participants eosinophils.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Basophils
This outcome measure reported change from baseline to Month 6 in participants basophils.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Neutrophils
This outcome measure reported change from baseline to Month 6 in participants neutrophils.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Lymphocytes/Leukocytes
This outcome measure reported change from baseline to Month 6 in the ratio of lymphocytes/leukocytes.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Monocytes/Leukocytes
This outcome measure reported change from baseline to Month 6 in the ratio of monocytes/leukocytes.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Eosinophils/Leukocytes
This outcome measure reported change from baseline to Month 6 in the ratio of eosinophils/leukocytes.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Basophils/Leukocytes
This outcome measure reported change from baseline to Month 6 in the ratio of basophils/leukocytes.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Neutrophils/Leukocytes
This outcome measure reported change from baseline to Month 6 in the ratio of neutrophils/leukocytes.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Alanine Aminotransferase
This outcome measure reported change from baseline to Month 6 in alanine aminotransferase.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Aspartate Aminotransferase
This outcome measure reported change from baseline to Month 6 in aspartate aminotransferase.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Lactate Dehydrogenase
This outcome measure reported change from baseline to Month 6 in lactate dehydrogenase.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Glutamate Dehydrogenase
This outcome measure reported change from baseline to Month 6 in glutamate dehydrogenase.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Gamma Glutamyl Transferase
This outcome measure reported change from baseline to Month 6 in gamma glutamyl transferase.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Alkaline Phosphatase
This outcome measure reported change from baseline to Month 6 in alkaline phosphatase.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Bilirubin and Direct Bilirubin
This outcome measure reported change from baseline to Month 6 in bilirubin and direct bilirubin.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Protein
This outcome measure reported change from baseline to Month 6 in protein.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Albumin
This outcome measure reported change from baseline to Month 6 in albumin.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Creatine Kinase
This outcome measure reported change from baseline to Month 6 in creatine kinase.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Sodium
This outcome measure reported change from baseline to Month 6 in sodium.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Chloride
This outcome measure reported change from baseline to Month 6 in chloride.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Potassium
This outcome measure reported change from baseline to Month 6 in potassium.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Creatinine
This outcome measure reported change from baseline to Month 6 in creatinine.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Blood Urea Nitrogen
This outcome measure reported change from baseline to Month 6 in blood urea nitrogen.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Cystatin C
This outcome measure reported change from baseline to Month 6 in blood urea Cystatin C.
Measured: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Plasma Oxalate
This outcome measure reported change from baseline to Month 6 in blood urea plasma oxalate.
Measured: Baseline (Week 0), Month 6
Plasma Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax), if Estimable
This outcome measure, if estimable, was expected to report Cmax which is defined as maximum observed concentration. However, in this study, a non-compartmental PK analysis was not planned or executed due to the limited PK samples (2 PK concentration - time data points between 0 to 4 hours and 4 to 24 hours following dose administration on Day 1) collected in pediatric participants per protocol, hence this PK parameter was not estimated. To estimate Cmax, at least one data point prior to Tmax and one data point post-Tmax at the designated time points are needed; however, only two flexible post-dose PK concentration data points were available in this study. Although Cmax was not estimated in this study, the PK data collected in this study will be used in a population PK analysis in the future.
Measured: Baseline (Week 0), Month 6
Plasma PK Parameters: Area Under the Concentration-time Curve Calculated to the Last Observable Concentration at Time t (AUCt), if Estimable
This outcome measure, if estimable, was expected to report AUCt which is defined as area under the concentration-time curve calculated from time zero to the last observable concentration at time t. However, in this study, a non-compartmental PK analysis was not planned or executed due to the limited PK samples (2 PK concentration - time data points between 0 to 4 hours and 4 to 24 hours following dose administration on Day 1) collected in pediatric participants per protocol, hence this PK parameter was not estimated. To estimate AUCt, at least one data point prior to Tmax and three data points post-Tmax at the designated time points are needed; however, only two flexible post-dose PK concentration data points were available in this study. Although AUCt was not estimated in this study, the PK data collected in this study shall be used in a population PK analysis in the future.
Measured: Day 1: Postdose 0- to 4-hour and 4- to 24-hour, Days 2, 30, and 90: post dose, Day 150: predose and Day 150: postdose: 0- to 4-hour and 4- to 24-hour
Plasma PK Parameters: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC∞), if Estimable
This outcome measure, if estimable, was expected to report AUC∞ which is defined as area under the concentration-time curve calculated to the last observable concentration at time t. However, in this study, a non-compartmental PK analysis was not planned or executed due to the limited PK samples (2 PK concentration - time data points between 0 to 4 hours and 4 to 24 hours following dose administration on Day 1) collected in pediatric participants per protocol, hence this PK parameter was not estimated. To estimate AUC∞, at least one data point prior to Tmax and three data points post-Tmax at the designated time points are needed; however, only two flexible post-dose PK concentration data points were available in this study. Although AUC∞ was not estimated in this study, the PK data collected in this study will be used in a population PK analysis in the future.
Measured: Day 1: Postdose 0- to 4-hour and 4- to 24-hour, Days 2, 30, and 90: post dose, Day 150: predose and Day 150: post-dose: 0- to 4-hour and 4- to 24-hour
Percentage of Participants With Spot Urinary Oxalate-to-Creatinine Ratio <=Upper Limit of Normal (ULN) or <=1.5*ULN at Any Time Point Through Month 6 in PH1, PH2, or PH3 Participant Subgroups
This outcome measure reported percentage of participants from baseline to Month 6 Oxalate-to-creatinine Ratio less than and equal to (<=) ULN or <=1.5*ULN at any time point through Month 6 in pediatric participants (birth to 11 years of age) with genetically confirmed PH1, PH2, or PH3 subgroups.
Measured: From baseline (week 0) through Month 6
Change From Baseline in eGFR at Month 6 (Only in Participants >=12 Months of Age at Screening) in PH1, PH2, or PH3 Participant Subgroups
This outcome measure reported Change from Baseline in GFR estimated Cystatin C at Month 6 (only in participants >=12 Months of age at Screening) in PH1, PH2, or PH3 participant subgroups. The eGFR was calculated using multivariate Schwartz equation using formula: eGFR=39.8*[ht/Scr]^0.456 [1.8/cysC]^0.418 [30/BUN]^0.0791.076^male[ht/1.4]^0.179 where ht (height) = meters, Scr (serum creatinine) = milligrams per deciliter (mg/dL), cysC (cystatin C) = mg/L, and BUN (blood urea nitrogen) = mg/dL.
Measured: Baseline (Week 0), Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2021
- Study start22 Feb 2022
- Primary completion5 Feb 2025
- Study completion5 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Primary HyperoxaluriaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Children 2-11 years of age will begin enrolling prior to the under 2 year old age group's open.
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sarb Shergill, PhD, Study director, Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05001269
- Sponsor's protocol ID
- DCR-PHXC-203
- Acronym
- PHYOX8
- Status last verified
- Mar 2026
- First submitted
- 30 Jun 2021
- Last updated
- 16 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40601241Cox 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.
PubMed 40193200Sas DJ, Bakkaloglu SA, Belostotsky V, Hayes W, Ariceta G, Zhou J, Rawson V. Nedosiran in pediatric patients with PH1 and relatively preserved kidney function, a phase 2 study (PHYOX8). Pediatr Nephrol. 2025 Jun;40(6):1939-1948. doi: 10.1007/s00467-025-06675-8. Epub 2025 Jan 28.
PubMed 39875734
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Open-Label Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Nedosiran in Pediatric Patients From Birth to 11Years of Age With Primary Hyperoxaluria and Relatively Intact Renal Function
- ClinicalTrials.gov ID
- NCT05001269
- Acronym / sponsor ID
- PHYOX8 / DCR-PHXC-203
- Conditions
- Primary Hyperoxaluria, Primary Hyperoxaluria Type 1, Primary Hyperoxaluria Type 2, Primary Hyperoxaluria Type 3
- Keywords
- PH1, PH2, PH3, pediatric
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Dicerna Pharmaceuticals, Inc., a Novo Nordisk companyIndustry (pharma, biotech, devices)
- Study start
- 22 Feb 2022 (actual)
- Primary completion
- 5 Feb 2025 (actual)
- Study completion
- 5 Feb 2025 (actual)
- First posted
- 11 Aug 2021 (actual)
- Results
- Posted 16 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is an open-label, repeat-dose, Phase 2 study of nedosiran in participants 11 years of age or younger who have PH1, PH2 or PH 3 and relatively intact renal function.
Following the up-to-35- day screening period, participants will return to the clinic for monthly dosing visits through Day 180.
