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

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

Sponsors

Lead Sponsor: Dicerna Pharmaceuticals, Inc.

Source Dicerna Pharmaceuticals, Inc.
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.

Overall Status Not yet recruiting
Start Date September 2020
Completion Date April 2021
Primary Completion Date April 2021
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Safety profile of a single dose of DCR-PHXC in PH3 Patients Screening through Day 85
Secondary Outcome
Measure Time Frame
Plasma pharmacokinetics (PK) of a single dose of DCR-PHXC in PH3 patients Day 1 (dosing) through Day 29
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.
Enrollment 6
Condition
Intervention

Intervention Type: Drug

Intervention Name: DCR-PHXC

Description: Intervention, drug, DCR-PHXC

Arm Group Label: DCR-PHXC

Other Name: Nedosiran

Intervention Type: Drug

Intervention Name: Sterile Normal Saline (0.9% NaCl)

Description: Placebo comparator

Arm Group Label: Sterile Normal Saline (0.9% NaCl)

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

Gender: All

Minimum Age: 6 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Alexandra Haagensen, MD, MBA Study Director Dicerna Pharmaceuticals
Overall Contact

Last Name: Medical Info

Phone: 617-621-8097

Email: [email protected]

Location
Facility:
Clinical Trial Site | Boston, Massachusetts, 02115, United States
Clinical Trial Site | Rochester, Minnesota, 55905, United States
Clinical Trial Site | New York, New York, 10016, United States
Clinical Trial Site | Bron, 69500, France
Clinical Trial Site | Heidelberg, Baden-Wuerttemberg, 69120, Germany
Clinical Trial Site | Bonn, 53127, Germany
Clinical Trial Site | Amsterdam, 1105 AZ, Netherlands
Clinical Trial Site | London, NW3 2QG, United Kingdom
Location Countries

France

Germany

Netherlands

United Kingdom

United States

Verification Date

September 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: DCR-PHXC

Type: Experimental

Description: 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.

Label: Sterile Normal Saline (0.9% NaCl)

Type: Placebo Comparator

Description: 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.

Acronym PHYOX4
Study Design Info

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.

Primary Purpose: Treatment

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

Source: ClinicalTrials.gov