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

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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.

Tracking Information
First Submitted Date  ICMJE September 2, 2020
First Posted Date  ICMJE September 18, 2020
Last Update Posted Date September 10, 2021
Actual Study Start Date  ICMJE September 14, 2020
Actual Primary Completion Date September 7, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 14, 2020)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2020)
  • 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
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate Safety, Tolerability, PK and PD of DCR-PHXC in PH Type 3 Patients
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE 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
Condition  ICMJE Primary Hyperoxaluria Type 3
Intervention  ICMJE
  • Drug: DCR-PHXC
    Intervention, drug, DCR-PHXC
    Other Name: Nedosiran
  • Drug: Sterile Normal Saline (0.9% NaCl)
    Placebo comparator
Study Arms  ICMJE
  • 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.
    Intervention: Drug: DCR-PHXC
  • 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.
    Intervention: Drug: Sterile Normal Saline (0.9% NaCl)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 14, 2020)
6
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 7, 2021
Actual Primary Completion Date September 7, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Netherlands,   United Kingdom,   United States
Removed Location Countries France
 
Administrative Information
NCT Number  ICMJE NCT04555486
Other Study ID Numbers  ICMJE DCR-PHXC-104
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dicerna Pharmaceuticals, Inc.
Study Sponsor  ICMJE Dicerna Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Alexandra Haagensen, MD, MBA Dicerna Pharmaceuticals
PRS Account Dicerna Pharmaceuticals, Inc.
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP