Nedosiran in Pediatric Patients From Birth to 11 Years of Age With PH and Relatively Intact Renal Function (PHYOX8)

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.

Study Overview

• Status: Completed
• Conditions: Primary Hyperoxaluria Type 3; Primary Hyperoxaluria Type 2; Primary Hyperoxaluria Type 1; Primary Hyperoxaluria
• Intervention / Treatment: Drug: nedosiran

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 Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4K1
      • Clinical Research Site
• Germany
  • Bonn, Germany, 53127
    • Clinical Trial Site
  • Heidelberg, Germany, 69120
    • Clinical Research Site
• Italy
  • Roma, Italy, 00165
    • Clinical Trial Site
• Japan
  • Fukuoka, Japan, 830-0011
    • Clinical Research Site
  • Nagoya, Japan, 467-8602
    • Clinical Research Site
• Lebanon
  • Beirut, Lebanon, 1100
    • Clinical Research Site
• Poland
  • Bialystok, Poland, 15-274
    • Clinical Research Site
• Spain
  • Barcelona, Spain, 08035
    • Clinical Research Site
• Turkey (Türkiye)
  • Ankara
    • Yenimahalle, Ankara, Turkey (Türkiye), 06506
      • Clinical Research Site
• United Arab Emirates
  • Dubai, United Arab Emirates, +971
    • Clinical Trial Site
• United Kingdom
  • London, United Kingdom, WC1N 3JH
    • Clinical Trial Site
• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Clinical Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 7 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Birth to 11 years of age inclusive, at the time of signing the informed consent.
2. Documented diagnosis of PH1 or PH2 or PH3 confirmed by genotyping (historically available genotype information is acceptable for study eligibility).

3. 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
4. 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).
5. 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.

6. 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.

7. 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.

   a. 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.

8. 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.
9. Affiliated with or is a beneficiary of a health insurance system (if applicable per national regulations)

Exclusion Criteria:

1. Prior renal or hepatic transplantation; or planned transplantation within the study period
2. Currently receiving dialysis or anticipating requirement for dialysis during the study period
3. Plasma oxalate (Pox) > 30 μmol/L at Screening
4. 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)

5. 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:

   1. Severe intercurrent illness
   2. Known causes of active liver disease/injury or transaminase elevation (e.g., alcoholic liver disease, nonalcoholic fatty liver disease/steatohepatitis [NAFLD/NASH])
   3. History of serious mental illness that includes, but is not limited to, schizophrenia, bipolar disorder, or severe depression requiring hospitalization or pharmacological intervention
   4. 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
6. Use of an RNAi drug within the last 6 months

7. History of 1 or more of the following reactions to an oligonucleotide-based therapy:

   1. Severe thrombocytopenia (platelet count ≤ 100,000/µL)
   2. Hepatotoxicity, defined as ALT or AST > 3 times the upper ULN and total bilirubin > 2 × ULN or INR > 1.5
   3. Severe flu-like symptoms leading to discontinuation of therapy
   4. Localized skin reaction from the injection (graded severe) leading to discontinuation of therapy
   5. Coagulopathy/clinically significant prolongation of clotting time

8. 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

   a. 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

9. Liver function test (LFT) abnormalities: ALT and/or AST > 1.5 × ULN for age and gender
10. Known hypersensitivity to nedosiran, or any of its ingredients
11. Inability or unwillingness to comply with the specified study procedures, including the lifestyle considerations detailed in Section 5.3.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open-Label DCR-PHXC; Open-Label monthly subcutaneous injection of DCR-PHXC based on age and weight.	Drug: nedosiran; Monthly subcutaneous dosing throughout study period; Other Names: DCR-PHXC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	Baseline (Week 0), Month 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Plasma Oxalate Concentration	Assess the effect of DCR-PHXC on Plasma Oxalate concentration from baseline	180 days
Change from Baseline number of kidney stones	Assess the effect of DCR-PHXC on stone burden from baseline on annualized stone events	180 days
Change from baseline PedsQL™	Change from Baseline in the Pediatric Quality of Life Inventory (PedsQL™)	180 days
Change from baseline WPAI	Change from Baseline in the Work Productivity and Activity Impairment Questionnaire: Primary Hyperoxaluria V2.0, Clinical Practice Version (WPAI:PH, V2.0, CPV) - Caregiver	180 days

Collaborators and Investigators

• Sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
• Investigators: Study Director: Sarb Shergill, PhD, Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2022
• Primary Completion (Actual): February 5, 2025
• Study Completion (Actual): February 5, 2025

Study Registration Dates

• First Submitted: June 30, 2021
• First Submitted That Met QC Criteria: August 4, 2021
• First Posted (Actual): August 11, 2021

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: pediatric; PH1; PH2; PH3
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Carbohydrate Metabolism, Inborn Errors; Hyperoxaluria; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hyperoxaluria, Primary; Primary hyperoxaluria type 1; Primary hyperoxaluria type 2; nedosiran
• Other Study ID Numbers: DCR-PHXC-203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No