A Study to Evaluate DCR-PHXC in Children and Adults With Primary Hyperoxaluria Type 1 and Primary Hyperoxaluria Type 2 (PHYOX2)

A Phase 2 Placebo-Controlled, Double-Blind, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of DCR-PHXC Solution for Injection (Subcutaneous Use) in Patients With Primary Hyperoxaluria

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)

Study Overview

• Status: Completed
• Conditions: Kidney Diseases; Urologic Diseases; Genetic Disease; Primary Hyperoxaluria Type 1 (PH1); Primary Hyperoxaluria Type 2 (PH2)
• Intervention / Treatment: Drug: DCR-PHXC; Drug: Sterile Normal Saline (0.9% NaCl)

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Herston, Australia, 4029
    • Clinical Trial Site
  • Parkville, Australia, 3052
    • Clinical Trial Site
• Canada
  • Hamilton, Canada
    • Clinical Trial Site
• France
  • Bron, France
    • Clinical Trial Site
  • Paris, France, 75019
    • Clinical Trial Site
• Germany
  • Bonn, Germany, 53127
    • Clinical Trial Site
  • Heidelberg, Germany, 69120
    • Clinical Trial Site
• Israel
  • Jerusalem, Israel, 9103102
    • Clinical Trial Site
• Italy
  • Roma, Italy, 00165
    • Clinical Trial Site
• Japan
  • Nagoya, Japan, 467-8601
    • Clinical Trial Site
  • Tochigi, Japan, 329-0431
    • Clinical Trial Site
  • Tokyo, Japan, 183-8561
    • Clinical Trial Site
• Lebanon
  • Beirut, Lebanon, 2807
    • Clinical Trial Site
  • Beirut, Lebanon
    • Clinical Trial Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Clinical Trial Site
• New Zealand
  • Auckland, New Zealand
    • Clinical Trial Site
• Poland
  • Białystok, Poland
    • Clinical Trial Site
• Romania
  • Bucharest, Romania
    • Clinical Trial Site
• Spain
  • Barcelona, Spain, 08035
    • Clinical Trial Site
  • Santa Cruz, Spain, 38320
    • Clinical Trial Site
• United Kingdom
  • Birmingham, United Kingdom
    • Clinical Trial Site
  • London, United Kingdom
    • Clinical Trial Site
  • London, United Kingdom, WCIN 3JH
    • Clinical Trial Site
• United States
  • California
    • San Francisco, California, United States, 94143
      • Clinical Trial Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Clinical Trial Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Clinical Trial Site
  • New York
    • New York, New York, United States, 10016
      • Clinical Trial Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• 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

