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    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   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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    Summary
    EudraCT Number:2021-005226-26
    Sponsor's Protocol Code Number:HIPRA-HH-2
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-11-02
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2021-005226-26
    A.3Full title of the trial
    A Phase IIb, double-blind, randomized, active controlled, multi-centre, non-inferiority trial followed by a Phase III, single arm, open label trial, to assess immunogenicity and safety of a booster vaccination with a recombinant protein RBD fusion dimer candidate (PHH-1V) against SARS-CoV-2, in adults fully vaccinated against COVID-19 followed with an extension period to study a fourth dose administration of PHH-1V.
    Un estudio de no inferioridad de fase IIb, doble ciego, aleatorizado, con control activo, multicéntrico, seguido de un estudio de fase III, de un solo brazo y abierto, para evaluar la inmunogenicidad y la seguridad de una vacuna de refuerzo con un candidato de proteína recombinante dimérica de fusión RBD (PHH-1V) contra el SARS-CoV-2, en adultos completamente vacunados contra COVID-19 con un período de extensión para estudiar la administración de PHH-1V como cuarta dosis
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A phase II study to evaluate safety and immunogenicity of recombinant protein
    candidate vaccine against SARS-CoV-2 in adults fully vaccinated against COVID-19 with extension period to evaluate a fourth dose
    Estudio de fase II para evaluar la seguridad e inmunogenicidad de una vacuna
    candidata de proteina recombinante frente al SARS-CoV-2 en adultos completamente vacunados contra COVID-19 con periodo de extensión para evaluar una cuarta dosis
    A.4.1Sponsor's protocol code numberHIPRA-HH-2
    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 SponsorHIPRA SCIENTIFIC
    B.1.3.4CountrySpain
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportHipra Scientific, S.L.U.
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationHIPRA SCIENTIFIC
    B.5.2Functional name of contact pointR&D and Regulatory Affairs Director
    B.5.3 Address:
    B.5.3.1Street AddressAvda. La Selva, 135
    B.5.3.2Town/ cityAmer, Girona
    B.5.3.3Post code17170
    B.5.3.4CountrySpain
    B.5.4Telephone number34972430660
    B.5.6E-mailelia.torroella@hipra.com
    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 namePHH-1V
    D.3.2Product code PHH-1V
    D.3.4Pharmaceutical form Emulsion 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.3.8INN - Proposed INNPHH-1V
    D.3.9.1CAS number -
    D.3.9.2Current sponsor codePHH-1V
    D.3.9.3Other descriptive namePHH-1V
    D.3.9.4EV Substance CodeSUB223972
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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 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 RoleComparator
    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 Comirnaty
    D.2.1.1.2Name of the Marketing Authorisation holderBioNTech Manufacturing GmbH
    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.3.4Pharmaceutical form Dispersion 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.3.8INN - Proposed INNTozinameran
    D.3.9.1CAS number -
    D.3.9.2Current sponsor code-
    D.3.9.4EV Substance CodeSUB210693
    D.3.10 Strength
    D.3.10.1Concentration unit ml millilitre(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.3
    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 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
    SARS-CoV-2
    SARS-CoV-2
    E.1.1.1Medical condition in easily understood language
    COVID-19 Infection
    Infección por COVID-19
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.0
    E.1.2Level LLT
    E.1.2Classification code 10084272
    E.1.2Term SARS-CoV-2 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
    Part A:
    To determine and compare the changes of the immunogenicity measured by pseudovirus neutralisation against Wuhan strain (also known as L strain) at Baseline and Day 14, after HIPRA’s vaccine (PHH-1V) versus subjects who have received complete vaccination, including homologous booster, with the Comirnaty vaccine at least 182 days and with a maximum of 365 days before Screening.
    To assess the safety and tolerability of PHH-1V as a booster dose in healthy adult subjects fully vaccinated against COVID-19 with the Comirnaty vaccine.
    Part B:
    To determine and compare the changes in the immunogenicity measured by PBNA against omicron BA.1 subvariant, at Day 14 post-dose 4 of PHH-1V versus post-dose 3 in cohort 2.
    To assess the safety and tolerability of PHH-1V as a fourth dose in adult subjects in cohort 1 and 2
    Parte A:
    Determinar y comparar los cambios de immunogenicitat medidos por neutralización pseudovirus contra cepas Wuhan en el día cero y 14 después de la administración de la vacuna de HIPRA (PHH-1V) versus booster de Comirnaty en sujetos que han recibido la pauta completa de vacunación con Comirnaty al menos 182 días, y como máximo 365 días, antes de la selección.
    Evaluar la seguridad y tolerabilidad de PHH-1V como dosis de refuerzo (booster) en sujetos adultos sanos con pauta completa contra COVID-19 con la vacuna Comirnaty.
    Parte B:
    Determinar y comparar los cambios en la inmunogenicidad medidos por PBNA contra la subvariante de Omicron BA.1 a los días 14 después de la cuarta dosis de PHH-1V versus después de la tercera dosis, en la cohorte 2.
    Evaluar la seguridad y tolerabilidad de PHH-1V como cuarta dosis en adultos de las cohortes 1 y 2
    E.2.2Secondary objectives of the trial
    Part A:
    To determine and compare the changes of the immunogenicity measured by SARS-CoV-2 PBNA against the Variants of Concern (VOC)
    To determine and compare the changes in immunogenicity measured by wild type SARS-CoV-2 neutralisation test (VNA)
    To evaluate the immunogenicity measured by enzyme-linked immunosorbent assay (ELISA) to the SARS-CoV-2 spike glycoprotein.
    To evaluate T-cell mediated responses against the SARS-CoV-2 S glycoprotein
    To assess Th-1/Th-2 T-cell mediated responses against the SARS-CoV-2 S glycoprotein

    Part B:
    To determine and compare the changes of the immunogenicity measured by SARS-CoV-2 PBNA against the Variants of Concern (VOC)
    To evaluate the immunogenicity measured by enzyme-linked immunosorbent assay (ELISA) to the SARS-CoV-2 spike glycoprotein.
    To evaluate T-cell mediated responses against the SARS-CoV-2 S glycoprotein
    To assess Th-1/Th-2 T-cell mediated responses against the SARS-CoV-2 S glycoprotein
    Parte A:
    Determinar y comparar los cambios de la inmunogenicidad mediante PBNA de SARS-CoV-2 frente a las variantes de interés (VOC)
    Determinar y comparar los cambios en la inmunogenicidad medidos mediante la prueba de neutralización (VNA) de wild type SARS-CoV-2
    Evaluar la inmunogenicidad medida por ensayo inmunoabsorbente ligado a enzimas (ELISA) para spike glicoproteina del SARS-CoV-2.
    Evaluar las respuestas mediadas por linfocitos T contra la glicoproteína SARS-CoV-2
    Evaluar las respuestas mediadas por células T Th-1 / Th-2 contra la glicoproteína S del SARS-CoV-2

    Parte B:
    Determinar y comparar los cambios de la inmunogenicidad mediante PBNA de SARS-CoV-2 frente a las VOC
    Evaluar la inmunogenicidad medida por ELISA para spike glicoproteina del SARS-CoV-2.
    Evaluar las respuestas mediadas por linfocitos T contra la glicoproteína SARS-CoV-2
    Evaluar las respuestas mediadas por células T Th-1 / Th-2 contra la glicoproteína S del SARS-CoV-2
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Part A:
    - Male or female, by birth, ≥ 18 years old at Screening.
    - Willing and able to comply with scheduled visits, laboratory tests, complete diaries, and other study procedures.
    - Body Mass Index (BMI) between 18 to 40 kg/m2.
    - Has received a complete COVID-19 vaccination programme (two administrations, prime and boosting) at least 182 days and with a maximum of 365 days before Screening with Comirnaty vaccine.
    - Has a negative COVID-19 polymerase chain reaction (PCR) test at Screening.
    - Willing to avoid all other vaccines within 4 weeks before and after vaccination in this study (Day 0). Seasonal influenza vaccination is allowed if it is received at least 14 days before or after Day 0.
    - Willing to refrain from blood donation during the study.
    - Women of childbearing potential must have a negative urine pregnancy test at Screening and Day 0 (before vaccination).
    - Women of childbearing potential must be willing to use highly effective contraceptive methods or have practiced sexual abstinence from the screening visit until 8 weeks after the vaccination (Day 0). Highly effective contraceptive methods include oral, intravaginal, or transdermal combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation; intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion; vasectomised partner and sexual abstinence.
    - Males who are not sterilised, must be willing to avoid impregnating female partners from Screening until 8 weeks after vaccination (Day 0).
    - Willing and able to provide written informed consent prior the initiation of any study procedures.

    Part B:
    Adults ≥ 18 years old at Day 0
    Participant must provide consent and is willing and able to participate in this extension of the study
    Has received a primary vaccination of two doses of Comirnaty followed by a booster dose either with Comirnaty or PHH-1V. Last booster dose given between 6 and 12 months before Day 0
    Has a negative Rapid Antigen Test (RAT) at Day 0
    Participants may have underlying illnesses if are stable and well-controlled
    Participant is willing to avoid receiving live attenuated vaccines within 4 weeks before or after receiving study vaccine
    Participant agrees not to donate blood, blood products and bone marrow at least 12 weeks before and after vaccination
    Female participants have a negative pregnancy test on the day of vaccination
    Use of any acceptable contraceptive method that started at screening and until 8 weeks after vaccination
    Parte A:
    - Hombre o mujer, por nacimiento, ≥ 18 años en el momento del cribado.
    - Dispuesto y capaz de cumplir con las visitas programadas, las pruebas de laboratorio, los diarios completos y otros procedimientos del estudio.
    - Índice de masa corporal (IMC) entre 18 y 40 kg / m2.
    - Ha recibido un programa completo de vacunación COVID-19 (dos administraciones, prime y boosting) al menos 182 días y con un máximo de 365 días antes del cribado con vacuna Comirnaty.
    - Tiene una prueba PCR COVID-19 negativa en la selección.
    - Dispuesto a evitar todas las demás vacunas en las 4 semanas anteriores y posteriores a la vacunación en este estudio (día 0). Se permite la vacunación contra la influenza estacional si se recibe al menos 14 días antes o después del día 0.
    - Dispuesto a abstenerse de la donación de sangre durante el estudio.
    - Las mujeres en edad fértil deben tener una prueba de embarazo en orina negativa en la selección y el día 0 (antes de la vacunación).
    - Las mujeres en edad fértil deben estar dispuestas a utilizar métodos anticonceptivos altamente eficaces o haber practicado la abstinencia sexual desde la visita de selección hasta 8 semanas después de la vacunación (día 0). Los métodos anticonceptivos altamente efectivos incluyen anticoncepción hormonal combinada oral, intravaginal o transdérmica (que contiene estrógeno y progestágeno) asociada con la inhibición de la ovulación; anticoncepción hormonal de progestágeno solo oral, inyectable o implantable asociada con la inhibición de la ovulación; dispositivo intrauterino; sistema de liberación de hormonas intrauterinas; oclusión tubárica bilateral; pareja vasectomizada y abstinencia sexual.
    - Los hombres que no están esterilizados deben estar dispuestos a evitar embarazar a sus parejas femeninas desde la selección hasta 8 semanas después de la vacunación (día 0).
    - Dispuesto y capaz de proporcionar un consentimiento informado por escrito antes del inicio de cualquier procedimiento del estudio.

    Parte B:
    Adultos ≥ 18 años de edad a Día 0
    El participante debe dar su consentimiento y está dispuesto y es capaz de participar en el estudio
    Haber recibido una pauta de vacunación primaria de dos dosis de Comirnaty seguido de una dosis de refuerzo de o bien Comirnaty o bien PHH-1V. La última dosis de booster se debe haber recibido entre 6 y 12 meses antes del Día 0
    Tener un test de antígenos rápido (TAR) negativo a Día 0
    Los participantes pueden tener enfermedades subyacentes si están estables y bien controladas
    El participante está dispuesto a evitar recibir vacunas vivas atenuadas en las 4 semanas antes y después de recibir la vacuna del estudio
    El participante se compromete a no donar sangre, hemoderivados y médula ósea al menos 3 meses antes y después de la vacunación
    Mujeres participantes tener una prueba de embarazo negativa el día de la vacunación
    Uso de cualquier método anticonceptivo aceptable que debe iniciarse el día 0 y hasta 8 semanas después de la vacunación
    E.4Principal exclusion criteria
    Part A:
    - Pregnant or lactating or intending to become pregnant or plans to breastfeed during the study.
    - Positive pregnancy test at Screening or Day 0.
    - Any medical disease (acute, subacute, intermittent, or chronic) or condition that in the opinion of the Investigator compromises the subject's safety, preclude vaccination or compromises interpretation of the results.
    - Ongoing serious psychiatric condition likely to affect participation in the study (e.g., ongoing severe depression, recent suicidal ideation, bipolar disorder, personality disorder, alcohol and drug dependency, severe eating disorder, psychosis, use of mood stabilisers or antipsychotic medication).
    - History of respiratory disease requiring daily medications currently or any treatment of respiratory disease exacerbation in the last 6 months.
    - History of significant cardiovascular disease or history of myocarditis or pericarditis as an adult. Controlled hypertension will be permitted at the discretion of the Investigator.
    - History of neurological or neurodevelopmental conditions
    - Ongoing malignancy or recent diagnosis of malignancy in the last five years excluding basal cell and squamous cell carcinoma of the skin, which are allowed.
    - Any confirmed or suspected autoimmune, immunosuppressive or immunodeficiency disease/condition (iatrogenic or congenital), including human immunodeficiency virus (HIV) infection, asplenia, or recurrent severe infections.
    - Acute illness within 72 hours before Day 0
    - Received investigational drug within 90 days before Screening or plans to participate clinical study
    - History of hypersensitivity or severe allergic reactions, including anaphylaxis, generalised urticarial, angioedema and other significant reactions related to food, drugs, vaccines, or pharmaceutical agents, which are likely to be exacerbated by any component of the COVID-19 vaccine HIPRA.
    - Use of any immunosuppressant, glucocorticoids, or other immune-modifying drugs within 2 months before Day 0
    - Received immunoglobulin, blood-derived products, or other immunosuppressant drugs within 90 days before vaccination (Day 0).
    - Known bleeding disorder, blood dyscrasias, or prior history of significant bleeding or bruising following intramuscular (IM) injections or venepuncture.
    - Chronic liver disease.
    - Positive test for HIV types 1 or 2 infection, hepatitis B surface antigen (HBsAg), or hepatitis C virus antibodies (HCV Abs) at Screening.
    - Suspected or known current alcohol abuse or any other substances abuse.
    - History of COVID-19 infection.
    - Ever been included in a trial with an experimental vaccine against COVID-19.
    - Close contact with anyone known to have SARS-CoV-2 infection within 15 days before Screening.
    - Scheduled elective surgery during the study.
    - Life expectancy of less than 12 months.
    - Any condition and/or laboratory finding that, in the Investigators opinion, would interfere with the study or put the subject at risk.

    Part B:
    History of anaphylactic shock of any kind
    History of COVID-19 infection
    Participant received or plans to receive live attenuated vaccines within 4 weeks before and after Day 0, or other not live vaccines within 14 days before and after Day 0
    Pregnancy or breast-feeding at vaccination time-point
    Participant has a clinically significant acute illness or fever at screening or within 48 hours prior to Day 0
    Participant had a surgery requiring hospitalization before vaccination and he/she has not received the hospital discharge at day 0
    Participant has any active malignancy even if under treatment except for Non-melanoma skin cancer, uterine cervical carcinoma, anal carcinoma or Localized prostate cancer, all without evidence of disease.
    Participant has ongoing severe and non-stable psychiatric condition likely to affect participation in the study
    Participant has a problematic or risk use of substances including alcohol that can compromise the study follow-up
    Participant has a bleeding disorder that contraindicates intramuscular injections
    Participant has abnormal function of the immune system
    Participants have any other medical disorder as judged by the investigator and defined as disease requiring hospitalization or addition of new treatments or major dose adjustments within 3 months before screening
    Chronic or recurrent administration of systemic immunosuppressant medication
    Subject has received immunoglobulins and/or blood-derived products 12 weeks prior vaccination
    Participant received any immunotherapy aimed to prevent or treat COVID-19 within 90 days preceding Day 0
    Participation in any research involving an investigational product rather than PHH-1V vaccine
    Participant has donated ≥ 450ml of blood products within 12 weeks before screening
    Participant has any medical condition and/or finding that in the investigator opinion might increase participant risks, interfere with the study or impair interpretation of study data
    Parte A:
    Está embarazada o amamantando o tiene la intención de quedar embarazada o planea amamantar durante el estudio.
    - Prueba de embarazo positiva en la selección o el día 0.
    - Cualquier enfermedad médica (aguda, subaguda, intermitente o crónica) o condición que a juicio del Investigador comprometa la seguridad del sujeto, impida la vacunación o comprometa la interpretación de los resultados.
    - Enfermedad psiquiátrica grave en curso que pueda afectar la participación en el estudio (p. Ej., Depresión grave en curso, ideación suicida reciente, trastorno bipolar, trastorno de personalidad, dependencia del alcohol y las drogas, trastorno alimentario grave, psicosis, uso de estabilizadores del estado de ánimo o medicación antipsicótica).
    - Antecedentes de enfermedad respiratoria (p. Ej., Enfermedad pulmonar obstructiva crónica [EPOC]) que requieran medicación diaria en la actualidad o cualquier tratamiento de exacerbaciones de enfermedades respiratorias (p. Ej., Exacerbación del asma) en los últimos 6 meses.
    - Antecedentes de enfermedad cardiovascular significativa (p. Ej., Insuficiencia cardíaca congestiva, miocardiopatía, cardiopatía isquémica) o antecedentes de miocarditis o pericarditis en la edad adulta. Se permitirá la hipertensión controlada a discreción del investigador.
    - Antecedentes de afecciones neurológicas o del neurodesarrollo (p. Ej., Epilepsia, accidente cerebrovascular, convulsiones en los últimos 3 años, encefalopatía, déficits neurológicos focales, síndrome de Guillain-Barré, encefalomielitis o mielitis transversa).
    - Malignidad en curso o diagnóstico reciente de malignidad en los últimos cinco años, excluidos los carcinomas de células basales y escamosas de piel, que están permitidos.
    - Cualquier enfermedad / afección autoinmune, inmunosupresora o de inmunodeficiencia confirmada o sospechada (yatrógena o congénita), incluida la infección por el virus de la inmunodeficiencia humana (VIH), asplenia o infecciones graves recurrentes.

    Parte B:
    Antecedentes de choque anafiláctico de cualquier tipo
    Antecedentes de infección por COVID-19
    El participante recibió o planea recibir vacunas vivas atenuadas dentro de las 4 semanas antes o después de Día 0, o, otras vacunas no vivas dentro de los 14 días antes y después de Día 0
    Embarazo o lactancia en la selección o Día 0
    El participante tiene una enfermedad aguda clínicamente significativa en la selección o dentro de las 48 horas previas a Día 0
    El participante se sometió a una cirugía que requirió hospitalización antes de la vacunación y no había recibido el alta hospitalaria el día 0
    El participante tiene alguna neoplasia maligna activa incluso si está bajo tratamiento excepto: Cáncer de piel, carcinoma de cuello uterino, carcinoma anal o cáncer de próstata localizado, todos sin evidencia de enfermedad
    El participante tiene una patología psiquiátrica grave y no estable en curso que probablemente afecte la participación en el estudio
    El participante tiene un uso problemático o de riesgo de sustancias, incluido el alcohol, que pueden comprometer el seguimiento del estudio
    El participante tiene un trastorno hemorrágico que contraindique las inyecciones intramusculares
    El participante tiene una función anormal del sistema inmunológico
    Los participantes tienen un trastorno que según investigador requiera hospitalización o adición de nuevos tratamientos o ajustes importantes de dosis dentro de los 3 meses anteriores a la selección
    Administración crónica o recurrente de medicación inmunosupresora sistémica
    El sujeto ha recibido inmunoglobulinas y/o productos derivados de la sangre 12 semanas antes de la vacunación
    El participante recibió cualquier inmunoterapia para prevenir o tratar la COVID-19 en los 90 días anteriores a día 0
    Participación en cualquier investigación que involucre un producto en investigación excepto la vacuna PHH-1V
    El participante ha donado ≥ 450 ml de productos sanguíneos dentro de las 12 semanas anteriores a Día 0
    El participante tiene alguna condición médica y/o hallazgo que, en opinión del investigador, podría aumentar los riesgos del participante, interferir con el estudio o perjudicar la interpretación de los datos del estudio
    E.5 End points
    E.5.1Primary end point(s)
    Part A:
    Efficacy:
    Neutralisation titre against Wuhan strain measured as inhibitory concentration 50 (IC50) by a PBNA and reported as reciprocal concentration for each individual sample and geometric mean titre (GMT) for treatment group comparison at Baseline and Day 14.
