Clinical trial NCT04042402: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: 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
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2019-08-02
Enrollment: 75
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: The annual rate of decline in eGFR in participants with PH1
timeFrame: Annual change from baseline
Secondary outcomes:
measure: The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal 12 lead electrocardiogram (ECG) readings
timeFrame: TEAEs and SAEs are evaluated monthly for 6 years
measure: The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal physical examination findings
timeFrame: TEAEs and SAEs are evaluated monthly for 6 years
measure: The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal vital signs
timeFrame: TEAEs and SAEs are evaluated monthly for 6 years
measure: The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs related to abnormal clinical laboratory tests (hematology, chemistry, coagulation parameters, and urinalysis)
timeFrame: TEAEs and SAEs are evaluated monthly for 6 years
measure: To identify the proportion of participants with normalized or near-normalized 24 hour urinary oxalate (Uox)
timeFrame: 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.
measure: To identify the percentage of participants with spot urinary oxalate-to-creatinine ratio ≤ the ULN or ≤ 1.5 x ULN
timeFrame: 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.
measure: To assess the effect of DCR-PHXC on stone events in patients with PH
timeFrame: Evaluated yearly for 6 years
measure: To assess the effect of DCR-PHXC on stone burden grade in patients with PH
timeFrame: Evaluated yearly for 6 years
measure: To assess the effect of DCR-PHXC in nephrocalcinosis grade in patients with PH
timeFrame: Evaluated yearly for 6 years
measure: To evaluate the incidence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in participants with PH
timeFrame: 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.
measure: Change from Baseline in the Short Form (36) Health Survey (SF-36®) in PH1, PH2, and PH3 participant subgroups
timeFrame: Surveys are administered at screening, Day 180, yearly for 3.5 years, then at Month 72 (EOS).
measure: Change from Baseline in the EQ-5D-5L™ in adults in PH1, PH2, and PH3 participant subgroups
timeFrame: Surveys are administered at screening, Day 180, yearly for 3.5 years, then at Month 72 (EOS).
measure: Change from Baseline in the Pediatric Quality of Life Inventory (PedsQL™) in children in PH1, PH2, and PH3 participant subgroups
timeFrame: Surveys are administered at screening, Day 180, yearly for 3.5 years, then at Month 72 (EOS).
measure: To assess the efficacy of DCR PHXC in reducing Uox burden in patients with PH: TWS AUC
timeFrame: Monthly for 4 months (D90 through D180)
measure: To assess the long-term efficacy of DCR PHXC in reducing Uox burden in patients with PH
timeFrame: 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.
measure: To assess the long-term efficacy of DCR-PHXC in reducing Uox burden in patients with PH
timeFrame: 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 outcomes:
measure: To evaluate the effect of DCR PHXC on eGFR in participants with PH2 and PH3
timeFrame: Annual change from baseline
measure: To characterize the PK of DCR PHXC in patients with PH by observing minimum concentration (Cmin).
timeFrame: 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.
measure: To characterize the PK of DCR PHXC in patients with PH by observing maximum concentration (Tmax).
timeFrame: 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.
measure: To characterize the PK of DCR PHXC in patients with PH by observing terminal elimination half-life (t1/2).
timeFrame: 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.
measure: To characterize the PK of DCR PHXC in patients with PH by observing clearance.
timeFrame: 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.
measure: To characterize the PK of DCR PHXC in patients with PH by observing volume of distribution of estimates.
timeFrame: 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.
measure: To characterize the PK of DCR PHXC in patients with PH by observing the area under the curve (AUC)
timeFrame: 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.
measure: To characterize the PK of DCR PHXC in patients with PH by observing maximum observed concentration (Cmax).
timeFrame: 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.
Locations:
city: San Francisco
country: United States
facility: Clinical Research Site
state: California
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Rochester
country: United States
facility: Clinical Trial Site
state: Minnesota
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: Herston
country: Australia
facility: Clinical Research Site
state: Queensland
city: Melbourne
country: Australia
facility: Clinical Trial Site
city: Hamilton
country: Canada
facility: Clinical Research Site
state: Ontario
city: Bron
country: France
facility: Clinical Trial Site
city: Paris
country: France
facility: Clinical Trial Site
city: Bonn
country: Germany
facility: Clinical Trial Site
city: Heidelberg
country: Germany
facility: Clinical Trial Site
city: Roma
country: Italy
facility: Clinical Research Site
city: Fukuoka
country: Japan
facility: Clinical Trial Site
city: Nagoya
country: Japan
facility: Clinical Trial Site
city: Tokyo
country: Japan
facility: Clinical Trial Site
city: Beirut
country: Lebanon
facility: Clinical Trial Site
city: Amsterdam
country: Netherlands
facility: Clinical Trial Site
city: Tromsø
country: Norway
facility: Clinical Trial Site
city: Barcelona
country: Spain
facility: Clinical Research Site
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Ankara
country: Turkey
facility: Clinical Trial Site
city: Hampstead
country: United Kingdom
facility: Clinical Trial Site
state: London
city: Birmingham
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Dicerna, A Novo Nordisk Company
name: Verity Rawson, MB.CHB
role: STUDY_DIRECTOR
References: