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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)

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ClinicalTrials.gov Identifier: NCT03847909
Recruitment Status : Active, not recruiting
First Posted : February 20, 2019
Last Update Posted : January 20, 2021
Sponsor:
Information provided by (Responsible Party):
Dicerna Pharmaceuticals, Inc.

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)

Condition or disease Intervention/treatment Phase
Primary Hyperoxaluria Type 1 (PH1) Primary Hyperoxaluria Type 2 (PH2) Kidney Diseases Urologic Diseases Genetic Disease Drug: DCR-PHXC Drug: Sterile Normal Saline (0.9% NaCl) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : October 28, 2019
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021


Arm Intervention/treatment
Experimental: DCR-PHXC
Intervention, drug, DCR-PHXC
Drug: DCR-PHXC
Multiple fixed doses of DCR-PHXC by subcutaneous (SC) injection
Other Name: nedosiran

Placebo Comparator: Placebo - Sterile Normal Saline (0.9% NaCl)
Placebo, sterile normal saline (0.9% NaCl) for subcutaneous (SC) injection
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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) ]
  2. 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 ]
  3. 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

  4. Rate of change in eGFR from baseline to Day 180 [ Time Frame: 6 months ]
  5. AE and SAE throughout the study [ Time Frame: 6 months ]
  6. 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.


  7. 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.


  8. 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.


  9. 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.

  10. To characterize the PK of DCR-PHXC in PH patients [ Time Frame: 6 months ]
    Maximum observed plasma concentration (Cmax)

  11. To characterize the PK of DCR-PHXC in PH patients [ Time Frame: 6 months ]
    Area under the plasma concentration versus time curve (AUC)



Information from the National Library of Medicine

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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:

  • 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

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): NCT03847909


Locations
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United States, Massachusetts
Clinical Trial Site
Boston, Massachusetts, United States, 02115
United States, Minnesota
Clinical Trial Site
Minneapolis, Minnesota, United States, 55905
United States, New York
Clinical Trial Site
New York, New York, United States, 10016
United States, Pennsylvania
Clinical Trial Site
Pittsburgh, Pennsylvania, United States, 15224
Australia
Clinical Trial Site
Parkville, Australia, 3052
Canada
Clinical Trial Site
Hamilton, Canada
France
Clinical Trial Site
Bron, France
Clinical Trial Site
Paris, France, 75019
Germany
Clinical Trial Site
Bonn, Germany, 53127
Clinical Trial Site
Heidelberg, Germany, 69120
Israel
Clinical Trial Site
Jerusalem, Israel, 9103102
Italy
Clinical Trial Site
Roma, Italy, 00165
Japan
Clinical Trial Site
Nagoya, Japan, 467-8601
Clinical Trial Site
Tochigi, Japan, 329-0431
Clinical Trial Site
Tokyo, Japan, 183-8561
Lebanon
Clinical Trial Site
Beirut, Lebanon, 2807
Clinical Trial Site
Beirut, Lebanon
Netherlands
Clinical Trial Site
Amsterdam, Netherlands, 1105 AZ
New Zealand
Clinical Trial Site
Auckland, New Zealand
Poland
Clinical Trial Site
Białystok, Poland
Romania
Clinical Trial Site
Bucharest, Romania
Spain
Clinical Trial Site
Barcelona, Spain, 08035
Clinical Trial Site
Santa Cruz, Spain, 38320
United Kingdom
Clinical Trial Site
Birmingham, United Kingdom
Clinical Trial Site
London, United Kingdom, WCIN 3JH
Clinical Trial Site
London, United Kingdom
Sponsors and Collaborators
Dicerna Pharmaceuticals, Inc.
Investigators
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Study Director: Alexandra Haagensen, MD Dicerna Pharmaceuticals, Inc.
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Responsible Party: Dicerna Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03847909    
Other Study ID Numbers: DCR-PHXC-201
First Posted: February 20, 2019    Key Record Dates
Last Update Posted: January 20, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dicerna Pharmaceuticals, Inc.:
PH1
PH2
Primary Hyperoxaluria
RNAi
RNAi therapeutic
GalNAc
LDHA gene
LDH
siRNA
Additional relevant MeSH terms:
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Kidney Diseases
Hyperoxaluria, Primary
Urologic Diseases
Genetic Diseases, Inborn
Hyperoxaluria
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases