Clinical trial NCT04555486: Study to Evaluate Safety, Tolerability, PK and PD of DCR-PHXC in PH Type 3 Patients
Official title: A Phase 1 Placebo-Controlled, Double-Blind, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Dose of DCR-PHXC in Patients With Primary Hyperoxaluria Type 3
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Primary Hyperoxaluria Type 3
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
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2020-09-18
Enrollment: 6
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Safety profile of a single dose of DCR-PHXC in PH3 Patients
timeFrame: Screening through Day 85
Secondary outcomes:
measure: Plasma pharmacokinetics (PK) of a single dose of DCR-PHXC in PH3 patients
timeFrame: Day 1 (dosing) through Day 29
measure: The proportion of participants achieving a > 30% decrease from baseline in 24-hour Urine Oxalate (Uox) on 2 consecutive visits
timeFrame: After screening, 24-hour Uox will be measured at Days 29, 43, 57, and 85.
Other outcomes:
Locations:
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: Bonn
country: Germany
facility: Clinical Trial Site
city: Amsterdam
country: Netherlands
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Dicerna Pharmaceuticals
name: Alexandra Haagensen, MD, MBA
role: STUDY_DIRECTOR
References: