Phase 2 N=35 Randomized Quadruple-blind Treatment

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

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

Bottom Line

View on ClinicalTrials.gov: NCT03847909 ↗

Enrolled (actual)

Serious AEs

8.6%

Results posted

May 2024

Primary outcome: Primary: AUC From Day 90 To Day 180, Based on Percent Change From Baseline in 24-Hour Uox — 3507.4; -1664.4 Percent change in 24-hour Uox AUC — p=<0.0001

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: DCR-PHXC (Drug); Sterile Normal Saline (0.9% NaCl) (Drug)
Age: Pediatric, Adult, Older Adult · 6+ yrs
Sex: All
Sponsor: Novo Nordisk A/S
Primary completion: Jun 2021

Outcome Measures

Outcome	Result	p-value
PRIMARY AUC From Day 90 To Day 180, Based on Percent Change From Baseline in 24-Hour Uox	3507.4; -1664.4	<0.0001 sig
SECONDARY Percentage of Participants Whose 24-hour Uox Values Normalized or Near-normalized on at Least 2 Consecutive Visits	50; 0	—
SECONDARY Percent Change From Baseline to Day 180 in the Summed Surface Area of Kidney Stones	-2.13; 21.77	—
SECONDARY Percent Change From Baseline to Day 180 in the Number of Kidney Stones	0.00; 0.00	—
SECONDARY Percent Change From Baseline to Day 180 in Plasma Oxalate (For Adults Only)	-25.00; -0.00	—
SECONDARY Rate of Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Day 180	0.3533; 1.1008	—
SECONDARY Number of Treatment Emergent Adverse Events (TEAEs) And Serious Treatment Emergent Adverse Events (TEAEs)	101; 54; 1; 3	—
SECONDARY Change From Baseline in Electrocardiogram (ECG): Heart Rate	0.4; -1.8	—
SECONDARY Change From Baseline in ECG: PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval	-0.5; 1.3; 1.3; -1.5; -2.4; 4.0	—
SECONDARY Number of Participants With Most Abnormal Post-Baseline Shift in Physical Examination	1; 1; 21; 11; 1; 0	—
SECONDARY Change From Baseline in Vital Signs: Height	0.70; 1.08	—
SECONDARY Change From Baseline in Vital Signs: Weight	1.134; 1.350	—
SECONDARY Change From Baseline in Vital Signs: Body Mass Index (BMI)	0.23; 0.14	—
SECONDARY Change From Baseline in Vital Signs: Oral Body Temperature	0.01; 0.05	—
SECONDARY Change From Baseline in Vital Signs: Heart Rate	0.8; -3.1	—
SECONDARY Change From Baseline in Vital Signs: Respiratory Rate	-0.2; -1.1	—
SECONDARY Change From Baseline in Vital Signs: Systolic and Diastolic Blood Pressure	-2.0; -3.0; 0.8; -2.6	—
SECONDARY Change From Baseline in Clinical Chemistry Laboratory Tests: Alanine Aminotransferase, Aspartate Aminotransferase, Glutamate Dehydrogenase, Gamma Glutamyl Transferase, Alkaline Phosphatase, Lactate Dehydrogenase and Creatine Kinase	1.0; -1.1; -0.2; -1.3; -0.15; -0.38	—
SECONDARY Change From Baseline in Clinical Chemistry Laboratory Tests: Bilirubin, Direct Bilirubin and Creatinine	1.0; 0.4; 0.1; 0.1; -1.2; 4.3	—
SECONDARY Change From Baseline in Clinical Chemistry Laboratory Tests: Protein, Albumin	0.4; 1.5; 0.5; 1.2	—
SECONDARY Change From Baseline in Clinical Chemistry Laboratory Tests: Sodium, Chloride, Potassium and Urea	0.4; 0.2; 0.6; -0.4; -0.04; 0.05	—
SECONDARY Change From Baseline in Clinical Chemistry Laboratory Tests: Vitamin B6	34.60; -215.73	—
SECONDARY Change From Baseline in Clinical Hematology Laboratory Tests: Erythrocytes	-0.04; 0.02	—
SECONDARY Change From Baseline in Clinical Hematology Laboratory Tests: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin Concentration	-1.7; 0.1; 1.5; -4.8	—
SECONDARY Change From Baseline in Clinical Hematology Laboratory Tests: Hematocrit	-0.004; 0.006	—
SECONDARY Change From Baseline in Clinical Hematology Laboratory Tests: Erythrocytes (Ery.) Mean Corpuscular Volume and Mean Platelet Volume	0.0; 1.1; -0.03; 0.61	—
SECONDARY Change From Baseline in Clinical Hematology Laboratory Tests: Erythrocytes Mean Corpuscular Hemoglobin	-0.1; -0.1	—
SECONDARY Change From Baseline in Clinical Hematology Laboratory Tests: Reticulocytes, Platelets, Leukocytes, Lymphocytes, Monocytes, Eosinophils, Basophils, Neutrophils	0.2; -23.1; -11.4; 2.3; 0.18; -1.03	—
SECONDARY Change From Baseline in Clinical Hematology Laboratory Tests: Lymphocytes/Leukocytes	-1.3; 5.1	—
SECONDARY Change From Baseline in Clinical Hematology Laboratory Tests: Monocytes/Leukocytes	1.0; 0.9	—
SECONDARY Change From Baseline in Clinical Hematology Laboratory Tests: Eosinophils/Leukocyte	0.4; 0.9	—
SECONDARY Change From Baseline in Clinical Hematology Laboratory Tests: Basophils/Leukocytes	0.0; 0.1	—
SECONDARY Change From Baseline in Clinical Hematology Laboratory Tests: Neutrophils/Leukocytes	-0.3; -7.1	—
SECONDARY Change From Baseline in Clinical Urinalysis Laboratory Tests: Specific Gravity	0.0000; -0.0008	—
SECONDARY Change From Baseline in Clinical Urinalysis Laboratory Tests: pH	0.29; -0.10	—
SECONDARY Maximum Observed Plasma Concentration (Cmax) of DCR-PHXC	778; 363; 774; 350; 648	—
SECONDARY Area Under the Curve From Time of Administration to the Last Measurable Concentration (AUC0-last) of of DCR-PHXC	12500; 6450; 12800; 6400; 6100	—

Summary

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)

Eligibility Criteria

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03847909). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.