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    The EU Clinical Trials Register currently displays   41449   clinical trials with a EudraCT protocol, of which   6808   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2018-004732-30
    Sponsor's Protocol Code Number:257865
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2019-05-09
    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 ConcernedUK - MHRA
    A.2EudraCT number2018-004732-30
    A.3Full title of the trial
    A Phase IV, Randomised, Open-Label Pilot Study to Evaluate Switching from Protease-Inhibitor based regimen to Bictegravir/Emtricitabine/Tenofovir Alafenamide Single Tablet Regimen in Integrase Inhibitor-naïve, virologically suppressed HIV-1 infected adults harbouring drug resistance mutations.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Will switching HIV-1-infected patients who have drug resistant HIV and stable on a regimen based on a protease inhibitor to another regimen based on the integrase inhibitor bictegravir be as equally effective?
    A.3.2Name or abbreviated title of the trial where available
    PIBIK Study
    A.4.1Sponsor's protocol code number257865
    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 SponsorUniversity of Sussex
    B.1.3.4CountryUnited Kingdom
    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 supportGilead Pharmaceuticals
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity of Sussex
    B.5.2Functional name of contact pointNicky Perry
    B.5.3 Address:
    B.5.3.1Street AddressRoom 204, Bevendean House, Village Way
    B.5.3.2Town/ cityVillage Way
    B.5.3.3Post codeBN1 9PH
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number01273641469
    B.5.6E-mailbsctu@bsms.ac.uk
    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 Bictegravir
    D.2.1.1.2Name of the Marketing Authorisation holderGilead Sciences Ireland UC
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameBictegravir
    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 INNbictegravir
    D.3.9.1CAS number 1611493-60-7
    D.3.9.3Other descriptive nameBiktarvy
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    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.IMP: 2
    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 Tenofovir alafenamide fumarate
    D.2.1.1.2Name of the Marketing Authorisation holderGilead Sciences Ireland UC
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameTenofovir alafenamide fumarate
    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 INNtenofovir alafenamide
    D.3.9.1CAS number 1392275-56-7
    D.3.9.3Other descriptive nameBiktarvy
    D.3.9.4EV Substance CodeAS2
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    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.IMP: 3
    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 Emtricitabine
    D.2.1.1.2Name of the Marketing Authorisation holderGilead Sciences Ireland UC
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameEmtricitabine
    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 INNEmtricitabine
    D.3.9.1CAS number 143491-57-0
    D.3.9.3Other descriptive nameBiktarvy
    D.3.9.4EV Substance CodeAS3
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Human Immunodeficiency Virus
    E.1.1.1Medical condition in easily understood language
    HIV
    E.1.1.2Therapeutic area Body processes [G] - Immune system processes [G12]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10008919
    E.1.2Term Chronic HIV 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
    Switching HIV-positive individuals whose virus has selected drug resistance associated mutations and are virologically suppressed (this means the drugs are still working and HIV is under the level of detection in the blood) on a boosted protease inhibitor-based antiretroviral drug regimen to Biktarvy [bictegravir (B)/emtricitabine (F)/tenofovir alafenamide] (TAF) single tablet regimen will maintain virological efficacy (HIV-1 RNA <50 copies/mL) over 24 weeks.
    E.2.2Secondary objectives of the trial
    • To estimate proportion of patients with HIV-1 RNA <50 copies/mL at week 48 using pure virological response (PVR)
    • To estimate proportion of patients with HIV-1 RNA <50 copies/mL at weeks 24 and 48 using PVR in those with any archived resistance detected in proviral DNA
    • To evaluate the emergence of new resistance mutations in participants with two consecutive viral load ≥50 copies/mL measured 2-3 weeks apart.
    • To determine the safety and tolerability of B/F/TAF single tablet regimen in participants switching from boosted Protease Inhibitor-based regimens over 48 weeks
    • To evaluate the between group change from baseline in patient reported outcomes at weeks 24 and 48
    • To estimate the between group mean percentage change from baseline in serum lipid concentrations at weeks 24 and 48
    • To estimate the between arm mean percentage change from baseline in HBA1c at weeks 24 and 48
    • To estimate the between arm mean percentage change from baseline in weight and BMI at weeks 2
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    18 years and above
    Any nadir CD4 count and baseline VL
    On a bPI-based ART regimen with at least one documented HIV-1 RNA <50 copies/mL within the previous 6 months and at screening
    Eligible drug resistance mutations in historical genotype include the following:
    o M184V/I with or without any nucleoside analogue mutation (e.g. L74I/V, Y115F, K70E/G/Q/T/N/S)
    o M184V/I alone
    o Up to 2 TAMs (M41L, D67N, K70R, L210W, T215F/Y, or K219Q/E/N/R) with or without M184V/I
    o Any of the above with or without NNRTI mutations
    No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI)
    No known INSTI mutations
    Must have historical genotype
    Estimated GFR ≥ 50 mL/min (Cockcroft-Gault formula)
    Have the following laboratory values at screening within 30 days prior to baseline
    a) Alkaline phosphatase ≤ 3.0 x upper limit of normal (ULN)
    b) AST and ALT ≤ 5.0 x ULN
    c) Hemoglobin ≥9.0 g/dL (if female) or ≥10.0 g/dL (if male).
    Provides written, informed consent to participate
    Is willing to comply with the protocol requirements
    If female and of child bearing potential, is using effective birth control methods (as agreed by the investigator) and willing to continue practicing these birth control measures during the trial and for at least 30 days after the end of the trial.
    If male, and sexually-active with female partners of child bearing potential, is using effective barrier contraception, and willing to continue using this during the trial and for at least 30 days after the end of the trial.
    E.4Principal exclusion criteria
    Exclusion under drug resistance mutations include:
    o Presence of any of the following mutations: K65R/N/E
    o Presence of multidrug resistance mutations: T69ins, Q151M with or without A62V, V75I, F77L, F116Y
    o three or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, or K219Q/E/N/R)
    Individuals experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, or variceal bleeding)
    An opportunistic illness within the 30 days prior to screening
    Active tuberculosis infection
    Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (e.g., corticosteroids, immunoglobulins, and other immune- or cytokine based therapies)
    Current alcohol or substance use judged by the Investigator to potentially interfere with subjects’ adherence to study procedure.
    A history of or ongoing malignancy (including untreated carcinoma in-situ) other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Individuals with biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Day 1 and are not anticipated to require systemic therapy during the study
    Active, serious infections (other than HIV 1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 (except if the parenteral therapy is for syphilis infection)
    Any other clinical condition or prior therapy that will, in the opinion of the investigator, make the subject ineligible
    Any known allergies to the excipients of B/F/TAF FDC
    Females who are pregnant (as confirmed by positive urine pregnancy test)
    Females who are breastfeeding
    Women of child bearing age not using any reliable form of contraception (e.g. intrauterine device/intrauterine system, long-acting contraceptive injection, in addition to barrier methods)
    Acute hepatitis in the 30 days prior to study entry, anyone with HCV who is likely to need direct acting antivirals in study
    Any concomitant medications that cannot be administered with TAF (i.e strong inducers of p-glycoprotein) or bictegravir (dofetilide, rifampins)

    E.5 End points
    E.5.1Primary end point(s)
    Proportions of individuals with HIV RNA <50 copies/mL at 24 weeks will be estimated using pure virologic response (PVR).
    The percentage of participants with PVR for HIV-1 RNA cut-off at 50 copies/mL at Week 24 will be summarized.
    PVR will be assessed as follows:
    • On study treatment
    • No confirmed virologic rebound defined as:
    o HIV RNA ≥ 50 copies/mL on 2 consecutive visits
    o HIV-1 RNA ≥ 50 copies/mL during study followed by premature discontinuation
    Discontinuation prior to week 24 for reasons other than virologic rebound (i.e. no data in window and last HIV RNA < 50 copies/mL) are considered PVR
    E.5.1.1Timepoint(s) of evaluation of this end point
    Weeks 24 and 48
    E.5.2Secondary end point(s)
    To estimate proportion of patients with HIV-1 RNA <50 copies/mL at week 48 using pure virological response (PVR)
    To estimate proportion of patients with HIV-1 RNA <50 copies/mL at weeks 24 and 48 using PVR in those with any archived resistance detected in proviral DNA
    To evaluate the emergence of new resistance mutations in participants with two consecutive viral load ≥50 copies/mL measured 2-3 weeks apart.
    To determine the safety and tolerability of B/F/TAF single tablet regimen in participants switching from boosted Protease Inhibitor-based regimens over 48 weeks
    To evaluate the between group change from baseline in patient reported outcomes at weeks 24 and 48
    To estimate the between group mean percentage change from baseline in serum lipid concentrations at weeks 24 and 48
    To estimate the between arm mean percentage change from baseline in HBA1c at weeks 24 and 48
    To estimate the between arm mean percentage change from baseline in weight and BMI at weeks 24 and 48
    E.5.2.1Timepoint(s) of evaluation of this end point
    Weeks 24 and 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 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) 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 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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.3.1Comparator description
    Standard of care on a boosted Protease Inhibitor
    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 concerned7
    E.8.5The trial involves multiple Member States No
    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
    LVLS
    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 months0
    E.8.9.1In the Member State concerned days1
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days1
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 90
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    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 state100
    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)
    Tenofovir alafenamide/emtricitabine/bictegravir is licensed for use in Europe but it is not yet available in the NHS. If this is still the case at the end of the study, then participants will be switched to an alternative potent regimen selected by their doctor.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Royal Free London Hospital NHS Foundation Trust
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-06-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-06-28
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
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