Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04555486
Recruitment Status : Completed
First Posted : September 18, 2020
Last Update Posted : September 10, 2021
Sponsor:
Information provided by (Responsible Party):
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.

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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.
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 : September 14, 2020
Actual Primary Completion Date : September 7, 2021
Actual Study Completion Date : September 7, 2021


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 Name: 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




Primary Outcome Measures :
  1. Safety profile of a single dose of DCR-PHXC in PH3 Patients [ Time Frame: Screening through Day 85 ]
    Number of patients with abnormalities in clinically significant laboratory results, vital signs, and 12-lead ECG findings


Secondary Outcome Measures :
  1. Plasma pharmacokinetics (PK) of a single dose of DCR-PHXC in PH3 patients [ Time Frame: Day 1 (dosing) through Day 29 ]
    Measure maximum plasma concentration of DCR-PHXC

  2. The proportion of participants achieving a > 30% decrease from baseline in 24-hour Urine Oxalate (Uox) on 2 consecutive visits [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04555486


Locations
Layout table for location information
United States, Massachusetts
Clinical Trial Site
Boston, Massachusetts, United States, 02115
United States, Minnesota
Clinical Trial Site
Rochester, Minnesota, United States, 55905
United States, New York
Clinical Trial Site
New York, New York, United States, 10016
Germany
Clinical Trial Site
Bonn, Germany, 53127
Netherlands
Clinical Trial Site
Amsterdam, Netherlands, 1105 AZ
United Kingdom
Clinical Trial Site
London, United Kingdom, NW3 2QG
Sponsors and Collaborators
Dicerna Pharmaceuticals, Inc.
Investigators
Layout table for investigator information
Study Director: Alexandra Haagensen, MD, MBA Dicerna Pharmaceuticals
Layout table for additonal information
Responsible Party: Dicerna Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04555486    
Other Study ID Numbers: DCR-PHXC-104
First Posted: September 18, 2020    Key Record Dates
Last Update Posted: September 10, 2021
Last Verified: September 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dicerna Pharmaceuticals, Inc.:
primary hyperoxaluria
primary hyperoxaluria type 3
primary hyperoxaluria 3
PH
PH type 3
PH3
RNAi
RNAi therapeutic
LDHA
LDH
GalNAc
siRNA
nedosiran
DCR-PHXC
Additional relevant MeSH terms:
Layout table for MeSH terms
Hyperoxaluria, Primary
Hyperoxaluria
Kidney Diseases
Urologic Diseases
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases