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    The EU Clinical Trials Register currently displays   37220   clinical trials with a EudraCT protocol, of which   6123   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2014-005454-19
    Sponsor's Protocol Code Number:51858
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2015-02-16
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2014-005454-19
    A.3Full title of the trial
    The Dolutegravir Antiretroviral Mono-Therapy for HIV Trial
    De Dolutegravir mono-therapie voor HIV studie
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    De Dolutegravir Antiretroviral Mono-Therapy for HIV Trial
    De Dolutegravir mono-therapie voor HIV studie
    A.3.2Name or abbreviated title of the trial where available
    DOMONO
    DOMONO
    A.4.1Sponsor's protocol code number51858
    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 SponsorErasmus MC
    B.1.3.4CountryNetherlands
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportErasmus MC
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationErasmus MC
    B.5.2Functional name of contact pointCasper Rokx
    B.5.3 Address:
    B.5.3.1Street Address'sGravendijkwal 230
    B.5.3.2Town/ cityRotterdam
    B.5.3.3Post code3015 CE
    B.5.3.4CountryNetherlands
    B.5.4Telephone number+310681336328
    B.5.6E-mailc.rokx@erasmusmc.nl
    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 Tivicay
    D.2.1.1.2Name of the Marketing Authorisation holderViiV Healthcare
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    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 Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    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
    Evaluation of the efficacy and safety of a switch from cART to dolutegravir monotherapy in HIV
    Evaluatie van de effectiviteit en veiligheid van een switch van cART naar dolutegravir monotherapy voor HIV
    E.1.1.1Medical condition in easily understood language
    Therapy of HIV
    behandeling van HIV
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy and safety of a switch from cART to dolutegravir monotherapy
    Evaluatie van de effectiviteit en veiligheid van een switch van cART naar dolutegravir monotherapy voor HIV
    E.2.2Secondary objectives of the trial
    To evaluate the effect on biochemical markers (renal/liver/lipids), HIV reservoir, BMD, and cost effectiveness.
    Biochemie markers mbt nieren, lever, vetten, reservoir, botdichtheid, en kosteneffectiviteit
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    In a pilot study version 1.0 on 30 additional patients, the objective is to evaluate the safety of a direct switch to DTG monotherapy in patients with CD4 nadir pre-cART <200 cells/mm3, given that these patients have a CD4 cell of >350 cells/mm3 on current cART at screening. The same other in- and exclusion criteria and follow up will be used. This pilot will only be started if at least 40 patients in the main study have passed week 12, and no more than 3 patients have experienced per protocol defined treatment failure.
    In een sub- pilotstudie versie 1.0 op 30 andere patienten (buiten de 104 patienten om) zullen we bekijken hoe veilig een directe switch naar DTG monotherapie is in patienten met een CD4 nadir pre-CART <200 cellen/mm3 onder voorwaarde dat deze patienten een CD4 getal >350 hebben op hun huidige behandeling bij screening. Dezelfde in- en exclusie criteria en follow up zullen worden gebruikt. Deze te starten substudie zal alleen worden gestart wanneer minimaal 40 patienten week 12 in de main studie hebben gepasseerd waarvan er niet meer dan 3 patienten falen hebben ervaren volgens ons protocol gedefineerd.
    E.3Principal inclusion criteria
    18 years or older
    On cART and HIV-RNA <50 for last >24 weeks
    pre-cART: baseline HIVRNA <100.000 (unless measured during acute HIV)
    pre-cART: CD4 nadir >200
    Not on co-medication inducing UGT1A1/CYP3A4 as stated in DTG SPC
    General medical condition does not interfere with trial procedures

    A secondary objective is to test viralogical suppression in patients with a pre-cART CD4 count nadir of below 200
    cells/mm3. For this N=30 pilot study, the same inclusioncriteria as mentioned above will apply, except for the CD4
    count nadir pre-cART ≥200 cells/mm3 inclusion criterium. The 30 patients for this pilot study will need to have a
    pre-cART CD4 count BELOW 200 cells/mm3 with a CD4 count >350 cells/mm3 at the time of the screening visit.
    E.4Principal exclusion criteria
    Planning to be pregnant
    No use of double barrier contraceptive methods
    Previous virological failure on any ART.
    Patient without documented anti-HBs antibodies prior to vaccination, and unwilling to undergo vaccination against hepatitis B.
    Subjects positive for hepatitis B at screening (HBsAg+).
    Any documented genotypic HIV-1 resistance with at least low-level resistance according to stanford HIV drug resistance database
    No record of the historical baseline plasma viral load available
    Subjects with concomitant CDC-C opportunistic infections within 90 days of screening.
    Subjects with history of allergy to INI.
    Subjects with creatinine clearance <50mL/min according to CKD-EPI.
    Subjects with hepatic impairment of at least Child-Pugh B.
    Exposure to experimental drug or experimental HIV-1 vaccine within 90 days of start of DTG.
    Screening ALT >5x ULN or ALT>3xULN and bilirubin >2 ULN.
    Patient (man or woman) planning or hoping to conceive a child/become pregnant during the study
    Patients who cannot take DTG 2 hours before or 6 hours after antacids, calciumcarbonate or iron supplements.
    For the N=30 pilot study, the same exclusion criteria as mentiioned above will apply.
    E.5 End points
    E.5.1Primary end point(s)
    Difference in percentage of patients who switch to DTG monotherapy as compared to controls on conventional continued cART with HIV-RNA <200 c/mL at week 24 by OT analysis.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 24
    E.5.2Secondary end point(s)
    The time to loss of virological response (TLOVR) defined as the first of two confirmed HIV-RNA >50 c/mL at least 1 week apart.
    Percentage of patients with virological suppression with HIV-RNA <200 c/mL at week 24 by OT analysis in the entire study population which consists of the
    24 by OT analysis in the entire study population (n=104) which consists of the immediate switchers group (n=52) and the delayed switchers from the control arm (n=52).
    To evaluate the efficacy of DTG monotherapy in maintaining virological suppression with HIV-RNA <200 at week 12 by OT analysis.
    immediate switchers group and the delayed switchers from the control arm (n=104).
    Difference in percentage of patients with HIV-RNA <50, <200 c/mL at week 24 and 48 by OT and ITT analysis.
    Evaluation of safety (acquired resistance, and AE according to CTC 4.0) of DTG monotherapy.
    Evolution of CD4 associated HIV reservoir (total/integrated HIV-DNA, 2LTR) at baseline, week 24 and week 48.
    Number and type of INI resistance mutations in case of confirmed HIV-RNA >200 c/mL at any time-point.
    Difference in change in CD4 cell count at week 48.
    Changes from baseline to week 24 and 48 in blood-pressure, weight, BMI, fasting serum lipids, Framingham risk score, ATP-III treatment goals, inflammatory markers, renal function, urinalysis, bone mineral density at hip and spine.
    Cost-effectiveness of DTG monotherapy
    Viral suppression in HIV-patients on DTG monotherapy with pre-cART CD4 nadir below 200 cells/mm3.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 12, week 24 and week 48.
    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 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 Yes
    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) No
    E.7.4Therapeutic use (Phase IV) Yes
    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) Yes
    E.8.2.2Placebo No
    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 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 EEA3
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    End of the trial is when the last person included completes his/her last visit at week 48.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    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.1.2.1Number of subjects for this age range: 120
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 14
    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 state134
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 134
    F.4.2.2In the whole clinical trial 134
    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)
    After the trial, patients will be offered treatment according to the current standard of care for HIV-1 infected patients or to continue dolutegravir monotherapy.
    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 Decision2015-02-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-03-16
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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