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    The EU Clinical Trials Register currently displays   43692   clinical trials with a EudraCT protocol, of which   7246   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:2017-004040-38
    Sponsor's Protocol Code Number:SSCR105/NEAT33
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2018-09-04
    Trial results
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2017-004040-38
    A.3Full title of the trial
    An open-label, multi-centre, randomised, switch study to evaluate the virological efficacy over 96 weeks of 2-drug therapy with DTG+RPV FDC in antiretroviral treatment-experienced HIV-1 infected subjects virologically suppressed with NNRTIs resistance mutation K103N.
    Étude switch ouverte, multicentrique, randomisée, afin d’évaluer l’efficacité virologique sur 96 semaines d’une bithérapie par association à dose fixe de DTG/RPV chez des patients infectés par le VIH-1, prétraités par des antirétroviraux, virologiquement supprimés, porteurs de la mutation K103N de résistance aux INNTI.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    The effect of switching to Dolutegravir and Rilpivirine combination therapy in patients with HIV-1 and the K103N mutation.
    Étude switch ouverte, multicentrique, randomisée, afin d’évaluer l’efficacité virologique sur 96 semaines d’une bithérapie par association à dose fixe de DTG/RPV chez des patients infectés par le VIH-1, prétraités par des antirétroviraux, virologiquement supprimés, porteurs de la mutation K103N de résistance aux INNTI.
    A.3.2Name or abbreviated title of the trial where available
    WISARD: acronym of SWItch Study mutAtion Rilpivirine Dolutegravir.
    A.4.1Sponsor's protocol code numberSSCR105/NEAT33
    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 SponsorEuropean AIDS Treatment Network Infectious Disease Foundation (NEAT ID)
    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 supportViiv Healthcare UK Ltd
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationEuropean AIDS Treatment Network Infectious Disease Foundation (NEAT ID)
    B.5.2Functional name of contact pointAssociate Director
    B.5.3 Address:
    B.5.3.1Street AddressPL 709, Rue Haute 322
    B.5.3.2Town/ cityBrussels
    B.5.3.3Post code1000
    B.5.4Telephone number+44(0)2087465620
    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. name Juluca 50 mg/25 mg film-coated tablets dolutegravir/rilpivirine
    D. of the Marketing Authorisation holderViiV Healthcare UK Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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.3.1Product nameDolutegravir 50mg / 25mgRilpivirine FDC
    D.3.2Product code DTG+RPV FDC
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRILPIVIRINE
    D.3.9.1CAS number 500287-72-9
    D.3.9.4EV Substance CodeSUB31456
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 1051375-19-9
    D.3.9.4EV Substance CodeSUB35122
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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. 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 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
    HIV-1 infection
    E.1.1.1Medical condition in easily understood language
    HIV infection
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10000808
    E.1.2Term Acute human immunodeficiency virus type I infection
    E.1.2System Organ Class 100000004862
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare efficacy of DTG/RPV combined tablet versus continued antiretroviral treatment regimen at 48 weeks in individuals with the K103N resistance mutation.
    Comparer les résultats en termes de charge virale avec le schéma DTG/RPV à dose fixe (bras expérimental) aux résultats avec la poursuite du traitement antirétroviral (bras témoin) à 48 semaines, mesurés par un ARN du VIH-1 confirmé comme inférieur ou supérieur à 50 copies/ml.
    E.2.2Secondary objectives of the trial
    To investigate whether switching patients to DTG/RPV FDC is associated with improvement of lipid profile, patient satisfaction, quality of life and potential for drug-drug interactions, investigated over time through 96 weeks with evaluation (and comparison to control arm) at week 24, 48 and 96.

    To evaluate DTG & RPV concentrations in blood.

    To evaluate changes in cell associated virus.
    1. Déterminer si le switch des patients à DTG/RPV à dose fixe est associé à une amélioration du profil lipidique, de la satisfaction du patient, de sa qualité de vie et du potentiel d’interactions médicamenteuses. Investigation pendant 96 semaines avec évaluation aux semaines 24, 48 et 96.
    2. Évaluer les concentrations minimales de DTG et de RPV
    3. Changements au niveau du virus associé aux cellules (cellules mononucléaires du sang périphérique)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Is male or female aged 18 years or over.