    Number, percentage, and characteristics of solicited local reactions through Day 7 after vaccination.
    · Number, percentage, and characteristics of unsolicited local and systemic AEs through Day 28 after vaccination.
    · Number and percentage of serious adverse events (SAEs) through the end of the study.
    · Number and percentage of AESI through the end of the study.
    · Number and percentage of medically attended adverse events (MAAE) related to study vaccine through the end of the study.
    · Change from baseline in safety laboratory parameters at Days 14, 28, 182, and 364 after vaccination.

    Part B:
    Neutralisation titre against omicron BA.1 subvariant, measured as inhibitory concentration 50 (IC50) by PBNA and reported as log10 concentration for each individual sample and GMT, at Day 14 post-dose 4 of PHH-1V versus post-dose 3 in cohort 2
    Number, percentage, and characteristics of solicited local and systemic reactions after 4th dose vaccination through Day 7
    Number, percentage, and characteristics of unsolicited local and systemic adverse events (AEs) after 4th dose vaccination through Day 28
    Number and percentage of serious adverse events (SAEs) after 4th dose vaccination through the end of the study
    Number and percentage of adverse event of special interest (AESI) after 4th dose vaccination through the end of the study
    Number and percentage of all medically attended adverse events (MAAE) related or not related to study vaccine, up to Day 28 after the fourth dose; and number and percentage of MAAEs related to study vaccine after 4th dose vaccination through the end of the study
    Grades 3 or grade 4 change from Part B baseline values in safety laboratory parameters through the end of the study
    Parte A:
    Eficacia:
    El título de neutralización contra la cepa de Wuhan se midió como concentración inhibitoria 50 (IC50) por un PBNA y se informó como concentración recíproca para cada muestra individual y título de media geométrica (GMT) para la comparación del grupo de tratamiento en la línea de base y el día 14.
    Número, porcentaje y características de las reacciones locales solicitadas hasta el día 7 después de la vacunación.
    · Número, porcentaje y características de EA locales y sistémicos no solicitados hasta el día 28 después de la vacunación.
    · Número y porcentaje de eventos adversos graves (AAG) hasta el final del estudio.
    · Número y porcentaje de AESI hasta el final del estudio.
    · Número y porcentaje de eventos adversos atendidos por un médico (MAAE) relacionados con la vacuna del estudio hasta el final del estudio.
    · Cambio desde el inicio en los parámetros de laboratorio de seguridad en los días 14, 28, 182 y 364 después de la vacunación.

