A Randomized, Open-label, Dose-ranging Study in Adults and Pediatric Individuals ≥ 12 years of Age to Assess the Safety, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of AZD7442, for Pre-exposure Prophylaxis of COVID-19 - ENDURE

Study identifier:D8850C00010

ClinicalTrials.gov identifier:NCT05375760

EudraCT identifier:2022-001014-20

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

A Phase II Randomized, Open-label, Multicenter, Dose-ranging Study in Adults and Pediatric Individuals ≥ 12 years of Age to Assess the Safety, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of AZD7442, a Combination Product of Two Monoclonal Antibodies (Tixagevimab and Cilgavimab), for Pre-exposure Prophylaxis of COVID-19

Medical condition

Coronavirus disease 2019 (COVID-19)

Phase

Phase 2

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

251

Study type

Interventional

Age

12 Years - n/a

Date

Study Start Date: 09 Jun 2022

Primary Completion Date: 04 Oct 2023

Study Completion Date: 04 Oct 2023

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Prevention

Verification:

Verified 01 Sept 2024 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1. Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. For pediatric participants: informed assent is to be provided by the participant; informed consent must be provided by the participant’s legal guardian
2. Ensure that participants who are considered by the Investigator clinically unable to consent at screening and who are entered into the study by the consent of a legally acceptable representative show evidence of assent, as applicable in accordance with local regulations.
3. Participant must be an adult (≥ 18 years of age) or pediatric individual (≥ 12 to < 18 years of age weighing ≥ 40 kg) at the time of signing the ICF or assent (for pediatric participants).
4. Individuals with medical conditions or treatments that may result in moderate to severe immune compromise or an inadequate immune response to COVID-19 vaccination include but are not limited to:
(a) Active treatment for solid tumor and hematologic malignancies.
(b) Receipt of solid-organ transplant and taking immunosuppressive therapy.
(c) Receipt of chimeric antigen receptor T-cell or hematopoietic stem cell transplant (within 2 years of transplantation or taking immunosuppression therapy).
(d) Moderate or severe primary immunodeficiency (eg, DiGeorge syndrome, Wiskott-Aldrich syndrome).
(e) Advanced or untreated HIV infection (people with HIV and history of CD4 cellcounts < 200/mm3, history of an AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV).
(f) Active treatment with systemic high-dose 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, tumor necrosis factor blockers, and other biologic agents that are immunosuppressive or immunomodulatory (eg, B-cell depleting agents).
5 Documented negative SARS-CoV-2 RT-PCR test from an NP specimen collected ≤ 3 days prior to Day 1 or a negative SARS-CoV-2 rapid antigen test from an NP specimen at screening.

Exclusion Criteria

1. Any clinical signs and symptoms consistent with COVID-19, eg, fever, dry cough, dyspnea, sore throat, fatigue for ≥ 5 days or confirmed COVID-19 infection by appropriate laboratory test within 28 days prior to screening. Prior COVID-19 infection is not an exclusion.
2. History or current hospitalization for worsening disease during the one month prior to screening, with no change in condition at the time of study enrollment as judged by the Investigator.
3. Current need for hospitalization or immediate medical attention in a clinic or emergency room service in the clinical opinion of the Investigator.
4. Previous hypersensitivity, infusion-related reaction, or severe adverse reaction following administration of a mAb.
5. Known history of allergy to any component of the IMP formulation.
6. History of clinically significant bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IV infusions or venepuncture.
7. Any other significant disease, disorder, or finding that may significantly increase the risk to the participant because of participation in the study, affect the ability of the participant to participate in the study, or impair interpretation of the study data
8. Any co-morbidity requiring surgery within 7 days prior to study entry, or that is considered life-threatening in the opinion of the Investigator within 30 days prior to study entry.
9 Any prior receipt of investigational or licensed mAb or other biologic indicated for the prevention or treatment of SARS-CoV-2 or COVID-19 within 5 half-lives prior to screening or expected administration immediately after enrollment.
10 Have received a COVID-19 vaccination ≤ 14 days before Day 1 or plan to receive a COVID-19 vaccination ≤ 14 days after Day 1 (Such participants can subsequently be included in the study once they have reached > 14 days after their last dose of vaccine).
11 Receipt of convalescent COVID-19 plasma treatment within 90 days prior to screening.
12 Receipt of any IMP in the preceding 90 days or 5 half-lives, whichever is longer, or expected receipt of IMP during the period of study follow-up, or concurrent participation in another interventional study.
13 Judgment by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
14 For women only - currently pregnant (confirmed with positive pregnancy test) or breastfeeding.
15 Previous randomization in the present study.
16 Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 30 days prior to randomization.
17 Employees of the Sponsor involved in planning executing, supervising, or reviewing the AZD7442 program, clinical study site staff, or any other individuals involved with the conduct of the study, or immediate family members of such individuals.
18 In nations, states, or other jurisdictions that for legal or ethical reasons bar the enrollment of participants who lack capacity to provide their own informed consent, such subjects are excluded.

Location

Research Site

El Paso, TX, United States, 79925

Location

Research Site

Miami, FL, United States, 33125

Location

Research Site

West Palm Beach, FL, United States, 33409

Location

Research Site

St Louis, MO, United States, 63141

Location

Research Site

Austin, TX, United States, 78745

Location

Research Site

Annandale, VA, United States, 22003

Location

Research Site

Birmingham, AL, United States, 35215

Location

Research Site

Wesley Chapel, FL, United States, 33545

Arms	Assigned Interventions
Other: Arm A 600 mg AZD7442 following 300 mg AZD7442 every 3 months (5 doses totally)	Biological/Vaccine: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061]) Arm A - Day 1: 600 mg AZD7442 administered sequentially as a 3 mL IM injection containing 300 mg tixagevimab (AZD8895) and a 3 mL IM injection containing 300 mg cilgavimab (AZD1061), one injection in each gluteal region. Arm A - Days 92, 183, 274, 365: 300 mg AZD7442 administered sequentially as a 1.5 mL IM injection containing 150 mg tixagevimab (AZD8895) and a 1.5 mL IM injection containing 150 mg cilgavimab (AZD1061), one injection in each gluteal region.
Other: Arm B 1200mg AZD7442 following 600 mg AZD7442 every 6 months (3 doses totally)	Biological/Vaccine: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061]) Arm B – Day 1: 1200 mg AZD7442 (600 mg tixagevimab [AZD8895] and 600 mg cilgavimab [AZD1061]) administered by IV infusion. Arm B - Days 183, 365: 600 mg AZD7442 administered sequentially as a 3 mL IM injection containing 300 mg tixagevimab (AZD8895) and a 3 mL IM injection containing 300 mg cilgavimab (AZD1061), one injection in each gluteal region.

Arms

Assigned Interventions

Other: Arm A
600 mg AZD7442 following 300 mg AZD7442 every 3 months (5 doses totally)

Biological/Vaccine: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061])
Arm A - Day 1: 600 mg AZD7442 administered sequentially as a 3 mL IM injection containing 300 mg tixagevimab (AZD8895) and a 3 mL IM injection containing 300 mg cilgavimab (AZD1061), one injection in each gluteal region. Arm A - Days 92, 183, 274, 365: 300 mg AZD7442 administered sequentially as a 1.5 mL IM injection containing 150 mg tixagevimab (AZD8895) and a 1.5 mL IM injection containing 150 mg cilgavimab (AZD1061), one injection in each gluteal region.

Other: Arm B
1200mg AZD7442 following 600 mg AZD7442 every 6 months (3 doses totally)

Biological/Vaccine: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061])
Arm B – Day 1: 1200 mg AZD7442 (600 mg tixagevimab [AZD8895] and 600 mg cilgavimab [AZD1061]) administered by IV infusion. Arm B - Days 183, 365: 600 mg AZD7442 administered sequentially as a 3 mL IM injection containing 300 mg tixagevimab (AZD8895) and a 3 mL IM injection containing 300 mg cilgavimab (AZD1061), one injection in each gluteal region.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The participants were screened and randomized from the USA. First subject in was on 09Jun2022 and the last subject last visit was 04Oct2023. Sponsor terminated the study after review of FDA's request to halt further dosing (30Mar2023) and subjects were terminated prior to 1 year dose given that AZD7442 is not active against >99% of the currently circulating SARS-CoV-2 variants in the USA, the benefit risk assessment may not be favorable.

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

The participants were screened and randomized from the USA. First subject in was on 09Jun2022 and the last subject last visit was 04Oct2023. Sponsor terminated the study after review of FDA's request to halt further dosing (30Mar2023) and subjects were terminated prior to 1 year dose given that AZD7442 is not active against >99% of the currently circulating SARS-CoV-2 variants in the USA, the benefit risk assessment may not be favorable.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
AZD7442: 600 mg ONCE / 300mg Q3M	AZD7442 600 mg intramuscularly (IM) on Day 1 followed by 300 mg IM every 3 months (Q3M) for 12 months.
AZD7442: 1200mg ONCE / 600mg Q6M	AZD7442 1200 mg intravenously (IV) on Day 1 followed by 600 mg IM every 6 months (Q6M) for 12 months.

Participant Flow: Overall Study

	AZD7442: 600 mg ONCE / 300mg Q3M	AZD7442: 1200mg ONCE / 600mg Q6M
STARTED	125	126
Treated	124	124
COMPLETED	0	0
NOT COMPLETED	125	126
Adverse Event	1	0
Death	0	1
Lost to Follow-up	6	6
Withdrawal by Subject	17	19
Dosing halted by FDA	96	100
Not compliant with study visit	2	0
Physician Decision	1	0
Signed ICF addendum, however refused procedures	1	0
Participant moved	1	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Safety analysis set: participants who received IMP and classified according to the treatment they actually received.

Reporting Groups

	Description
AZD7442: 600mg ONCE / 300mg Q3M	AZD7442 600 mg intramuscularly (IM) on Day 1 followed by 300 mg IM every 3 months (Q3M) for 12 months.
AZD7442: 1200 mg ONCE / 600mg Q6M	AZD7442 1200 mg intravenously (IV) on Day 1 followed by 600 mg IM every 6 months (Q6M) for 12 months.

Baseline Measures

	AZD7442: 600mg ONCE / 300mg Q3M	AZD7442: 1200 mg ONCE / 600mg Q6M	Total
Number of Participants [units: Participants]	124	124	248
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	63	60	123
Not Hispanic or Latino	60	64	124
Not reported	1	0	1
Unknown	0	0	0
Sex: Female, Male [units: Participants]
Male	59	57	116
Female	65	67	132
Race (NIH/OMB) [units: Participants]
White	96	94	190
Black or African American	20	23	43
Asian	3	3	6
American Indian or Alaska Native	1	1	2
Native Hawaiian or Other Pacific Islander	0	0	0
Multiple	2	0	2
Unknown	1	0	1
Not reported	1	3	4
Screening result from Nasopharyngeal swab for SARS-CoV-2 RT-PCR [units: Participants]
Negative	124	124	248
Positive	0	0	0
Previous COVID-19 vaccination ^[1] [units: Participants]
Yes	26	19	45
No	98	105	203
Time since previous COVID-19 vaccination ^[2] [units: Days] Median ( Inter-Quartile Range )	107.0 (79.0 to 305.0)	205.0 (105.0 to 354.0)	138.0 (85.0 to 320.0)
Smoking history [units: Participants]
Current	23	13	36
Former	28	24	52
Never	73	87	160
Number of pack years (Current or Former) [units: percentages] Mean ± Standard Deviation	18.9 ± 19.27	20.0 ± 18.74	19.3 ± 18.95
Weight (kg) [units: kg] Mean ± Standard Deviation	81.17 ± 20.764	83.27 ± 19.258	82.22 ± 20.013
Height (cm) [units: cm] Mean ± Standard Deviation	168.18 ± 10.406	167.68 ± 9.946	167.93 ± 10.162
Body Mass Index (kg/m^2) [units: kg/m^2] Mean ± Standard Deviation	28.66 ± 6.884	29.66 ± 6.582	29.16 ± 6.740
Body Mass Index (kg/m^2) Category [units: Participants]
< 25	32	26	58
25 - <30	52	47	99
30 - <35	25	29	54
>= 35	15	22	37
Age Continuous [units: Years] Mean ± Standard Deviation	57.3 ± 13.97	54.2 ± 14.85	55.7 ± 14.47
Age, Customized [units: Participants]
>=12 - <18	0	0	0
>=18 - <65	86	98	184
>=65 - <75	26	12	38
>=75 - <80	9	7	16
>=80	3	7	10

Outcome Measures

1. Primary Outcome Measure: AEs, SAEs, and AESIs [ Time Frame: Safety data were recorded from the time of the first IMP administration throughout the study for an average safety follow up time of 48.85 weeks. This was shorter than the planned one of 105 weeks due to FDA’s request to halt dosing. ]

Measure Type	Primary
Measure Name	AEs, SAEs, and AESIs
Measure Description	To evaluate the safety and tolerability of AZD7442
Time Frame	Safety data were recorded from the time of the first IMP administration throughout the study for an average safety follow up time of 48.85 weeks. This was shorter than the planned one of 105 weeks due to FDA’s request to halt dosing.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set

Reporting Groups

	Description
AZD7442: 600mg ONCE / 300mg Q3M	AZD7442 600 mg intramuscularly (IM) on Day 1 followed by 300 mg IM every 3 months (Q3M) for 12 months.
AZD7442: 1200 mg ONCE / 600mg Q6M	AZD7442 1200 mg intravenously (IV) on Day 1 followed by 600 mg IM every 6 months (Q6M) for 12 months.

