| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
1. To determine and compare the changes of the immunogenicity measured by pseudovirus neutralisation against Omicron strain at Baseline and Day 14, in subjects who have received two doses of Vaxzevria vaccine and PHH-1V as a booster, versus subjects who have received two doses of Vaxzevria and Comirnaty as a booster, at least 91 days and with a maximum of 365 days before day 0.
2. To assess the safety and tolerability of PHH-1V as a booster dose in healthy adult subjects fully vaccinated against COVID-19 with the Vaxzevria vaccine. |
1. Determinar y comparar los cambios en la immunogenicidad medida mediante neutralización por pseudovirión contra la cepa Omicron en la visita basal y el día 14, en los sujetos que han recibido dos dosis de Vazxevria y PHH-1V como booster, versus aquellos sujetos que han recibido dos dosis de Vaxzevria y Comirnaty como booster, al menos 91 días y hasta 365 días antes del día 0.
2. Evaluar la seguridad y tolerabilidad del booster de PHH-1V en adultos sanos vacunados con pauta completa de Vazxevria contra COVID-19. |
|
| E.2.2 | Secondary objectives of the trial |
1. To determine and compare the changes of the immunogenicity (PBNA) against VOCs Beta and Delta, at Baseline and at Day 14, 98 and 182 in subjects of both arms.
2. To determine and compare the changes of the immunogenicity measured by SARS-CoV-2 PBNA against Omicron at Day 98 and 182 in subjects of both arms.
3. To determine and compare the changes of the immunogenicity measured by wild type SARS-CoV-2 neutralisation test (VNA) against Omicron at Baseline and Days 14, 98 and 182 in subjects of both arms. Wild type neutralisation assay will be performed only in a subset of approximately 20% of the total subjects included in the study.
4. To evaluate the immunogenicity measured by means of total antibody against RBD of the Spike protein of SARS-CoV-2 quantification, measured by an electrochemiluminescence immunoassay (ECLIA) at Baseline and at Days 14, 98 and 182 in subjects of both arms. |
1. Determinar y comparar los cambios en la immunogenicidad medida mediante PBNA contra VOCs beta y delta, en la visita basal y en los días 14, 98 y 182 en sujetos de los dos brazos.
2. Determinar y comparar los cambios en la immunogenicidad medidos mediante neutralización por pseudovirión contra Omicron en los días 98 y 182 en sujetosde los dos brazos.
3. Determinar y comparar los cambios en la immunogenicidad medidos mediante neutralización por virus salvaje (VNA) contra Omicon en la visita basal y en los días 14, 98 y 182 en los sujetos de los dos brazos. El ensayo de neutralización en virus vivo solo se realizará aproximadamente en un 20% de los sujetos incluidos en el estudio.
4. Evaluar la immunogenicidad medida por la quantificación total de anticuerpos contra Receptor Binding Domain (RBD) de la proteína Spike de SARS-COV-2, medido por immunonesayo de electroquimioluminiscencia (ECLIA) en la visita basal y en los días 14, 98 y 182 en sujetos de los dos brazos.
. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects must meet all the following criteria to be considered eligible for the study:
1. Male or female, ≥ 18 years old at Day 0.
2. Participant must 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 (scheduled visits, laboratory tests, complete diaries, etc).
3. Participant who has been vaccinated with two doses of Vaxzevria at least 91 days before Day 0 and a maximum of 365 days of the second dose.
4. Has a negative Rapid Antigen Test (RAT) at Day 0
5. Participants may have underlying illnesses if are stable and well-controlled according to the investigator judgment. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months prior to screening and for which neither a significant change in treatment or hospitalization for worsening is expected in the near future.
6. Participant agrees not to donate blood, blood products and bone marrow at least 12 weeks before and after vaccination.
7. Contraceptive use should be consistent with local regulation for participants in clinical trials. A. Female participants of childbearing potential [defined as any female who has experienced menarche and until becoming postmenopausal* (defined as having ≥ 12 months amenorrhea prior to screening without an alternative cause) unless is surgically sterile]:
i. Have a negative pregnancy test on the day of vaccination.
ii. Use of any acceptable contraceptive method that should be started at screening and until 8 weeks after vaccination except hormonal contraception. Acceptable contraceptive methods are: 1) Hormonal contraception (progestogen-only or combined): oral, injectable or transdermal (patch) at least 30 days before Day 0 and until 8 weeks after vaccination. 2) Intrauterine device. 3)Vasectomized partner (the vasectomized partner should be the sole partner for that participant). 4) Sexual abstinence **, as a form of contraception, is acceptable if in line with the participant’s lifestyle. 5)Condom
B. Male participants:
i. Vasectomized participants.
ii. Refrain from donating sperm for at least 28 days after day 0.
iii. Agree to use a male condom may be considered in women of childbearing potential partners, from screening and for at least 28 days after day 0.
iv. Sexual abstinence**, as a form of contraception, is acceptable if in line with the participant’s lifestyle. |
Los voluntarios deben cumplir todos los siguientes criterios para ser elegibles para el ensayo:
1. Hombre o mujer ≥ 18 años a día 0.
2. 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.
