E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 |
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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 |
Main Cohort 1.To evaluate the safety of AZD3152 and AZD7442 2.To compare the nAb responses to the SARS-CoV-2 Alpha variant in serum following AZD3152 and AZD7442 administration Sentinel Safety Cohort 1.To evaluate the safety of AZD5156 |
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E.2.2 | Secondary objectives of the trial |
Main Cohort 1..To compare the efficacy of AZD3152 to AZD7442 in the prevention of symptomatic COVID-19 2.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 AZD3152 and AZD7442 administration 3.To describe the incidence of symptomatic COVID-19, severe COVID-19, COVID-19 related hospitalization, and COVID-19 related death in participants receiving study intervention 4.To characterize the PK of AZD5156 and AZD7442 in serum 5.To evaluate the ADA responses to AZD3152 and AZD7442 in serum Sentinel Safety Cohort 1.To characterize the PK of AZ5156 and AZD3152 in serum 2.To evaluate the ADA responses to AZD5156, AZD3152 and AZD1061 in serum |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Sentinel Safety Cohort Participants (Phase I) Participants are eligible to be included in the Part A Sentinel Safety Cohort only if all of the following criteria apply: 1.Healthy participants according to medical history, physical examination, baseline safety laboratory tests, and screening parameters, according to the judgment of the investigator, with no concomitant disease or concomitant medication (except for medication specifically permitted by the protocol). 2.Age 18 to 55 years at the time of signing the informed consent. 3.Negative rapid antigen test at Visit 1. 4.Weight ≥ 45 kg and ≤ 110 kg at screening. Main Cohort Participants (Phase III) Participants are eligible to be included in the Part A Main Cohort only if all of the following criteria apply: 1.Participant must be 12 years of age or older at the time of signing the informed consent. 2.Negative rapid antigen test at Visit 1 and Visit 5. 3.Weight ≥ 40 kg at Visit 1 and Visit 5. 4.Participants must satisfy at least 1 of the following risk factors at enrollment: •Have solid tumor cancer and be on active treatment except for adequately treated: Non-melanoma skin cancer or lentigo maligna Uterine cervical carcinoma in situ Local prostate carcinoma •Have hematologic malignancy •Have solid organ transplant or a hematopoietic stem cell transplant (within 2 years of transplantation, are taking immunosuppression therapy or who have chronic graft versus-host disease) •Are actively taking immunosuppressive medicines (eg, are using corticosteroids [ie, ≥ 20 mg prednisone or equivalent per day when administered for ≥ 2 weeks], high dose alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive [eg, Bruton’s tyrosine kinase inhibitors], tumor-necrosis blockers, or other immunosuppressive or immunomodulatory biologic agents for rheumatic diseases) •Received chimeric antigen receptor T cell therapy •Within 1 year of receiving B-cell depleting therapies (eg, rituximab, ocrelizumab, ofatumumab, alemtuzumab) •Have a moderate or severe primary immunodeficiency (eg, DiGeorge syndrome, Wiskott-Aldrich syndrome, severe combined immunodeficiency, common variable immunodeficiency, agammaglobulinemia) 5.Medically stable defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 1 month prior to enrollment, with no acute change in condition at the time of study enrollment as judged by the Investigator and no expected changes at the time of the enrollment. |
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E.4 | Principal exclusion criteria |
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 adm and until at least 6 months after study intervention adm (see details in CSP) 2.Known hypersensitivity to any component of the study intervention. 3.Previous hypersensitivity or severe adverse reaction following admof a mAb. 4.Acute (time-limited) or febrile (temperature ≥ 38.0°C 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 inj 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.Receipt of a COVID-19 antiviral for prophylaxis within at least 2 weeks prior to Visit 1 11.COVID-19 within 3 months prior to Visit 1 (confirmed either by laboratory testing or a rapid test [including at home testing]). 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(see details in CSP) 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 11.Receipt of a COVID-19 antiviral within at least 2 weeks prior to Visit 1 12.COVID-19 within 6 months prior to Visit 1 (confirmed either by laboratory testing or a rapid test including at-home testing). 13. 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Main Cohort 1.Occurrence of AEs collected through 90 days after IMP administration; SAEs, MAAEs and AESIs collected throughout the study 2.GMTs for SARS-CoV-2 Alpha variant nAbs Sentinel Safety Cohort 1.Occurrence of AEs collected through 90 days after IMP administration; SAEs, MAAEs, and AESIs collected through the study |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Through 90 days after IMP administration |
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E.5.2 | Secondary end point(s) |
1.Time from the first dose of IMP to the first occurrence of a symptomatic COVID-19 case which is defined as: •Negative RT-PCR at baseline to positive at any time up to Visit 9 (12months) AND •Satisfying modified WHO definition of symptomatic COVID-19 2.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). 3.Incidence of a post treatment: •Symptomatic 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) 4. AZD3152, AZD7442, AZD1061, and AZD8895 concentrations over time and PK parameters In the Main Cohort: AZD5156, and AZD7442, AZD1061, AZD3152, and AZD8895 concentrations over time 5.Incidence of ADA Sentinel Safety Cohort 1.AZD5156, AZD1061, and AZD3152 concentrations over time and PK parameters 2.Incidence of ADA |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At Visit 3 (Day 29) Through the study |
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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 |
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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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 |
Canada |
Israel |
Korea, Democratic People's Republic of |
Malaysia |
Mexico |
Philippines |
Taiwan |
Thailand |
United States |
Turkey |
Belgium |
Denmark |
France |
Germany |
Poland |
Spain |
Sweden |
United Kingdom |
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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
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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 | 20 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 24 |