Key Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DCR-PHXC; Intervention, drug, DCR-PHXC	Drug: DCR-PHXC; Multiple fixed doses of DCR-PHXC by subcutaneous (SC) injection; Other Names: nedosiran
Placebo Comparator: Placebo - Sterile Normal Saline (0.9% NaCl); Placebo, sterile normal saline (0.9% NaCl) for subcutaneous (SC) injection	Drug: Sterile Normal Saline (0.9% NaCl); Sterile Normal Saline (0.9% NaCl) for subcutaneous (SC) injection, administered at same injection volume as DCR-PHXC, to serve as placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Whose 24-hour Uox Values Normalized or Near-normalized on at Least 2 Consecutive Visits	Percentage of participants whose 24-hour Uox values normalized or near-normalized on at least 2 consecutive visits are presented. Normalization of Uox was defined as less than (<) 0.46 millimole per 24 hours (mmol/24 hours) and near normalization was defined as greater than or equal to (>=) 0.46 to < 0.60 mmol/24 hours (values adjusted per 1.73 square meter [1.73 m^2] body surface area [BSA] in participants aged <18 years).	From Day 90 to 180
Percent Change From Baseline to Day 180 in the Summed Surface Area of Kidney Stones	Percent change from baseline to Day 180 in the summed surface area measured in millimetre square (mm^2) of kidney stones is presented.	Baseline, Day 180
Percent Change From Baseline to Day 180 in the Number of Kidney Stones	Percent change from baseline to Day 180 in the number of kidney stones is presented.	Baseline, Day 180
Percent Change From Baseline to Day 180 in Plasma Oxalate (For Adults Only)	Percent change from baseline to Day 180 in plasma oxalate (for adults only) is presented.	Baseline, Day 180
Rate of Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Day 180	Monthly rate of eGFR change is presented. eGFR was calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and creatinine-based equation.	Baseline, Day 180
Number of Treatment Emergent Adverse Events (TEAEs) And Serious Treatment Emergent Adverse Events (TEAEs)	Number of TEAEs and TESAEs are presented. 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 was defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalisation, results in persistent disability/incapacity or is a congenital anomaly/birth defect. TEAE was defined as any AE with an onset date/time on or after administration (including any partial administration) of the first dose of study intervention and through the study completion date from the end of study case report form (CRF).	From Baseline up to Day 180
Change From Baseline in Electrocardiogram (ECG): Heart Rate	Change from baseline in heart rate is presented.	Baseline, Day 180
Change From Baseline in ECG: PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval	Change from baseline in PR interval, QRS duration, QT interval, QTcB interval, QTcF interval and RR interval is presented.	Baseline, Day 180
Number of Participants With Most Abnormal Post-Baseline Shift in Physical Examination	Number of participants who had most abnormal post-baseline shift in physical examination are presented. Physical examination shifts were categories into 4 categories: 1) missing; 2) normal; 3) abnormal-not clinically significant (NCS) and 4) abnormal-clinically significant (CS). Each category was presented according body systems including: 1) eyes, ears, nose and throat; 2) chest/respiratory; 3) heart/cardiovascular; 4) gastrointestinal/liver; 5) musculoskeletal/extremities; 6) dermatological/skin; 7) thyroid/neck; 8) lymph nodes; 9) neurological.	Baseline up to Day 180
Change From Baseline in Vital Signs: Height	Change from baseline to Day 180 in height is presented.	Baseline, Day 180
Change From Baseline in Vital Signs: Weight	Change from baseline to Day 180 in weight is presented.	Baseline, Day 180
Change From Baseline in Vital Signs: Body Mass Index (BMI)	Change from baseline to Day 180 in BMI is presented.	Baseline, Day 180
Change From Baseline in Vital Signs: Oral Body Temperature	Change from baseline to Day 180 in oral body temperature is presented.	Baseline, Day 180
Change From Baseline in Vital Signs: Heart Rate	Change from baseline to Day 180 in heart rate is presented.	Baseline, Day 180
Change From Baseline in Vital Signs: Respiratory Rate	Change from baseline to Day 180 in respiratory rate is presented.	Baseline, Day 180
Change From Baseline in Vital Signs: Systolic and Diastolic Blood Pressure	Change from baseline to Day 180 in systolic and diastolic blood pressure is presented.	Baseline, Day 180
Change From Baseline in Clinical Chemistry Laboratory Tests: Alanine Aminotransferase, Aspartate Aminotransferase, Glutamate Dehydrogenase, Gamma Glutamyl Transferase, Alkaline Phosphatase, Lactate Dehydrogenase and Creatine Kinase	Change from baseline to Day 180 in alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase, gamma glutamyl transferase, alkaline phosphatase, lactate dehydrogenase and creatine kinase are presented.	Baseline, Day 180
Change From Baseline in Clinical Chemistry Laboratory Tests: Bilirubin, Direct Bilirubin and Creatinine	Change from baseline to Day 180 in bilirubin, direct bilirubin and creatinine are presented.	Baseline, Day 180
