Clinical Trials Register

Summary
EudraCT Number:	2022-000074-25
Sponsor's Protocol Code Number:	HIPRA-HH-5
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:	2022-01-25
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

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2022-000074-25

A.3

Full title of the trial

A PHASE III, OPEN LABEL TRIAL, SINGLE ARM, MULTI-CENTER, TRIAL TO ASSESS THE SAFETY AND IMMUNOGENICITY OF A BOOSTER VACCINATION WITH A RECOMBINANT PROTEIN RBD FUSION HETERODIMER CANDIDATE (PHH-1V) AGAINST SARS-COV-2, IN ADULTS VACCINATED AGAINST COVID-19

Estudio fase III, no ciego, de un único brazo, multicéntrico para valorar la seguridad y inmunogenicidad de una vacunación de booster con el candidato de proteína recombinante RBD fusion heterodimer (PHH-1V) contra SARS-CoV-2, en adultos previamente vacunados contra la COVID-19

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A phase III study to evaluate safety and immunogenicity of recombinant protein candidate vaccine against SARS-CoV-2 in adults vaccinated against COVID-19

Estudio fase III para evaluar la seguridad e inmunogenicidad de una vacuna candidata de proteína recombinante frente al SARS-CoV-2 en adultos vacunados contra COVID-19

A.4.1

Sponsor's protocol code number

HIPRA-HH-5

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
B.5.3.3	Post code	17170
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34972430660
B.5.5	Fax 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)	Yes
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

To assess the safety and tolerability of PHH-1V as a booster dose in healthy adult subjects vaccinated against COVID-19 with the Comirnaty, Spikevax, Vaxevria or Janssen vaccine

Evaluar la seguridad y tolerabilidad de PHH-1V como dosis de refuerzo en adultos sanos vacunados contra COVID-19 con las vacunas Comirnaty, Spikevax, Vaxevria o Janssen.

E.2.2

Secondary objectives of the trial

To determine and compare the changes of the immunogenicity measured by pseudovirus neutralisation against Wuhan strain (also known as L strain) and against Omicron, and any other relevant Variants of Concern (VOC) in the epidemiologic moment, at Baseline and at Days 14, 91, 182 and 365, after booster of HIPRA’s vaccine (PHH-1V) in a subset of participants.
To evaluate the immunogenicity measured by means of total antibody against Receptor Binding Domain of the Spike protein of SARS-CoV-2 quantification, measured by an electrochemiluminescence immunoassay (ECLIA) at Baseline and at Days 14, 91, 182 and 365 after booster of HIPRA’s vaccine (PHH-1V) in a subset of participants

Determinar y comparar los cambios de inmunogenicidad medidos por neutralización de pseudovirus contra la variante Wuhan y Omicron, y otras variantes de preocupación en el momento epidemiológico, en la visita basal y en los días 14, 91, 182 y 365 después de la vacunación, y solo en un subset de participantes.
Evaluar la inmunogenicidad medida con los anticuerpos totales contra RBD de la proteína Spike de SARS-CoV-2, medidos por ECLIA en el basal y a los días 14, 91, 182 y 365 después de la vacunación con el booster de HIPRA (PHH-1V) en un subset de participantes.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Male or female, ≥ 16 years old at Day 0. / Willing to provide consent indicating that she or he understands the purpose and potential risks and is willing and able to participate in the study and comply with all the study requirements and procedures. / Have a recognized primary vaccination scheme recognized by the authorities with Comirnaty, Spikevax, Vaxevria or Janssen at least 91 days and preferably a maximum of 240 days before Day 0. / Participants may have underlying illnesses if are stable and well-controlled according to the investigator judgment. / Participant is willing to avoid receiving live attenuated vaccines (licensed) within 4 weeks before screening or after receiving any study vaccine, or other not live vaccines (licensed) within 14 days before and after receiving any study vaccine. / Participant agrees not to donate blood, blood products and bone marrow at least 3 months before and after vaccination. / Female participants of childbearing potential must have a negative pregnancy test on the on Day 0 prior to vaccination. / Female participants of childbearing potential must use any acceptable contraceptive method that should be started on day 0 and until 8 weeks after vaccination (hormonal contraception: oral, injectable or transdermal patch, intrauterine device, vasectomized partner, sexual abstinence or condom). / Male participants must use any acceptable contraceptive method that should be started on day 0 and until 8 weeks after vaccination (vasectomized participants, condom, sexual abstinence). / Male participants must refrain from donating sperm for at least 28 days after day 0.

