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    The EU Clinical Trials Register currently displays   43845   clinical trials with a EudraCT protocol, of which   7282   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).

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    Summary
    EudraCT Number:2018-003099-10
    Sponsor's Protocol Code Number:DCR-PHXC-301
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2019-04-17
    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 ConcernedPoland - Office for Medicinal Products
    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.5.3WHO 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 pointRalf Rosskamp
    B.5.3 Address:
    B.5.3.1Street Address87 Cambridge Park Drive
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeMA 02140
    B.5.3.4CountryUnited States
    B.5.4Telephone number001617 612 6275
    B.5.6E-mailrrosskamp@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 nameDCR-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.3.10 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 safety and tolerability of DCR-PHXC when administered monthly to patients with PH
    E.2.2Secondary objectives of the trial
    1.To identify the proportion of participants with normalized or near-normalized Uox
    2.To identify the change in relative risk of participants with PH for end-stage renal disease (ESRD)
    3.To assess the effect of DCR-PHXC on stone events in patients with PH
    4.To assess the effect of DCR-PHXC on stone burden in patients with PH
    5.To evaluate the incidence of ESRD in participants with PH
    6.To evaluate the effect of DCR-PHXC on Quality of Life (QoL) assessments in patients with PH.
    7.To evaluate the effect on DCR-PHXC on estimated glomerular filtration rate (eGFR)

    Exploratory objectives:
    1.To assess the efficacy of DCR-PHXC in reducing Uox burden in patients with PH
    2.To evaluate the long-term pharmacoeconomics of PH
    3.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.
    a. For participants rolling over from Study DCR-PHXC-101, a minimum 12 weeks must have elapsed from dosing in DCR-PHXC-101 and 24-hour Uox excretion must have returned to ≥80% of study DCR-PHXC-101 baseline.
    4. Estimated GFR at screening ≥ 30 mL/min normalized to 1.73 m2 BSA calculated using the Modification of Diet in Renal Disease (MDRD) formula in participants aged > 16 years, or the formula by Schwartz in participants aged 6 to 16 years (Levey et al., 1999; Schwartz et al., 2009; National Kidney Foundation, 2002).

    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 or anticipating requirement for dialysis during the study period
    3. Documented evidence of clinical manifestations of systemic oxalosis
    4. Presence of any condition or comorbidities that would interfere with study compliance
    or data interpretation or potentially impact study participant safety including, but not
    restricted to:
    a. severe intercurrent illness
    b. known causes of active liver disease/injury or transaminase elevation (e.g., alcoholic liver disease, nonalcoholic fatty liver disease/steatohepatitis [NAFLD/NASH])
    c. physician concerns about intake of drugs of abuse or excessive alcohol intake or history of excessive alcohol intake in the 2 years prior to enrollment (defined as ≥ 21 units of alcohol per week in men and ≥ 14 units of alcohol per week in women; where a “unit” of alcohol is equivalent to a 12-ounce beer, 4-ounce glass of wine, or 1-ounce shot of hard liquor)
    d. history of serious mental illness that includes, but is not limited to schizophrenia, bipolar disorder, severe depression requiring hospitalization or pharmacological intervention.
    e. 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.

    Prior/Concomitant Therapy
    5. Routine or chronic use of more than 3 grams of acetaminophen/paracetamol daily
    6. Use of an RNAi drug (other than DCR-PHXC) within the last 6 months
    7. 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.
    8. 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
    9. Participation in any clinical study in which they received an investigational medicinal product (investigational medicinal product [IMP]; other than DCR-PHXC) within 4 months 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.

    Diagnostic assessments
    10. Liver function test abnormalities: ALT and/or AST >1.5 × ULN for age and gender
    11. Positive screening for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus antibodies, or anti-human immunodeficiency virus (HIV) 1 and 2 antibodies. If subject has been tested in the past 3 months, medical record documentation of this testing can be used for screening.

    Other Exclusions
    12. Known hypersensitivity to DCR-PHXC
    13. 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 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)
    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)
    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 BSA in participants aged < 18 years]) on at least 2 consecutive visits, beginning with Day 90 (for participants rolling over from DCR-PHXC-101) or Month 3 (participants rolling over from repeat-dose studies of DCR PHXC)
    2.Change from Baseline in the proportion of participants with 24-hour urinary oxalate excretion (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 [values adjusted per 1.73 m2 body surface area (BSA) in participants aged < 18 years])
    3.Change from Baseline in the number of stone events over a 12-month period, annually in Year 1, Year 2, etc.
    4.Change from Baseline in the stone burden observed over a 12-month period, annually in Year 1, Year 2, etc.
    5.The number of participants with ESRD, defined as eGFR < 30 mL/min
    6.Change from Baseline in the Short Form (36) Health Survey (SF-36) and EQ-5D-5L in adults; and in the Pediatric Quality of Life Inventory (PedsQL) in children
    7.Annual change in eGFR

    Exploratory:
    1.TWS area under the curve (AUC) of 24-hour Uox from Day 1 to Day 180, based on percent change from Baseline
    2.Change in Quality Adjusted Life Years (QALY)
    3.Population and individual pharmacokinetic (PK) parameters for DCR-PHXC, including clearance (CL) and volume of distribution (V) estimates along with secondary parameters of 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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA23
    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
    France
    Germany
    Israel
    Italy
    Netherlands
    New Zealand
    Poland
    Romania
    Spain
    United Kingdom
    United States
    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 years2
    E.8.9.1In the Member State concerned months6
    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 state10
    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 Decision2019-06-01
    N.Ethics Committee Opinion of the trial application
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion
    P. End of Trial
    P.End of Trial StatusCompleted
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