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

Phase 2

Completed

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

• Registration Number: NCT03847909
• Lead Sponsor: Novo Nordisk A/S

Brief 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)

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-02-15
• Study First Submitted QC: 2019-02-18
• Study First Posted: 2019-02-20
• Study Start: 2019-10-28
• Primary Completion: 2021-06-21
• Study Completion: 2021-06-29
• Disposition First Submitted: 2022-06-20
• Results First Submitted: 2024-03-27
• Status Verified: 2024-05
• Results First Submitted QC: 2024-05-17
• Last Update Submitted: 2024-05-17
• Results First Posted: 2024-05-22
• Disposition First Posted: 2024-05-22
• Last Update Posted: 2024-05-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 35

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DCR-PHXC	DCR-PHXC	Intervention, drug, DCR-PHXC
Placebo - Sterile Normal Saline (0.9% NaCl)	Sterile Normal Saline (0.9% NaCl)	Placebo, sterile normal saline (0.9% NaCl) for subcutaneous (SC) injection

Primary Outcome Measures

Name	Time	Method
AUC From Day 90 To Day 180, Based on Percent Change From Baseline in 24-Hour Uox	From Day 90 to 180	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Vital Signs: Heart Rate	Baseline, Day 180	Change from baseline to Day 180 in heart rate is presented.
Change From Baseline in Electrocardiogram (ECG): Heart Rate	Baseline, Day 180	Change from baseline in heart rate is presented.
Change From Baseline in Clinical Hematology Laboratory Tests: Basophils/Leukocytes	Baseline, Day 180	Change from baseline to Day 180 in basophils/leukocytes is presented.
Change From Baseline in Vital Signs: Height	Baseline, Day 180	Change from baseline to Day 180 in height is presented.
Change From Baseline in Clinical Chemistry Laboratory Tests: Sodium, Chloride, Potassium and Urea	Baseline, Day 180	Change from baseline to Day 180 in sodium, chloride, potassium and urea are presented.
Change From Baseline in Clinical Hematology Laboratory Tests: Erythrocytes	Baseline, Day 180	Change from baseline to Day 180 in erythrocytes is presented.
Change From Baseline in Clinical Hematology Laboratory Tests: Erythrocytes (Ery.) Mean Corpuscular Volume and Mean Platelet Volume	Baseline, Day 180	Change from baseline to Day 180 in ery. mean corpuscular volume and mean platelet volume are presented.
Change From Baseline in Clinical Hematology Laboratory Tests: Reticulocytes, Platelets, Leukocytes, Lymphocytes, Monocytes, Eosinophils, Basophils, Neutrophils	Baseline, Day 180	Change from baseline to Day 180 in reticulocytes, platelets, leukocytes, lymphocytes, monocytes, eosinophils, basophils, neutrophils are presented.
Percent Change From Baseline to Day 180 in Plasma Oxalate (For Adults Only)	Baseline, Day 180	Percent change from baseline to Day 180 in plasma oxalate (for adults only) is presented.
Number of Treatment Emergent Adverse Events (TEAEs) And Serious Treatment Emergent Adverse Events (TEAEs)	From Baseline up to Day 180	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).
Change From Baseline in Clinical Chemistry Laboratory Tests: Alanine Aminotransferase, Aspartate Aminotransferase, Glutamate Dehydrogenase, Gamma Glutamyl Transferase, Alkaline Phosphatase, Lactate Dehydrogenase and Creatine Kinase	Baseline, Day 180	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.
Change From Baseline in Clinical Chemistry Laboratory Tests: Protein, Albumin	Baseline, Day 180	Change from baseline to Day 180 in protein and albumin are presented.
Percent Change From Baseline to Day 180 in the Summed Surface Area of Kidney Stones	Baseline, Day 180	Percent change from baseline to Day 180 in the summed surface area measured in millimetre square (mm\^2) of kidney stones is presented.
Change From Baseline in ECG: PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval	Baseline, Day 180	Change from baseline in PR interval, QRS duration, QT interval, QTcB interval, QTcF interval and RR interval is presented.
