Long Term Extension Study in Patients With Primary Hyperoxaluria (PHYOX3)

• ClinicalTrials.gov Identifier: NCT04042402
• Recruitment Status: Enrolling by invitation
• First Posted: August 2, 2019
• Last Update Posted: January 12, 2024
• Sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
• Information provided by (Responsible Party): Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Tracking Information

• First Submitted Date: July 10, 2019
• First Posted Date: August 2, 2019
• Last Update Posted Date: January 12, 2024
• Actual Study Start Date: July 9, 2019
• Estimated Primary Completion Date: April 1, 2030 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 22, 2022)

The annual rate of decline in eGFR in participants with PH1 [ Time Frame: Annual change from baseline ]

To evaluate the effect of DCR PHXC on estimated glomerular filtration rate (eGFR) in participants with PH1

Original Primary Outcome Measures (submitted: July 30, 2019)

• The incidence and severity of treatment-emergent adverse events (TEAE) and serious adverse events (SAE) [ Time Frame: 3 years ]
• Change from Baseline in 12-lead electrocardiogram (ECG) [ Time Frame: 3 years ]
  Frequency counts will be presented per treatment for both change and absolute values for QTcF and uncorrected QT
• Change from Baseline in clinical hematology laboratory test for hemoglobin [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical hematology laboratory test for hematocrit [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical hematology laboratory test for platelet count [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical hematology laboratory test for mean platelet volume (MPV) [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical hematology laboratory test for reticulocytes [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical hematology laboratory test for mean corpuscular volume (MCV) [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical hematology laboratory test for mean corpuscular hemoglobin (MCH) [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical hematology laboratory test for mean corpuscular hemoglobin concentration (MCHC) [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical hematology laboratory test for lymphocytes [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical hematology laboratory test for monocytes [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical hematology laboratory test for eosinophils [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical hematology laboratory test for basophils [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical hematology laboratory test for neutrophils [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical chemistry laboratory test for alanine aminotransferase (ALT) [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical chemistry laboratory test for glutamate dehydrogenase (GLDH) [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical chemistry laboratory test for gamma-glutamyl transferase (GGT) [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical chemistry laboratory test for alkaline phosphatase (ALP) [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical chemistry laboratory test for bilirubin [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical chemistry laboratory test for lactate dehydrogenase (LDH) [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical chemistry laboratory test for total protein [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical chemistry laboratory test for creatine kinase [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical chemistry laboratory test for sodium [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical chemistry laboratory test for chloride [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical chemistry laboratory test for potassium [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical chemistry laboratory test for creatinine [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical chemistry laboratory test for blood urea nitrogen (BUN) [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical chemistry laboratory test for plasma oxalate [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical coagulation laboratory test for activated partial thromboplastin time (aPTT) [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical coagulation laboratory test for prothrombin time (PT) [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical coagulation laboratory test for international normalized ratio (INR) [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical urinalysis laboratory test for specific gravity [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical urinalysis laboratory test for pH [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical urinalysis laboratory test for glucose [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical urinalysis laboratory test for protein [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical urinalysis laboratory test for blood [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical urinalysis laboratory test for ketones [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical urinalysis laboratory test for bilirubin [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical urinalysis laboratory test for urobilinogen [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical urinalysis laboratory test for nitrite [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in clinical urinalysis laboratory test for leukocyte esterase [ Time Frame: 3 years ]
  Laboratory parameter shifts from baseline to abnormal post-baseline values
• Change from Baseline in blood pressure [ Time Frame: 3 years ]
  Change of systolic blood pressure and diastolic blood pressure from baseline to post-baseline values
• Change from Baseline in body temperature [ Time Frame: 3 years ]
  Change from baseline to post-baseline values
• Change from Baseline in heart rate [ Time Frame: 3 years ]
  Change from baseline to post-baseline values
• Change from Baseline in respiration rate [ Time Frame: 3 years ]
  Change from baseline to post-baseline values
• Change from Baseline in physical examination findings [ Time Frame: 3 years ]
  Each site/system will be summarized with respect to being normal or abnormal, or not performed.

Current Secondary Outcome Measures (submitted: July 27, 2023)

• The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal 12 lead electrocardiogram (ECG) readings [ Time Frame: TEAEs and SAEs are evaluated monthly for 6 years ]
  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.
• The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal physical examination findings [ Time Frame: TEAEs and SAEs are evaluated monthly for 6 years ]
  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.
• The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal vital signs [ Time Frame: TEAEs and SAEs are evaluated monthly for 6 years ]
  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.
• The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs related to abnormal clinical laboratory tests (hematology, chemistry, coagulation parameters, and urinalysis) [ Time Frame: TEAEs and SAEs are evaluated monthly for 6 years ]
  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.
• To identify the proportion of participants with normalized or near-normalized 24 hour urinary oxalate (Uox) [ Time Frame: 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. ]
  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
• To identify the percentage of participants with spot urinary oxalate-to-creatinine ratio ≤ the ULN or ≤ 1.5 x ULN [ Time Frame: 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. ]
  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
• To assess the effect of DCR-PHXC on stone events in patients with PH [ Time Frame: Evaluated yearly for 6 years ]
  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
• To assess the effect of DCR-PHXC on stone burden grade in patients with PH [ Time Frame: Evaluated yearly for 6 years ]
  Change from Baseline in the stone burden grade at Year 1, Year 2, etc. in PH1, PH2, and PH3 participant subgroups
• To assess the effect of DCR-PHXC in nephrocalcinosis grade in patients with PH [ Time Frame: Evaluated yearly for 6 years ]
  Change from Baseline in nephrocalcinosis grade at Year 1, Year 2, etc. in PH1, PH2, and PH3 participant subgroups
• To evaluate the incidence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in participants with PH [ Time Frame: 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. ]
  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
• Change from Baseline in the Short Form (36) Health Survey (SF-36®) in PH1, PH2, and PH3 participant subgroups [ Time Frame: Surveys are administered at screening, Day 180, yearly for 3.5 years, then at Month 72 (EOS). ]
  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.
• Change from Baseline in the EQ-5D-5L™ in adults in PH1, PH2, and PH3 participant subgroups [ Time Frame: Surveys are administered at screening, Day 180, yearly for 3.5 years, then at Month 72 (EOS). ]
  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.
• Change from Baseline in the Pediatric Quality of Life Inventory (PedsQL™) in children in PH1, PH2, and PH3 participant subgroups [ Time Frame: Surveys are administered at screening, Day 180, yearly for 3.5 years, then at Month 72 (EOS). ]
  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.
• To assess the efficacy of DCR PHXC in reducing Uox burden in patients with PH: TWS AUC [ Time Frame: Monthly for 4 months (D90 through D180) ]
  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.
• To assess the long-term efficacy of DCR PHXC in reducing Uox burden in patients with PH [ Time Frame: 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. ]
  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
• To assess the long-term efficacy of DCR-PHXC in reducing Uox burden in patients with PH [ Time Frame: 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. ]
  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

Original Secondary Outcome Measures (submitted: July 30, 2019)

• 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 BSA in participants aged < 18 years]) on at least 2 consecutive visits [ Time Frame: 3 months ]
• Proportion of participants with 24-hour Uox levels in each of 4 quartile ranges (< 1.1 mmol, 1.1 to < 1.6 mmol, 1.6 to ≤ 2.4 mmol, and > 2.4 mmol/24 hours from baseline to end of study [ Time Frame: 3 months ]
• Change from Baseline in the number of stone events over a 12-month period, annually in Year 1, Year 2, etc. [ Time Frame: 3 years ]
• Change from Baseline in the stone burden observed over a 12-month period, annually in Year 1, Year 2, etc. [ Time Frame: 3 years ]
• The number of participants with ESRD, defined as eGFR < 30 mL/min [ Time Frame: 3 years ]
• Change from Baseline in the Short Form Health Survey (SF-36) [ Time Frame: 1 year ]
• Change from Baseline in the Wisconsin Stone Quality of Life Questionnaire (WISQOL) [ Time Frame: 1 year ]
• Change from Baseline in the EQ-5D-5L in adults [ Time Frame: 1 year ]
• Change from Baseline in the ;Pediatric Quality of Life Inventory (PedsQL) in children [ Time Frame: 1 year ]
• Annual change in eGFR [ Time Frame: 3 years ]

Current Other Pre-specified Outcome Measures (submitted: July 27, 2023)

• To evaluate the effect of DCR PHXC on eGFR in participants with PH2 and PH3 [ Time Frame: Annual change from baseline ]
  The annual rate of decline in eGFR in participants with PH2 and PH3
• To characterize the PK of DCR PHXC in patients with PH by observing minimum concentration (Cmin). [ Time Frame: Participants rolling from a single dose study will be analyzed at Day 1, Day 2, Day 30, Day 31, Day 150, and Day 180; multidose rollovers will just collect Day 1 and 180. Then there will be analyses every 6 months for 2.5 years, and annually for 3 years. ]
  Population and/or individual pharmacokinetic (PK) parameters for DCR PHXC, including minimum observed concentration (Cmin)
• To characterize the PK of DCR PHXC in patients with PH by observing maximum concentration (Tmax). [ Time Frame: Participants rolling from a single dose study will be analyzed at Day 1, Day 2, Day 30, Day 31, Day 150, and Day 180; multidose rollovers will just collect Day 1 and 180. Then there will be analyses every 6 months for 2.5 years, and annually for 3 years. ]
  Population and/or individual pharmacokinetic (PK) parameters for DCR PHXC, including time to maximum concentration (Tmax)
• To characterize the PK of DCR PHXC in patients with PH by observing terminal elimination half-life (t1/2). [ Time Frame: Participants rolling from a single dose study will be analyzed at Day 1, Day 2, Day 30, Day 31, Day 150, and Day 180; multidose rollovers will just collect Day 1 and 180. Then there will be analyses every 6 months for 2.5 years, and annually for 3 years. ]
  Population and/or individual pharmacokinetic (PK) parameters for DCR PHXC, including terminal elimination half-life (t1/2)
• To characterize the PK of DCR PHXC in patients with PH by observing clearance. [ Time Frame: Participants rolling from a single dose study will be analyzed at Day 1, Day 2, Day 30, Day 31, Day 150, and Day 180; multidose rollovers will just collect Day 1 and 180. Then there will be analyses every 6 months for 2.5 years, and annually for 3 years. ]
  Population and/or individual pharmacokinetic (PK) parameters for DCR PHXC, including clearance (CL)
• To characterize the PK of DCR PHXC in patients with PH by observing volume of distribution of estimates. [ Time Frame: Participants rolling from a single dose study will be analyzed at Day 1, Day 2, Day 30, Day 31, Day 150, and Day 180; multidose rollovers will just collect Day 1 and 180. Then there will be analyses every 6 months for 2.5 years, and annually for 3 years. ]
  Population and/or individual pharmacokinetic (PK) parameters for DCR PHXC, including volume of distribution (V) estimates
• To characterize the PK of DCR PHXC in patients with PH by observing the area under the curve (AUC) [ Time Frame: Participants rolling from a single dose study will be analyzed at Day 1, Day 2, Day 30, Day 31, Day 150, and Day 180; multidose rollovers will just collect Day 1 and 180. Then there will be analyses every 6 months for 2.5 years, and annually for 3 years. ]
  Population and/or individual pharmacokinetic (PK) parameters for DCR PHXC, including secondary parameters of area under the curve (AUC)
• To characterize the PK of DCR PHXC in patients with PH by observing maximum observed concentration (Cmax). [ Time Frame: Participants rolling from a single dose study will be analyzed at Day 1, Day 2, Day 30, Day 31, Day 150, and Day 180; multidose rollovers will just collect Day 1 and 180. Then there will be analyses every 6 months for 2.5 years, and annually for 3 years. ]
  Population and/or individual pharmacokinetic (PK) parameters for DCR PHXC, including maximum observed concentration (Cmax)

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Long Term Extension Study in Patients With Primary Hyperoxaluria
• Official 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Primary Hyperoxaluria Type 1 (PH1)
• Primary Hyperoxaluria Type 2 (PH2)
• Kidney Diseases
• Urologic Diseases
• Genetic Disease
• Primary Hyperoxaluria Type 3 (PH3)

Intervention

Drug: DCR-PHXC

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

Other Name: Nedosiran

Study Arms

Experimental: Open Label

Open label, monthly subcutaneous injection

Intervention: Drug: DCR-PHXC

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Enrolling by invitation
• Estimated Enrollment (submitted: June 22, 2022): 75
• Original Estimated Enrollment (submitted: July 30, 2019): 50
• Estimated Study Completion Date: April 1, 2030
• Estimated Primary Completion Date: April 1, 2030 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

•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.

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, France, Germany, Italy, Japan, Lebanon, Netherlands, Norway, Spain, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT04042402
• Other Study ID Numbers: DCR-PHXC-301
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
• Original Responsible Party: Same as current
• Current Study Sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Verity Rawson, MB.CHB; Dicerna, A Novo Nordisk Company

• PRS Account: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
• Verification Date: January 2024