Primary Hyperoxaluria Type 3
Conditions
Keywords
primary hyperoxaluria, primary hyperoxaluria type 3, primary hyperoxaluria 3, PH, PH type 3, PH3, RNAi, RNAi therapeutic, LDHA, LDH, GalNAc, siRNA, nedosiran, DCR-PHXC
Brief summary
The DCR-PHXC-104 study is designed to assess the safety, tolerability, and pharmacological parameters of a single dose of DCR-PHXC in Primary Hyperoxaluria Type 3 (PH3). Participants should have had at least one stone event within 12 months of screening and intact renal function.
Detailed description
Potential participants are screened over an up-to-35-day period (with an extra 7-day period for participants who are required to repeat screening 24-hour urine collections or initially unanalyzable screening laboratory assessment samples) prior to randomization. Eligible participants will receive a single dose of DCR-PHXC or placebo on Day 1. In order to maintain the treatment blind, 24-hour urine oxalate (Uox) results that could unblind the study will not be reported to investigative sites or other blinded personnel until the study has been unblinded. It is expected that approximately 10 participants will be screened in order to randomize 6 participants (2:1 randomization; 4 nedosiran:2 placebo) to the study. Following the up-to-6-week screening period, participants will return to the clinic for interim visits up to Day 85. Visits occurring between the Day 1 and the Day 85 visit may be conducted as at-home telemedicine visits at the discretion of the Investigator. The total time on study for each participant is approximately 18 weeks.
Interventions
DRUGDCR-PHXC
Intervention, drug, DCR-PHXC
DRUGSterile Normal Saline (0.9% NaCl)
Placebo comparator
Sponsors
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Participants are randomly assigned to one of two interventions: the study drug DCR-PHXC (also known as nedosiran) or the placebo comparator Sterile Normal Saline. For every 2 participants that receive DCR-PHXC, 1 participant will receive placebo. Thus, 4 participants are expected to receive DCR-PHXC, and 2 participants are expected to receive placebo.
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Genetically confirmed PH3 * 24-hour Uox excretion ≥ 0.7 mmol (adjusted per 1.73 m\^2 body surface area \[BSA\] in participants \< 18 years of age) on both assessments conducted in the screening period * Less than 20% variation between the two 24-hour urinary creatinine excretion values (mmol/kg/24 hours) in the screening period * Estimated glomerular filtration rate (eGFR) at screening ≥ 30 mL/min, normalized to 1.73 m\^2 BSA * History of at least one stone event within the last 12 months. Stone events are defined as any of the following: * renal stone requiring medical intervention, e.g., outpatient procedures such as lithotripsy, or hospitalization or inpatient surgical intervention for confirmed stone-related pain and/or complications; * stone passage with or without hematuria; or * renal colic requiring medication. Key
Exclusion criteria
* Documented evidence of clinical manifestations of systemic oxalosis (including pre-existing retinal, heart, or skin calcifications, or history of severe bone pain, pathological fractures, or bone deformations) * Plasma oxalate \> 30 μmol/L
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety profile of a single dose of DCR-PHXC in PH3 Patients | Screening through Day 85 | Number of patients with abnormalities in clinically significant laboratory results, vital signs, and 12-lead ECG findings |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma pharmacokinetics (PK) of a single dose of DCR-PHXC in PH3 patients | Day 1 (dosing) through Day 29 | Measure maximum plasma concentration of DCR-PHXC |
| The proportion of participants achieving a > 30% decrease from baseline in 24-hour Urine Oxalate (Uox) on 2 consecutive visits | After screening, 24-hour Uox will be measured at Days 29, 43, 57, and 85. | Participants must maintain at least a 30% decrease from the average of 2 screening 24-hour Uox values to be considered responders to treatment. The proportion of responders to non-responders will be utilize to assess the efficacy of a single dose of DCR-PHXC in PH3 patients. |
Countries
Germany, Netherlands, United Kingdom, United States
Outcome results
None listed