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Trial record 1 of 1 for:    05001269
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Nedosiran in Pediatric Patients From Birth to 11 Years of Age With PH and Relatively Intact Renal Function (PHYOX8)

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ClinicalTrials.gov Identifier: NCT05001269
Recruitment Status : Recruiting
First Posted : August 11, 2021
Last Update Posted : December 1, 2022
Sponsor:
Information provided by (Responsible Party):
Dicerna Pharmaceuticals, Inc.

Study Description
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Brief Summary:
The aim of this study is to evaluate nedosiran in participants 11 years of age and younger who have Primary Hyperoxaluria with relatively intact renal function.

Condition or disease Intervention/treatment Phase
Primary Hyperoxaluria Primary Hyperoxaluria Type 1 Primary Hyperoxaluria Type 2 Primary Hyperoxaluria Type 3 Drug: nedosiran Phase 2

Detailed Description:

This is an open-label, repeat-dose, Phase 2 study of nedosiran in participants 11 years of age or younger who have PH1, PH2 or PH 3 and relatively intact renal function.

Following the up-to-35- day screening period, participants will return to the clinic for monthly dosing visits through Day 180.

The total duration of this study is approximately 15 months from first participant, first visit, until last participant, last visit.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: Children 2-11 years of age will begin enrolling prior to the under 2 year old age group's open.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Open-Label Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Nedosiran in Pediatric Patients From Birth to 11Years of Age With Primary Hyperoxaluria and Relatively Intact Renal Function
Actual Study Start Date : February 22, 2022
Estimated Primary Completion Date : November 2023
Estimated Study Completion Date : November 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Tests

Arms and Interventions
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Arm Intervention/treatment
Experimental: Open-Label DCR-PHXC
Open-Label monthly subcutaneous injection of DCR-PHXC based on age and weight.
 Drug: nedosiran
Monthly subcutaneous dosing throughout study period
Other Name: DCR-PHXC


Outcome Measures
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Primary Outcome Measures :
  1. Efficacy: Percent change in urinary oxalate to creatinine ratio [ Time Frame: 180 days ]
    Evaluate the effect of nedosiran on percent change in urinary oxalate-to-creatinine ratio

  2. Efficacy: Absolute change in urinary oxalate to creatinine ratio [ Time Frame: 180 days ]
    Evaluate the effect of nedosiran on absolute change in urinary oxalate-to-creatinine ratio


Secondary Outcome Measures :
  1. Safety: Incidence of Events [ Time Frame: 180 days ]
    Characterize the safety of nedosiran in children 11 years of age and younger based on treatment emergent adverse events, and serious adverse events.

  2. Safety: Changes from baseline in ECG: Rhythm [ Time Frame: 180 days ]
    Characterize the safety of nedosiran in children 11 years of age and younger changes from baseline in ECG.

  3. Safety: Changes from baseline in ECG: Ventricular Rate [ Time Frame: 180 days ]
    Characterize the safety of nedosiran in children 11 years of age and younger changes from baseline in ECG.

  4. Safety: Changes from baseline in ECG: PR interval [ Time Frame: 180 days ]
    Characterize the safety of nedosiran in children 11 years of age and younger changes from baseline in ECG.

  5. Safety: Changes from baseline in ECG: QRS duration [ Time Frame: 180 days ]
    Characterize the safety of nedosiran in children 11 years of age and younger changes from baseline in ECG.

  6. Safety: Changes from baseline in ECG: QT interval [ Time Frame: 180 days ]
    Characterize the safety of nedosiran in children 11 years of age and younger changes from baseline in ECG.

  7. Safety: Changes from baseline: Physical Exam [ Time Frame: 180 days ]
    Characterize the safety of nedosiran in children 11 years of age and younger changes from baseline in physical exam and physician review of systems based on CTCAE v5.0

  8. Safety: Changes from baseline in Vitals: temperature [ Time Frame: 180 days ]
    Characterize the safety of nedosiran in children 11 years of age and younger changes from baseline in vital signs.

  9. Safety: Changes from baseline in Vitals: pulse rate [ Time Frame: 180 days ]
    Characterize the safety of nedosiran in children 11 years of age and younger changes from baseline in vital signs.

  10. Safety: Changes from baseline in Vitals: respiratory rate [ Time Frame: 180 days ]
    Characterize the safety of nedosiran in children 11 years of age and younger changes from baseline in vital signs.

  11. Safety: Changes from baseline in Vitals: blood pressure [ Time Frame: 180 days ]
    Characterize the safety of nedosiran in children 11 years of age and younger changes from baseline in vital signs.

  12. Safety: Changes from baseline: Labs - Hematology [ Time Frame: 180 days ]
    Characterize the safety of nedosiran in children 11 years of age and younger changes from baseline in clinical laboratory tests.

  13. Safety: Changes from baseline: Labs - Clinical Chemistry [ Time Frame: 180 days ]
    Characterize the safety of nedosiran in children 11 years of age and younger changes from baseline in clinical laboratory tests.

  14. Safety: Changes from baseline: Labs - Coagulation [ Time Frame: 180 days ]
    Characterize the safety of nedosiran in children 11 years of age and younger changes from baseline in clinical laboratory tests.

  15. Safety: Changes from baseline: Labs - Antibody [ Time Frame: 180 days ]
    Characterize the safety of nedosiran in children 11 years of age and younger changes from baseline in clinical laboratory tests.

  16. Safety: Changes from baseline: Labs - Plasma Oxalate [ Time Frame: 180 days ]
    Characterize the safety of nedosiran in children 11 years of age and younger changes from baseline in clinical laboratory tests.

  17. Safety: Changes from baseline: Labs - Urinalysis [ Time Frame: 180 days ]
    Characterize the safety of nedosiran in children 11 years of age and younger changes from baseline in clinical laboratory tests.

  18. Safety: Changes from baseline: Labs - Urine Oxalate [ Time Frame: 180 days ]
    Characterize the safety of nedosiran in children 11 years of age and younger changes from baseline in clinical laboratory tests.

  19. To characterize the PK of DCR PHXC in patients with PH by observing secondary parameters of the area under the curve. [ Time Frame: 180 days ]
    Population and individual pharmacokinetic (PK) parameters for DCR PHXC, including secondary parameters of area under the curve (AUC)

  20. To characterize the PK of DCR PHXC in patients with PH by observing maximum observed concentration (Cmax). [ Time Frame: 180 days ]
    Population and individual pharmacokinetic (PK) parameters for DCR PHXC, including maximum observed concentration (Cmax)

  21. To characterize the PK of DCR PHXC in patients with PH by observing minimum concentration (Cmin). [ Time Frame: 180 days ]
    Population and individual pharmacokinetic (PK) parameters for DCR PHXC, including minimum observed concentration (Cmin)

  22. To characterize the PK of DCR PHXC in patients with PH by observing maximum concentration (Tmax). [ Time Frame: 180 days ]
    Population and individual pharmacokinetic (PK) parameters for DCR PHXC, including time to maximum concentration (Tmax)

  23. To characterize the PK of DCR PHXC in patients with PH by observing terminal elimination half-life (t1/2). [ Time Frame: 180 days ]
    Population and individual pharmacokinetic (PK) parameters for DCR PHXC, including terminal elimination half-life (t1/2)

  24. Efficacy: eGFR changes [ Time Frame: 180 days ]
    Evaluate the effect of nedosiran on eGFR from baseline


Other Outcome Measures:
  1. Change from Baseline in Plasma Oxalate Concentration [ Time Frame: 180 days ]
    Assess the effect of DCR-PHXC on Plasma Oxalate concentration from baseline

  2. Change from Baseline number of kidney stones [ Time Frame: 180 days ]
    Assess the effect of DCR-PHXC on stone burden from baseline on annualized stone events

  3. Change from baseline PedsQL™ [ Time Frame: 180 days ]
    Change from Baseline in the Pediatric Quality of Life Inventory (PedsQL™)

  4. Change from baseline WPAI [ Time Frame: 180 days ]
    Change from Baseline in the Work Productivity and Activity Impairment Questionnaire: Primary Hyperoxaluria V2.0, Clinical Practice Version (WPAI:PH, V2.0, CPV) - Caregiver


Eligibility Criteria
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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.


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Ages Eligible for Study:   up to 11 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Birth to 11 years of age inclusive, at the time of signing the informed consent.
  2. Documented diagnosis of PH1 or PH2 or PH3 confirmed by genotyping (historically available genotype information is acceptable for study eligibility).

  3. Average spot Uox to creatinine ratio at Screening above 2 times the 95th percentile for age (Matos et al, 1999):

    • > 0.44 mol/mol in participants < 6 months
    • > 0.34 mol/mol in participants from 6 months to < 12 months
    • > 0.26 mol/mol in participants 12 months to < 2 years
    • > 0.20 mol/mol in participants from 2 to < 3 years and
    • > 0.16 mol/mol in participants from 3 to < 5 years > 0.14 mol/mol in participants from 5 to <7 years > 0.12 mol/mol in participants from 7 to 11 years
  4. Estimated GFR at Screening ≥ 30 mL/min normalized to 1.73 m2 BSA. See Section 8.2.6.1 for equations. For infants aged less than 12 months, serum creatinine below the 97th percentile of a healthy population (Boer et al., 2010).
  5. Participants must have been on a stable treatment regimen for PH for 3 months prior to Day 1 and parent(s)/legal guardian should be willing to ensure participant remains on the same stable treatment regimen during the study.
  6. Body weight ≥10 kg

  7. Male or Female

    Male participants:

    A male participant with a female partner of childbearing potential must agree to use contraception, as detailed in Section 10.4.2, during the treatment period and for at least 12 weeks after the last dose of study intervention and refrain from donating sperm during this period.

    Female participants:

    A female participant is eligible to participate if she is not pregnant (see Section 10.4.1), not breastfeeding, and at least 1 of the following conditions applies:

    Not a woman of childbearing potential (WOCBP) as defined in Section 10.4.1 OR A WOCBP who agrees to follow the contraceptive guidance in Section 10.4.2 during the treatment period and for at least 12 weeks after the last dose of study intervention.

    Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

    Note: If the childbearing potential changes after start of the study (e.g., a premenarchal female participant experiences menarche) or the risk of pregnancy changes (e.g., a female participant who is not heterosexually active becomes active), the participant must discuss this with the Investigator, who should determine if a female participant must begin a highly effective method of contraception or a male participant must use a condom. If reproductive status is questionable, additional evaluation should be considered.

  8. Participant's parent or legal guardian is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

    a. For children younger than 12 years of age, assent will be based on local regulation. If assent is required, participant must be able to provide written assent for participation.

  9. A legal guardian or primary caregiver must be available to help the study-site personnel ensure follow up; accompany the participant to the study site on each assessment day according to the SoA (e.g., able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures); consistently and consecutively be available to provide information on the participant using the rating scales during the scheduled study visits; accurately and reliably dispense study intervention as directed.
  10. Affiliated with or is a beneficiary of a health insurance system (if applicable per national regulations)

Exclusion Criteria:

  1. Prior renal or hepatic transplantation; or planned transplantation within the study period
  2. Currently receiving dialysis or anticipating requirement for dialysis during the study period
  3. Plasma oxalate (Pox) > 30 μmol/L at Screening
  4. Documented evidence of clinical manifestations of severe systemic oxalosis (including preexisting retinal, heart, or skin calcifications, or history of severe bone pain, pathological fractures, or bone deformations)

  5. Presence of any condition or comorbidities that would interfere with study compliance or data interpretation or potentially impact participant's safety including, but not restricted to:

    1. Severe intercurrent illness
    2. Known causes of active liver disease/injury or transaminase elevation (e.g., alcoholic liver disease, nonalcoholic fatty liver disease/steatohepatitis [NAFLD/NASH])
    3. History of serious mental illness that includes, but is not limited to, schizophrenia, bipolar disorder, or severe depression requiring hospitalization or pharmacological intervention
    4. Clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, hematological, lymphatic, neurological, musculoskeletal, genitourinary, immunological diseases, including dermatological including rash, severe eczema or dermatitis, or connective tissue diseases or disorders
  6. Use of an RNAi drug within the last 6 months

  7. History of 1 or more of the following reactions to an oligonucleotide-based therapy:

    1. Severe thrombocytopenia (platelet count ≤ 100,000/µL)
    2. Hepatotoxicity, defined as ALT or AST > 3 times the upper ULN and total bilirubin > 2 × ULN or INR > 1.5
    3. Severe flu-like symptoms leading to discontinuation of therapy
    4. Localized skin reaction from the injection (graded severe) leading to discontinuation of therapy
    5. Coagulopathy/clinically significant prolongation of clotting time

  8. Participation in any clinical study in which they received an IMP within 4 months or 5 times the half-life of the drug (whichever is longer) before Screening

    a. For IMPs with the potential to reduce urine and/or plasma oxalate concentrations, these concentrations must have returned to historical baseline levels prior to Screening

  9. Liver function test (LFT) abnormalities: ALT and/or AST > 1.5 × ULN for age and gender
  10. Known hypersensitivity to nedosiran, or any of its ingredients
  11. Inability or unwillingness to comply with the specified study procedures, including the lifestyle considerations detailed in Section 5.3.
Contacts and Locations
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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): NCT05001269


Contacts
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Contact: Medical Information 617-621-8097 medicalinfo@dicerna.com

Locations
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United States, Georgia
Clinical Trial Site Not yet recruiting
Atlanta, Georgia, United States, 30329
Contact: Clinical Coordinator         
United States, Minnesota
Clinical Research Site Recruiting
Rochester, Minnesota, United States, 55905
Contact: Research Coordinator         
Canada, Ontario
Clinical Research Site Recruiting
Hamilton, Ontario, Canada, L8S 4K1
Contact: Research Coordinator         
France
Clinical Trial Site Not yet recruiting
Bron, France, 69677
Contact: Trial Coordinator         
Clinical Trial Site Not yet recruiting
Paris, France, 75019
Contact: Clinical Coordinator         
Germany
Clinical Trial Site Recruiting
Bonn, Germany, 53127
Contact: Clinical Coordinator         
Clinical Research Site Recruiting
Heidelberg, Germany, 69120
Contact: Research Coordinator         
Italy
Clinical Trial Site Recruiting
Roma, Italy, 00165
Contact: Clinical Coordinator         
Japan
Clinical Research Site Recruiting
Fukuoka, Japan, 830-0011
Contact: Research Coordinator         
Clinical Research Site Recruiting
Nagoya, Japan, 467-8602
Contact: Research Coordinator         
Lebanon
Clinical Research Site Recruiting
Beirut, Lebanon, 1100
Contact: Research Coordinator         
Clinical Research Site Not yet recruiting
Beirut, Lebanon, 2807
Contact: Research Coordinator         
Morocco
Clinical Trial Site Not yet recruiting
Casablanca, Maroc, Morocco, 20360
Contact: Clinical Coordinator         
Poland
Clinical Research Site Recruiting
Białystok, Poland, 15-274
Contact: Research Coordinator         
Spain
Clinical Research Site Recruiting
Barcelona, Spain, 08035
Contact: Research Coordinator         
Turkey
Clinical Research Site Recruiting
Yenimahalle, Ankara, Turkey, 06506
Contact: Research Coordinator         
United Arab Emirates
Clinical Trial Site Not yet recruiting
Dubai, United Arab Emirates, +971
Contact: Clinical Coordinator         
United Kingdom
Clinical Trial Site Recruiting
London, United Kingdom, WC1N 3JH
Contact: Research Coordinator         
Sponsors and Collaborators
Dicerna Pharmaceuticals, Inc.
Investigators
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Study Director: Sarb Shergill, PhD Dicerna Pharmaceuticals, Inc.
More Information
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Responsible Party: Dicerna Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT05001269    
Other Study ID Numbers: DCR-PHXC-203
First Posted: August 11, 2021    Key Record Dates
Last Update Posted: December 1, 2022
Last Verified: November 2022
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
PH3
pediatric
Additional relevant MeSH terms:
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Hyperoxaluria, Primary
Hyperoxaluria
Kidney Diseases
Urologic Diseases
 Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases