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

Novo Nordisk A/S35 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

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

Interventions

DCR-PHXCDRUG

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

Sterile Normal Saline (0.9% NaCl)DRUG

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

Eligibility

Sex: ALLMin age: 6 Years

Medical Language ↔ Plain English

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

Locations (28)

Clinical Trial Site

San Francisco, California, United States

Outcomes

Primary Outcomes

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.

Time frame: From Day 90 to 180

Secondary Outcomes

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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline, Day 180

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

Data from ClinicalTrials.gov

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Clinical Trial Site

Boston, Massachusetts, United States

Clinical Trial Site

Rochester, Minnesota, United States

Clinical Trial Site

New York, New York, United States

Clinical Trial Site

Pittsburgh, Pennsylvania, United States

Clinical Trial Site

Herston, Australia

Clinical Trial Site

Parkville, Australia

Clinical Trial Site

Hamilton, Canada

Clinical Trial Site

Bron, France

Clinical Trial Site

Paris, France

...and 18 more locations

Monthly rate of eGFR change is presented. eGFR was calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and creatinine-based equation.

Time frame: 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).

Time frame: From Baseline up to Day 180

Change From Baseline in Electrocardiogram (ECG): Heart Rate

Change from baseline in heart rate is presented.

Time frame: 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.

Time frame: 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.

Time frame: Baseline up to Day 180

Change From Baseline in Vital Signs: Height

Change from baseline to Day 180 in height is presented.

Time frame: Baseline, Day 180

Change From Baseline in Vital Signs: Weight

Change from baseline to Day 180 in weight is presented.

Time frame: Baseline, Day 180

Change From Baseline in Vital Signs: Body Mass Index (BMI)

Change from baseline to Day 180 in BMI is presented.

Time frame: Baseline, Day 180

Change From Baseline in Vital Signs: Oral Body Temperature

Change from baseline to Day 180 in oral body temperature is presented.

Time frame: Baseline, Day 180

Change From Baseline in Vital Signs: Heart Rate

Change from baseline to Day 180 in heart rate is presented.

Time frame: Baseline, Day 180

Change From Baseline in Vital Signs: Respiratory Rate

Change from baseline to Day 180 in respiratory rate is presented.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline, Day 180

Change From Baseline in Clinical Chemistry Laboratory Tests: Vitamin B6

Change from baseline to Day 180 in vitamin B6 is presented.

Time frame: Baseline, Day 180

Change From Baseline in Clinical Hematology Laboratory Tests: Erythrocytes

Change from baseline to Day 180 in erythrocytes is presented.

Time frame: 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.

Time frame: Baseline, Day 180

Change From Baseline in Clinical Hematology Laboratory Tests: Hematocrit

Change from baseline to Day 180 in hematocrit is presented.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline, Day 180

Change From Baseline in Clinical Hematology Laboratory Tests: Lymphocytes/Leukocytes

Change from baseline to Day 180 in lymphocytes/leukocytes is presented.

Time frame: Baseline, Day 180

Change From Baseline in Clinical Hematology Laboratory Tests: Monocytes/Leukocytes

Change from baseline to Day 180 in monocytes/leukocytes is presented.

Time frame: Baseline, Day 180

Change From Baseline in Clinical Hematology Laboratory Tests: Eosinophils/Leukocyte

Change from baseline to Day 180 in eosinophils/leukocytes is presented.

Time frame: Baseline, Day 180

Change From Baseline in Clinical Hematology Laboratory Tests: Basophils/Leukocytes

Change from baseline to Day 180 in basophils/leukocytes is presented.

Time frame: Baseline, Day 180

Change From Baseline in Clinical Hematology Laboratory Tests: Neutrophils/Leukocytes

Change from baseline to Day 180 in neutrophils/leukocytes is presented.

Time frame: 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.

Time frame: Baseline, Day 180

Change From Baseline in Clinical Urinalysis Laboratory Tests: pH

Change from baseline to Day 180 in urine pH is presented.

Time frame: 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.

Time frame: 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.

Time frame: 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