Clinical trial NCT03847909: A Study to Evaluate DCR-PHXC in Children and Adults With Primary Hyperoxaluria Type 1 and Primary Hyperoxaluria Type 2
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Hyperoxaluria Type 1 (PH1)
Primary Hyperoxaluria Type 2 (PH2)
Kidney Diseases
Urologic Diseases
Genetic Disease
Keywords: PH1
PH2
Primary Hyperoxaluria
RNAi
RNAi therapeutic
GalNAc
LDHA gene
LDH
siRNA
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2019-02-20
Enrollment: 35
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


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

Primary outcomes:
measure: AUC From Day 90 To Day 180, Based on Percent Change From Baseline in 24-Hour Uox
timeFrame: From Day 90 to 180
Secondary outcomes:
measure: Percentage of Participants Whose 24-hour Uox Values Normalized or Near-normalized on at Least 2 Consecutive Visits
timeFrame: From Day 90 to 180
measure: Percent Change From Baseline to Day 180 in the Summed Surface Area of Kidney Stones
timeFrame: Baseline, Day 180
measure: Percent Change From Baseline to Day 180 in the Number of Kidney Stones
timeFrame: Baseline, Day 180
measure: Percent Change From Baseline to Day 180 in Plasma Oxalate (For Adults Only)
timeFrame: Baseline, Day 180
measure: Rate of Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Day 180
timeFrame: Baseline, Day 180
measure: Number of Treatment Emergent Adverse Events (TEAEs) And Serious Treatment Emergent Adverse Events (TEAEs)
timeFrame: From Baseline up to Day 180
measure: Change From Baseline in Electrocardiogram (ECG): Heart Rate
timeFrame: Baseline, Day 180
measure: Change From Baseline in ECG: PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval
timeFrame: Baseline, Day 180
measure: Number of Participants With Most Abnormal Post-Baseline Shift in Physical Examination
timeFrame: Baseline up to Day 180
measure: Change From Baseline in Vital Signs: Height
timeFrame: Baseline, Day 180
measure: Change From Baseline in Vital Signs: Weight
timeFrame: Baseline, Day 180
measure: Change From Baseline in Vital Signs: Body Mass Index (BMI)
timeFrame: Baseline, Day 180
measure: Change From Baseline in Vital Signs: Oral Body Temperature
timeFrame: Baseline, Day 180
measure: Change From Baseline in Vital Signs: Heart Rate
timeFrame: Baseline, Day 180
measure: Change From Baseline in Vital Signs: Respiratory Rate
timeFrame: Baseline, Day 180
measure: Change From Baseline in Vital Signs: Systolic and Diastolic Blood Pressure
timeFrame: Baseline, Day 180
measure: Change From Baseline in Clinical Chemistry Laboratory Tests: Alanine Aminotransferase, Aspartate Aminotransferase, Glutamate Dehydrogenase, Gamma Glutamyl Transferase, Alkaline Phosphatase, Lactate Dehydrogenase and Creatine Kinase
timeFrame: Baseline, Day 180
measure: Change From Baseline in Clinical Chemistry Laboratory Tests: Bilirubin, Direct Bilirubin and Creatinine
timeFrame: Baseline, Day 180
measure: Change From Baseline in Clinical Chemistry Laboratory Tests: Protein, Albumin
timeFrame: Baseline, Day 180
measure: Change From Baseline in Clinical Chemistry Laboratory Tests: Sodium, Chloride, Potassium and Urea
timeFrame: Baseline, Day 180
measure: Change From Baseline in Clinical Chemistry Laboratory Tests: Vitamin B6
timeFrame: Baseline, Day 180
measure: Change From Baseline in Clinical Hematology Laboratory Tests: Erythrocytes
timeFrame: Baseline, Day 180
measure: Change From Baseline in Clinical Hematology Laboratory Tests: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin Concentration
timeFrame: Baseline, Day 180
measure: Change From Baseline in Clinical Hematology Laboratory Tests: Hematocrit
timeFrame: Baseline, Day 180
measure: Change From Baseline in Clinical Hematology Laboratory Tests: Erythrocytes (Ery.) Mean Corpuscular Volume and Mean Platelet Volume
timeFrame: Baseline, Day 180
measure: Change From Baseline in Clinical Hematology Laboratory Tests: Erythrocytes Mean Corpuscular Hemoglobin
timeFrame: Baseline, Day 180
measure: Change From Baseline in Clinical Hematology Laboratory Tests: Reticulocytes, Platelets, Leukocytes, Lymphocytes, Monocytes, Eosinophils, Basophils, Neutrophils
timeFrame: Baseline, Day 180
measure: Change From Baseline in Clinical Hematology Laboratory Tests: Lymphocytes/Leukocytes
timeFrame: Baseline, Day 180
measure: Change From Baseline in Clinical Hematology Laboratory Tests: Monocytes/Leukocytes
timeFrame: Baseline, Day 180
measure: Change From Baseline in Clinical Hematology Laboratory Tests: Eosinophils/Leukocyte
timeFrame: Baseline, Day 180
measure: Change From Baseline in Clinical Hematology Laboratory Tests: Basophils/Leukocytes
timeFrame: Baseline, Day 180
measure: Change From Baseline in Clinical Hematology Laboratory Tests: Neutrophils/Leukocytes
timeFrame: Baseline, Day 180
measure: Change From Baseline in Clinical Urinalysis Laboratory Tests: Specific Gravity
timeFrame: Baseline, Day 180
measure: Change From Baseline in Clinical Urinalysis Laboratory Tests: pH
timeFrame: Baseline, Day 180
measure: Maximum Observed Plasma Concentration (Cmax) of DCR-PHXC
timeFrame: 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
measure: Area Under the Curve From Time of Administration to the Last Measurable Concentration (AUC0-last) of of DCR-PHXC
timeFrame: 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
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Clinical Trial Site
state: California
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Rochester
country: United States
facility: Clinical Trial Site
state: Minnesota
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: Pittsburgh
country: United States
facility: Clinical Trial Site
state: Pennsylvania
city: Herston
country: Australia
facility: Clinical Trial Site
city: Parkville
country: Australia
facility: Clinical Trial Site
city: Hamilton
country: Canada
facility: Clinical Trial Site
city: Bron
country: France
facility: Clinical Trial Site
city: Paris
country: France
facility: Clinical Trial Site
city: Bonn
country: Germany
facility: Clinical Trial Site
city: Heidelberg
country: Germany
facility: Clinical Trial Site
city: Jerusalem
country: Israel
facility: Clinical Trial Site
city: Roma
country: Italy
facility: Clinical Trial Site
city: Nagoya
country: Japan
facility: Clinical Trial Site
city: Tochigi
country: Japan
facility: Clinical Trial Site
city: Tokyo
country: Japan
facility: Clinical Trial Site
city: Beirut
country: Lebanon
facility: Clinical Trial Site
city: Beirut
country: Lebanon
facility: Clinical Trial Site
city: Amsterdam
country: Netherlands
facility: Clinical Trial Site
city: Auckland
country: New Zealand
facility: Clinical Trial Site
city: Białystok
country: Poland
facility: Clinical Trial Site
city: Bucharest
country: Romania
facility: Clinical Trial Site
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Santa Cruz
country: Spain
facility: Clinical Trial Site
city: Birmingham
country: United Kingdom
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 1452)
role: STUDY_DIRECTOR
References: