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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Pediatric, Healthy volunteers

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

21 Jun 2023 → 11 Feb 2025

Decision date (initial)

2024-07-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB, Sweden

External identifiers

EU CT number

2024-512554-15-00

EudraCT number

2022-002378-95

ClinicalTrials.gov

NCT05648110

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Prophylaxis, Safety, Pharmacodynamic, Others, Pharmacokinetic

Main Cohort
1.To evaluate the safety of AZD3152 and EVUSHELD and/or placebo
2. To compare the efficacy of AZD3152 to EVUSHELD and/or placebo in the prevention of symptomatic COVID-19 caused by any SARS CoV 2 variant
3. To compare the efficacy of AZD3152 to EVUSHELD and/or placebo in the prevention of symptomatic COVID-19 attributable to matched variants (variants that do not contain the F456L mutation)

Sentinel Safety Cohort
1.To evaluate the safety of AZD5156

Secondary objectives 6

1. Main Cohort: To compare the nAb responses to the SARS-CoV-2 variants Alpha, Omicron BA.2, Omicron BA.4/5 and/or Omicron XBB.1.5 in serum following AZD3152 and EVUSHELD and/or placebo administration
2. Main Cohort: To describe the incidence of symptomatic COVID-19, severe COVID19, COVID-19 related hospitalization, and COVID-19 related death in participants receiving study intervention
3. Main Cohort: To characterize the PK of AZD3152 and AZD7442 in serum
4. Main Cohort: To evaluate the ADA responses to AZD3152 and AZD7442 in serum
5. Sentinel Safety Cohort: To characterize the PK of AZ5156 and AZD3152 in serum
6. Sentinel Safety Cohort: To evaluate the ADA responses to AZD5156, AZD3152 and AZD1061 in serum

Conditions and MedDRA coding

COVID-19

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Sentinel Safety Cohort: 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. Sentinel Safety Cohort: Age 18 to 55 years at the time of signing the informed consent
3. Sentinel Safety Cohort: Written informed consent and any locally required authorization (eg, HIPAA in the US) obtained from the participant prior to performing any protocol-related procedures, including screening evaluations.
4. Sentinel Safety Cohort: Negative rapid antigen test at Visit 1
5. Sentinel Safety Cohort: Weight ≥ 45 kg and ≤ 110 kg at screening.
6. Sentinel Safety Cohort: Able to understand and comply with all study requirements/procedures (if applicable, with assistance by caregiver, surrogate, or legally authorized representative or equivalent representative as locally defined) based on the assessment of the Investigator.
7. Main Cohort: Participant must be 12 years of age or older at the time of signing the informed consent.
8. Main Cohort: Written informed consent and any locally required authorization (eg, HIPAA in the US) obtained from the participant prior to performing any protocol-related procedures, including screening evaluations. For participants from 12 to < 18 years of age, their parents or legal guardians must give their signed written informed consent, as appropriate, and participants will sign an assent form.
9. Main Cohort: Negative rapid antigen test prior to dosing at Visit 1.
10. Main Cohort: Weight ≥ 40 kg at screening
11. Main Cohort: Participants must satisfy at least 1 of the following risk factors at enrollment: •Have solid tumor cancer and be on active immunosuppressive treatment •Have hematologic malignancy •Transplant participants must satisfy at least one of the following: - Have had a solid organ transplant within 2 years and / or - Had a hematopoietic stem cell transplant within 2 years and / or - Who have chronic graft-versus-host disease - Participants who previously had a solid organ transplant or hematopoietic stem cell transplant more than 2 years prior to Visit 1 may also be eligible based on the inclusion criterion for immunosuppressive treatment. •Are actively taking immunosuppressive medicines (eg, are using corticosteroids [ie,≥ 20 mg prednisone or equivalent per day when administered for ≥ 2 weeks], 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 biologic agents (eg, 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 (eg, DiGeorge syndrome) or secondary (eg, hemodialysis) immunodeficiency • Advanced or untreated HIV infection (people with HIV and CD4 cell counts < 200/mm3 within 6 months of Visit 1, history of an AIDSdefining illness without immune reconstitution, or clinical manifestations of symptomatic HIV)
12. Main Cohort: Medically stable defined as disease not requiring significant change in maintenance therapy or hospitalization for worsening disease or any recent CV event (eg, acute myocardial infarction, thromboembolic event) 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.
13. Main Cohort: Able to understand and comply with all study requirements/procedures (if applicable, with assistance by caregiver, surrogate, or legally authorized representative or equivalent representative as locally defined), including those at Illness Visits, based on the assessment of the Investigator.

Exclusion criteria 29

1. Sentinel Safety Cohort: 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, (see details in CSP).
2. Sentinel Safety Cohort: Known hypersensitivity to any component of the study intervention.
3. Sentinel Safety Cohort: Previous hypersensitivity or severe adverse reaction following administration of a mAb.
4. Sentinel Safety Cohort: 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 and may be rescreened for enrollment once.
5. Sentinel Safety Cohort: Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 30 days prior to Visit 1.
6. Sentinel Safety Cohort: 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. Sentinel Safety Cohort: Receipt of immunoglobulin (non-COVID related) or blood products within 6 months prior to Visit 1
8. Sentinel Safety Cohort: Previous receipt of a mAb against SARS-CoV-2
9. Sentinel Safety Cohort: Receipt of a COVID-19 vaccine within 3 months prior to Visit 1
10. Sentinel Safety Cohort: Receipt of a COVID-19 antiviral for prophylaxis within at least 2 weeks prior to Visit 1
11. Sentinel Safety Cohort: COVID-19 within 3 months prior to Visit 1 (confirmed either by laboratory testing or a rapid test [including at home testing])
12. Sentinel Safety Cohort: 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.
13. Main Cohort: 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).
14. Main Cohort: Known hypersensitivity to any component of the study intervention.
15. Main Cohort: Previous hypersensitivity or severe adverse reaction following administration of a mAb
16. Main Cohort: 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 and may be rescreened for enrollment once.
17. Main Cohort: Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 30 days prior to Visit 1.
18. Main Cohort: Clinically significant bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture.
19. Main Cohort: Receipt of IV or SC immunoglobulin within 6 months prior to Visit 1 or expected to receive IV or SC immunoglobulin 6 months after dosing.
20. Main Cohort: Receipt of convalescent COVID-19 plasma treatment within 6 months prior to Visit 1.
21. Main Cohort: Previous receipt of a mAb against SARS-CoV-2 within 6 months prior to Visit 1.
22. Main Cohort: Receipt of a COVID-19 vaccine within 3 months prior to Visit 1.
23. Main Cohort: Receipt of a COVID-19 antiviral for prophylaxis within at least 2 weeks prior to Visit 1.
24. Main Cohort: COVID-19 within 3 months prior to Visit 1 (confirmed either by laboratory testing or a rapid test [including at-home testing]).
25. Main Cohort: 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 (except where the participant ceased IMP treatment >90 days and is in the follow-up period of the study and not expected to receive further IMP).
26. Main Cohort: Alcohol or substance abuse that, in the opinion of the Investigator, might interfere with the trial conduct or completion.
27. Main Cohort: Deprived of freedom by an administrative or court order, or in emergency setting, or hospitalized involuntarily.
28. Main Cohort: 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.
29. Main Cohort: Employees of AstraZeneca involved in planning, executing, supervising, or reviewing the AZD5156/AZD3152 program, clinical study site staff, or any other individuals involved with the conduct of the study, or family members of such individuals.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Main Cohort: Occurrence of AEs collected through approximately 90 days after each IMP administration SAEs, MAAEs and AESIs collected through the study
2. Main Cohort: Population: SARS-CoV-2-Negative Set Endpoint: Confirmed symptomatic COVID-19 case, classified as a binary outcome incorporating the time from the first dose of IMP until a participant develops their first symptoms for COVID-19. Summary measure: Prophylactic efficacy, calculated as 1-HR (AZD3152 versus EVUSHELD and/or placebo) using a hazard regression model.
3. Main Cohort: Population: SARS-CoV-2-Negative Set Endpoint: Confirmed symptomatic COVID-19 case attributable to matched variants, classified as a binary outcome incorporating the time from the first dose of IMP until a participant develops their first symptoms for COVID-19. Summary measure: Prophylactic efficacy, calculated as 1-HR (AZD3152 versus EVUSHELD and/or placebo) using a hazard regression model.
4. Sentinel Safety Cohort: Occurrence of AEs collected through approximately 90 days after IMP administration; SAEs, MAAEs, and AESIs collected through the study.

Secondary endpoints 6

1. Main Cohort: 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. Main Cohort: Incidence of a post treatment: - Symptomatic COVID-19 case caused by any SARS-CoV-2 variant; - Symptomatic COVID-19 case caused by any SARS-CoV-2 matched variants •Severe COVID-19 caused by any SARS-CoV-2 variant; • Severe COVID-19 caused by any SARS-CoV-2 matched variants; •Composite of COVID-19 related hospitalization and/or COVID-19 related death; •COVID-19 related hospitalization (separately); •COVID-19 related death (separately).
3. Main Cohort: AZD3152, AZD7442, AZD1061 and AZD8895 concentrations over time and PK parameters.
4. Main Cohort: Incidence of ADA to AZD3152, AZD7442, AZD1061, and AZD8895, ADA titers.
5. Sentinel Safety Cohort: AZD5156, AZD1061, and AZD3152 concentrations over time and PK parameters.
6. Sentinel Safety Cohort: Incidence of ADA.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

Information Center

Third parties 12

Locations

6 EU/EEA countries · 41 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 44 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications