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    Summary
    EudraCT Number:2005-005697-71
    Sponsor's Protocol Code Number:060402
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2009-03-23
    Trial results View 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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2005-005697-71
    A.3Full title of the trial
    “Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method (rAHF–PFM): A Phase 3/4, prospective, controlled, randomized, multi-center Study to compare the efficacy and safety of continous infusion (CI) versus intermittent bolus infusion (BI) in subjects With Severe Or Moderately Severe Hemophilia A undergoing unilateral primary total knee replacement”
    A.3.2Name or abbreviated title of the trial where available
    Advate Randomized Surgery Study
    A.4.1Sponsor's protocol code number060402
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberND
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorBaxter Innovations GmbH
    B.1.3.4CountryAustria
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 Yes
    D.2.1.1.1Trade name ADVATE
    D.2.1.1.2Name of the Marketing Authorisation holderBaxter AG
    D.2.1.2Country which granted the Marketing AuthorisationAustria
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Powder and solvent for solution for injection
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNCoagulation factor VIII
    D.3.10 Strength
    D.3.10.1Concentration unit IU international unit(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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 Yes
    D.3.11.13.1Other medicinal product typeNon Applicabile
    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
    Patients suffering from severe to moderately severe Haemophilia A (basal level of factor VIII < 2% of normal) undergoing Primary Total Unilateral Substitution of the Knee.
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10061992
    E.1.2Term Haemophilia
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare the hemostatic efficacy and safety of continuous infusion (CI)to intermittent bolus infusion (BI) in the intra- and postoperative environment using rAHF-PFM in previously treated patients (PTP’s) suffering from severe to moderately severe haemophilia A (basal level of factor VIII <2% of normal) undergoing primary total unilateral substitution of the knee.
    E.2.2Secondary objectives of the trial
    (a)To assess and compare the cumulative packed PRBC volume and the total amount of hemoglobine in the drainage fluid during the first 24 hours following surgery (and until time of drain removal for the hemoglobine) between subjects receiving CI versus BI,(b)to determine the blood loss compared with the predicted blood loss during the first 24 hours following surgery and until removal drain, (c) to determine the number of bleeding episodes during treatment with CI or BI, (d)To record the occurrence and dimensions of any clinically relevant postoperative hematomas, (e) To assess the number of units of PRBCs transfused, (f) to assess and compare the global hemostatic efficacy between subjects receiving CI versus BI, (g) To determine the total weight-adjusted dose of rAHF PFM per subject through postoperative day 7, (h) To calculate the total daily intra-and post-operative weight-adjusted dose of rAHF PFM during administration of CI and BI, (i) To record the number of ADR
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.The subject or subject’s legally authorized representative has provided signed informed consent 2.The subject is within 18 to 70 years of age, 3. The subject is suffering from severe to moderately severe Haemophilia A (basal level of factor VIII &amp;#8804;2% of normal) at screenig.A subgroup of 15 subjects in each group will show a basal level of factor VIII <1% of normal. 4.The aPTT must be within the range of normal after administration of F VIII concentrate, ad determined in the preoperative pharmacokinetic evaluation, or as documented in the medical history, if available. 5 The subject is scheduled to undergo an elective unilateral primary total knee replacement (with cemented or uncemented prothesis) 6. The subject has a documented history of at least 150 exposure days to factor VIII concentrates, before entering the study. 6.HIV positive subjects must be immunocompetent as determined with a CD4 count&amp;#8805; 400 cells/mm³ (CD4 at screening), but HIV negative subjects with CD count <400 qualify, if immunocompetency is documented. 8. The subject has a life expectancy of at least 28 days from the day of surgery
    E.4Principal exclusion criteria
    1. The subject has an history of factor VIII inhibitors or a detectable factor VIII inhibitors at screening with a titer &amp;#8805; 0,4 BU; 2.The subject has an history of factor VIII inhibitors with a titer &amp;#8805; 0,4 BU(by Nijmegen assay)or &amp;#8805;0,5 BU (by Bethesda assay)at any time prior to screening 3. The subject is scheduled to undergo any other current minor or major surgery during the course of the study.The placement of a central venous lines and the performance of fine needle aspiration biopsies are permitted; 4.Excluding hemophilia-related physical impairments, the subject is assigned to NYHA&amp;#8805;III according to New York Heart Association classification. 5. The subject with an abnormal renal function (serum creatinine >1.5mg/dL), 6. an active hepatic disease( [ALT]or [AST] levels >5 times the upper limit of normal), 7. a severe chronic liver disease (as evidenced by but not limited to INR >1.4, hypoalbuminemia,portal vein hypertansion, including presence of otherwise unexplained splenomegaly and history of esophageal varices, 9.The subject is currently receiving or scheduled to receive an immunomodulating drug other than antiretroviral chemotherapy; 10.a known hypersensitivity to mouse or hampster proteins. 11.The subject has received another investigational drug within 30 days prior to the screening and /or is scheduled to recieve additional investigational drug during the course of the trial in the context of another investigational drug study. 12.The subject is identified by the investigator as being unable or unwilling to cooperate with the study procedures.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint, the cumulative volume of PRBC in the drainage fluid during the first 24 hours after surgery, will be used to establish the non-inferiority of CI compared to BI. A one-way t-test at a 2.5% level of statistical significance on the transformed logarithmic data will test the null hypothesis that the average PRBC volume with CI is 200% of the average with BI, as opposed to the alternative hypothesis, which is lower. This is equivalent to the higher confidence limit of a 95% two-way confidence interval for an average percentage not exceeding 200%.
    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 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
    Fase III/IV
    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 Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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 No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    stesso farmaco con differente modalita` di dosaggio
    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 concerned1
    E.8.5The trial involves multiple Member States Yes
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    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
    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 months10
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months10
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    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) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2009-03-23. Yes
    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 Yes
    F.3.3.7.1Details of other specific vulnerable populations
    Soggetti affetti da Emofilia A Grave o Moderatamente Grave Sottoposti a Sostituzione UnilateraleTot
    F.4 Planned number of subjects to be included
    F.4.1In the member state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 40
    F.4.2.2In the whole clinical trial 60
    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 Decision2007-12-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2006-12-15
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-12-09
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