    Parte B:
    Título de neutralización (PBNA) contra la subvariante de Omicron BA.1 medido como CI50 y reportado como la concentración en log10 para cada muestra individual y la MGT, a los días 14 post-4ta dosis de PHH-1V versus post-3ra dosis e la cohorte 2
    Número, porcentaje y características de las reacciones locales solicitadas y sistémicas, durante los 7 días posteriores a la vacunación de la 4ta dosis
    Número, porcentaje y características de AE no solicitados durante los 28 días posteriores a la vacunación de la 4ta dosis
    Número y porcentaje de eventos adversos graves (SAEs) después de la 4ta dosis y a lo largo de todo el estudio
    Número y porcentaje de eventos adversos de especial interés (AESIs) después de la 4ta dosis y a lo largo de todo el estudio
    Número y porcentaje de eventos adversos atendidos por un médico (MAAE) relacionados o no relacionados con la vacuna hasta los 28 días después de la 4ta dosis; y número y porcentaje de MAAEs relacionados con la vacuna en estudio después de la 4ta dosis y a lo largo de todo el estudio
    Cambios en los parámetros de seguridad del laboratorio, de grado 3 o grado 4 en relación al valor basal de la parte B del estudio, a lo largo de todo el estudio
    E.5.1.1Timepoint(s) of evaluation of this end point
    D14, 28, 98, 182 and 364 (Part A)
    D14, 98, 182 (Part B)
    D14, 28, 98, 182 y 364 (Parte A)
    D14, 98 y 182 (Parte B)
    E.5.2Secondary end point(s)
    Part A:
    · Neutralisation titre against VOC measured as IC50 by PBNA and reported as reciprocal concentration for each individual sample and GMT for treatment group comparison at Baseline and Days 14, 28, 98 (for a subset of participants), 182, and 364.
    · Geometric mean fold rise (GMFR) in neutralising antibodies titres for treatment group comparison at Baseline and Days 14, 28, 98 (for a subset of participants) 182, and 364.
    · Neutralisation titre measured as inhibitory dilution 50 (ID50) by a VNA and reported as reciprocal dilution for each individual sample, and GMT for treatment group comparison at Baseline and Days 14, 28, 182, and 364. This analysis will be performed in a subset of subjects.
    · Binding antibodies titre measured for each individual sample and GMT for treatment group comparison at Baseline and Days 14, 28, 98 (for a subset of participants), 182, and 364.
    · Geometric mean fold rise (GMFR) in binding antibodies titre from Baseline and Days 14, 28, 98 (for a subset of participants), 182, and 364.
    · Percentage of subjects that, after a booster dose, have a ≥4-fold change in binding antibodies titre from Baseline and Days 14, 28, 182, and 364.
    · T-cell-mediated response to the SARS-CoV-2 S protein as measured by whole peripheral blood mononuclear cell (PBMC) stimulation by enzyme-linked immune absorbent spot (ELISpot) at Baseline, Day 14 and Day 182. This analysis will be performed in a subset of subjects.
    · CD4+/CD8+ T-cell response to the SARS-CoV-2 S protein as measured by in vitro PBMC stimulation by cytokine staining assays at Baseline, Day 14 and Day 182. This analysis will be performed in a subset of subjects.

    Part B:
    Neutralisation titre against omicron BA.1 subvariant, measured as inhibitory concentration 50 (IC50) by PBNA and reported as log10 concentration for each individual sample and GMT, at Day 98 and 182 post-dose 4 of PHH-1V versus post-dose 3 in cohort 2
    To determine the geometric mean fold rise (GMFR) in neutralising antibody titres at Day 14 post-dose 4 of PHH-1V versus Part B baseline value in cohort 2, for Omicron BA.1 subvariant
    Neutralisation titre against omicron BA4/5 subvariant and other VOCs, measured as IC50 by PBNA and reported as log10 concentration for each individual sample and GMT, at Days 14, 98 and 182 post-dose 4 of PHH-1V versus post-dose 3 in cohort 2
    GMFR in neutralising antibodies titres at Day 14 post-dose 4 of PHH-1V versus Part B baseline value in cohort 2, for omicron BA4/5 subvariant and other VOCs
    Neutralisation titre against omicron BA.1, BA4/5 subvariants and other VOCs, measured as inhibitory concentration 50 (IC50) by PBNA and reported as log10 concentration for each individual sample and GMT, at Day 14, 98 and 182 post-dose 4 of PHH-1V in cohort 1 versus post-dose 3 in cohort 2
    GMFR in neutralising antibodies titres at Day 14 post-dose 4 of PHH-1V versus Part B baseline value in cohort 1 for Omicron BA.1, BA4/5 subvariants and other VOCs
    Parte A:
    Título de neutralización contra VOC medido como IC50 por PBNA y reportado como concentración recíproca para cada muestra individual y GMT para la comparación del grupo de tratamiento en la línea de base y los días 14, 28, 98 (por un subset de sujetos), 182 y 364.
    · Aumento de veces en la media geométrica (GMFR) en los títulos de anticuerpos neutralizantes para la comparación del grupo de tratamiento al inicio y los días 14, 28, 98 (por un subset de sujetos), 182 y 364.
    · Título de neutralización medido como dilución inhibitoria 50 (ID50) por un VNA y reportado como dilución recíproca para cada muestra individual, y GMT para la comparación del grupo de tratamiento al inicio y los días 14, 28, 182 y 364. Este análisis se realizará en un subconjunto de sujetos.
    · Título de anticuerpos de unión medido para cada muestra individual y GMT para la comparación del grupo de tratamiento al inicio y los días 14, 28, 98 (por un subset de sujetos), 182 y 364.
    · Aumento de veces medio geométrico (GMFR) en el título de anticuerpos de unión desde el inicio y los días 14, 28, 98 (por un subset de sujetos), 182 y 364.
    · Porcentaje de sujetos que, después de una dosis de refuerzo, tienen un cambio ≥4 veces en el título de anticuerpos de unión desde el inicio y los días 14, 28, 98 (por un subset de sujetos), 182 y 364.
    · Respuesta mediada por células T a la proteína SARS-CoV-2 S medida por estimulación de células mononucleares de sangre periférica completa (PBMC) por mancha inmunoabsorbente ligada a enzimas (ELISpot) al inicio, día 14 y día 182. Este análisis se realizará en un subconjunto de sujetos.
    · Respuesta de células T CD4 + / CD8 + a la proteína SARS-CoV-2 S medida por estimulación de PBMC in vitro mediante ensayos de tinción de citocinas al inicio, día 14 y día 182. Este análisis se realizará en un subconjunto de sujetos.

    Parte B:
    Título de neutralización (PBNA) contra la subvariante de Omicron BA.1 medido como CI50 y reportado como la concentración en log10 para cada muestra individual y la MGT, a los días 98 y 182 post-4ta dosis de PHH-1V versus post-3ra dosis en la cohorte 2
    Determinar la mediana geométrica del fold-rise (GMFR) en los títulos de anticuerpos neutralizantes al día 14 post-4ta dosis de PHH-1V versus los valores basales de la parte B en la cohorte 2 y para la subvariante de Omicron BA.1
    Título de neutralización (PBNA) contra la subvariante de Omicron BA4/5 medido como CI50 y reportado como la concentración en log10 para cada muestra individual y la MGT, a los días 14, 98 y 182 post-4ta dosis de PHH-1V versus post-3ra dosis en la cohorte 2
    GMFR en los títulos de anticuerpos neutralizantes a los días 14 post-4ta dosis de PHH-1V versus los valores basales de la Parte B en la cohorte 2, para la subvariante de Omicron BA4/5 y otras VOC
    Título de neutralización (PBNA) contra las subvariantes BA.1, BA4/5 y otras VOC medido como CI50 y reportado como la concentración en log10 para cada muestra individual y GMT, a los días 14, 98 y 182 post-4ta dosis de PHH-1V en la cohorte 1, versus post-3ra dosis de la cohorte 2
    GMFR en los títulos de anticuerpos neutralizantes a los días 14 post-4ta dosis de PHH-1V versus los valores basales de la Parte B en la cohorte 1, para la subvariante de Omicron BA.1, BA4/5 y otras VOC
    E.5.2.1Timepoint(s) of evaluation of this end point
    D14, 28, 98, 182 and 364 (Part A)
    D14, 98, 182 (Part B)
    D14, 28, 98, 182 y 364 (Parte A)
    D14, 98 y 182 (Parte B)
    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) 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 No
    E.8.1.4Double blind Yes
    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) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Comirnaty
    Comirnaty
    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 Yes
    E.8.4.1Number of sites anticipated in Member State concerned10
    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 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
    LVLS
    Última visita
    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 months6
    E.8.9.1In the Member State concerned days
    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: 802
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 60
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers Yes
    F.3.2Patients No
    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 state802
    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)
    none
    ninguno
    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 Decision2021-11-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-11-05
    P. End of Trial
    P.End of Trial StatusOngoing
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