Change From Baseline in Vital Signs: Respiratory Rate	Baseline, Day 180	Change from baseline to Day 180 in respiratory rate is presented.
Change From Baseline in Vital Signs: Systolic and Diastolic Blood Pressure	Baseline, Day 180	Change from baseline to Day 180 in systolic and diastolic blood pressure is presented.
Change From Baseline in Clinical Chemistry Laboratory Tests: Vitamin B6	Baseline, Day 180	Change from baseline to Day 180 in vitamin B6 is presented.
Percent Change From Baseline to Day 180 in the Number of Kidney Stones	Baseline, Day 180	Percent change from baseline to Day 180 in the number of kidney stones is presented.
Rate of Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Day 180	Baseline, Day 180	Monthly rate of eGFR change is presented. eGFR was calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and creatinine-based equation.
Number of Participants With Most Abnormal Post-Baseline Shift in Physical Examination	Baseline up to Day 180	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.
Change From Baseline in Vital Signs: Weight	Baseline, Day 180	Change from baseline to Day 180 in weight is presented.
Change From Baseline in Vital Signs: Body Mass Index (BMI)	Baseline, Day 180	Change from baseline to Day 180 in BMI is presented.
Change From Baseline in Clinical Chemistry Laboratory Tests: Bilirubin, Direct Bilirubin and Creatinine	Baseline, Day 180	Change from baseline to Day 180 in bilirubin, direct bilirubin and creatinine are presented.
Change From Baseline in Clinical Hematology Laboratory Tests: Hematocrit	Baseline, Day 180	Change from baseline to Day 180 in hematocrit is presented.
Change From Baseline in Clinical Hematology Laboratory Tests: Lymphocytes/Leukocytes	Baseline, Day 180	Change from baseline to Day 180 in lymphocytes/leukocytes is presented.
Change From Baseline in Clinical Hematology Laboratory Tests: Neutrophils/Leukocytes	Baseline, Day 180	Change from baseline to Day 180 in neutrophils/leukocytes is presented.
Change From Baseline in Clinical Urinalysis Laboratory Tests: pH	Baseline, Day 180	Change from baseline to Day 180 in urine pH is presented.
Area Under the Curve From Time of Administration to the Last Measurable Concentration (AUC0-last) of of DCR-PHXC	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	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.
Percentage of Participants Whose 24-hour Uox Values Normalized or Near-normalized on at Least 2 Consecutive Visits	From Day 90 to 180	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).
Change From Baseline in Vital Signs: Oral Body Temperature	Baseline, Day 180	Change from baseline to Day 180 in oral body temperature is presented.
Change From Baseline in Clinical Hematology Laboratory Tests: Monocytes/Leukocytes	Baseline, Day 180	Change from baseline to Day 180 in monocytes/leukocytes is presented.
Maximum Observed Plasma Concentration (Cmax) of DCR-PHXC	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	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.
Change From Baseline in Clinical Hematology Laboratory Tests: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin Concentration	Baseline, Day 180	Change from baseline to Day 180 in hemoglobin and erythrocytes mean corpuscular hemoglobin concentration are presented.
Change From Baseline in Clinical Hematology Laboratory Tests: Erythrocytes Mean Corpuscular Hemoglobin	Baseline, Day 180	Change from baseline to Day 180 in erythrocytes mean corpuscular hemoglobin is presented.
Change From Baseline in Clinical Hematology Laboratory Tests: Eosinophils/Leukocyte	Baseline, Day 180	Change from baseline to Day 180 in eosinophils/leukocytes is presented.
Change From Baseline in Clinical Urinalysis Laboratory Tests: Specific Gravity	Baseline, Day 180	Change from baseline to Day 180 in urine specific gravity is presented.

Trial Locations

Locations (1)

Clinical Trial Site; 🇬🇧 London, United Kingdom