Novel Antibody Prophylaxis for COVID-19

(SUPERNOVA Trial)

Recruiting at 233 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

3882 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug, AZD3152, and a combination drug to see if they can prevent COVID-19. It focuses on people with weak immune systems who might not respond well to vaccines, as well as healthy adults. The drug works by blocking the virus from entering cells.

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.

What data supports the effectiveness of the drug AZD7442 for COVID-19 prevention and treatment?

AZD7442, a combination of two antibodies, has shown promise in preventing COVID-19 infection and reducing severe cases and deaths in high-risk individuals. Studies indicate it can provide long-lasting protection, with effectiveness confirmed in both animal models and real-world data, especially for those with weakened immune systems. ^{1 2 3 4 5}

How is the drug AZD7442 different from other COVID-19 treatments?

AZD7442 is unique because it combines two monoclonal antibodies, tixagevimab and cilgavimab, which target different parts of the virus's spike protein to prevent it from entering human cells. This drug is administered as an intramuscular injection and has an extended half-life, potentially providing up to 12 months of protection, which is longer than many other treatments. ^{1 2 6 7 8}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

1. United States 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. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Tixagevimab/Cilgavimab in SARS-CoV-2 Prophylaxis and Therapy: A Comprehensive Review of Clinical Experience. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Safety, Tolerability and Pharmacokinetics of Half-Life Extended Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Monoclonal Antibodies AZD7442 (Tixagevimab-Cilgavimab) in Healthy Adults. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Analysis of SARS-CoV-2 Emergent Variants Following AZD7442 (Tixagevimab/Cilgavimab) for Early Outpatient Treatment of COVID-19 (TACKLE Trial). [2023]

6. England pubmed.ncbi.nlm.nih.gov

Neutralizing anti-spike monoclonal antibodies for COVID-19 in vulnerable populations: lessons learned and future directions. [2023]

7. England pubmed.ncbi.nlm.nih.gov

A non-ACE2 competing human single-domain antibody confers broad neutralization against SARS-CoV-2 and circulating variants. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants. [2022]