PHYOX4: Study to Evaluate Safety, Tolerability, PK and PD of DCR-PHXC in PH Type 3 Patients

Sponsor

Dicerna Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT04555486

Collaborator

(none)

Enrollment

Locations

Arms

11.8

Actual Duration (Months)

Patient Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Hyperoxaluria Type 3	Drug: DCR-PHXC Drug: Sterile Normal Saline (0.9% NaCl)	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 14, 2020

Actual Primary Completion Date :

Sep 7, 2021

Actual Study Completion Date :

Sep 7, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DCR-PHXC Participants that are at least 12 years old will receive a single dose of 3 mg/kg DCR-PHXC (or nedosiran) via subcutaneous (SC) injection. Participants that are 6-11 years old will receive a single dose of 3.5 mg/kg DCR-PHXC (nedosiran) via SC injection.	Drug: DCR-PHXC Intervention, drug, DCR-PHXC Other Names: Nedosiran
Placebo Comparator: Sterile Normal Saline (0.9% NaCl) Participants will receive a single dose of Sterile Normal Saline (0.9% NaCl) for subcutaneous (SC) injection, administered at same injection volume as DCR-PHXC, to serve as placebo.	Drug: Sterile Normal Saline (0.9% NaCl) Placebo comparator

Arm

Intervention/Treatment

Experimental: DCR-PHXC

Participants that are at least 12 years old will receive a single dose of 3 mg/kg DCR-PHXC (or nedosiran) via subcutaneous (SC) injection. Participants that are 6-11 years old will receive a single dose of 3.5 mg/kg DCR-PHXC (nedosiran) via SC injection.

Drug: DCR-PHXC

Intervention, drug, DCR-PHXC

Other Names:

Nedosiran

Placebo Comparator: Sterile Normal Saline (0.9% NaCl)

Participants will receive a single dose of Sterile Normal Saline (0.9% NaCl) for subcutaneous (SC) injection, administered at same injection volume as DCR-PHXC, to serve as placebo.

Drug: Sterile Normal Saline (0.9% NaCl)

Placebo comparator

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Trial Site	Boston	Massachusetts	United States	02115
2	Clinical Trial Site	Rochester	Minnesota	United States	55905
3	Clinical Trial Site	New York	New York	United States	10016
4	Clinical Trial Site	Bonn		Germany	53127
5	Clinical Trial Site	Amsterdam		Netherlands	1105 AZ
6	Clinical Trial Site	London		United Kingdom	NW3 2QG