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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT04042402
Registration number
NCT04042402
Ethics application status
Date submitted
10/07/2019
Date registered
2/08/2019
Titles & IDs
Public title
Long Term Extension Study in Patients With Primary Hyperoxaluria
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Scientific title
An Open-Label Roll-Over Study to Evaluate the Long-Term Safety and Efficacy of DCR-PHXC Solution for Injection (Subcutaneous Use) in Patients With Primary Hyperoxaluria
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Secondary ID [1]
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DCR-PHXC-301
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Universal Trial Number (UTN)
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Trial acronym
PHYOX3
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Primary Hyperoxaluria Type 1 (PH1)
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Primary Hyperoxaluria Type 2 (PH2)
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Kidney Diseases
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Urologic Diseases
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Genetic Disease
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Primary Hyperoxaluria Type 3 (PH3)
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Condition category
Condition code
Renal and Urogenital
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Kidney disease
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Renal and Urogenital
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Other renal and urogenital disorders
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Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Metabolic and Endocrine
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Other metabolic disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - DCR-PHXC
Experimental: Open Label - Open label, monthly subcutaneous injection
Treatment: Drugs: DCR-PHXC
Multiple fixed doses of DCR-PHXC by subcutaneous (SC) injection
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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The annual rate of decline in eGFR in participants with PH1
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Assessment method [1]
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To evaluate the effect of DCR PHXC on estimated glomerular filtration rate (eGFR) in participants with PH1
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Timepoint [1]
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Annual change from baseline
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Secondary outcome [1]
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The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal 12 lead electrocardiogram (ECG) readings
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Assessment method [1]
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To evaluate the safety and tolerability of DCR PHXC when administered monthly to patients with primary hyperoxaluria (PH) via change from baseline and abnormal ECG findings.
Standard 12-lead ECGs will be performed in the supine position after the subject has rested comfortably for 10 minutes. The parameters assessed will be rhythm, ventricular rate, PR interval, QRS duration, QT interval, and corrected QT interval (QTcF, Fridericia correction). The Investigator or designee is responsible for reviewing the ECG(s) to assess whether the results are within normal limits and to determine the clinical significance of the results.
Standardized ECG acquisition equipment will be provided to all clinical trial sites at the start of the trial, to ensure parity across all sites.
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Timepoint [1]
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TEAEs and SAEs are evaluated monthly for 6 years
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Secondary outcome [2]
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The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal physical examination findings
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Assessment method [2]
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To evaluate the safety and tolerability of DCR PHXC when administered monthly to patients with primary hyperoxaluria (PH) via change from baseline and incidence of abnormal physical exam findings.
A full physical examination will include a complete review of body systems: eyes, ears, nose, and throat, chest/respiratory, heart/cardiovascular, gastrointestinal/liver, musculoskeletal/extremities, dermatological/skin, thyroid/neck, lymph nodes, and neurological. A full physical exam is done at Screening, Day 180 and if a participant ends the study early.
A brief physical examination will minimally include chest/respiratory, heart/cardiovascular, dermatological/skin, and gastrointestinal/liver. A brief physical examination will be performed at the Investigator's discretion at all other visits.
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Timepoint [2]
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TEAEs and SAEs are evaluated monthly for 6 years
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Secondary outcome [3]
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The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal vital signs
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Assessment method [3]
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To evaluate the safety and tolerability of DCR PHXC when administered monthly to patients with primary hyperoxaluria (PH) via the change from baseline and incidence of abnormal vital signs.
Vital signs include blood pressure, pulse/heart rate, oral body temperature, and respiratory rate.
Parameters will be measured in the supine position, using an automated instrument or manually, after the participant has rested comfortably for 10 minutes. In the pediatric population, an age-appropriate cuff size should be used for blood pressure measurements.
Temperature will be obtained in degrees Celsius (°C), pulse rate will be counted for a full minute and recorded in beats per minute, and respirations will be counted for a full minute and recorded in breaths per minute.
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Timepoint [3]
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TEAEs and SAEs are evaluated monthly for 6 years
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Secondary outcome [4]
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The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs related to abnormal clinical laboratory tests (hematology, chemistry, coagulation parameters, and urinalysis)
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Assessment method [4]
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To evaluate the safety and tolerability of DCR PHXC when administered monthly to patients with primary hyperoxaluria (PH) via the change from baseline and incidence of abnormal clinical laboratory tests.
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Timepoint [4]
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TEAEs and SAEs are evaluated monthly for 6 years
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Secondary outcome [5]
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To identify the proportion of participants with normalized or near-normalized 24 hour urinary oxalate (Uox)
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Assessment method [5]
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The proportion of participants with a 24 hour Uox level (\< 0.46 mmol/24 hours or = 0.46 - \< 0.60 mmol/24 hours \[adjusted per 1.73 m2 body surface area (BSA) in participants aged \< 18 years\]) at each assessment time point throughout the study in PH1, PH2, and PH3 participant subgroups
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Timepoint [5]
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24 hour urine collections (if applicable) are performed monthly for 6 months (or quarterly for PH1 multidose rollovers), quarterly for 2 1/2 years (or monthly for PH2/PH3 multidose rollovers until Month 12), and every 6 months for 3 years after that.
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Secondary outcome [6]
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To identify the percentage of participants with spot urinary oxalate-to-creatinine ratio = the ULN or = 1.5 x ULN
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Assessment method [6]
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The percentage of participants with spot urinary oxalate-to-creatinine ratio = the ULN or = 1.5 x ULN at each assessment time point throughout the study in PH1, PH2, and PH3 participant subgroups
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Timepoint [6]
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Spot urine collections are performed monthly for 6 months (or quarterly for PH1 multidose rollovers), quarterly for 2 1/2 years (or monthly for PH2/PH3 multidose rollovers until Month 12), and every 6 months for 3 years after that.
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Secondary outcome [7]
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To assess the effect of DCR-PHXC on stone events in patients with PH
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Assessment method [7]
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Change from Baseline in the number of stone events over a 12-month period, annually in Year 1, Year 2, etc. in PH1, PH2, and PH3 participant subgroups
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Timepoint [7]
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Evaluated yearly for 6 years
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Secondary outcome [8]
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To assess the effect of DCR-PHXC on stone burden grade in patients with PH
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Assessment method [8]
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Change from Baseline in the stone burden grade at Year 1, Year 2, etc. in PH1, PH2, and PH3 participant subgroups
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Timepoint [8]
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Evaluated yearly for 6 years
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Secondary outcome [9]
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To assess the effect of DCR-PHXC in nephrocalcinosis grade in patients with PH
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Assessment method [9]
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Change from Baseline in nephrocalcinosis grade at Year 1, Year 2, etc. in PH1, PH2, and PH3 participant subgroups
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Timepoint [9]
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Evaluated yearly for 6 years
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Secondary outcome [10]
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To evaluate the incidence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in participants with PH
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Assessment method [10]
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The number of participants with severe CKD (GFR = 15-29 mL/min) or ESRD (GFR \<15 mL/min); adjusted per 1.73 m2 BSA in participants aged \< 18 years in PH1, PH2, and PH3 participant subgroups
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Timepoint [10]
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eGFR is evaluated monthly for 6 months (or quarterly for multidose rollovers), quarterly for 2 1/2 years, and every 6 months for 3 years after that.
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Secondary outcome [11]
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Change from Baseline in the Short Form (36) Health Survey (SF-36®) in PH1, PH2, and PH3 participant subgroups
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Assessment method [11]
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To evaluate the effect of DCR-PHXC on Quality of Life (QoL) assessments in patients with PH.
The SF 36 is a set of generic, coherent, and easily administered quality-of-life measures that taps 8 health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. It also includes a single item that provides an indication of perceived change in health. The 36 items are identical to the MOS SF 36 described in Ware and Sherbourne (1992). Participants respond to each item on a categorical scale. Categorical answers are transformed to a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. All items are scored so that a high score defines a more favorable health state.
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Timepoint [11]
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Surveys are administered at screening, Day 180, yearly for 3.5 years, then at Month 72 (EOS).
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Secondary outcome [12]
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Change from Baseline in the EQ-5D-5L™ in adults in PH1, PH2, and PH3 participant subgroups
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Assessment method [12]
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To evaluate the effect of DCR-PHXC on Quality of Life (QoL) assessments in patients with PH.
The EQ-5D-5L consists of the EQ 5D descriptive system and the EQ visual analogue scale (EQ VAS).
The descriptive system has 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The digits for the 5 dimensions can be combined into a 5-digit number that describes the participant's health state.
The EQ VAS records the participant's self-rated health on a 20-cm vertical VAS, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine.' Participants are asked to place an "X" on the line that represents their health on that day.
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Timepoint [12]
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Surveys are administered at screening, Day 180, yearly for 3.5 years, then at Month 72 (EOS).
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Secondary outcome [13]
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Change from Baseline in the Pediatric Quality of Life Inventory (PedsQL™) in children in PH1, PH2, and PH3 participant subgroups
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Assessment method [13]
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To evaluate the effect of DCR-PHXC on Quality of Life (QoL) assessments in patients with PH.
The 23-item PedsQL is comprised of 5 items in the Emotional, Social, and School Functioning dimensions (Psychosocial Health) and 8 items in the Physical Functioning (Physical Health) dimension. Items are reverse-scored on a 0 to 4 Likert scale and linearly transformed to a 0 to 100 scale, so that higher scores indicate better functioning and HRQOL. Scale Scores are the sum of the items in each dimension, divided by the number of items answered.
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Timepoint [13]
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Surveys are administered at screening, Day 180, yearly for 3.5 years, then at Month 72 (EOS).
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Secondary outcome [14]
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To assess the efficacy of DCR PHXC in reducing Uox burden in patients with PH: TWS AUC
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Assessment method [14]
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Time-weighted standardized area under the curve (TWS AUC) of 24-hour Uox from Day 90 to Day 180, based on percent change from Baseline in PH1, PH2, and PH3 participant subgroups. This endpoint will only be assessed in participants previously randomized to placebo in a previous study of DCR- PHXC and pediatric siblings.
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Timepoint [14]
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Monthly for 4 months (D90 through D180)
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Secondary outcome [15]
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To assess the long-term efficacy of DCR PHXC in reducing Uox burden in patients with PH
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Assessment method [15]
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Percent change from Baseline in 24-hour Uox at each assessment time point throughout the study in PH1, PH2, and PH3 participant subgroups. In those participants randomized to placebo in a previous study of DCR-PHXC and pediatric siblings, this endpoint will be assessed only after Month 6
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Timepoint [15]
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24 hour urine collections (if applicable) are performed monthly for 6 months (or quarterly for PH1 multidose rollovers), quarterly for 2 1/2 years (or monthly for PH2/PH3 multidose rollovers until Month 12), and every 6 months for 3 years after that.
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Secondary outcome [16]
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To assess the long-term efficacy of DCR-PHXC in reducing Uox burden in patients with PH
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Assessment method [16]
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Percent and absolute change from Baseline in spot urinary oxalate-to-creatinine ratio at each assessment time point throughout the study in PH1, PH2, and PH3 participant subgroups. In pediatric siblings, this endpoint will be assessed only after Month 6
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Timepoint [16]
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Spot urine collections are performed monthly for 6 months (or quarterly for PH1 multidose rollovers), quarterly for 2 1/2 years (or monthly for PH2/PH3 multidose rollovers until Month 12), and every 6 months for 3 years after that.
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Eligibility
Key inclusion criteria
Key
•Participant successfully completed a Dicerna Pharmaceuticals, Inc. study of DCR PHXC.
OR Participant is the sibling of a participant who successfully completed a Dicerna Pharmaceuticals, Inc. study of DCR PHXC. Siblings must be younger than 18 years of age and must have genetically confirmed PH.
* For participants rolling over from a multidose study of DCR-PHXC, enrollment should occur within a window of 25 to 75 days from the last dose of study intervention.
* Estimated GFR at screening = 30 mL/min normalized to 1.73 m2 body surface area (BSA), calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) formula in participants aged = 18 years, or the multivariate equation by Schwartz in participants aged 12 months to 17 years. In Japan, the cystatin C-based Uemura formula will be used for participants aged 12 months to <2 years, the creatinine-based Uemura formula by will be used for participants aged 2 to 17 years, and the equation by Matsuo will be used in participants aged = 18 years.
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Minimum age
No limit
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Renal or hepatic transplantation (prior or planned within the study period)
* Plasma oxalate > 30 µmol/L
* Currently on dialysis
* Documented evidence of clinical manifestations of systemic oxalosis
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Study design
Purpose of the study
Treatment
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Allocation to intervention
NA
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
9/07/2019
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
1/04/2030
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Actual
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Sample size
Target
75
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
QLD
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Recruitment hospital [1]
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Clinical Research Site - Herston
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Recruitment hospital [2]
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Clinical Trial Site - Melbourne
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Recruitment postcode(s) [1]
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4029 - Herston
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Recruitment postcode(s) [2]
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3052 - Melbourne
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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Country [2]
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United States of America
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State/province [2]
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Massachusetts
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United States of America
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State/province [3]
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Minnesota
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Country [4]
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United States of America
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State/province [4]
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New York
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Country [5]
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Canada
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State/province [5]
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Ontario
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Country [6]
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France
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State/province [6]
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Bron
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Country [7]
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France
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State/province [7]
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Paris
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Country [8]
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Germany
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State/province [8]
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Bonn
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Country [9]
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Germany
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State/province [9]
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Heidelberg
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Country [10]
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Italy
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State/province [10]
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Roma
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Country [11]
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Japan
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State/province [11]
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Fukuoka
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Country [12]
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Japan
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State/province [12]
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Nagoya
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Country [13]
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Japan
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State/province [13]
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Tokyo
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Country [14]
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Lebanon
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State/province [14]
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Beirut
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Country [15]
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Netherlands
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State/province [15]
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Amsterdam
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Country [16]
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Norway
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State/province [16]
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Tromsø
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Country [17]
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Spain
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State/province [17]
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Barcelona
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Country [18]
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Turkey
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State/province [18]
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Ankara
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Country [19]
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United Kingdom
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State/province [19]
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London
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Country [20]
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United Kingdom
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State/province [20]
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Birmingham
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
The proposed study is designed to provide patients previously enrolled in Phase 1 and 2 studies of DCR-PHXC and their siblings (\<18 years old) long-term access to DCR-PHXC, and to evaluate the long-term safety and efficacy of DCR-PHXC in patients with PH.
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Trial website
https://clinicaltrials.gov/study/NCT04042402
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Verity Rawson, MB.CHB
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Address
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Dicerna, A Novo Nordisk Company
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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No/undecided IPD sharing reason/comment
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT04042402