Study to Evaluate Safety, Tolerability, PK and PD of DCR-PHXC in PH Type 3 Patients

Primary Hyperoxaluria Type 3 Clinical Trial

— PHYOX4  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04555486
• Other study ID #: DCR-PHXC-104
• Status: Completed
• Phase: Phase 1
• Start date: September 14, 2020
• Est. completion date: September 7, 2021

Study information

• Verified date: September 2021
• Source: Dicerna Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: September 7, 2021
• Est. primary completion date: September 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hyperoxaluria, Primary
• Primary Hyperoxaluria Type 3

Intervention

Drug:
• DCR-PHXC
Intervention, drug, DCR-PHXC
• Sterile Normal Saline (0.9% NaCl)
Placebo comparator

Locations

Country	Name	City	State
Germany	Clinical Trial Site	Bonn
Netherlands	Clinical Trial Site	Amsterdam
United Kingdom	Clinical Trial Site	London
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Dicerna Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Germany,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety profile of a single dose of DCR-PHXC in PH3 Patients	Number of patients with abnormalities in clinically significant laboratory results, vital signs, and 12-lead ECG findings	Screening through Day 85
Secondary	Plasma pharmacokinetics (PK) of a single dose of DCR-PHXC in PH3 patients	Measure maximum plasma concentration of DCR-PHXC	Day 1 (dosing) through Day 29
Secondary	The proportion of participants achieving a > 30% decrease from baseline in 24-hour Urine Oxalate (Uox) on 2 consecutive visits	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.	After screening, 24-hour Uox will be measured at Days 29, 43, 57, and 85.