Novel Antibody Prophylaxis for COVID-19

(SUPERNOVA Trial)

No longer recruiting at 247 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: AstraZeneca

Must not be taking: Immunoglobulins, COVID-19 antivirals

Disqualifiers: Pregnancy, HIV, Hepatitis B/C, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 453

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new antibody treatments, AZD3152 and AZD5156, to determine their ability to prevent COVID-19 before virus exposure. The goal is to assess whether these treatments are safe, effective, and capable of neutralizing various COVID-19 variants. Participants may receive a combination of antibodies or compare the new treatments against EVUSHELD, a current COVID-19 prevention drug. Individuals with a solid tumor or blood cancer, those who have had a transplant, or those on immunosuppressive medication might be suitable for this study. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to significant advancements in COVID-19 prevention.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that participants should not have any significant changes in their maintenance therapy. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments AZD3152, AZD5156, and AZD7442 (also known as EVUSHELD) are under study for their safety in humans.

AZD3152 aims to protect against various COVID-19 variants. Studies suggest it is generally well-tolerated, with no major safety issues reported.

AZD5156, a combination of AZD3152 with another antibody, has been tested in healthy adults. Early results indicate it is generally safe, with no significant side effects.

AZD7442, or EVUSHELD, has FDA approval to help prevent COVID-19 in people with weakened immune systems. Past studies have shown it to be well-tolerated, with expected safety results.

Overall, these treatments have demonstrated a promising safety profile in studies so far. Participants have tolerated them well, suggesting they may be safe for wider use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the novel antibody treatments AZD3152, AZD5156, and AZD7442 (EVUSHELD™) for COVID-19 because they offer a fresh approach compared to existing options like antiviral drugs and vaccines. Unlike traditional vaccines that stimulate the immune system to produce antibodies, these treatments provide antibodies directly, which can offer immediate protection. AZD3152 and AZD5156 are administered intramuscularly, either in the thigh or gluteal area, which could be more convenient and potentially have fewer side effects than intravenous treatments. Additionally, AZD7442 is specifically designed for those who are immunocompromised, offering targeted protection for individuals who might not respond well to standard vaccines. This combination of immediate action and tailored protection makes these treatments particularly promising.

What evidence suggests that this trial's treatments could be effective for COVID-19?

Research has shown that AZD3152, one of the treatments in this trial, is promising in fighting all known versions of the SARS-CoV-2 virus. Early lab tests confirmed its effectiveness against these variants. AZD3152 aims to provide strong protection, especially for people at higher risk of COVID-19. Meanwhile, AZD5156, another treatment option in this trial, combines two antibodies and is under study for its ability to prevent severe cases of COVID-19. Evidence suggests that similar treatments have successfully reduced symptoms and prevented serious illness. For AZD7442, also known as Evusheld, studies have demonstrated its effectiveness in lowering severe COVID-19 cases and hospitalizations. This combination of treatments in the trial shows great potential in protecting against COVID-19. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for people aged 18-55 with certain immune deficiencies or conditions like DiGeorge syndrome, Wiskott-Aldrich syndrome, or those who have had specific treatments like CAR T cell therapy. It's also open to healthy individuals without concomitant diseases and those with stable chronic graft-versus-host disease or active cancer on immunosuppressants. Participants must not be pregnant, using effective contraception if of childbearing potential.

Inclusion Criteria

My weight is between 45 and 110 kg.

I weigh at least 40 kg.

I am 12 years old or older.

Exclusion Criteria

I have taken a COVID-19 antiviral for prevention in the last 3 months.

I have received EVUSHELD within the last year.

Known hypersensitivity to any component of the study intervention

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD3152 or comparator for pre-exposure prophylaxis of COVID-19, with doses given at a 6-month interval

12 months

2 visits (in-person) for dosing

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular visits up to Day 451

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• AZD3152
• AZD5156
• AZD7442

Trial Overview The study tests AZD3152 alone and in combination (AZD5156) against EVUSHELD for COVID-19 pre-exposure prophylaxis. The main study evaluates safety and efficacy while the sub-study focuses on comparing AZD3152 with EVUSHELD specifically in immunocompromised patients.

How Is the Trial Designed?

Group I: Sub-study - AZD7442 (EVUSHELD™) Immunocompromised participants offered AZD3152 1200mg IV Experimental Treatment 1 Intervention

This sub-study will enroll approximately 450 participants, ≥ 18 years of age with a minimum weight of 40 kg. An initial Sentinel Safety Cohort will include 12 healthy volunteers; all other participants in the study will be either immunocompromised or immunocompetent (including healthy participants) with all degrees of SARS-CoV-2 infection risk.

Group II: Sub-study - AZD3152 Experimental Treatment 1 Intervention

This sub-study will enroll approximately 450 participants, ≥ 18 years of age with a minimum weight of 40 kg. An initial Sentinel Safety Cohort will include 12 healthy volunteers; all other participants in the study will be either immunocompromised or immunocompetent (including healthy participants) with all degrees of SARS-CoV-2 infection risk.

Group III: Parent study Sentinel Safety Cohort - Subcohort 2b Thigh - AZD5156 Experimental Treatment 1 Intervention

The Sentinel Safety Cohort of the Parent study 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).

Group IV: Parent study Sentinel Safety Cohort - Subcohort 2a Gluteal- AZD5156 Experimental Treatment 1 Intervention

The Sentinel Safety Cohort of the Parent study 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).

Group V: Parent study Sentinel Safety Cohort - Subcohort 1b Thigh - AZD5156 Experimental Treatment 1 Intervention

The Sentinel Safety Cohort of the Parent study 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).

Group VI: Parent study Sentinel Safety Cohort - Subcohort 1a Gluteal - AZD5156 Experimental Treatment 1 Intervention

The Sentinel Safety Cohort of the Parent Study 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).

Group VII: Parent study Main Cohort - AZD3152 Experimental Treatment 2 Interventions

The Main Cohort of the Parent study will enroll approximately 3200 participants. Dosing in the Main Cohort will be staggered, so that it starts with adult participants aged 18 years and older, with no adolescent participants dosed in the Main Cohort until safety data from Visit 2a (Day 8) and Visit 2b (Day 15) have been reviewed by the DSMB for at least 80 adult Main Cohort participants (which will include at least 40 participants who have received AZD3152). Participants in the Main Cohort will be randomized 1:1 to receive AZD3152 300 mg or comparator administered IM in the anterolateral thigh on Day 1. Participants will receive a second dose of their original randomized study intervention (ie, active treatment or comparator) 6 months after Visit 1.

Group VIII: Parent study Main Cohort - EVUSHELD™ Active Control 1 Intervention

Participants in the Main Cohort of the Parent study will be randomized 1:1 to receive AZD3152 300 mg or comparator administered IM in the anterolateral thigh on Day 1. Participants will receive a second dose of their original randomized study intervention (ie, active treatment or comparator) 6 months after Visit 1. At the request of regulatory authorities the active comparator will be changed to placebo. As the comparator is given on two occasions, this means that a participant randomized to the comparator arm may receive (a) two doses of EVUSHELD, (b) a dose of EVUSHELD and a dose of placebo, or (c) two doses of placebo.

Group IX: Sub-study - AZD7442 (EVUSHELD™) Active Control 1 Intervention

This sub-study will enroll approximately 450 participants, ≥ 18 years of age with a minimum weight of 40 kg. An initial Sentinel Safety Cohort will include 12 healthy volunteers; all other participants in the study will be either immunocompromised or immunocompetent (including healthy participants) with all degrees of SARS-CoV-2 infection risk.

Group X: Parent study Sentinel Safety Cohort - Subcohort 2a Gluteal - Placebo Placebo Group 1 Intervention

The Sentinel Safety Cohort of the Parent study 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).

Group XI: Parent study Sentinel Safety Cohort - Subcohort 1b Thigh - Placebo Placebo Group 1 Intervention

The Sentinel Safety Cohort of the Parent study 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).

Group XII: Parent study Main Cohort - Placebo Placebo Group 1 Intervention

Participants in the Main Cohort of the Parent study will be randomized 1:1 to receive AZD3152 300 mg or comparator administered IM in the anterolateral thigh on Day 1. Participants will receive a second dose of their original randomized study intervention (ie, active treatment or comparator) 6 months after Visit 1. At the request of regulatory authorities the active comparator will be changed to placebo. As the comparator is given on two occasions, this means that a participant randomized to the comparator arm may receive (a) two doses of EVUSHELD, (b) a dose of EVUSHELD and a dose of placebo, or (c) two doses of placebo.

Group XIII: Parent study Sentinel Safety Cohort - Subcohort 1a Gluteal - Placebo Placebo Group 1 Intervention

The Sentinel Safety Cohort of the Parent study 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).

Group XIV: Parent study Sentinel Safety Cohort - Subcohort 2b Thigh - Placebo Placebo Group 1 Intervention

The Sentinel Safety Cohort of the Parent study 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).

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

AZD7442, a combination of two monoclonal antibodies, effectively prevents SARS-CoV-2 infection and accelerates virus clearance in nonhuman primates, indicating its potential for both prevention and treatment of COVID-19.

In a phase 1 study with healthy participants, a single 300-mg injection of AZD7442 resulted in neutralizing antibody levels significantly higher than those found in convalescent serum, providing protection for at least 9 months, suggesting it could be a long-lasting option for high-risk individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in nonhuman primates and has an extended half-life in humans. Loo, YM., McTamney, PM., Arends, RH., et al.[2023]

Citations

1. science.org science.org/doi/10.1126/scitranslmed.ado2817

AZD3152 neutralizes SARS-CoV-2 historical and ... We describe AZD3152, a SARS-CoV-2–neutralizing monoclonal antibody designed to provide improved potency and coverage against emerging variants.

2. astrazeneca.com astrazeneca.com/media-centre/press-releases/2023/eccmid-data-reinforces-astrazenecas-commitment-to-transform-protection-for-the-most-vulnerable-by-advancing-science-in-vaccines-and-immune-therapies.html

ECCMID data reinforces AstraZeneca's commitment to ... First in vitro data on AZD3152 shows the investigational COVID-19 long-acting antibody neutralises all known variants of concern identified ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38924429/

AZD3152 neutralizes SARS-CoV-2 historical and ... We describe AZD3152, a SARS-CoV-2-neutralizing monoclonal antibody designed to provide improved potency and coverage against emerging variants.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05648110

NCT05648110 | Study Understanding Pre-Exposure ... AZD3152 neutralizes SARS-CoV-2 historical and contemporary variants and is protective in hamsters and well tolerated in adults. Sci Transl Med. 2024 Jun 26 ...

5. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2023/astrazeneca-reinforces-commitment-to-protecting-the-most-vulnerable-from-serious-infectious-diseases-at-idweek-2023.html

AstraZeneca reinforces commitment to protecting the most ... AstraZeneca will present updated in vitro neutralization data for the investigational long-acting antibody AZD3152 against historical and ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7222/528044/Sipavibart-AZD-3152-a-COVID-19-Pre-Exposure

Sipavibart (AZD-3152), a COVID-19 Pre-Exposure ... Sipavibart (AZD-3152) is an investigational long-lasting monoclonal antibody designed to provide COVID-19 coverage including new variants.

7. astrazeneca.com astrazeneca.com/media-centre/press-releases/2024/supernova-trial-met-covid-19-prevention-endpoint.html

SUPERNOVA Phase III trial of sipavibart long-acting ... The SARS-CoV-2 Monoclonal Antibody AZD3152 Potently Neutralizes Historical and Emerging Variants and is Being Developed for the Prevention and ...

8. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/AZ-RU-00002

Study will assess the safety, neutralizing activity and ... AZD3152, a single mAb, is being developed to have broad neutralizing activity across known SARS-CoV-2 variants of concern for pre-exposure prophylaxis of COVID ...

9. thelancet.com thelancet.com/journals/laninf/article/PIIS1473-3099(24)00804-1/fulltext

Efficacy and safety of sipavibart for prevention of COVID-19 ... ... AZD3152) for prevention of symptomatic COVID-19 in participants who were immunocompromised. Sipavibart is derived from an antibody isolated ...