The total duration of this study is approximately 15 months from first participant, first visit, until last participant, last visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Children 2-11 years of age will begin enrolling prior to the under 2 year old age group's open.
| Arm | Type | Receives |
|---|---|---|
| Open-Label DCR-PHXC | Experimental | Drug: nedosiranOpen-Label monthly subcutaneous injection of DCR-PHXC based on age and weight. |
Who may qualify
- Ages
- Up to 11 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (22 listed)
- 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):
- 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.
Key exclusion criteria (21 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nedosiranAlso: DCR-PHXCMonthly subcutaneous dosing throughout study period | Drug | Open-Label DCR-PHXC |
Primary outcome
Percent Change From Baseline to Month 6 in Spot Urinary Oxalate-to-creatinine Ratio in PH1, PH2, or PH3 Participant Subgroups
Time frame: Baseline (Week 0), Month 6
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.
Absolute Change From Baseline to Month 6 in Spot Urinary Oxalate-to-creatinine Ratio in PH1, PH2, or PH3 Participant Subgroups
Time frame: Baseline (Week 0), Month 6
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.
58 secondary outcomes
Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From baseline (Week 0) up to Month 6
Number of Treatment Emergent Adverse Events and Serious Adverse Events-Nature
Time frame: From baseline (Week 0) up to Month 6
Change From Baseline in 12-lead Electrocardiogram (ECG)- ECG Mean Heart Rate
Time frame: Baseline (Week 0), Month 6
Change From Baseline in 12-lead ECG- RR Interval
Time frame: Baseline (Week 0), Month 6
Change From Baseline in 12-lead ECG-PR Interval, Aggregate
Time frame: Baseline (Week 0), Month 6
Change From Baseline in 12-lead ECG-QRS Duration, Aggregate
Time frame: Baseline (Week 0), Month 6
Change From Baseline in 12-lead ECG-QT Interval, Aggregate
Time frame: Baseline (Week 0), Month 6
Change From Baseline in 12-lead ECG-QTcF Interval, Aggregate
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Participants With Significant Findings- Physical Examination
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Vital Sign Assessment- Height
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Vital Sign Assessment-Weight
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Vital Sign Assessment-Body Mass Index (BMI)
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Vital Sign Assessment-Oral Body Temperature
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Vital Sign Assessment-Respiratory Rate
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Vital Sign Assessment-Heart Rate
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Vital Sign Assessment-Systolic Blood Pressure and Diastolic Blood Pressure
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Erythrocytes
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Hemoglobin
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Hematocrit
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Erythrocytes Mean Corpuscular Volume
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Erythrocytes Mean Corpuscular Hemoglobin
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Erythrocytes Mean Corpuscular Hemoglobin Concentration
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Reticulocytes
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Haematology Assessment: Platelets
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Mean Platelet Volume
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Leukocytes
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Lymphocytes
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Monocytes
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Eosinophils
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Basophils
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Neutrophils
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Lymphocytes/Leukocytes
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Monocytes/Leukocytes
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Eosinophils/Leukocytes
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Basophils/Leukocytes
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Hematology Assessment: Neutrophils/Leukocytes
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Alanine Aminotransferase
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Aspartate Aminotransferase
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Lactate Dehydrogenase
Time frame: Baseline (Week 0), Month 6
Change From Baseline in Clinical Chemistry Parameter: Glutamate Dehydrogenase
Time frame: Baseline (Week 0), Month 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40601241Zhang 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.
- Derived from this study: PubMed 40193200Cox 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.
- Derived from this study: PubMed 39875734Sas DJ, Bakkaloglu SA, Belostotsky V, Hayes W, Ariceta G, Zhou J, Rawson V. Nedosiran in pediatric patients with PH1 and relatively preserved kidney function, a phase 2 study (PHYOX8). Pediatr Nephrol. 2025 Jun;40(6):1939-1948. doi: 10.1007/s00467-025-06675-8. Epub 2025 Jan 28.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sarb Shergill, PhD study director
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
13 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing nedosiran in people with Primary Hyperoxaluria and Primary Hyperoxaluria Type 1, run by Dicerna Pharmaceuticals, Inc., a Novo Nordisk company at 13 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Germany, Japan, United States, Canada, Italy and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline to Month 6 in Spot Urinary Oxalate-to-creatinine Ratio in PH1, PH2, or PH3 Participant Subgroups (time frame: Baseline (Week 0), Month 6). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05001269, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2026.