Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2018-003099-10
    Sponsor's Protocol Code Number:DCR-PHXC-301
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2018-12-07
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2018-003099-10
    A.3Full title of the trial
    An Open-Label Roll-Over Study to Evaluate the Long-Term Safety and Efficacy of DCR PHXC Solution for Injection (subcutaneous use) in Patients with Primary Hyperoxaluria
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study for patients with Primary Hyperoxaluria to evaluate the Long-Term Safety and Efficacy of DCR-PHXC Solution for Injection
    A.3.2Name or abbreviated title of the trial where available
    PHYOX-3
    A.4.1Sponsor's protocol code numberDCR-PHXC-301
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04042402
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1224-7484
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorDicerna Pharmaceuticals Inc
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportDicerna Pharmaceuticals Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationDicerna Pharmaceuticals Inc
    B.5.2Functional name of contact pointKerry Russell
    B.5.3 Address:
    B.5.3.1Street Address75 Hayden Ave. Suite 400
    B.5.3.2Town/ cityLexington
    B.5.3.3Post codeMA 02421
    B.5.3.4CountryUnited States
    B.5.4Telephone number001607-621-8097 0393
    B.5.6E-mailKRussell@dicerna.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/18/2052
    D.3 Description of the IMP
    D.3.1Product nameNedosiran
    D.3.2Product code DCR-PHXC
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDCR-L1360
    D.3.9.2Current sponsor codeDCR-PHXC
    D.3.9.3Other descriptive nameNedosiran
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number170
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Primary Hyperoxaluria
    E.1.1.1Medical condition in easily understood language
    Primary hyperoxaluria is where the liver overproduces oxalate. As a result calcium-oxalate crystals form in the urinary system and lead to stones and impaired kidney function.
    E.1.1.2Therapeutic area Diseases [C] - Nutritional and Metabolic Diseases [C18]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10020703
    E.1.2Term Hyperoxaluria
    E.1.2System Organ Class 10038359 - Renal and urinary disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the effect of DCR PHXC on estimated glomerular filtration rate (eGFR)
    E.2.2Secondary objectives of the trial
    Key Secondary:
    To evaluate the safety and tolerability of DCR PHXC when administered monthly to patients with PH
    Secondary:
    1. To identify the proportion of participants with normalized or near-normalized 24-hour Uox
    2. To assess the effect of DCR-PHXC on stone events in patients with PH
    3. To assess the effect of DCR-PHXC on stone burden in patients with PH
    4. To evaluate the incidence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in participants with PH
    5. To evaluate the effect of DCR-PHXC on Quality of Life (QoL) assessments in patients with PH
    6. To assess the efficacy of DCR PHXC in reducing Uox burden in patients with PH
    7. To assess the long-term efficacy of DCR PHXC in reducing Uox burden in patients with PH

    Exploratory objectives:
    1. To characterize the PK of DCR-PHXC in patients with PH
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    In order to be eligible to participate in this study, an individual must meet all of the following criteria:
    Age
    1. Participant must be at least 6 years of age, at the time of signing the informed consent/assent.
    Type of Participant and Disease Characteristics
    2. Documented diagnosis of PH, confirmed by genotyping (historically available genotype information is acceptable for study eligibility)
    3. Participant successfully completed a Dicerna Pharmaceuticals, Inc. study of DCR PHXC, or is the sibling of a participant who successfully completed a Dicerna Pharmaceuticals, Inc. study of DCR PHXC.
    a. For participants rolling over from a multidose study of DCR-PHXC, enrollment should occur within a window of 25 to 75 days from the last dose of study intervention. In order to minimize any gap in administration of DCR-PHXC, every effort should be made to enroll participants as soon as all assessments from the previous study have been completed. It should be noted if the participant was required to repeat the end-of-study (EOS) 24-hour Uox collection for violation of completeness criteria.
    b. Siblings must
    i. be younger than 18 years of age
    ii. meet all other eligibility criteria (including genotyping)
    iii. have two 24-hour Uox values ≥  0.7 mmol (adjusted per 1.73 m2 BSA) at screening
    iv. have less than 20% variation between the two 24-hour urinary creatinine excretion values obtained in the screening period. Individuals who do not achieve < 20% variation between the 2 screening values may undergo a second round of urine collection. An extra 7 calendar days may be added to the screening window for participants to complete a second round of urine collection. Should potential participants again fail to achieve the within-20% variation, they will be excluded from participation.
    4. Estimated GFR at screening ≥ 30 mL/min normalized to 1.73 m2 BSA, calculated using the CKD-EPI equation in participants aged ≥ 18 years (Levey & Stevens, 2010), or the 2012 multivariate equation by Schwartz in participants aged 6 to 17 years (Schwartz et al., 2012). In Japan, the equation by Uemura et al. will be used for participants aged 6 to 17 years and the equation by Matsuo et al. will be used in participants aged ≥ 18 years (Uemura et al., 2014; Matsuo et al., 2009).
    Note: For participants rolling over from a 6-month multidose study of DCR-PHXC, the eGFR value from either the Day 150 or Day 180 (EOS) visit may be used for screening.
    Sex
    5. 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 one 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.
    Informed Consent/Assent
    6. Participant (and/or participant’s parent or legal guardian if participant is a minor [defined as patient < 18 years of age, or younger than the age of majority, according to local regulations]) is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
    a. Adolescents (12 to < 18 years of age, or older than 12 years but younger than the age of majority, according to local regulations) must be able to provide written assent for participation.
    b. For children younger than 12 years of age, assent will be based on local regulations.
    E.4Principal exclusion criteria
    An individual who meets any of the following criteria will be excluded from participation in this study:
    Medical Conditions
    1. Prior renal or hepatic transplantation; or planned transplantation within the study period
    2. Currently receiving dialysis
    3. 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)
    Prior/Concomitant Therapy
    4. Use of an RNAi drug (other than DCR-PHXC) within the last 6 months
    5. History of one or more of the following reactions to an oligonucleotide-based therapy:
    a. severe thrombocytopenia (platelet count ≤ 100,000/µL)
    b. hepatotoxicity, defined as (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 3 × the upper limit of normal [ULN]) and (total bilirubin > 2 × ULN or International Normalized Ratio [INR] >1.5)
    c. severe flu-like symptoms leading to discontinuation of therapy
    d. localized skin reaction from the injection (graded severe) leading to discontinuation of therapy
    e. coagulopathy/clinically significant prolongation of clotting time
    6. Participants receiving pyridoxine (vitamin B6) must have been at a stable dose for at least 4 weeks prior to Day 1 and must be willing to remain on the same stable dose throughout the study.
    Prior/Concurrent Clinical Study Experience
    7. Participation in any clinical study in which they received an investigational medicinal product (IMP) other than DCR-PHXC within 4 months before Screening.
    a. For IMPs (other than DCR-PHXC) with the potential to reduce urine and/or plasma oxalate concentrations, these concentrations must have returned to historical baseline levels prior to Screening.
    Diagnostic Assessments
    8. Plasma oxalate > 30 µmol/L
    Note: For participants > 18 years of age rolling over from a 6-month multidose study of DCR-PHXC, the plasma oxalate value from either the Day 150 or Day 180 (EOS) visit may be used for screening. If the previous study is blinded at the time of entry in DCR PHXC-301, plasma oxalate values will be reviewed by the unblinded Medical Monitor. For participants ≤ 18 years of age rolling over from a 6 month multidose study of DCR-PHXC, the plasma oxalate value from Screening in the previous study will be used.
    Other Exclusions
    9. Known hypersensitivity to DCR PHXC or any of its ingredients
    10. Inability or unwillingness to comply with the specified study procedures, including collection of 24-hour urine samples, and the lifestyle considerations detailed in Section 5.3.
    E.5 End points
    E.5.1Primary end point(s)
    The annual rate of decline in eGFR.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Ongoing evaluation of all medical assessments and patient’s quality of life questionnaires. Continuous risk-benefit assessments will be conducted by the Sponsor and the Medical Monitor of the CRO.
    E.5.2Secondary end point(s)
    Key Secondary:
    •The incidence and severity of treatment-emergent adverse events (TEAE) and serious adverse events (SAE)
    •Change from Baseline in 12-lead electrocardiogram (ECG), physical examination findings, vital signs, and clinical laboratory tests (hematology, chemistry, coagulation parameters, and urinalysis)
    Secondary:
    1. The 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 body surface area (BSA) in participants aged < 18 years]) at quarterly intervals throughout the study
    2. Change from Baseline in the number of stone events over a 12-month period, annually in Year 1, Year 2, etc.
    3. Change from Baseline in the stone burden at Year 1, Year 2, etc.
    4. The number of participants with severe CKD (GFR = 15 29 mL/min) or ESRD (GFR <15 mL/min); adjusted per 1.73 m2 BSA in participants aged < 18 years
    5. Change from Baseline in the Short Form (36) Health Survey (SF-36®), Wisconsin Stone Quality of Life Questionnaire (WISQOL), and EQ-5D-5L in adults; and in the Pediatric Quality of Life Inventory (PedsQL) in children
    6. Area under the curve (AUC) of 24-hour Uox from Day 90 to Day 180, based on percent change from Baseline. This endpoint will only be assessed in participants randomized to placebo in a previous study of DCR-PHXC and pediatric siblings of participants who successfully completed a Dicerna study of DCR-PHXC
    7. Percent change from Baseline in 24-hour Uox at 3-month intervals throughout the study. This endpoint will be assessed only after Month 6 in those participants randomized to placebo in a previous study of DCR PHXC and pediatric siblings of participants who successfully completed a Dicerna study of DCR-PHXC

    Exploratory:
    1. Population and individual pharmacokinetic (PK) parameters for DCR PHXC, including clearance (CL) and volume of distribution (V) estimates along with secondary parameters of area under the curve (AUC), maximum observed concentration (Cmax), minimum observed concentration (Cmin), time to maximum concentration (Tmax), and terminal elimination half-life (t1/2)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Ongoing evaluation of all medical assessments and patient’s quality of life questionnaires. Continuous risk-benefit assessments will be conducted by the Sponsor and the Medical Monitor of the CRO.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA30
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Canada
    Israel
    Japan
    Lebanon
    New Zealand
    United States
    France
    Germany
    Italy
    Netherlands
    Poland
    Romania
    Spain
    United Kingdom
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    A participant is considered to have completed the study if he or she has completed all phases of the study including the last visit or the last scheduled procedure shown in the Schedule of Activities (SoA), Section 1.3 in the protocol.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 20
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 10
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 10
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 28
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 2
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 32
    F.4.2.2In the whole clinical trial 50
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    All participants will receive open-label DCR-PHXC until commercial approval of DCR-PHXC in the participant’s country or the program is terminated by Sponsor.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-01-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-03-01
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri Apr 26 20:39:46 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA