Clincosm LogoSign in Get a demo

Study Understanding Pre-Exposure pRophylaxis of NOVel Antibodies (SUPERNOVA)

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05648110
Collaborator
(none)
3,256
Enrollment
21
Locations
10
Arms
21.7
Anticipated Duration (Months)
155
Patients Per Site
7.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of this study is to assess the safety and neutralizing activity of AZD5156 for prevention of COVID-19 in immunocompromised individuals.

Condition or Disease Intervention/Treatment Phase
  • Biological: AZD5156
  • Biological: Placebo
  • Biological: AZD7442 (EVUSHELD™)
 Phase 3

Detailed Description

The purpose of this study is to demonstrate the safety and neutralizing activity of AZD5156 compared to AZD7442 (EVUSHELD) for prevention of COVID-19 in 3200 immunocompromised adults and adolescents 12 years of age or older (weighing at least 40 kg) in approximately 20 countries.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
3256 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
D7000C00001 is a Phase I/III study that will be conducted in approximately 3256 participants to evaluate the safety and neutralizing activity of AZD5156 compared with AZD7442 for pre-exposure prophylaxis of COVID-19. The study will be conducted globally. The study will consist of 2 cohorts: a Sentinel Safety Cohort and a Main Cohort. The Sentinel Safety Cohort will enroll 56 healthy adults, 18 to 55 years of age, who will be randomized to receive AZD5156 (40 participants) or placebo (16 participants). Dosing within the Sentinel Safety Cohort will be staggered, with participants allocated sequentially to 4 subcohorts (1a, 1b, 2a, and 2b). An ESDR will be conducted after Visit 4 (Day 8) and Visit 5 (Day 15) of each subcohort. Participants in the Main Cohort will be randomized 1:1 to receive AZD5156 or AZD7442 administered IM in the anterolateral thigh on Day 1. Participants will receive a second dose of their original randomized study intervention 6 months after Visit 1.D7000C00001 is a Phase I/III study that will be conducted in approximately 3256 participants to evaluate the safety and neutralizing activity of AZD5156 compared with AZD7442 for pre-exposure prophylaxis of COVID-19. The study will be conducted globally. The study will consist of 2 cohorts: a Sentinel Safety Cohort and a Main Cohort. The Sentinel Safety Cohort will enroll 56 healthy adults, 18 to 55 years of age, who will be randomized to receive AZD5156 (40 participants) or placebo (16 participants). Dosing within the Sentinel Safety Cohort will be staggered, with participants allocated sequentially to 4 subcohorts (1a, 1b, 2a, and 2b). An ESDR will be conducted after Visit 4 (Day 8) and Visit 5 (Day 15) of each subcohort. Participants in the Main Cohort will be randomized 1:1 to receive AZD5156 or AZD7442 administered IM in the anterolateral thigh on Day 1. Participants will receive a second dose of their original randomized study intervention 6 months after Visit 1.
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
A Phase I/III Randomized, Double Blind Study to Evaluate the Safety and Neutralizing Activity of AZD5156 for Pre Exposure Prophylaxis of COVID 19 in Participants With Conditions Causing Immune Impairment
Actual Study Start Date :
Dec 16, 2022
Anticipated Primary Completion Date :
Jan 3, 2024
Anticipated Study Completion Date :
Oct 8, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Sentinel Safety Cohort - Subcohort 1a Gluteal - AZD5156

The Sentinel Safety Cohort will enroll 56 healthy adults, 18 to 55 years of age, who will be randomized to receive AZD5156 (40 participants) or placebo (16 participants). Participants will be randomized to receive study intervention IM either in the gluteal or the anterolateral thigh. Dosing within the Sentinel Safety Cohort will be staggered, with participants allocated sequentially to 4 subcohorts (1a, 1b, 2a, and 2b).

Biological: AZD5156
Sentinel safety cohorts: single dose of AZD5156 IM Main cohort: two doses of AZD5156 IM
Placebo Comparator: Sentinel Safety Cohort - Subcohort 1a Gluteal - Placebo

The Sentinel Safety Cohort will enroll 56 healthy adults, 18 to 55 years of age, who will be randomized to receive AZD5156 (40 participants) or placebo (16 participants). Participants will be randomized to receive study intervention IM either in the gluteal or the anterolateral thigh. Dosing within the Sentinel Safety Cohort will be staggered, with participants allocated sequentially to 4 subcohorts (1a, 1b, 2a, and 2b).

Biological: Placebo
single dose of Placebo IM
Experimental: Sentinel Safety Cohort - Subcohort 1b Thigh - AZD5156

The Sentinel Safety Cohort will enroll 56 healthy adults, 18 to 55 years of age, who will be randomized to receive AZD5156 (40 participants) or placebo (16 participants). Participants will be randomized to receive study intervention IM either in the gluteal or the anterolateral thigh. Dosing within the Sentinel Safety Cohort will be staggered, with participants allocated sequentially to 4 subcohorts (1a, 1b, 2a, and 2b).

Biological: AZD5156
Sentinel safety cohorts: single dose of AZD5156 IM Main cohort: two doses of AZD5156 IM
Placebo Comparator: Sentinel Safety Cohort - Subcohort 1b Thigh - Placebo

The Sentinel Safety Cohort will enroll 56 healthy adults, 18 to 55 years of age, who will be randomized to receive AZD5156 (40 participants) or placebo (16 participants). Participants will be randomized to receive study intervention IM either in the gluteal or the anterolateral thigh. Dosing within the Sentinel Safety Cohort will be staggered, with participants allocated sequentially to 4 subcohorts (1a, 1b, 2a, and 2b).

Biological: Placebo
single dose of Placebo IM
Experimental: Sentinel Safety Cohort - Subcohort 2a Gluteal- AZD5156

The Sentinel Safety Cohort will enroll 56 healthy adults, 18 to 55 years of age, who will be randomized to receive AZD5156 (40 participants) or placebo (16 participants). Participants will be randomized to receive study intervention IM either in the gluteal or the anterolateral thigh. Dosing within the Sentinel Safety Cohort will be staggered, with participants allocated sequentially to 4 subcohorts (1a, 1b, 2a, and 2b).

Biological: AZD5156
Sentinel safety cohorts: single dose of AZD5156 IM Main cohort: two doses of AZD5156 IM
Placebo Comparator: Sentinel Safety Cohort - Subcohort 2a Gluteal - Placebo

The Sentinel Safety Cohort will enroll 56 healthy adults, 18 to 55 years of age, who will be randomized to receive AZD5156 (40 participants) or placebo (16 participants). Participants will be randomized to receive study intervention IM either in the gluteal or the anterolateral thigh. Dosing within the Sentinel Safety Cohort will be staggered, with participants allocated sequentially to 4 subcohorts (1a, 1b, 2a, and 2b).

Biological: Placebo
single dose of Placebo IM
Experimental: Sentinel Safety Cohort - Subcohort 2b Thigh - AZD5156

The Sentinel Safety Cohort will enroll 56 healthy adults, 18 to 55 years of age, who will be randomized to receive AZD5156 (40 participants) or placebo (16 participants). Participants will be randomized to receive study intervention IM either in the gluteal or the anterolateral thigh. Dosing within the Sentinel Safety Cohort will be staggered, with participants allocated sequentially to 4 subcohorts (1a, 1b, 2a, and 2b).

Biological: AZD5156
Sentinel safety cohorts: single dose of AZD5156 IM Main cohort: two doses of AZD5156 IM
Placebo Comparator: Sentinel Safety Cohort - Subcohort 2b Thigh - Placebo

The Sentinel Safety Cohort will enroll 56 healthy adults, 18 to 55 years of age, who will be randomized to receive AZD5156 (40 participants) or placebo (16 participants). Participants will be randomized to receive study intervention IM either in the gluteal or the anterolateral thigh. Dosing within the Sentinel Safety Cohort will be staggered, with participants allocated sequentially to 4 subcohorts (1a, 1b, 2a, and 2b).

Biological: Placebo
single dose of Placebo IM
Experimental: Main Cohort - AZD5156

Main Cohort will enroll approximately 3200 participants, 12 years of age or older with a minimum weight of 40 kg with conditions causing immune impairment, who are less likely to mount an adequate protective immune response after vaccination and thus are at high risk of developing severe COVID-19. Participants in the Main Cohort will be randomized 1:1 to receive AZD5156 or AZD7442 administered IM on Day 1 and will receive a second dose of their original randomized study intervention 6 months after Visit 1.

Biological: AZD5156
Sentinel safety cohorts: single dose of AZD5156 IM Main cohort: two doses of AZD5156 IM
Active Comparator: Main Cohort - AZD7442 (EVUSHELD™)

Main Cohort will enroll approximately 3200 participants, 12 years of age or older with a minimum weight of 40 kg with conditions causing immune impairment, who are less likely to mount an adequate protective immune response after vaccination and thus are at high risk of developing severe COVID-19. Participants in the Main Cohort will be randomized 1:1 to receive AZD5156 or AZD7442 administered IM on Day 1 and will receive a second dose of their original randomized study intervention 6 months after Visit 1.

Biological: AZD7442 (EVUSHELD™)
two doses of AZD7442 IM
Other Names:
  • EVUSHELD™

    		•

    Outcome Measures

    Primary Outcome Measures

    1. To evaluate the safety of AZD5156 and AZD7442 [SAEs, MAAEs, and AESIs will be collected throughout the study]

      Occurrence of AEs collected through 90 days after IMP administration

    2. To compare the nAb responses in serum following AZD5156 and AZD7442 administration to the SARS-CoV-2 Alpha variant in serum [GMT ratio of SARS-CoV-2 nAbs between the treatment arms at Visit 3 (Day 29). Descriptive statistics of SARS-CoV-2 nAb titers will be made by visit.]

      Participants who experience a protocol deviation that can interfere with an antibody response or violate adherence to the assigned dose, become infected, receive COVID 19 treatment or vaccination that can alter nAb levels will have data collected after the intercurrent event set to missing for analysis of the primary endpoint.

    Secondary Outcome Measures

    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 & AZD7442 administration [Visit 3 (Day 29)]

      GMT and GMFR ratio of SARS-CoV-2 nAbs between the treatment arms at Visit 3 (Day 29). Descriptive statistics for GMTs and GMFRs will include the number of participants, geometric mean, gSD, 95% CI, minimum, and maximum and summarized by treatment arm and visit

    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 [Data collected throughout entire study duration]

      Incidence of a post treatment: 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 (WHO COVID-19 Clinical Progression Scale score ≥ 4) COVID-19 related hospitalization (separately) COVID-19 related death (separately)

    3. To characterize the PK of AZD5156 and AZD7442 in serum [Samples collected and analyzed throughout entire study duration]

      In the Sentinel Safety Cohort: AZD5156, AZD1061 and AZD8895 concentrations over time and PK parameters (eg, Cmax, tmax, t½, AUClast, and AUCinf) In the Main Cohort: AZD5156 and AZD7442, AZD1061, AZD3152, AZD8895 concentrations over time

    4. To evaluate the ADA responses to AZD5156 and AZD7442 in serum [Samples collected and analyzed throughout entire study duration]

      Incidence of ADA

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes

    For Sentinel Safety Cohort Participants (Phase I)

    Inclusion Criteria

    • 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).

    • Age 18 to 55 years at the time of signing the informed consent.

    • Negative rapid antigen test at Visit 1.

    • Weight ≥ 45 kg and ≤ 110 kg at screening.

    Exclusion Criteria

    • Previous hypersensitivity or severe adverse reaction following administration of a mAb.

    • Receipt of immunoglobulin (non-COVID related) or blood products within 6 months prior to Visit 1.

    • Previous receipt of a mAb against SARS-CoV-2.

    • Receipt of a COVID-19 vaccine within 3 months prior to Visit 1.

    • Receipt of a COVID-19 antiviral within 3 months prior to Visit 1

    • COVID-19 within 3 months prior to Visit 1 (confirmed either by laboratory testing or a rapid test [including at home testing]).

    • 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.

    • Known or suspected congenital or acquired immunodeficiency, or receipt of immunosuppressive therapy, including any course of glucocorticoid therapy exceeding 2 weeks of prednisone or equivalent at a dose of 20 mg daily or every other day within 6 months prior to screening.

    • Active infection with hepatitis B or C.

    • Serum creatinine, AST, or ALT above 1.5 × ULN.

    For Main Cohort Participants (Phase III)

    Inclusion Criteria

    • Participant must be 12 years of age or older at the time of signing the informed consent.

    • Negative rapid antigen test at Visit 1.

    • Participants must satisfy at least 1 of the following risk factors at enrollment:

    • Have cancer (eg, active solid tumors and hematologic malignancies) except for adequately treated:

    1. Non-melanoma skin cancer or lentigo maligna

    2. Uterine cervical carcinoma in situ

    3. Local prostate carcinoma

    • 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)

    • 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.

    Exclusion Criteria

    • Previous hypersensitivity or severe adverse reaction following administration of a mAb.

    • Has HIV infection.

    • Receipt of convalescent COVID-19 plasma treatment within 6 months prior to Visit 1.

    • Previous receipt of a mAb against SARS-CoV-2 within 6 months prior to Visit 1.

    • Receipt of a COVID-19 vaccine within 3 months prior to Visit 1.

    • Receipt of a COVID-19 antiviral within 3 months prior to Visit 1.

    • COVID-19 within 3 months prior to Visit 1 (confirmed either by laboratory testing or a rapid test [including at home testing]).

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Buenos Aires Argentina C1039
    2 Research Site Buenos Aires Argentina C1056ABJ
    3 Research Site Buenos Aires Argentina C1202ABB
    4 Research Site Mar del Plata Argentina 7600
    5 Research Site Aarhus Denmark 8200
    6 Research Site København Ø Denmark 2100
    7 Research Site København Denmark 2300
    8 Research Site Dijon cedex France 21033
    9 Research Site Paris France 75014
    10 Research Site Paris France 75475
    11 Research Site Krakow Poland 30-510
    12 Research Site Lublin Poland 20-362
    13 Research Site Newton South Africa 2113
    14 Research Site Taipei Taiwan TAIWAN
    15 Research Site Kocaeli Turkey 41380
    16 Research Site London United Kingdom SE1 7EH
    17 Research Site London United Kingdom W1T 7HA
    18 Research Site London United Kingdom W1T 7HA
    19 Research Site Manchester United Kingdom M8 5RB
    20 Research Site Manchester United Kingdom M8 5RB
    21 Research Site Nottingham United Kingdom NG5 1PB

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT05648110
    Other Study ID Numbers:
    • D7000C00001
    First Posted:
    Dec 13, 2022
    Last Update Posted:
    Jan 13, 2023
    Last Verified:
    Jan 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by AstraZeneca
    Pre-exposure Prophylaxis of COVID-19
    Additional relevant MeSH terms:
    COVID-19

    Study Results

    No Results Posted as of Jan 13, 2023