Hombre o mujer ≥ 16 años a día 0. / Dispuesto a dar el consentimiento informado indicando que entiende el objetivo del estudio y los riesgos potenciales, y es capaz de participar en el estudio y cumplir con los requisitos y procedimientos del estudio. / Tener una pauta de vacunación primaria reconocida por las autoridades, con las vacunas de Comirnaty, Spikevax, Vaxevria o Janssen como mínimo hace 91 días y como máximo hace 240 días antes de día 0. / Los participantes pueden tenir alguna patología o enfermedad si está bajo control, según criterio del investigador. / Dispuesto a evitar recibir vacunas vivas atenuadas (autorizadas) en 4 semanas antes del screening o después de recibir la vacuna en estudio; u otras vacunas no vivas (autorizadas) en los 14 días antes y después de recibir la vacuna en estudio. / Aceptar no dar sangre, productos derivados de la sangre, o médula ósea como mínimo 3 meses antes y después de la vacunación. / Mujeres en edad fértil deben tener un test de embarazo en orina negativo el día 0 antes de la vacunación. / Mujeres en edad fértil deben usar un método anticonceptivo aceptado, y debe empezar el uso el día 0 y debe durar hasta 8 semanas después de la vacunación (anticonceptivos hormonales: oral, inyectable o parche, dispositivo intrauterino, pareja vasectomizada, abstinencia sexual, o condón). / Los hombres deben usar un método anticonceptivo aceptado, y debe empezar el uso del día 0 y debe durar hasta 8 semanas después de la vacunación (participantes vasectomizados, condón o abstinencia sexual). / Los hombres deben abstenerse de donar esperma como mínimo hasta 28 días después de la vacunación.

E.4

Principal exclusion criteria

History of anaphylaxis to any prior vaccine. / Previous severe SARS-CoV-2 infections are not permitted (mild infections are permitted). / 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 screening or Day 0 or willingness/intention to become pregnant during the study. / Participant has a clinically significant acute illness or fever (temperature ≥38º C (100.4ºF)) 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; or has a surgery requiring hospitalization planned within 12 weeks after study vaccine administration. / Participant has any active malignancy even if under treatment except for non-melanoma skin cancer, uterine cervical carcinoma, anal carcinoma, localized prostate cancer. / 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 or has any condition that in the opinion of the investigator contraindicates intramuscular injections. / Participant has abnormal function of the immune system, except stable clinical conditions like controlled HIV. / Participants have clinically significant and unstable cardiovascular, respiratory, hepatic, neurological, gastrointestinal, renal, or any other medical disorder judged by the investigator 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 (Day 0) or expects to receive them during the study. / Participant received any immunotherapy (monoclonal antibodies, plasma) aimed to prevent or treat COVID-19 within 90 days before day 0. / Participation in any research involving an investigational product (drug, biologic, device) within 12 weeks prior to vaccination and during the study. / 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.

Historia de anafilaxis a alguna vacunación anterior. / Infecciones severas de SARS-CoV-2 no están permitidas (se permiten infecciones leves). / El participante ha recibido o planea recibir vacuna/s vivas atenuadas 4 semanas antes y después del día 0; u otras vacunas no vivas 14 días antes y después del día 0. / Embarazada o dando pecho a día 0, o esperar quedar embarazada durante el estudio. / El participante tiene una patología aguda clínicamente significativa o fiebre ( ≥38º C (100.4ºF)) en el screening o 48 horas antes del día 0. / El participante ha tenido una cirugía que ha requerido hospitalización antes de la vacunación y aún no ha recibido el alta médica a día 0; o tiene una cirugía planeada que requiera hospitalización en las 12 semanas posteriores a la administración de la vacuna. / El participante tiene algún episodio de malignidad aunque esté en tratamiento, excepto el cancer de piel no-melanómico, carcinoma cervical uterino, carcinoma anal, cancer de prostata localizado. / El participante tiene una patología psiquiátrica severa y no estable que puede afectar la participación en el estudio. / El participante tiene un uso arriesgado o problemático de sustancias incluyendo el alcohol que puede comprometer el seguimiento del estudio. / El participante tiene un desorden del sangrado, o tiene alguna condición que a criterio del investigador contraindica la inyección intramuscular. / El participante tiene una función anormal del sistema inmune, excepto condiciones estables, como el HIV controlado. / El participante tiene una condición cardiovascular, respiratoria, hepática, neurológica, gastrointestinal, renal, o algún otro desorden que no esté estable a juicio del investigador en los 3 meses anteriores al screening o día 0. / Administración recurrente o crónica de medicación inmunosupresora. / El sujeto ha recibido inmunoglobulinas y/o productos derivados de la sangre 12 semanas antes de la vacunación (día 0) o espera recibirlos durante en estudio. / El participante ha recibido algún tipo de inmunoterapia (anticuerpos monoclonales, plasma) para prevenir el COVID-19 en los últimos 90 días antes de día 0. / Participación en alguna investigación que involucre productos en investigación (medicamento, biológico, equipo) en las 12 semanas antes de la vacunación y durante el transcurso del estudio. / El participante ha donado ≥ 450ml de sangre o productos derivador 12 semanas antes del screening. / El participante tiene alguna condición médica, que a juicio del investigador puede incrementar los riesgos del participante, interferir en el estudio o perjudicar la interpretación de los datos del estudio.

E.5 End points

E.5.1

Primary end point(s)

Number, percentage, and characteristics of solicited local reactions through Day 7 after vaccination.
Number, percentage, and characteristics of unsolicited local and systemic adverse events (AEs) through Day 28 after vaccination.
Number and percentage of serious adverse events (SAEs) through the end of the study.
Number and percentage of adverse event of special interest (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.
Grade 3 and 4 change from baseline in safety laboratory parameters at Days 14, 91 and 182 after vaccination

Número, porcentaje, y características de los solicited adverse events (efectos adversos) hasta el día 7 después de la vacunación.
Número, porcentaje, y características de los unsolicited adverse events (efectos adversos) y los efectos adversos sistémicos hasta el día 28 después de la vacunación.
Número y porcentaje de efectos adversos serios (SAE) durante todo el estudio.
Número y porcentaje de efectos adversos de especial interés (AESI) durante todo el estudio.
Número y porcentaje de efectos adversos atendidos médicamente (MAAE) relacionados con la vacuna del estudio, durante todo el estudio.
Evaluar los cambios de grado 3 o grado 4 de los parámetros de laboratorio, des de el día basal a días 14, 91 y 182 después de la vacunación.

E.5.1.1

Timepoint(s) of evaluation of this end point

D0, D14, D91, D182.

E.5.2

Secondary end point(s)

Neutralisation titre against Wuhan and Omicron strains, and any other relevant VOC in the epidemiologic moment, measured as inhibitory concentration 50 (IC50) by a pseudovirion-based neutralisation assay (PBNA) and reported as reciprocal concentration for each individual sample and geometric mean titre (GMT) for descriptive analysis at Baseline and at Days 14, 91, 182 and 365.
The geometric mean fold rise (GMFR) in neutralising antibody titre from baseline to Day 14.
Binding antibodies titre measured for each individual sample and GMT for descriptive analysis at Baseline and Days 14, 91, 182 and 365.
The geometric mean fold rise (GMFR) in binding antibody titre from baseline to Day 14.
The percentage of subjects that after the booster dose have a ≥4-fold change in binding antibodies titre from Baseline to Day 14.

Título neutralizante contra las variantes de Wuhan y Ómicron, y otras variantes de preocupación en el momento epidemiológico, medido como la concentración inhibitoria 50 (IC50) mediante ensayos de neutralización de pseudovirión (PBNA) y reportado como la concentración recíproca de cada muestra individual y la mediana geométrica (GMT) para análisis descriptivo a la visita basal y en los días 14, 91, 182 y 365.
La mediana geométrica del fold-rise (GMFR) en los títulos de anticuerpos neutralizantes des del basal hasta día 14.
Anticuerpos totales mesurados para cada muestra individual y la GMT para el análisis descriptivo a la visita basal y en los días 14, 91, 182 y 365.
La mediana geométrica del fold-rise (GMFR) en los títulos de anticuerpos totales des del basal hasta día 14.
El porcentaje de sujetos que después del booster dienen un cambio en el fold-change ≥4 en el título de anticuerpos totales des del basal hasta día 14.

E.5.2.1

Timepoint(s) of evaluation of this end point

D0, D14, D91, D182, D365.

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

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

E.8.3

The trial involves single site in the Member State concerned

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

ultima visita ultimo paciente

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

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

3000

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

3000

F.4.2

For a multinational trial

F.4.2.1

In the EEA

3000

F.4.2.2

In the whole clinical trial

3000

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

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-02-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-01-31

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

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