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    Summary
    EudraCT Number:2019-003102-26
    Sponsor's Protocol Code Number:HIV-CORE007
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-06-07
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2019-003102-26
    A.3Full title of the trial
    Therapeutic vaccination: A Phase I/II Randomized, Placebo-Controlled Trial of ChAdOx1.tHIVconsvX prime-MVA.tHIVconsvX Boost Vaccination Regimen in Early-treated durably-controlling HIV-1 positive Adults.
    Vaccinazione terapeutica: Studio clinico di fase I/II randomizzato, controllato verso placebo, di un regime vaccinale con ChAdOx1.tHIVconsvX prime - MVA.tHIVconsvX boost in adulti HIV-1 positivi trattati precocemente e in grado di controllare per lungo tempo l’infezione.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Therapeutic vaccination: Phase I / II clinical study on patients randomized blinded to the experimental vaccine or placebo regimen. we want to evaluate the safety and the immunogenicity of a vaccine that includes a first administration of the ChAdOx1.tHIVconsvX product and a second one with MVA.tHIVconsvX in HIV-1 positive adults treated early and able to control the infection for a long time.
    Vaccinazione terapeutica: Studio clinico di fase I/II su pazienti randomizzati in cieco al regime con vaccino sperimentale o al placebo. si vuole valutare la sicurezza e l'immunogenicità di un vaccino che comprende una prima somministrazione del prodotto ChAdOx1.tHIVconsvX e una seconda con MVA.tHIVconsvX in adulti HIV-1 positivi trattati precocemente e in grado di controllare per lungo tempo l’infezione.
    A.3.2Name or abbreviated title of the trial where available
    HIV-CORE 007
    HIV-CORE 007
    A.4.1Sponsor's protocol code numberHIV-CORE007
    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 SponsorOSPEDALE SAN RAFFAELE
    B.1.3.4CountryItaly
    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 supportMinistero della Salute - Ricerca Finalizzata RF-GR-2018-12367076
    B.4.2CountryItaly
    B.4.1Name of organisation providing supportEuropean AIDS Vaccine Initiative 2020 - Horizon 2020 (EAVI2020)
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIRCCS OSPEDALE SAN RAFFAELE
    B.5.2Functional name of contact pointUFFICIO PROTOCOLLI CLINICI
    B.5.3 Address:
    B.5.3.1Street AddressVIA STAMIRA D'ANCONA, 20
    B.5.3.2Town/ cityMILANO
    B.5.3.3Post code20127
    B.5.3.4CountryItaly
    B.5.4Telephone number0226433646
    B.5.5Fax number0226437903
    B.5.6E-mailparisi.mariarita@hsr.it
    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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameChAdOx1.tHIVconsv1
    D.3.2Product code [C1]
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntramuscular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeChAdOx1.tHIVconsv1
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number1
    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.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    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 No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
    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 Yes
    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 No
    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 nameMVA.tHIVconsv3
    D.3.2Product code [M3]
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntramuscular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeMVA.tHIVconsv3
    D.3.10 Strength
    D.3.10.1Concentration unit PFU/ml plaque forming unit(s)/millilitre
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number100000000
    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.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    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 No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
    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 Yes
    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 No
    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 nameMVA.tHIVconsv4
    D.3.2Product code [M4]
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntramuscular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeMVA.tHIVconsv4
    D.3.10 Strength
    D.3.10.1Concentration unit PFU/ml plaque forming unit(s)/millilitre
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number100000000
    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.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    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 No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
    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 Yes
    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 placeboSolvent for parenteral use
    D.8.4Route of administration of the placeboIntramuscular use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    HIV infection
    INFEZIONE DA HIV
    E.1.1.1Medical condition in easily understood language
    HIV infection
    INFEZIONE DA virus HIV
    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 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
    Evaluate the safety of vaccination with C1 in HIV-1 infected participants on cART with plasma HIV-1 RNA load (pVL) suppressed below the level of quantification.
    Valutare la sicurezza della vaccinazione con C1 in adulti HIV-1 infetti in cART con carica di HIV-1 RNA plasmatica (pVL) soppressa ossia inferiore ai limiti di quantificazione.
    E.2.2Secondary objectives of the trial
    Safety:
    • Evaluate the safety of vaccination with M3+M4 given as boost to C1 in HIV-1 infected participants on cART with pVL suppressed below the level of quantification.


    Vaccine immunogenicity:
    • Evaluate vaccine induced HIV-specific CD8+ T cell responses, in terms of magnitude and breath, as determined by IFN-gamma ELISPOT assay to vaccine sequences.
    • Evaluate vaccine induced T cell responses in controlling HIV-1 replication in vitro against a panel of HIV from major global clades.

    Viro-immunological assessment during ATI:
    • Evaluate the role of vaccination in controlling viral replication in HIV-1 infected participants who undergo ATI.
    Sicurezza:
    • Valutare la sicurezza del richiamo con M3+M4 a C1 quando somministrato ad adulti HIV-1 infetti in cART con pVL soppressa ossia inferiore ai limiti di quantificazione.
    Immunogenicità del vaccino:
    • Valutare le risposte delle cellule T CD8+ indotte dal vaccino, in termini d’intensità e ampiezza, determinate mediante IFN-gamma ELISPOT contro le sequenze di HIV del vaccino.
    • Valutare la capacità delle risposte delle cellule T indotte dal vaccino di controllare la replicazione di HIV-1 in vitro verso un pannello di virus che comprende i principali sottotipi globali di HIV-1.
    Viro-immunologici durante ATI:
    • Valutare il ruolo della vaccinazione nel controllo della replicazione virale in pazienti HIV-1 positivi che si sottopongono ad ATI.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    a. Male or female, aged 18-60 years
    b. Confirmed HIV-1 seropositive documented
    c. ART commenced during primary HIV infection, as defined by Fiebig stage
    d. Plasma HIV-RNA < 50 copies/ml for at least 24 months
    e. Stable ART regimen = 3 months

    f. Willing and able to give written informed consent for participation in the study
    g. Willing and able to adhere to an effective ART regimen for the duration of the study
    h. CD4+ T cell count >= 500 cells/mm3 at screening
    i. No new AIDS-defining diagnosis or progression of HIV-related disease
    j. Haematological and biochemical laboratory parameters as follows:
    1. Haemoglobin > 10g/dl
    2. Platelets > 100.000/dl
    3. ALT = 2.5 x ULN
    4. Creatinine = 1.3 x ULN
    k. Serology: negative for hepatitis B surface antigen OR HbsAg positive with HBV DNA < 1000 copies/ml; negative for hepatitis C antibodies OR confirmed clearance of HCV infection (spontaneous or following treatment); negative syphilis serology or documented adequate treatment of syphilis if positive EIA IgG or TPHA
    l. Subjects with SARS-CoV-2 Asymptomatic or Pre-symptomatic Infection and Mild Illness (NIH COVID-19 Treatment Guidelines criteria - https://www.covid19treatmentguidelines.nih.gov). Volunteers will be enrolled following the current Italian Ministry of Health rules (https://www.trovanorme.salute.gov.it/norme/renderNormsanPdf?anno=2020&codLeg=76613&parte=1%20&serie=null): COVID-19 positive case without symptoms (CDC Asymptomatic Illness) can return to the community after a period of isolation of at least 10 days after the appearance of positivity, at the end of which a molecular test with negative result (10 days + test). COVID-19 positive case with symptoms (Mild Illness) may return to the community after a period of isolation of at least 10 days after the onset of symptoms (excluding anosmia and ageusia/dysgeusia that may have prolonged persistence over time) accompanied by a molecular test with negative result performed after at least 3 days without symptoms (10 days, of which at least 3 days without symptoms + test).
    m. Available for follow up for duration of study and willing to comply with the protocol requirements
    n. Women of child-bearing age must not be pregnant, not be planning a pregnancy or breast-feeding. Sexually active women must be willing to use an approved method of contraception from screening until 4 months after the second immunization. Sexually active men in heterosexual relationships must be willing to use an approved method of contraception with their partners from screening until 4 months after the second immunization.
    o. Subjects with no immunization against COVID-19 or previous immunization with mRNA or protein vaccines (Moderna, Pfizer, Novavax) administered before the ChAdOx1.tHIVconsv1 vaccine;
    a. Maschi o femmine, età 18-60 anni
    b. Conferma documentata di HIV-1 sieropositività
    c. ART iniziata durante l’infezione primaria con HIV-1, come definita dallo stadio Fiebig
    d. Plasma HIV-RNA < 50 copie/ml per almeno 24 mesi
    e. Regime ART stabile = 3 months
    f. Disponibilità e capacità di fornire il consenso informato scritto per la partecipazione allo studio
    g. Dispinibilità e capacità di aderire alla terapia antiretroviarle per la durata dello studio
    h. Conta delle cellule T CD4+ >= 500 cellule/mm3 alla selezione
    i. Assenza di nuove diagnosi che definiscono l’AIDS o progressione di malattie correlate ad HIV
    j. Parametri di laboratorio ematologici e biochimici come segue:
    1. Emoglobina > 10g/dl
    2. Piastrine > 100.000/dl
    3. ALT = 2.5 x ULN
    4. Creatinina = 1.3 x ULN
    k. Sierologia: negativa per l’antigene di superficie dell’epatite B (hepatitis B surface antigen (HBsAg)) o positiva per HBsAg con HBV DNA < 1000 copie/ml; negativa per gli anticorpi dell’epatite C o negative for hepatitis C antibodies o guarigione confermeta dall’infezione con HCV (spontanea o a seguito di trattamento); negativa per la sifilide o trattamento adeguato documentato per la sifilide nel caso sia positiva per EIA IgG o TPHA
    l. Soggetti affetti da SARS-CoV-2 Infezione asintomatica o pre-sintomatica e malattia lieve (criteri delle linee guida per il trattamento NIH COVID-19 - https://www.covid19treatmentguidelines.nih.gov). I volontari saranno iscritti secondo le norme vigenti del Ministero della Salute (https://www.trovanorme.salute.gov.it/norme/renderNormsanPdf?anno=2020&codLeg=76613&parte=1%20&serie=null): COVID-19 caso positivo senza sintomi (Malattia asintomatica CDC) può tornare in comunità dopo un periodo di isolamento di almeno 10 giorni dalla comparsa della positività, al termine del quale un test molecolare con esito negativo (10 giorni + test). COVID-19 caso positivo con sintomi (Malattia lieve) può tornare nella comunità dopo un periodo di isolamento di almeno 10 giorni dall'insorgenza dei sintomi (escluse anosmia e ageusia/disgeusia che possono avere persistenza prolungata nel tempo) accompagnato da un test molecolare con risultato negativo eseguito dopo almeno 3 giorni senza sintomi (10 giorni, di cui almeno 3 giorni senza sintomi + test).
    m. Disponibilità al follow-up per la durata dello studio e adesione al disegno del protocollo
    n. Le donne in età fertile non devono essere incinte, non devono pianificare una gravidanza o l'allattamento. Le donne sessualmente attive devono essere disposte ad usare un metodo contraccettivo approvato dalla selezione fino a 4 mesi dopo la seconda vaccinazione. Gli uomini sessualmente attivi in relazioni eterosessuali devono essere disposti ad usare un metodo contraccettivo approvato con i loro partner dalla selezione fino a 4 mesi dopo la seconda immunizzazione.
    o. Soggetti che non abbiano ricevuto alcun tipo di immunizzazione contro COVID-19 o con precedente immunizzazione con vaccini ad mRNA o proteici (Moderna, Pfizer, Novavax).
    E.4Principal exclusion criteria
    a. Confirmed HIV-2 seropositive
    b. Women who are pregnant or breastfeeding
    c. Participation in another clinical trial within 12 weeks of study entry
    d. Active or chronic hepatitis B virus infection, with detectable hepatitis B surface antigen, hepatitis B virus DNA, or both active and chronic hepatitis C virus infection, with detectable virus RNA, and syphilis
    e. History of systemic cancers, such as Kaposi’s sarcoma and lymphoma, or other virus-associated malignancies and/or history of AIDS-defining illness according to Centers for Disease Control and Prevention criteria
    f. Resistance to two or more classes of antiretroviral drugs
    g. History of cardiovascular event or at high risk of an event (eg, atherosclerotic cardiovascular disease score >15%)
    h. History of CD4+ T cell nadir <200 cells per µl during chronic stages of infection
    i. Advanced non-alcoholic fatty liver and advanced nonalcoholic steatohepatitis, if evidence for substantial fibrosis (fibrosis score =F2) or evidence of cirrhosis
    j. HIV-related kidney disease or moderate-to-severe decrease in estimated glomerular filtration rate (<45–60 ml/min/1·73 m²)
    k. History of autoimmune disease other than HIV-related auto-immune disease.
    l. History of HIV-associated dementia or progressive multifocal leukoencephalopathy and/or history or clinical manifestations of any physical or psychiatric disorder which could impair the subject’s ability to complete the study
    m. Seizure disorder or any history of prior seizure, history of syncope or fainting episodes within 12 months of study screening.
    n. History of anaphylaxis or severe adverse reaction to vaccines, allergy or hypersensitivity to latex.
    o. Unstable asthma (e.g. sudden acute attacks occurring without an obvious trigger) or asthma requiring:
    • Daily steroid or long acting beta-agonist prevention
    • Hospitalization in the last two years
    p. SARS-CoV-2 Moderate, Severe and Critical Illness (NIH COVID-19 Treatment Guidelines criteria: https://www.covid19treatmentguidelines.nih.gov).
    q. Previous immunization with Group E adenoviruses (i.e. ChAdOx1/ChAd63, AZD1222) within last 3 months.
    r. Previous immunisation with any experimental immunogens, current or recent use (within last 3 months) of interferon or systemic corticosteroids or other immunosuppressive agents
    s. Any other prior therapy, which, in the opinion of the investigators, would make the individual unsuitable for the study or influence the results of the study.
    a. Sieropositività confermata per HIV-2
    b. Donne incinte o che allattano
    c. Partecipazione ad altri studi clinici entro le 12 settimane dalla partecipazione allo studio
    d. Infezione da virus dell’epatite B acuta o cronica, con Active or chronic hepatitis B virus infection, with HBsAg rilevabile, DNA virale o infezione da virus dell’epatite C acuta o cronica, con RNA virale rilevabile, e sifilide
    e. Storia di cancro sistemico, come il sarcoma di Kaposi e il linfoma, o altri tumori associati al virus e/o storia di malattie riconducibili all’AIDS secondo i criteri del Centro per il Controllo e la Prevenzione delle Malattie
    f. Resistenza a due o più classi di farmaci antiretrovirali
    g. Storia di eventi cardiovascolari o ad alto rischio di un evento (per esempio, punteggio per la malattia cardiovascolare aterosclerotica >15%)
    h. Storia di cellule T CD4+ nadir <200 cellule per µl durante la fase cronica dell’infezione
    i. Steatoepatite non alcolica con fegato grasso avanzata e steatoepatite non alcolica avanzata, se ci sono evidenze di fibrosi sostanziale (=F2) o evidenze di cirrosi
    j. Malattia del rene correlata a HIV o diminuzione da moderata a grave del tasso stimato di filtrazione glomerulare (<45–60 ml/min/1·73 m²)
    k. Storia di malattie autoimmuni diverse dalle malattie autoimmuni correlate all'HIV
    l. Storia di demenza associata all'HIV o leucoencefalopatia multifocale progressiva e/o storia o manifestazioni cliniche di qualsiasi disturbo fisico o psichiatrico che possa compromettere la capacità del soggetto di completare lo studio
    m. Convulsioni o qualsiasi episodio di convulsioni precedenti, storia di sincope o episodi di svenimento entro i 12 mesi dalla selezione per lo studio
    n. Anamnesi di anafilassi o reazione avversa grave ai vaccini, allergia o ipersensibilità al lattice
    o. Asma instabile (ad es. attacchi acuti improvvisi che si verificano senza un ovvio innesco) o asma che richiede:
    • Prevenzione con steroidi assunti quotidianamente o con beta-agonisti a lunga durata
    • Ricoveri ospedalieri negli ultimi 2 anni
    p. SARS-CoV-2 Malattia moderata, grave e critica (criteri delle linee guida per il trattamento NIH COVID-19: https://www.covid19treatmentguidelines.nih.gov)
    q. Immunizzazione nei tre mesi precedenti con adenovirus del gruppo E (cioè vaccino Janssen ChAdOx1/ChAd63 e vaccino AstraZeneca AZD1222).
    r. Precedente immunizzazione con qualsiasi immunogeno sperimentale, uso attuale o recente (negli ultimi 3 mesi) di interferone, corticosteroidi sistemici o altri agenti immunosoppressori.
    s. Qualsiasi altra terapia precedente, che, a giudizio dei ricercatori, renderebbe l'individuo inadatto allo studio o influenzerebbe i risultati dello studio.
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of participants who develop at least one = Grade 3 Adverse Event (AE) including local and systemic reactions, lab toxicities, and/or clinical events, that is possibly, probably or definitely related to study treatment any time from the first day of treatment through further 28 days following vaccination with C1.
    Proporzione dei partecipanti che sviluppa almeno un evento avverso (Adverse Event (AE)) di grado = 3 comprese reazioni sistemiche e locali, tossicità di laboratorio, e/o eventi clinici, che siano possibilmente, probabilmente o definitivamente correlati al trattamento in studio in qualsiasi momento dal primo giorno del trattamento fino a 28 giorni dopo la vaccinazione con C1.
    E.5.1.1Timepoint(s) of evaluation of this end point
    At any time from the first day of treatment through further 28 days following vaccination with C1.
    Dal primo giorno del trattamento fino a 28 giorni dopo la vaccinazione con C1.
    E.5.2Secondary end point(s)
    Safety:
    - Proportion of participants who develop at least one = Grade 3 Adverse Event (AE) including signs/symptoms, lab toxicities, and/or clinical events, that is possibly, probably or definitely related to study treatment any time from the first day of treatment through further 28 days following vaccination with M3+M4 given as boost to C1.

    Vaccine Immunogenicity:
    - Evaluate vaccine immunogenicity as a proportion of volunteers responding to vaccination.
    - Relative change in magnitude of T-cell responses to HIV-1 conserved regions from pre-vaccination (Day 0) to post-vaccination at week 8 by IFN-y ELISPOT.
    - Change in breadth of T-cell responses targeting HIV conserved regions from pre-vaccination (Day 0) to post-vaccination at week 8 by IFN-y ELISPOT.
    - Relative change in HIV p24 levels in CD4+ T cells from pre-vaccination (Day 0) to post-vaccination at week 8 by Viral Inhibition Assay (VIA).

    Viro-immunological assessment during ATI:
    - Proportion of patients with pVL =1000 copies/mm3 at week 24.
    - Proportion of individuals in whom ART is reinitiated due to viral rebound (pVL =100,000 copies/ml or 2 consecutive pVL =10,000 copies/ml 7 days apart), >50% drop in CD4 cell counts, <350 cells/mm3 and/or symptomatic acute retroviral syndrome
    - Time to viral rebound during ATI.
    - Proportion of patients with low-level plasma viremia as measured by single copy assay after C1 vaccination and with booster M3+M4.
    - Change in total HIV DNA in CD4+ T cells at baseline, after vaccination and at ART re-initiation.
    - Proportion of patients with viral suppression 6 months after treatment resumption.
    - Proportion of patients with onset of new HIV-1 resistance as viral genotype to ART during ATI.
    - Proportion of patients with onset of vaccine-induced breakthrough viral gag and pol genes by sieve analysis at ART re-initiation.
    - Change in function and phenotype of HIV-1-specific T cell responses in participants from pre-vaccination (Day 0) to post-vaccination at week 8.
    - Change of cellular activation status of total CD8+ T cells and NK cells from pre-vaccination (Day 0) to post-vaccination at week 8.
    Endpoint secondario: sicurezza
    • Proporzione dei partecipanti che sviluppa almeno un evento avverso (Adverse Event (AE)) di grado = 3 compresi segnali/sintomi, tossicità di laboratorio, e/o eventi clinici, che siano possibilmente, probabilmente o definitivamente correlati al trattamento in studio in qualsiasi momento dal primo giorno del trattamento fino a 28 giorni dopo la vaccinazione con M3+M4 data come richiamo a C1.

    Endpoints secondari: immunogenicità
    • proporzione di volontari che rispondono alla vaccinazione.
    • Variazione dell’intensità della risposta delle cellule T diretta contro le regioni conservate di HIV-1 da prima della vaccinazione (day 0) a 8 settimane dopo la vaccinazione determinata mediante IFN-¿ ELISPOT.
    • Variazione dell’ampiezza della risposta delle cellule T diretta contro le regioni conservate di HIV-1 da prima della vaccinazione (day 0) a 8 settimane dopo la vaccinazione determinata mediante IFN-¿ ELISPOT.
    • Variazione dei livelli di HIV p24 nelle cellule T CD4+ da prima della vaccinazione (day 0) a 8 settimane dopo la vaccinazione determinato mediante test di inibizione virale (Virus Inhibition Assay (VIA)).

    Endpoints secondari: viro-immunologici durante ATI
    • Proporzione di pazienti con pVL =1000 copie/mm3 a 36 settimane.
    • Proporzione di pazienti che riprendono l’ART a causa del rialzo virale (pVL =100,000 copie/ml o 2 pVL =10,000 copies/ml consecutive a distanza di 7 giorni), diminuzione della conta delle cellule T CD4+ >50%, <350 cellule/mm3 e/o sindrome retrovirale acuta sintomatica.
    • tempo al rebound virale durante ATI.
    • Proporzione di pazienti con viremia plasmatica residua misurata mediante test a singola copia dopo vaccinazione con C1 e dopo somministrazione del booster M3+M4.
    • variazione di HIV DNA totale nelle cellule CD4+ iniziale, dopo vaccinazione e alla ripresa dell’ART.
    • tassi di soppressione virale a 6 mesi dalla ripresa del trattamento.
    • proporzione di pazienti con insorgenza di varianti virali resistenti all’ART durante ATI
    • proporzione di pazienti con insorgenza di varianti delle sequenze virali gag e pol come risposta di resistenza al vaccino.
    • variazione nella funzione e nel fenotipo delle risposte delle cellule T specifiche per HIV-1 nei partecipanti da prima della vaccinazione (day 0) a 8 settimane dopo la vaccinazione.
    • variazione dei marker di attivazione delle cellule CD8+ e Natural Killer (NK) da prima della vaccinazione (day 0) a 8 settimane dopo la vaccinazione.
    Le cellule mononucleate del sangue periferico (Peripheral Blood Mononuclear Cells (PBMCs)) saranno conservate per studi futuri.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1.any time from the first day of treatment through further 28 days following vaccination with M3+M4 given as boost to C1.
    2.from pre-vaccination (Day 0) to post-vaccination at week 8
    3.Variable and specified in section E.5.2EN
    1. in qualsiasi momento dal primo giorno del trattamento fino a 28 giorni dopo la vaccinazione con M3+M4 data come richiamo a C1.
    2.da prima della vaccinazione (day 0) a 8 settimane dopo la vaccinazione
    3.variabile e specificato nella sezione E.5.2IT
    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) Yes
    E.7.1.1First administration to humans Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    PROOF-OF-CONCEPT
    PROOF-OF-CONCEPT
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 Yes
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    PROOF OF CONCEPT
    PROOF OF CONCEPT
    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 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 Information not present in EudraCT
    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
    LVLS
    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 months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months0
    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: 33
    F.1.3Elderly (>=65 years) No
    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 state33
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 33
    F.4.2.2In the whole clinical trial 33
    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)
    At the end of the participation in the study, the subjects will receive the standard therapies foreseen for the pathology from which they are suffering and the doctors will continue to follow them with the due care attention.
    Al termine della partecipazione allo studio, i soggetti riceveranno le terapie standard previste per la patologia da cui sono affetti ed i medici continueranno a seguirli con la dovuta attenzione assistenziale.
    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 Decision2021-07-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-07-14
    P. End of Trial
    P.End of Trial StatusOngoing
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