Change From Baseline in Clinical Chemistry Laboratory Tests: Protein, Albumin	Change from baseline to Day 180 in protein and albumin are presented.	Baseline, Day 180
Change From Baseline in Clinical Chemistry Laboratory Tests: Sodium, Chloride, Potassium and Urea	Change from baseline to Day 180 in sodium, chloride, potassium and urea are presented.	Baseline, Day 180
Change From Baseline in Clinical Chemistry Laboratory Tests: Vitamin B6	Change from baseline to Day 180 in vitamin B6 is presented.	Baseline, Day 180
Change From Baseline in Clinical Hematology Laboratory Tests: Erythrocytes	Change from baseline to Day 180 in erythrocytes is presented.	Baseline, Day 180
Change From Baseline in Clinical Hematology Laboratory Tests: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin Concentration	Change from baseline to Day 180 in hemoglobin and erythrocytes mean corpuscular hemoglobin concentration are presented.	Baseline, Day 180
Change From Baseline in Clinical Hematology Laboratory Tests: Hematocrit	Change from baseline to Day 180 in hematocrit is presented.	Baseline, Day 180
Change From Baseline in Clinical Hematology Laboratory Tests: Erythrocytes (Ery.) Mean Corpuscular Volume and Mean Platelet Volume	Change from baseline to Day 180 in ery. mean corpuscular volume and mean platelet volume are presented.	Baseline, Day 180
Change From Baseline in Clinical Hematology Laboratory Tests: Erythrocytes Mean Corpuscular Hemoglobin	Change from baseline to Day 180 in erythrocytes mean corpuscular hemoglobin is presented.	Baseline, Day 180
Change From Baseline in Clinical Hematology Laboratory Tests: Reticulocytes, Platelets, Leukocytes, Lymphocytes, Monocytes, Eosinophils, Basophils, Neutrophils	Change from baseline to Day 180 in reticulocytes, platelets, leukocytes, lymphocytes, monocytes, eosinophils, basophils, neutrophils are presented.	Baseline, Day 180
Change From Baseline in Clinical Hematology Laboratory Tests: Lymphocytes/Leukocytes	Change from baseline to Day 180 in lymphocytes/leukocytes is presented.	Baseline, Day 180
Change From Baseline in Clinical Hematology Laboratory Tests: Monocytes/Leukocytes	Change from baseline to Day 180 in monocytes/leukocytes is presented.	Baseline, Day 180
Change From Baseline in Clinical Hematology Laboratory Tests: Eosinophils/Leukocyte	Change from baseline to Day 180 in eosinophils/leukocytes is presented.	Baseline, Day 180
Change From Baseline in Clinical Hematology Laboratory Tests: Basophils/Leukocytes	Change from baseline to Day 180 in basophils/leukocytes is presented.	Baseline, Day 180
Change From Baseline in Clinical Hematology Laboratory Tests: Neutrophils/Leukocytes	Change from baseline to Day 180 in neutrophils/leukocytes is presented.	Baseline, Day 180
Change From Baseline in Clinical Urinalysis Laboratory Tests: Specific Gravity	Change from baseline to Day 180 in urine specific gravity is presented.	Baseline, Day 180
Change From Baseline in Clinical Urinalysis Laboratory Tests: pH	Change from baseline to Day 180 in urine pH is presented.	Baseline, Day 180
Maximum Observed Plasma Concentration (Cmax) of DCR-PHXC	The Cmax was defined as the maximum observed plasma concentration during a dosing interval. Data for this endpoint is reported only for adults and adolescent participants from PK population.	For adults: Day 1 and 30: predose, 5, 15, and 30 minutes and 1, 2, 4, 6, 10, and 12 hours (hrs) postdose; Day 150: predose, 2, 6, and 12 hours postdose For adolescents: Days 1 and 30: predose, 30 minutes and 2 and 10 hours postdose
Area Under the Curve From Time of Administration to the Last Measurable Concentration (AUC0-last) of of DCR-PHXC	AUC0-last was defined as the area under the curve from time of administration to the last measurable concentration. Data for this endpoint is reported only for adults and adolescent participants from PK population.	For adults: Day 1 and 30: predose, 5, 15, and 30 minutes and 1, 2, 4, 6, 10, and 12 hours postdose; Day 150: predose, 2, 6, and 12 hours postdose For adolescents: Days 1 and 30: predose, 30 minutes and 2 and 10 hours postdose

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 1452), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2019
• Primary Completion (Actual): June 21, 2021
• Study Completion (Actual): June 29, 2021

Study Registration Dates

• First Submitted: February 15, 2019
• First Submitted That Met QC Criteria: February 18, 2019
• First Posted (Actual): February 20, 2019

Study Record Updates

• Last Update Posted (Actual): May 22, 2024
• Last Update Submitted That Met QC Criteria: May 17, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: RNAi therapeutic; siRNA; RNAi; PH1; PH2; Primary Hyperoxaluria; GalNAc; LDHA gene; LDH
• Additional Relevant MeSH Terms: Metabolic Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Hyperoxaluria; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Genetic Diseases, Inborn; Urologic Diseases; Hyperoxaluria, Primary
• Other Study ID Numbers: DCR-PHXC-201

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