3. Tener una pauta de vacunación con dos dosis de Vaxzevria como mínimo 91 días y como máximo 365 días antes del día 0.
4. Tienes un test rápido de antígenos negativo a día 0.
5. Los participantes pueden tener alguna patología o enfermedad si está estable y bien controlada, según criterio del investigador. Una patología se considera estable si no ha requerido cambios significativos en la medicación o hospitalización por empeoramiento de la enfermedad en los 3 meses previos a la visita de preselección y no se prevén cambios significativos en la medicación o hospitalización por empeoramiento de la enfermedad en un futuro próximo.
6. Aceptar no dar sangre, productos derivados de la sangre, o médula ósea como mínimo 3 meses antes y después de la vacunación.
7. Tiene que seguir los métodos anticonceptivos para la participación en ensayos clínicos aceptados por las autoridades reguladoras locales.
A) Las mujeres con capacidad reproductiva: Deben tener un test de embarazo en orina negativo el día 0 antes de la vacunación. Deben usar un método anticonceptivo como mínimo desde la visita de selección hasta 8 semanas después de la vacunación excepto en el caso de los anticonceptivos hormonales.
Los métodos anticonceptivos aceptados son: anticonceptivos hormonales (iniciados almenos 30 días antes del Día 0 y hasta almenos 8 semanas después de la vacunación.), dispositivo intrauterino, pareja vasectomizada (si es la única pareja sexual), abstinencia sexual, o condón.
B) 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 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 screening or Day 0 (vaccination time-point) or willingness/intention to become pregnant during the study.
- Participant has a clinically significant acute illness (this does not include minor self-limited illness such as mild diarrhoea) or fever (temperature ≥38º C (100.4ºF) at screening or within 48 hours prior to the planned vaccination (Day 0).
- Participant had a surgery requiring hospitalization (defined as inpatient stay for > 24 hours) 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. Minor surgical procedures not requiring hospitalization are accepted.
- Participant has any active malignancy even if under treatment except for (at the discretion of the investigator): Non-melanoma adequately treated skin cancer without evidence of disease, or, adequately treated uterine cervical carcinoma in situ without evidence of disease, or, adequately treated anal carcinoma in situ without evidence of disease, or, localized prostate cancer.
- Participant has ongoing severe and non-stable psychiatric condition likely to affect participation in the study (e.g., ongoing and non-stable severe depression, recent suicidal ideation, severe eating disorder, psychosis).
- Participant has a problematic or risk use of substances including alcohol (except tobacco) that can compromise the study follow-up. Problematic or risk use of psychoactive substances is understood as the one that causes evident damage, whether it is dependence or any other physical, psychological, or social problem or that carries a high risk of suffering these damages. The negative consequences that consumption causes to third parties could be included.
- Participant has a bleeding disorder (e.g., factor deficiency, platelet disorder), blood dyscrasia, or continuous use of anticoagulants or has any condition that in the opinion of the investigator contraindicates intramuscular injections or frequent phlebotomy. The use of ≤ 325mg of aspirin or ≤ 75mg of clopidogrel per day as prophylaxis is permitted but not combined.
- Participant has abnormal function of the immune system as in autoimmune diseases, asplenia, recurrent infections or congenital/acquired immunodeficiency. Participants under immune-modifying treatment for any cause. Permitted: participants with stable clinical conditions (e.g., autoimmune thyroiditis, celiac disease, type 1- diabetes) and participants living with HIV with CD4 T cell count ≥ 400 cells/mm3 under stable antiretroviral treatment with a fully suppressed viral load ≥ 1 year are permitted [one or two non-consecutives blips (HIV viral load ≤ 500 viral copies)].
- Participants have clinically significant and unstable cardiovascular, respiratory, hepatic, neurological, gastrointestinal, renal, or 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 (during at least 14 days) of systemic immunosuppressant medication (defined as given by oral or parenteral routes) within 12 weeks preceding the planned administration of study vaccine (Day 0). The use of an oral prednisone dose <10mg per day or equivalent, ocular, topical, inhaled and nasal corticoids are allowed.
- 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 preceding the planned administration of study vaccine. Monoclonal antibodies for other indications are allowed.
- 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 choque anafiláctico de cualquier tipo
- Historia de infección por COVID-19
- 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. Los anticuerpos monoclonales para otras indicaciones estan permitidos.
- 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) |
1.1. Neutralisation titre against Omicron strain 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 treatment group comparison at Baseline and Day 14
2.1 Number, percentage, and characteristics of solicited local and systemic reactions through Day 7 after vaccination.
2.2 Number, percentage, and characteristics of unsolicited local and systemic adverse events (AEs) through Day 28 after vaccination.
2.3 Number and percentage of serious adverse events (SAEs) through the study duration.
2.4 Number and percentage of adverse event of special interest (AESI) through the study duration.
2.5 Number and percentage of medically attended adverse events (MAAE) related to study vaccine through the study duration.
2.6 Change from Baseline in safety laboratory parameters at Days 14, 98 and 182 after vaccination. |
1.1 Título neutralizante contra la cepa Omicron medido como la concentración inhibitoria 50 (IC50) mediante ensayo de neutralización en pseudovirión y expresado como la concentración recíproca para cada muestra individual y la mediana geométrica del título (GMT) para la comparación de los grupos de tratamiento en la visita basal y el día 14.
2.1 Número, porcentaje y características de las reacciones locales y las reacciones adversas sistémicas hasta el dia 7 post-vacunación
2.2 Número, porcentaje y características de los eventos adversos no solicitados y los eventos adverso sistémicos (AEs) hasta el día 28 post-vacunación.
2.3 Número y porcentaje de los eventos adversos serios (SAEs) durante todo el estudio.
2.4 Número y porcentaje de los eventos adversos de especial interés (AESI) durante todo el estudio.
2.5 Número y porcentaje de los eventos adversos médicamente atendidos (MAAE) y relacionados con la vacuna, durante todo el estudio.
2.6 Cambios en los parámetros de laboratorio en los días 14, 98 y 182 después de la vacunación. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| D0, D14, D98, D182 |
| D0, D14, D98, D182 |
|
| E.5.2 | Secondary end point(s) |
1.1. Neutralisation titre against VOCs (Beta and Delta) 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, 98 and 182.
1.2. Geometric mean fold rise (GMFR) in neutralising antibodies titres against Omicron and VOCs (Beta and Delta) for treatment group comparison at Baseline and Day 14.
1.3. Neutralisation titre against Omicron measured as IC50 by PBNA and reported as reciprocal concentration for each individual sample and GMT for treatment group comparison at Days 98 and 182.
1.4. Neutralisation titre measured as inhibitory dilution 50 (ID50) against Omicron by a VNA and reported as reciprocal dilution for each individual sample, and GMT for treatment group comparison at Baseline and Day 14, 98 and 182. This analysis will only be performed in a subset of participants.
4.1 Binding antibodies titre measured for each individual sample and GMT for treatment group comparison at Baseline and Days 14, 98 and 182.
4.2 Geometric mean fold rise (GMFR) in binding antibodies titre from Baseline and Days 14.
4.3 Percentage of subjects that, after a booster dose, have a ≥4-fold change in binding antibodies titre from Baseline and Days 14, 98 and 182. |
1.1 Título neutralizante contra VOCs (Beta y Delta) medidos como el IC50 mediante PBNA y expresado como la concentración recíproca de cada muestra individual, y la GMT para la comparación de los grupos de tratamiento en la visita basal y en los días 14, 98 y 182.
1.2 Mediana geométrica del fold-rise (GMFR) en los títulos de anticuerpos neutralizantes contra Omicron y las VOCs (Beta y Delta) para la comparación de los grupos de tratamiento en la visita basal y el día 14.
1.3 Título neutralizante contra Omicron medido como el IC50 mediante PBNA y expresado como la concentración recíproca para cada muestra individual, y la GMT para la comparación entre grupos de tratamiento a día 98 y día 182.
1.4 Título neutralizante medido como la dilución inhibitoria 50 (ID50) contra omicron mediante VNA y expresado como la dilución recíproca para cada muestra individual, y la GMT para la comparación entre grupos de tratamiento en la visita basal y días 14, 98 y 182. Este análisis solo será realizado en un subset de participantes.
4.1 El título de anticuerpos de unión para cada muestra individual, y la GMT para la comparación entre grupos de tratamiento en la visita basal y en los días 14, 98 y 182.
4.2 Mediana geométrica del fold-rise (GMFR) en los títulos de anticuerpos de unión de la visita basal y el día 14.
4.3 Porcentaje de sujetos que, después de la dosis de refuerzo, tienen un cambio de ≥4 veces en los títulos de anticuerpos des de la visita basal y los días 14, 98 y 182. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| D0, D14, D98, D182 |
| D0, D14, D98, D182 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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 último paciente |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
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