    2. Has documented HIV-1 infection
    3. Is capable of giving informed consent, or if appropriate, subjects having an acceptable individual capable of giving
    consent on the subject’s behalf.
    4. Is willing to comply with the protocol requirements
    5. Virologically suppressed (plasma HIV-RNA <50 copies/mL for >24 weeks) and on a stable regimen.
    6. Subjects are required to have a history of the K103N mutation. Subjects who at any time have had the mutations
    100I, 101E/P, 106A/M, 138K/G/Q, 181C/I/V, 188L, 190A/S/E/Q, 230L mutations are to be excluded. Other NNRTI region
    variants can be included. Study sites may ask the coordinating centre for advice as required.
    7. Subjects must have never failed INSTI (2 x VL >200 >2 weeks apart) but current regimen can include INSTI.
    8. A female, may be eligible to enter and participate in the study if she:
    a. is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥
    45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or
    bilateral oophorectomy or,
    b. is of child-bearing potential with a negative pregnancy test at Screening (& baseline visit) and agrees to use one of
    the following methods of contraception to avoid pregnancy:
    • True abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and
    for at least 2 weeks after discontinuation of all study medications (When this is in line with the preferred and usual
    lifestyle of the subject.) (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), and
    withdrawal are not acceptable methods of contraception].
    • Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide);
    • Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs
    meet this criterion, see Appendix 3 for an example listing of approved IUDs);
    • Male partner sterilization confirmed prior to the female subject’s entry into the study, and this male is the sole partner
    for that subject;
    • Approved hormonal contraception (see appendix 4 for a listing of examples of approved hormonal contraception);
    • Any other method with published data showing that the expected failure rate is <1% per year.
    • Any contraceptive method must be used consistently and for at least 2 weeks after discontinuation of IP
    9. If a heterosexually active male, he is using effective birth control methods and is willing to continue practising these birth control methods during the trial and until follow-up visit
    10. Subjects currently receiving DTG or RPV, but not both, can be included.
    E.4Principal exclusion criteria
    1. Infected with HIV-2
    2. Detectable HIV-1 RNA at screening (HIV-1 RNA measurement >=50 c/mL).
    3. Subjects requiring regular dosing doing with H2 or PPI antacid medications or a history of achlorhidria or drug
    known to interact with RPV or DTG.
    4. Use of medications which are associated with Torsades de Pointes
    5. Corrected QT interval (QTc [Bazett]) >450 milliseconds or QTc (Bazett) >480 milliseconds for participants with bundle
    branch block. The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB).
    6. Unstable health conditions (i.e. opportunistic infections, cancers, unstable liver disease etc).
    7. Any evidence of an active Centers for Disease Control and Prevention Category C disease. Exceptions include
    cutaneous Kaposi's sarcoma not requiring systemic therapy and historic CD4+ lymphocyte counts of <200
    8. History or presence of allergy to the study drugs or their components or drugs of their class;
    9. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive
    cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require
    agreement between the investigator and the Study medical monitor for inclusion of the subject prior to randomization;
    10. Any pre-existing physical or mental condition which, in the opinion of the Investigator, may interfere with the
    subject's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety
    of the participants. Subjects considered to pose a significant risk of suicide should be excluded.
    11. Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or
    excretion of the study drugs or render the subject unable to take oral medication;
    12. Using any concomitant therapy disallowed as per the reference safety information and product labelling for the study drugs
    13. Has acute viral hepatitis including, but not limited to, A, B, or C
    14. Active hepatitis B/ Hep B non-immune subjects who have failed vaccination (antibody concentration < 10
    international units). (Note: subjects can be re screened if they receive vaccination and subsequently meet eligibility
    15. Evidence of Hepatitis B virus (HBV) infection based on the results of testing at Screening for Hepatitis B surface
    antigen (HBsAg), Hepatitis B core antibody (anti-HBc), and Hepatitis B surface antibody (HBsAb) as follows:
    Participants positive for HBsAg are excluded; Participants positive for anti-HBc (negative HBsAg status) and negative
    for HBsAb are excluded. Note: Subject positive for anti-HBc (negative HBsAg status) and positive for HBsAb are
    immune to HBV and are not excluded.
    16. Participants with an anticipated need for any Hepatitis C virus (HCV) therapy during the Early Switch Phase and for
    interferon-based therapy for HCV throughout the entire study period.
    17. Any investigational drug within 30 days prior to the trial drug administration
    18. Any evidence of viral resistance different to the one described in the inclusion criteria.
    19. Dialysis or renal insufficiency (creatinine clearance < 50ml/min)
    20. History of decompensated liver disease (Alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal
    (ULN), OR ALT ≥3xULN and bilirubin ≥1.5xULN (with >35% direct bilirubin)
    21. Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia,
    esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of
    Gilbert's syndrome or asymptomatic gallstones)
    22. Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification (see appendix 4)
    23. Opportunistic infection within 4 weeks prior to first dose of DTG plus RPV.
    24. Clinical decision that a switch of antiretroviral therapy should be immediate
    25. Screening blood result with any grade 3/4 toxicity according to Division of AIDS (DAIDS) grading scale, except:
    asymptomatic grade 3 glucose, amylase or lipid elevation or asymptomatic grade 4 triglyceride elevation (re-test
    26. Any condition (including illicit drug use or alcohol abuse) or laboratory results which, in the investigator’s opinion,
    interfere with assessments or completion of the trial.
    27. Women planning pregnancy or who are pregnant or breast feeding.
    28. Females of childbearing potential and males must be willing to use a highly effective method of contraception (hormonal method of birth control; true abstinence). Contraceptive methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods.
    E.5 End points
    E.5.1Primary end point(s)
    1. Virological suppression (<50 copies/ml HIV RNA) at week 48 in individuals with previous NNRTIs virological failure and/or baseline
    transmitted resistance with the k103N resistance mutation, switching to DTG/RPV FDC. (Analysed in line with FDA snapshot)
    2. Virological failure defined by 2 consecutive viral loads >50 copies at least 2 weeks apart, investigated over 96 weeks.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Virological suppression after 48 weeks
    Virological failure after 96 weeks
    E.5.2Secondary end point(s)
    1a. Proportion of participants with plasma HIV-1 RNA <50 c/mL at week 24, 48 and 96.
    b. Changes in laboratory parameter from baseline
    c. Changes in renal markers, bone markers, and fasting lipids from baseline, week 24, week 48 and week 96.
    d. Resistance in failures (descriptive analysis) and baseline factors associated with failures.
    e. Changes in QoL and patient satisfaction from baseline.
    f. Number of participants with adverse events (AEs), Severity of AEs, and treatment discontinuations due to AEs.
    g. Number of potential DDIs avoided.
    h. Virological suppression (<200 copies/ml HIV RNA) at week 24, 48, 96 in individuals with previous NNRTIs
    virological failure and/or baseline transmitted resistance with the k103N resistance mutation, switching to DTG/RPV
    FDC. Analysed in line with FDA Snapshot method.
    i. Pre-dose plasma concentrations of DTG and RPV at week 4 (experimental arm only), 48 (experimental arm only) & 96. Plus pre/post-dose (as appropriate) at early termination visit and /or in the event of virological failure (see section 6.12) a post dose sample will be taken within 20-28 hours.
    j. Changes in cell associated virus using PBMC Illumina MiSeq sequencing at week 48 and week 96.
    E.5.2.1Timepoint(s) of evaluation of this end point
    24, 48 & 96 weeks
    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 No
    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. 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 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 No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E. trial design description
    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. description
    Switch immediately or after 48 weeks
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA27
    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 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
    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 years2
    E.8.9.2In all countries concerned by the trial months6
    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 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: 135
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 15
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 150
    F.4.2.2In the whole clinical trial 150
    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)
    When the research study stops, the participant will be prescribed enough antiretroviral treatment until their next followup visit, following discussion with their regular clinic doctor and depending on clinic policy/national guidelines. The DTG+RPV combined treatment used in the study is not yet approved in the EU. This will be discussed with the patient at the beginning of the study.
    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 Decision2018-12-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-07-10
    P. End of Trial
    P.End of Trial StatusOngoing
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