Clinical Trials Register

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.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2021-005226-26

A.3

Full 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.3.1

Title 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.4.1

Sponsor's protocol code number

HIPRA-HH-2

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	HIPRA SCIENTIFIC
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Hipra Scientific, S.L.U.
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	HIPRA SCIENTIFIC
B.5.2	Functional name of contact point	R&D and Regulatory Affairs Director
B.5.3	Address:
B.5.3.1	Street Address	Avda. La Selva, 135
B.5.3.2	Town/ city	Amer, Girona
B.5.3.3	Post code	17170
B.5.3.4	Country	Spain
B.5.4	Telephone number	34972430660
B.5.6	E-mail	elia.torroella@hipra.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	PHH-1V
D.3.2	Product code	PHH-1V
D.3.4	Pharmaceutical form	Emulsion for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PHH-1V
D.3.9.1	CAS number	-
D.3.9.2	Current sponsor code	PHH-1V
D.3.9.3	Other descriptive name	PHH-1V
D.3.9.4	EV Substance Code	SUB223972
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Comirnaty
D.2.1.1.2	Name of the Marketing Authorisation holder	BioNTech Manufacturing GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Dispersion for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tozinameran
D.3.9.1	CAS number	-
D.3.9.2	Current sponsor code	-
D.3.9.4	EV Substance Code	SUB210693
D.3.10	Strength
D.3.10.1	Concentration unit	ml millilitre(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.3
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another 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.1.1

Medical condition(s) being investigated

SARS-CoV-2

E.1.1.1

Medical condition in easily understood language

COVID-19 Infection

Infección por COVID-19

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.0
E.1.2	Level	LLT
E.1.2	Classification code	10084272
E.1.2	Term	SARS-CoV-2 infection
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main 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.2.2

Secondary 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.2.3

Trial contains a sub-study

E.3

Principal 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.4

Principal 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.5.1

Primary 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.5.1.1

Timepoint(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.5.2

Secondary 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.5.2.1

Timepoint(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.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Comirnaty

E.8.2.4

Number of treatment arms in the trial

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.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial 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.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

802

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

802

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-11-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-11-05

P. End of Trial
P.	End of Trial Status	Ongoing

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials