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A Study to Evaluate DCR-PHXC in Children and Adults With Primary Hyperoxaluria Type 1 and Primary Hyperoxaluria Type 2 (PHYOX2)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03847909
Recruitment Status : Recruiting
First Posted : February 20, 2019
Last Update Posted : September 29, 2020
Sponsor:
Information provided by (Responsible Party):
Dicerna Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE February 15, 2019
First Posted Date  ICMJE February 20, 2019
Last Update Posted Date September 29, 2020
Actual Study Start Date  ICMJE October 28, 2019
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 18, 2020)
Area under the curve (AUC) of percent change from baseline in 24-hour urinary oxalate excretion between Day 90 and Day 180 [ Time Frame: 3 months (Last 3 months of the 6 month treatment period) ]
Four measurements of percent change from baseline in 24-hour urinary oxalate are combined to determine a single AUC value
Original Primary Outcome Measures  ICMJE
 (submitted: February 18, 2019)
Time-weighted standardized (TWS) area under the curve (AUC) of percent change from baseline in 24-hour urinary oxalate excretion between Day 90 and Day 180 [ Time Frame: 3 months (Last 3 months of the 6 month treatment period) ]
Four measurements of percent change from baseline in 24-hour urinary oxalate are combined to determine a single AUC value
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2020)
  • Proportion of participants with a 24-hour Uox level < 0.46 mmol/24 hours or ≥ 0.46 - < 0.60 mmol/24 hours (adjusted per 1.73 m2 BSA in participants aged <18 years) on at least two consecutive study visits commencing at Day 90 and ending at Day 180 [ Time Frame: 3 months (Last 3 months of the 6 month treatment period) ]
  • Percent change in the summed surface area and number of kidney stones identified via kidney ultrasound from baseline to Day 180 [ Time Frame: 6 months ]
  • Percent change from baseline to Day 180 in plasma oxalate (for adults only) [ Time Frame: 6 months ]
    Four measurements of percent change from baseline in plasma oxalate are combined to determine a single AUC value
  • Rate of change in eGFR from baseline to Day 180 [ Time Frame: 6 months ]
  • AE and SAE throughout the study [ Time Frame: 6 months ]
  • Change from baseline in 12-lead ECG [ Time Frame: 6 months ]
    Standard 12-lead ECGs will be performed in the supine position after the subject has rested comfortably for 10 minutes. The parameters assessed will be rhythm, ventricular rate, PR interval, QRS duration, QT interval, and corrected QT interval (QTcF, Fridericia correction). The Investigator or designee is responsible for reviewing the ECG(s) to assess whether the results are within normal limits and to determine the clinical significance of the results. Standardized ECG acquisition equipment will be provided to all clinical trial sites at the start of the trial, to ensure parity across all sites.
  • The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal physical examination findings [ Time Frame: 6 months ]
    A full physical examination will include a complete review of body systems: eyes, ears, nose, and throat, chest/respiratory, heart/cardiovascular, gastrointestinal/liver, musculoskeletal/extremities, dermatological/skin, thyroid/neck, lymph nodes, and neurological. A full physical exam is done at Screening, Day 180 and if a participant ends the study early. A brief physical examination will minimally include chest/respiratory, heart/cardiovascular, dermatological/skin, and gastrointestinal/liver. A brief physical examination will be performed may be performed at the Investigator's discretion at all other visits.
  • The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs associated with abnormal vital signs [ Time Frame: 6 months ]
    Vital signs include blood pressure, pulse/heart rate, oral body temperature, and respiratory rate. Parameters will be measured in the supine position, using an automated instrument or manually, after the participant has rested comfortably for 10 minutes. In the pediatric population, an age-appropriate cuff size should be used for blood pressure measurements. Temperature will be obtained in degrees Celsius (°C), pulse rate will be counted for a full minute and recorded in beats per minute, and respirations will be counted for a full minute and recorded in breaths per minute.
  • The incidence and severity of treatment-emergent adverse events (TEAE) and SAEs related to abnormal clinical laboratory tests (hematology, chemistry, coagulation parameters, and urinalysis) [ Time Frame: 6 months ]
    To evaluate the safety and tolerability of DCR PHXC when administered monthly to patients with primary hyperoxaluria (PH) via the change from baseline and incidence of abnormal clinical laboratory tests.
  • To characterize the PK of DCR-PHXC in PH patients [ Time Frame: 6 months ]
    Maximum observed plasma concentration (Cmax)
  • To characterize the PK of DCR-PHXC in PH patients [ Time Frame: 6 months ]
