search
Back to results

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

Primary Purpose

Primary Hyperoxaluria Type 1 (PH1), Primary Hyperoxaluria Type 2 (PH2), Kidney Diseases

Status
Enrolling by invitation
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
DCR-PHXC
Sponsored by
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Hyperoxaluria Type 1 (PH1) focused on measuring Primary Hyperoxaluria, PH1, PH2, RNAi, GalNAc, LDHA, LDH, siRNA, PH3

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 (Levey & Stevens, 2010), or the multivariate equation by Schwartz in participants aged 6 to 17 years (Schwartz et al., 2012). In Japan, the formula by Uemura et al. will be used for participants aged 6 to 17 years, and the equation by Matsuo et al. will be used in participants aged ≥ 18 years (Uemura et al., 2014; Matsuo et al., 2009).

Key Exclusion Criteria:

  • Renal or hepatic transplantation (prior or planned within the study period)
  • Plasma oxalate > 30 µmol/L
  • Currently dialysis
  • Documented evidence of clinical manifestations of systemic oxalosis

Sites / Locations

  • Clinical Research Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Research Site
  • Clinical Trial Site
  • Clinical Research Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Research Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Research Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site
  • Clinical Trial Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Open Label

Arm Description

Open label, monthly subcutaneous injection

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal 12 lead electrocardiogram (ECG) readings
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
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
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)
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)
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
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
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
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
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
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
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
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
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-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
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
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

Full Information

First Posted
July 10, 2019
Last Updated
July 27, 2023
Sponsor
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
search

1. Study Identification

Unique Protocol Identification Number
NCT04042402
Brief Title
Long Term Extension Study in Patients With Primary Hyperoxaluria
Acronym
PHYOX3
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
July 9, 2019 (Actual)
Primary Completion Date
April 1, 2030 (Anticipated)
Study Completion Date
April 1, 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Hyperoxaluria Type 1 (PH1), Primary Hyperoxaluria Type 2 (PH2), Kidney Diseases, Urologic Diseases, Genetic Disease, Primary Hyperoxaluria Type 3 (PH3)
Keywords
Primary Hyperoxaluria, PH1, PH2, RNAi, GalNAc, LDHA, LDH, siRNA, PH3

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Open Label
Arm Type
Experimental
Arm Description
Open label, monthly subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
DCR-PHXC
Other Intervention Name(s)
Nedosiran
Intervention Description
Multiple fixed doses of DCR-PHXC by subcutaneous (SC) injection
Primary Outcome Measure Information:
Title
The annual rate of decline in eGFR in participants with PH1
Description
To evaluate the effect of DCR PHXC on estimated glomerular filtration rate (eGFR) in participants with PH1
Time Frame
Annual change from baseline
Secondary Outcome Measure Information:
Title
The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal 12 lead electrocardiogram (ECG) readings
Description
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.
Time Frame
TEAEs and SAEs are evaluated monthly for 6 years
Title
The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal physical examination findings
Description
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.
Time Frame
TEAEs and SAEs are evaluated monthly for 6 years
Title
The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal vital signs
Description
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.
Time Frame
TEAEs and SAEs are evaluated monthly for 6 years
Title
The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs related to abnormal clinical laboratory tests (hematology, chemistry, coagulation parameters, and urinalysis)
Description
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.
Time Frame
TEAEs and SAEs are evaluated monthly for 6 years
Title
To identify the proportion of participants with normalized or near-normalized 24 hour urinary oxalate (Uox)
Description
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
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.
Title
To identify the percentage of participants with spot urinary oxalate-to-creatinine ratio ≤ the ULN or ≤ 1.5 x ULN
Description
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
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.
Title
To assess the effect of DCR-PHXC on stone events in patients with PH
Description
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
Time Frame
Evaluated yearly for 6 years
Title
To assess the effect of DCR-PHXC on stone burden grade in patients with PH
Description
Change from Baseline in the stone burden grade at Year 1, Year 2, etc. in PH1, PH2, and PH3 participant subgroups
Time Frame
Evaluated yearly for 6 years
Title
To assess the effect of DCR-PHXC in nephrocalcinosis grade in patients with PH
Description
Change from Baseline in nephrocalcinosis grade at Year 1, Year 2, etc. in PH1, PH2, and PH3 participant subgroups
Time Frame
Evaluated yearly for 6 years
Title
To evaluate the incidence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in participants with PH
Description
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
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.
Title
Change from Baseline in the Short Form (36) Health Survey (SF-36®) in PH1, PH2, and PH3 participant subgroups
Description
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.
Time Frame
Surveys are administered at screening, Day 180, yearly for 3.5 years, then at Month 72 (EOS).
Title
Change from Baseline in the EQ-5D-5L™ in adults in PH1, PH2, and PH3 participant subgroups
Description
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.
Time Frame
Surveys are administered at screening, Day 180, yearly for 3.5 years, then at Month 72 (EOS).
Title
Change from Baseline in the Pediatric Quality of Life Inventory (PedsQL™) in children in PH1, PH2, and PH3 participant subgroups
Description
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.
Time Frame
Surveys are administered at screening, Day 180, yearly for 3.5 years, then at Month 72 (EOS).
Title
To assess the efficacy of DCR PHXC in reducing Uox burden in patients with PH: TWS AUC
Description
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.
Time Frame
Monthly for 4 months (D90 through D180)
Title
To assess the long-term efficacy of DCR PHXC in reducing Uox burden in patients with PH
Description
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
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.
Title
To assess the long-term efficacy of DCR-PHXC in reducing Uox burden in patients with PH
Description
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
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.
Other Pre-specified Outcome Measures:
Title
To evaluate the effect of DCR PHXC on eGFR in participants with PH2 and PH3
Description
The annual rate of decline in eGFR in participants with PH2 and PH3
Time Frame
Annual change from baseline
Title
To characterize the PK of DCR PHXC in patients with PH by observing minimum concentration (Cmin).
Description
Population and/or individual pharmacokinetic (PK) parameters for DCR PHXC, including minimum observed 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.
Title
To characterize the PK of DCR PHXC in patients with PH by observing maximum concentration (Tmax).
Description
Population and/or individual pharmacokinetic (PK) parameters for DCR PHXC, including time to 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.
Title
To characterize the PK of DCR PHXC in patients with PH by observing terminal elimination half-life (t1/2).
Description
Population and/or individual pharmacokinetic (PK) parameters for DCR PHXC, including 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.
Title
To characterize the PK of DCR PHXC in patients with PH by observing clearance.
Description
Population and/or individual pharmacokinetic (PK) parameters for DCR PHXC, including clearance (CL)
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.
Title
To characterize the PK of DCR PHXC in patients with PH by observing volume of distribution of estimates.
Description
Population and/or individual pharmacokinetic (PK) parameters for DCR PHXC, including volume of distribution (V) 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.
Title
To characterize the PK of DCR PHXC in patients with PH by observing the area under the curve (AUC)
Description
Population and/or individual pharmacokinetic (PK) parameters for DCR PHXC, including secondary parameters of 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.
Title
To characterize the PK of DCR PHXC in patients with PH by observing maximum observed concentration (Cmax).
Description
Population and/or individual pharmacokinetic (PK) parameters for DCR PHXC, including 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.

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
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 (Levey & Stevens, 2010), or the multivariate equation by Schwartz in participants aged 12 months to 17 years (Schwartz et al., 2012). In Japan, the cystatin C-based formula by Uemura et al. will be used for participants aged 12 months to <2 years, the creatinine-based formula by Uemura et al. will be used for participants aged 2 to 17 years, and the equation by Matsuo et al. will be used in participants aged ≥ 18 years (Uemura et al., 2014a; Uemura et al., 2014b; Matsuo et al., 2009). 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
Facility Information:
Facility Name
Clinical Research Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Clinical Trial Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Clinical Trial Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Clinical Trial Site
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Clinical Research Site
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Clinical Trial Site
City
Melbourne
ZIP/Postal Code
3052
Country
Australia
Facility Name
Clinical Research Site
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8S 4K1
Country
Canada
Facility Name
Clinical Trial Site
City
Bron
ZIP/Postal Code
69500
Country
France
Facility Name
Clinical Trial Site
City
Paris
ZIP/Postal Code
75019
Country
France
Facility Name
Clinical Trial Site
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
Clinical Trial Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Clinical Research Site
City
Roma
ZIP/Postal Code
00165
Country
Italy
Facility Name
Clinical Trial Site
City
Fukuoka
ZIP/Postal Code
830-0011
Country
Japan
Facility Name
Clinical Trial Site
City
Nagoya
ZIP/Postal Code
467-8601
Country
Japan
Facility Name
Clinical Trial Site
City
Tokyo
ZIP/Postal Code
183-8561
Country
Japan
Facility Name
Clinical Trial Site
City
Beirut
Country
Lebanon
Facility Name
Clinical Trial Site
City
Amsterdam
ZIP/Postal Code
1105AZ
Country
Netherlands
Facility Name
Clinical Trial Site
City
Tromsø
ZIP/Postal Code
9019
Country
Norway
Facility Name
Clinical Research Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Clinical Trial Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Clinical Trial Site
City
Ankara
ZIP/Postal Code
06560
Country
Turkey
Facility Name
Clinical Trial Site
City
Hampstead
State/Province
London
Country
United Kingdom
Facility Name
Clinical Trial Site
City
Birmingham
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Long Term Extension Study in Patients With Primary Hyperoxaluria

We'll reach out to this number within 24 hrs