| 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 | |
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 23.0 | | E.1.2 | Level | PT | | E.1.2 | Classification code | 10051905 | | E.1.2 | Term | Coronavirus infection | | E.1.2 | System Organ Class | 10021881 - Infections and infestations | |
| 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 | Part A
1.To evaluate the safety of AZD5156 and AZD7442
2.To compare the nAb responses to the SARS-CoV-2 Alpha variant in serum following AZD5156 and AZD7442 administration
Part B
1.To describe the safety of an open label dose of AZD5156 600 mg IM among participants who received AZD5156 or AZD7442 during Part A Main Cohort | Parte A
1. Evaluar la seguridad de AZD5156 y AZD7442.
2. Comparar las respuestas de los AcN contra la variante alfa del SARS-CoV-2 en suero tras la administración de AZD5156 y AZD7442.
Parte B
1.Describir la seguridad de una dosis en abierto de 600 mg de AZD5156 i.m. entre los participantes que recibieron AZD5156 o AZD7442 durante la cohorte principal de la parte A. | |
| E.2.2 | Secondary objectives of the trial | Part A
1.To compare the nAb responses to the SARS-CoV-2 Omicron variant BA.4/5 and the emerging dominant variant of concern circulating during the course of the study in serum following AZD5156 and AZD7442 administration
2.To describe the incidence of COVID-19, severe COVID-19, COVID-19 related hospitalization, and COVID-19 related death in participants receiving study intervention
3.To characterize the PK of AZD5156 and AZD7442 in serum
Part B
1.To characterize the PK of an open label dose of AZD5156 among participants who received AZD5156 during Part A Main Cohort
2.To characterize the PK of AZD1061, AZD3152, and AZD8895 during Part B among participants who received AZD7442 during Part A Main Cohort
3.To describe ADA responses to an open label dose of AZD5156 among participants who received AZD5156 or AZD7442 during Part A Main Cohort
For complete set of Secondary and Exploratory Objectives please see Protocol | Parte A
1. Comparar las respuestas de los AcN contra la variante ómicron BA.4/5 del SARS-CoV-2 y la variante dominante emergente de interés circulante durante el transcurso del estudio en suero después de la administración de AZD5156 y AZD7442.
2.Describir la incidencia de COVID-19, COVID-19 grave, la hospitalización relacionada con la COVID-19 y la muerte relacionada con la COVID-19 en los participantes que reciben el tratamiento del estudio.
3.Caracterizar la FC de AZD5156 y AZD7442 en suero.
Parte B
1. Determinar la FC de una dosis en abierto de 600 mg de AZD5156 i.m. entre los participantes que recibieron AZD5156 durante la cohorte principal de la parte A.
2.Determinar la FC de AZD1061, AZD3152 y AZD8895 durante la parte B entre los participantes que recibieron AZD7442 durante la cohorte principal de la parte A.
3. Describir las respuestas de AAF a una dosis en abierto de 600 mg de AZD5156 i.m. entre los participantes que recibieron AZD5156 [..]
revisar protocolo | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | |
| E.4 | Principal exclusion criteria | For Part A Sentinel Safety Cohort Participants (Phase I)
Participants are excluded from the Part A Sentinel Safety Cohort if any of the following criteria apply:
1.Women who are pregnant, lactating, or of childbearing potential and not using a highly effective method of contraception or abstinence from at least 4 weeks prior to study intervention administration and until at least 6 months after study intervention administration.
2.Known hypersensitivity to any component of the study intervention.
3.Previous hypersensitivity or severe adverse reaction following administration of a mAb.
4.Acute (time-limited) or febrile (temperature ≥ 38.0°C [100.4ºF]) illness/infection on day prior to or day of planned dosing; participants excluded for transient acute illness may be dosed if illness resolves within the screening period or may be rescreened once.
5.Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 30 days prior to Visit 1.
6.Clinically significant bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture.
7.Receipt of immunoglobulin (non-COVID related) or blood products within 6 months prior to Visit 1
8.Previous receipt of a mAb against SARS-CoV-2.
9.Receipt of a COVID-19 vaccine within 3 months prior to Visit 1.
10.COVID-19 within 6 months prior to Visit 1 (confirmed either by laboratory testing or a rapid test [including at home testing]).
For Part A Main Cohort Participants (Phase III)
Participants are excluded from the Part A Main Cohort if any of the following criteria apply:
1.Women who are pregnant, lactating, or of childbearing potential and not using a highly effective method of contraception or abstinence from at least 4 weeks prior to study intervention administration and until at least 6 months after study intervention administration. Note: female participants aged > 12 years will be considered to be a woman of childbearing potential.
2.Known hypersensitivity to any component of the study intervention.
3.Previous hypersensitivity or severe adverse reaction following administration of a mAb.
4.Acute (time-limited) or febrile (temperature ≥ 38.0°C [100.4ºF]) illness/infection on day prior to or day of planned dosing; participants excluded for transient acute illness may be dosed if illness resolves and may be rescreened for enrollment once.
5.Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 30 days prior to Visit 1.
6.Clinically significant bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture.
7.Has HIV infection.
8.Receipt of convalescent COVID-19 plasma treatment within 6 months prior to Visit 1.
9.Previous receipt of a mAb against SARS CoV 2 within 6 months prior to Visit 1.
10.Receipt of a COVID-19 vaccine within 3 months prior to Visit 1.
For Part B Participants
Participants are excluded from Part B if any of the following exclusion criteria apply:
1.Women who are pregnant, lactating, or of childbearing potential and not using a highly effective method of contraception or abstinence from at least 4 weeks prior to study intervention administration and until at least 6 months after study intervention administration. Note: female participants aged > 12 years will be considered to be a woman of childbearing potential.
2.Known hypersensitivity to any component of the study intervention.
3.Previous hypersensitivity or severe adverse reaction following administration of a mAb.
4.Acute (time-limited) or febrile (temperature ≥ 38.0°C [100.4ºF]) illness/infection on day prior to or day of planned dosing; participants excluded for transient acute illness may be dosed if illness resolves and may be rescreened for enrollment once.
5.Clinically significant bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture.
6.Receipt of any IMP in the preceding 90 days or expected receipt of IMP during the period of study follow-up, or concurrent participation in another interventional study.
7.Alcohol or substance abuse that, in the opinion of the Investigator, might interfere with the trial conduct or completion.
8.Deprived of freedom by an administrative or court order, or in emergency setting, or hospitalized involuntarily.
9.Any condition that, in the opinion of the Investigator, might compromise participant safety or interfere with evaluation of the study intervention or interpretation of participant safety or study results.
10.Employees of AstraZeneca involved in planning, executing, supervising, or reviewing the AZD5156 program, clinical study site staff, or any other individuals involved with the conduct of the study, or family members of such individuals.
For full list of Exclusion Ctr. please see Protocol | Para los participantes de la cohorte de seguridad Sentinel de la Parte A (Fase I)
Los participantes están excluidos de la Cohorte de seguridad Sentinel de la Parte A si se aplica alguno de los siguientes criterios:
1. Mujeres embarazadas, lactantes o en edad fértil que no utilicen un método anticonceptivo altamente efectivo o abstinencia desde al menos 4 semanas antes de la administración de la intervención del estudio y hasta al menos 6 meses después de la administración de la intervención del estudio.
2. Hipersensibilidad conocida a cualquier componente de la intervención del estudio.
3.Hipersensibilidad previa o reacción adversa grave tras la administración de un mAb.
4.Enfermedad/infección aguda (limitada en el tiempo) o febril (temperatura ≥ 38,0°C [100,4ºF]) el día anterior o el día de la dosificación planificada; los participantes excluidos por enfermedad aguda transitoria pueden recibir dosis si la enfermedad se resuelve dentro del período de selección o pueden volver a examinarse una vez.
5. Extracción de sangre en exceso de un total de 450 ml (1 unidad) por cualquier motivo dentro de los 30 días anteriores a la Visita 1.
6. Trastorno hemorrágico clínicamente significativo (p. ej., deficiencia de factor, coagulopatía o trastorno plaquetario), o antecedentes de sangrado significativo o hematomas después de inyecciones IM o venopunción.
7. Recepción de inmunoglobulina (no relacionada con COVID) o productos sanguíneos dentro de los 6 meses anteriores a la Visita 1
8. Recepción previa de un mAb contra el SARS-CoV-2.
9.Recepción de una vacuna COVID-19 dentro de los 3 meses anteriores a la Visita 1.
10.COVID-19 dentro de los 6 meses anteriores a la Visita 1 (confirmado por pruebas de laboratorio o una prueba rápida [incluidas las pruebas en el hogar]).
Para los participantes de la cohorte principal de la Parte A (Fase III)
Los participantes están excluidos de la cohorte principal de la Parte A si se aplica alguno de los siguientes criterios:
1. Mujeres embarazadas, lactantes o en edad fértil que no utilicen un método anticonceptivo altamente efectivo o abstinencia desde al menos 4 semanas antes de la administración de la intervención del estudio y hasta al menos 6 meses después de la administración de la intervención del estudio. Nota: las participantes femeninas mayores de 12 años se considerarán mujeres en edad fértil.
2. Hipersensibilidad conocida a cualquier componente de la intervención del estudio.
3.Hipersensibilidad previa o reacción adversa grave tras la administración de un mAb.
4.Enfermedad/infección aguda (limitada en el tiempo) o febril (temperatura ≥ 38,0°C [100,4ºF]) el día anterior o el día de la dosificación planificada; los participantes excluidos por enfermedad aguda transitoria pueden recibir dosificación si la enfermedad se resuelve y pueden volver a ser evaluados para la inscripción una vez
5. Extracción de sangre en exceso de un total de 450 ml (1 unidad) por cualquier motivo dentro de los 30 días anteriores a la Visita 1.
6. Trastorno hemorrágico clínicamente significativo (p. ej., deficiencia de factor, coagulopatía o trastorno plaquetario), o antecedentes de sangrado significativo o hematomas después de inyecciones IM o venopunción.
7. Tiene infección por VIH.
8. Recibo de tratamiento con plasma COVID-19 convaleciente dentro de los 6 meses anteriores a la Visita 1.
9.Recepción anterior de un mAb contra SARS CoV 2 dentro de los 6 meses anteriores a la Visita 1.
10.Recepción de una vacuna COVID-19 dentro de los 3 meses anteriores a la Visita 1.
Para participantes de la Parte B
Los participantes quedan excluidos de la Parte B si se aplica alguno de los siguientes criterios de exclusión:
1. Mujeres embarazadas, lactantes o en edad fértil que no utilicen un método anticonceptivo altamente efectivo o abstinencia desde al menos 4 semanas antes de la administración de la intervención del estudio y hasta al menos 6 meses después de la administración de la intervención del estudio. Nota: las participantes femeninas mayores de 12 años se considerarán mujeres en edad fértil.
2. Hipersensibilidad conocida a cualquier componente de la intervención del estudio.
3.Hipersensibilidad previa o reacción adversa grave tras la administración de un mAb.
4.Enfermedad/infección aguda (limitada en el tiempo) o febril (temperatura ≥ 38,0°C [100,4ºF]) el día anterior o el día de la dosificación planificada; los participantes excluidos por enfermedad aguda transitoria pueden recibir dosificación si la enfermedad se resuelve y pueden volver a ser evaluados para la inscripción una vez.
5. Trastorno hemorrágico clínicamente significativo (p. ej., deficiencia de factor, coagulopatía o trastorno plaquetario), o antecedentes de sangrado significativo o hematomas después de inyecciones IM o venopunción.
Para obtener una lista completa de Exclusion Ctr. por favor vea Protocolo | |
| E.5 End points |
| E.5.1 | Primary end point(s) | Part A
1.Occurrence of AEs collected through Day 29; SAEs and AESIs collected throughout the study
2.GMTs for SARS-CoV-2 Alpha variant nAbs
Part B
1.Proportion of AEs through 29 days after second dose of study intervention given at 6 months;
SAEs and AESIs through last visit (Visit 9) | Parte A
1. Ocurrencia de EA recopilados hasta el día 29; SAE y AESI recopilados a lo largo del estudio
2. GMT para SARS-CoV-2 variante alfa nAb
Parte B
1. Proporción de AA hasta 29 días después de la segunda dosis de la intervención del estudio administrada a los 6 meses;
SAE y AESI hasta la última visita (Visita 9 | |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | Part A
At Day 29
Part B
At Day 29 | Parte A
En el dia 29
Parte B
En el día 29 | |
| E.5.2 | Secondary end point(s) | Part A
1.Geometric mean titer (GMT) and geometric mean fold rise (GMFR) ratio of SARS-CoV-2 nAbs between the treatment arms at Visit 3 (Day 29).
2.Incidence of a post treatment:
•Symptomatic COVID 19 case
•COVID-19 case (negative RT PCR at baseline to positive at any time up to 6 and 12 months)
•Severe COVID-19
•Composite of COVID-19 related hospitalization and/or COVID-19 related death
•COVID-19 related hospitalization (separately)
•COVID 19 related death (separately)
3.In the Sentinel Safety Cohort: AZD5156, AZD1061, and AZD3152 concentrations over time and PK parameters
In the Main Cohort: AZD5156, and AZD7442, AZD1061, AZD3152, and AZD8895 concentrations over time
Part B
1.Serum AZD5156, AZD1061, and AZD3152 concentrations
2.Serum AZD1061, AZD3152, and AZD8895 concentrations
3.Incidence of ADA following a dose of AZD5156 given at 6 months | Parte A
1. Relación media geométrica del título (GMT) y aumento medio geométrico (GMFR) de nAbs del SARS-CoV-2 entre los brazos de tratamiento en la visita 3 (día 29).
2.Incidencia de un post tratamiento:
•Caso sintomático de COVID 19
•Caso de COVID-19 (RT PCR negativo al inicio a positivo en cualquier momento hasta los 6 y 12 meses)
•COVID-19 grave
•Compuesto de hospitalización relacionada con COVID-19 y/o muerte relacionada con COVID-19
•Hospitalización relacionada con COVID-19 (por separado)
•Muerte relacionada con COVID 19 (por separado)
3. En la cohorte de seguridad Sentinel: concentraciones de AZD5156, AZD1061 y AZD3152 a lo largo del tiempo y parámetros farmacocinéticos
En la cohorte principal: concentraciones de AZD5156 y AZD7442, AZD1061, AZD3152 y AZD8895 a lo largo del tiempo
Parte B
1.Concentraciones séricas de AZD5156, AZD1061 y AZD3152
2.Concentraciones séricas de AZD1061, AZD3152 y AZD8895
3. Incidencia de ADA luego de una dosis de AZD5156 administrada a los 6 meses | |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | Part A
1.At Visit 3 (Day 29)
2.Through the study
3.Through the study
Part B
1.Through the study
2.6 months through 12 months
3.At 6 month | Parte A
1.En la visita 3 (día 29)
2.A través del estudio
3.A través del estudio
Parte B
1.A través del estudio
2,6 meses a 12 meses
3.A los 6 meses | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description | | Immunogenicity | | Inmunogenicidad | |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | Yes |
| 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 | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 33 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | | Argentina | | Malaysia | | Mexico | | Philippines | | South Africa | | Taiwan | | Thailand | | France | | Poland | | Spain | | Germany | | Belgium | | Denmark | | Turkey | | United Kingdom | |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
