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The European Union Clinical Trials Register   allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   43801   clinical trials with a EudraCT protocol, of which   7272   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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    EudraCT Number:2015-000371-26
    Sponsor's Protocol Code Number:DFI12712
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2015-06-02
    Trial results View results
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    A. Protocol Information
    A.1Member State ConcernedGermany - BfArM
    A.2EudraCT number2015-000371-26
    A.3Full title of the trial
    A Phase 2/3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled,
    Repeat Dose Study to Evaluate the Efficacy, Safety, Pharmacodynamics and
    Pharmacokinetics of olipudase alfa in Patients With Acid Sphingomyelinase
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Efficacy, Safety, Pharmacodynamic, and Pharmacokinetics Study of Olipudase Alfa in Patients with Acid Sphingomyelinase Deficiency
    A.3.2Name or abbreviated title of the trial where available
    A.4.1Sponsor's protocol code numberDFI12712
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02004691
    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 SponsorGenzyme Corporation
    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 supportGenzyme Corporation
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGenzyme Europe B.V.
    B.5.2Functional name of contact pointMedical Information
    B.5.3 Address:
    B.5.3.1Street AddressPaasheuvelweg 25
    B.5.3.2Town/ cityAmsterdam
    B.5.3.3Post code1105 BP
    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/3/01/056
    D.3 Description of the IMP
    D.3.1Product nameOlipudase alfa
    D.3.2Product code GZ402665
    D.3.4Pharmaceutical form Powder for concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOlipudase alfa
    D.3.9.1CAS number 927883-84-9
    D.3.9.2Current sponsor codeGZ402665
    D.3.9.4EV Substance CodeSUB75088
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. 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 Yes
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Patients with acid sphingomyelinase deficiency (Niemann-Pick Type B disease)
    E.1.1.1Medical condition in easily understood language
    Patients with Niemann-Pick Type B disease
    E.1.1.2Therapeutic area Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10041515
    E.1.2Term Sphingomyelin lipidosis
    E.1.2System Organ Class 100000004850
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this phase 2/3 study is to evaluate the efficacy
    of olipudase alfa
    (recombinant human acid sphingomyelinase) administered intravenously
    once every 2 weeks for 52 weeks in adult patients with acid
    sphingomyelinase deficiency (ASMD) by assessing changes in 1) spleen
    volume as measured by abdominal magnetic resonance imaging (MRI)
    (and, for the United States [US] only, in association with patient
    perception related to spleen volume as measured by splenomegaly
    related score [SRS]); and 2) infiltrative lung disease as measured by the
    pulmonary function test, diffusing capacity of the lung for carbon
    monoxide (DLCO).
    E.2.2Secondary objectives of the trial
    -To confirm the safety of olipudase alfa administered intravenously once
    every 2 weeks for 52 weeks.
    -To characterize the effect of olipudase alfa on the patient perception
    related to spleen volume as measured by the SRS after 52 weeks of
    study drug administration. (For the US, the effect of olipudase alfa on
    the splenomegaly related score is part of the primary objective).
    -To characterize the effect of olipudase alfa after 52 weeks of study drug
    administration on the following endpoints assessed sequentially:
    -The effect of olipudase alfa on liver volume;
    -The effect of olipudase alfa on platelet count;
    -The effect of olipudase alfa on fatigue;
    -The effect of olipudase alfa on pain;
    -The effect of olipudase alfa on dyspnea.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    -The patient is willing and able to provide signed written informed consent.
    -The patient is male or female aged 18 years or older.
    -The patient has documented deficiency of acid sphingomyelinase as
    measured in peripheral leukocytes, cultured fibroblasts, or lymphocytes;
    and a clinical diagnosis consistent with Niemann-Pick disease type B
    (NPD B).
    -The patient has diffuse capacity of the lung for carbon monoxide ≤70%
    of the predicted normal value.
    -The patient has a spleen volume ≥6 multiples of normal (MN) measured
    by MRI; patients who have had partial splenectomy will be allowed if the
    procedure was performed ≥1 year before screening/baseline and the
    residual spleen volume is ≥6 MN.
    -The patient has an SRS ≥5..
    -Female patients of childbearing potential must have a negative serum
    pregnancy test for beta-human chorionic gonadotropin (β-HCG).
    -Female patients of childbearing potential and male patients must be
    willing to practice true abstinence in line with their preferred and usual
    lifestyle, or use 2 acceptable, effective methods of contraception for up
    to 15 days following their last dose of study drug.
    E.4Principal exclusion criteria
    -The patient has received an investigational drug within 30 days before study enrollment.
    -The patient has a medical condition, including significant intercurrent illness; significant cardiac disease (e.g., clinically significant arrhythmia,
    moderate or severe pulmonary hypertension or clinically significant valve dysfunction, or <40% left ventricular ejection fraction by echocardiogram); active hepatitis B or hepatitis C, or infection with human immunodeficiency virus (HIV); malignancy diagnosed within the
    past 5 years (other than non-melanoma skin cancer), or any other serious medical condition that may preclude participation in the study.
    -The patient has a platelet count <60,000/μL based on the average of 2 samples.
    -The patient has an international normalized ratio (INR) >1.5.
    -The patient has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >250 IU/L or total bilirubin >1.5 mg/dL (except for patients with Gilbert's syndrome).
    -The patient has had a major organ transplant (eg, bone marrow or liver).
    -The patient is scheduled during the study for in-patient hospitalization including elective surgery and excluding the liver biopsies required per
    -The patient, in the opinion of the investigator, is unable to adhere to the requirements of the study.
    -The patient is unwilling or unable to abstain from the use of alcohol for 1 day before and 3 days after each study drug infusion. Testing for blood alcohol levels will not be required.
    -The patient is unwilling or unable to avoid 10 days before and 3 days after the protocol scheduled liver biopsies the use of medications or
    herbal supplements that are potentially hepatotoxic (eg, 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors, erythromycin, valproic acid, anti-depressants, kava, echinacea) and/or may cause or prolong bleeding (eg, anti-coagulants, ibuprofen, aspirin, garlic supplements, ginkgo, ginseng).
    -The patient requires medications that may decrease olipudase alfa activity (eg, fluoxetine, chlorpromazine, tricyclic antidepressants [eg,
    imipramine, or desipramine]).
    -The patient requires use of invasive ventilatory support.
    -The patient requires use of noninvasive ventilator support while awake for longer than 12 hours daily.
    -The patient is breast-feeding.
    E.5 End points
    E.5.1Primary end point(s)
    - Percentage change in spleen volume (combined with change in SRS in the US only, and referred to as "combination spleen endpoint").
    - Percentage change in diffusing capacity of the lung for carbon monoxide.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline to Week 52
    E.5.2Secondary end point(s)
    1 - Percentage change in liver volume
    2 - Percentage change in platelet count
    3 - Change in fatigue severity as measured by item 3 of the Brief Fatigue
    Inventory scale
    4 - Change in pain severity as measured by item 3 of the Brief Pain
    Inventory scale
    5 - Change in dyspnea severity as measured by the Fonctional
    Assessment of Chronic Illness Therapy dyspnea tool
    6 - Number of adverse events
    7 - Change in SRS (except US, where it is part of the primary
    "combination spleen endpoint")
    E.5.2.1Timepoint(s) of evaluation of this end point
    1-2-3-4-5 : Baseline to Week 52
    6 : Baseline to approximately 5 years
    7 : Baseline to Week 52
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    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. trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    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 Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA10
    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
    United States
    United Kingdom
    E.8.7Trial has a data monitoring committee Yes
    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
    Last visit of the last subject
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years8
    E.8.9.2In all countries concerned by the trial months3
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F. of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F. of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F. of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F. of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F. of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F. of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 35
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 1
    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 state4
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 10
    F.4.2.2In the whole clinical trial 36
    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)
    As part of the trial, all patients will receive active treatment in the extension treatment period which will last up to 4 year.
    After the end of the trial the patients will be treated according to the standard of care in Germany.
    In case of marketing authorization of Olipudase alfa the patients can switch to commercial product.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-08-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-07-23
    P. End of Trial
    P.End of Trial StatusOngoing
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