    Area under the plasma concentration versus time curve (AUC)
Original Secondary Outcome Measures  ICMJE
 (submitted: February 18, 2019)
  • TWS AUC of percent change from baseline in 24-hour urinary oxalate-to-creatinine ratio (value/upper limit of normal [ULN]) between Day 90 and Day 180 [ Time Frame: 3 months (Last 3 months of the 6 month treatment period) ]
    Four measurements of percent change from baseline in 24-hour urinary oxalate-to-creatinine ratio are combined to determine a single AUC value
  • Proportion of participants with a 24-hour Uox level < 0.46 mmol/24 hours or ≥ 0.46 - < 0.60 mmol/24 hours at at least two consecutive study visits commencing at Day 90 and ending at Day 180 [ Time Frame: At least 2 months starting at Day 90 and through Day 180 ]
  • Proportion of participants with 24-hour Uox levels in each of 4 quartile ranges (< 1.1 mmol, 1.1 to < 1.6 mmol, 1.6 to ≤ 2.4 mmol, and > 2.4 mmol/24 hours from baseline to Day 180 [ Time Frame: 7 months ]
  • TWS AUC of percent change from baseline in 24-hour urinary oxalate-to-creatinine ratio (value/upper limit of normal [ULN]) between baseline and Day 180 [ Time Frame: 7 months ]
  • TWS AUC of percent change from baseline in plasma oxalate [ Time Frame: 3 months (Last 3 months of the 6 month treatment period) ]
    Four measurements of percent change from baseline in plasma oxalate are combined to determine a single AUC value
  • Frequency of Adverse events (AE) from baseline to study completion [ Time Frame: 7 months ]
  • Frequency of serious adverse events (SAE) from baseline to study completion [ Time Frame: 7 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate DCR-PHXC in Children and Adults With Primary Hyperoxaluria Type 1 and Primary Hyperoxaluria Type 2
Official Title  ICMJE A Phase 2 Placebo-Controlled, Double-Blind, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of DCR-PHXC Solution for Injection (Subcutaneous Use) in Patients With Primary Hyperoxaluria
Brief Summary The purpose of this study is to evaluate the efficacy and safety of DCR-PHXC in Children and Adults with Primary Hyperoxaluria Type 1 (PH1) and Primary Hyperoxaluria Type 2 (PH2)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Primary Hyperoxaluria Type 1 (PH1)
  • Primary Hyperoxaluria Type 2 (PH2)
  • Kidney Diseases
  • Urologic Diseases
  • Genetic Disease
Intervention  ICMJE
  • Drug: DCR-PHXC
    Multiple fixed doses of DCR-PHXC by subcutaneous (SC) injection
    Other Name: nedosiran
  • Drug: Sterile Normal Saline (0.9% NaCl)
    Sterile Normal Saline (0.9% NaCl) for subcutaneous (SC) injection, administered at same injection volume as DCR-PHXC, to serve as placebo
Study Arms  ICMJE
  • Experimental: DCR-PHXC
    Intervention, drug, DCR-PHXC
    Intervention: Drug: DCR-PHXC
  • Placebo Comparator: Placebo - Sterile Normal Saline (0.9% NaCl)
    Placebo, sterile normal saline (0.9% NaCl) for subcutaneous (SC) injection
    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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 18, 2019)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Capable and willing to provide written informed consent or assent
  • Documented diagnosis of PH1 or PH2, confirmed by genotyping
  • Must meet the 24 hour urine oxalate excretion requirements
  • Less than 20% variation between the two 24-hour urinary creatinine excretion values derived from the two 24-hour urine collections in the screening period
  • Estimated GFR at screening ≥ 30 mL/min normalized to 1.73 m2 BSA

Key Exclusion Criteria:

  • Renal or hepatic transplantation (prior or planned within the study period)
  • Currently on dialysis or anticipated requirement for dialysis during the study period
  • Plasma oxalate >30 µmol/L
  • 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)
  • Use of an RNA interference (RNAi) drug within the last 6 months
  • Participation in any clinical study in which you received an investigational medicinal product (IMP) within 4 months before Screening
  • Liver function test (LFT) abnormalities: Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >1.5 times upper limit of normal (ULN) for age and gender
  • Inability or unwillingness to comply with study procedures
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: Medical Info 617-621-8097 medicalinfo@dicerna.com
Listed Location Countries  ICMJE Australia,   Canada,   France,   Germany,   Israel,   Italy,   Japan,   Lebanon,   Netherlands,   New Zealand,   Poland,   Romania,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03847909
Other Study ID Numbers  ICMJE DCR-PHXC-201
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
Plan to Share IPD: No
Responsible Party Dicerna Pharmaceuticals, Inc.
Study Sponsor  ICMJE Dicerna Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Alexandra Haagensen, MD Dicerna Pharmaceuticals, Inc.
PRS Account Dicerna Pharmaceuticals, Inc.
Verification Date September 2020

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