Measured Values

	AZD7442: 600mg ONCE / 300mg Q3M	AZD7442: 1200 mg ONCE / 600mg Q6M
Number of Participants Analyzed [units:participants]	124	124
AEs, SAEs, and AESIs [units: Participants]
Adverse Events	84	66
Serious Adverse Events	13	10
Adverse Events of Special Interest	9	7

No statistical analysis provided for AEs, SAEs, and AESIs

2. Primary Outcome Measure: ADA in serum responses [ Time Frame: Serum ADA were assessed through the treatment period at the specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365, 456 days or early discontinuation visit after the first IMP administration. ]

Measure Type	Primary
Measure Name	ADA in serum responses
Measure Description	To evaluate the immunogenicity of AZD7442
Time Frame	Serum ADA were assessed through the treatment period at the specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365, 456 days or early discontinuation visit after the first IMP administration.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ADA Evaluable Analysis set

Reporting Groups

	Description
AZD7442: 600mg ONCE / 300mg Q3M	AZD7442 600 mg intramuscularly (IM) on Day 1 followed by 300 mg IM every 3 months (Q3M) for 12 months.
AZD7442: 1200 mg ONCE / 600mg Q6M	AZD7442 1200 mg intravenously (IV) on Day 1 followed by 600 mg IM every 6 months (Q6M) for 12 months.

Measured Values

	AZD7442: 600mg ONCE / 300mg Q3M	AZD7442: 1200 mg ONCE / 600mg Q6M
Number of Participants Analyzed [units:participants]	106	111
ADA in serum responses [units: Participants]	1	3

No statistical analysis provided for ADA in serum responses

3. Secondary Outcome Measure: Serum AZD7442 concentrations [ Time Frame: Serum PK was assessed through the treatment period at the specific timepoints: day 1 post-dose (600mg Q6M arm only), 3, 11, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early discontinuation visit after the first IMP administration. ]

Measure Type	Secondary
Measure Name	Serum AZD7442 concentrations
Measure Description	To evaluate the PK of AZD7442 in serum
Time Frame	Serum PK was assessed through the treatment period at the specific timepoints: day 1 post-dose (600mg Q6M arm only), 3, 11, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early discontinuation visit after the first IMP administration.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK Analysis Set

Reporting Groups

	Description
AZD7442: 600mg ONCE / 300mg Q3M	AZD7442 600 mg intramuscularly (IM) on Day 1 followed by 300 mg IM every 3 months (Q3M) for 12 months.
AZD7442: 1200 mg ONCE / 600mg Q6M	AZD7442 1200 mg intravenously (IV) on Day 1 followed by 600 mg IM every 6 months (Q6M) for 12 months.

Measured Values

	AZD7442: 600mg ONCE / 300mg Q3M	AZD7442: 1200 mg ONCE / 600mg Q6M
Number of Participants Analyzed [units:participants]	107	116
Serum AZD7442 concentrations [units: ug/mL] Geometric Mean (Geometric Coefficient of Variation)
Day 1, Post-dose		285.8539 (176.0959%)
Day 3	30.0089 (83.7707%)	165.1457 (196.9756%)
Day 11	45.5626 (53.9503%)	123.2505 (160.5606%)
Day 29	40.0381 (48.7457%)	105.8292 (76.5535%)
Day 92	27.9754 (48.9241%)	63.0711 (76.0487%)
Day 121	42.1820 (53.2624%)
Day 183	23.8985 (58.4175%)	26.4300 (85.1380%)
Day 212	36.5360 (54.5622%)	60.5211 (44.6566%)
Day 274	24.3601 (59.3582%)	38.1694 (55.8293%)
Day 365	21.2009 (46.2521%)	17.2078 (91.1273%)
Confirmed Illness 1 Day 1	36.2743 (30.3957%)	103.0573 (43.1944%)
Confirmed Illness 1 Day 14	37.2795 (25.1834%)	79.1638 (29.7188%)

No statistical analysis provided for Serum AZD7442 concentrations

4. Secondary Outcome Measure: Changes from baseline in GMTs values in SARSCoV- 2 nAbs (wild-type assay) [ Time Frame: SARSCoV-2 nAbs (Wild Type Assay) were assessed through the treatment period at these specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early termination visit after the first IMP administration. ]

Measure Type	Secondary
Measure Name	Changes from baseline in GMTs values in SARSCoV- 2 nAbs (wild-type assay)
Measure Description	To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442
Time Frame	SARSCoV-2 nAbs (Wild Type Assay) were assessed through the treatment period at these specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early termination visit after the first IMP administration.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
nAb Evaluable Analysis Set - Authentic Virus

Reporting Groups

	Description
AZD7442: 600mg ONCE / 300mg Q3M	AZD7442 600 mg intramuscularly (IM) on Day 1 followed by 300 mg IM every 3 months (Q3M) for 12 months.
AZD7442: 1200 mg ONCE / 600mg Q6M	AZD7442 1200 mg intravenously (IV) on Day 1 followed by 600 mg IM every 6 months (Q6M) for 12 months.

Measured Values

	AZD7442: 600mg ONCE / 300mg Q3M	AZD7442: 1200 mg ONCE / 600mg Q6M
Number of Participants Analyzed [units:participants]	112	119
Changes from baseline in GMTs values in SARSCoV- 2 nAbs (wild-type assay) [units: Titer] Geometric Mean (Standard Deviation)
Baseline Titer	203.5 (6.43)	198.9 (7.70)
Day 29 Titer	1442.8 (1.88)	3497.1 (2.10)
Day 92 Titer	1052.5 (2.22)	2268.6 (2.30)
Day 121 Titer	1520.2 (1.97)
Day 183 Titer	1209.8 (1.95)	1337.9 (2.10)
Day 212 Titer	941.2 (2.08)	1436.1 (1.78)
Day 274 Titer	488.5 (2.38)	864.7 (1.98)
Day 365 Titer	482.1 (1.21)	578.9 (2.21)

No statistical analysis provided for Changes from baseline in GMTs values in SARSCoV- 2 nAbs (wild-type assay)

5. Secondary Outcome Measure: Changes from baseline in GMTs in SARSCoV- 2 nAbs (pseudo neutralization assay) [ Time Frame: SARSCoV-2 nAbs (Pseudo Neutralization Assay) were assessed through the study at these specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early termination visit after the first IMP administration. ]

Measure Type	Secondary
Measure Name	Changes from baseline in GMTs in SARSCoV- 2 nAbs (pseudo neutralization assay)
Measure Description	To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442
Time Frame	SARSCoV-2 nAbs (Pseudo Neutralization Assay) were assessed through the study at these specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early termination visit after the first IMP administration.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
nAb Evaluable Analysis Set - Pseudo Virus

Reporting Groups

	Description
AZD7442: 600mg ONCE / 300mg Q3M	AZD7442 600 mg intramuscularly (IM) on Day 1 followed by 300 mg IM every 3 months (Q3M) for 12 months.
AZD7442: 1200 mg ONCE / 600mg Q6M	AZD7442 1200 mg intravenously (IV) on Day 1 followed by 600 mg IM every 6 months (Q6M) for 12 months.

Measured Values

	AZD7442: 600mg ONCE / 300mg Q3M	AZD7442: 1200 mg ONCE / 600mg Q6M
Number of Participants Analyzed [units:participants]	112	119
Changes from baseline in GMTs in SARSCoV- 2 nAbs (pseudo neutralization assay) [units: Titer] Geometric Mean (Standard Deviation)
Baseline Titer	1613.3 (7.96)	1735.8 (8.35)
Day 29 Titer	32170.5 (1.86)	111726.8 (1.75)
Day 92 Titer	13940.9 (1.88)	38048.0 (1.73)
Day 121 Titer	23177.5 (1.87)
Day 183 Titer	12018.5 (1.75)	15554.6 (1.80)
Day 212 Titer	19353.3 (1.72)	36519.3 (1.67)
Day 274 Titer	12816.8 (1.93)	23583.5 (1.91)
Day 365 Titer	5068.4 (1.55)	7155.4 (2.01)

No statistical analysis provided for Changes from baseline in GMTs in SARSCoV- 2 nAbs (pseudo neutralization assay)

6. Secondary Outcome Measure: Changes from baseline in GMFRs values in SARSCoV- 2 nAbs (wild-type assay) [ Time Frame: SARSCoV-2 nAbs (Wild Type Assay) were assessed through the treatment period at these specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early termination visit after the first IMP administration. ]

Measure Type	Secondary
Measure Name	Changes from baseline in GMFRs values in SARSCoV- 2 nAbs (wild-type assay)
Measure Description	To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442
Time Frame	SARSCoV-2 nAbs (Wild Type Assay) were assessed through the treatment period at these specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early termination visit after the first IMP administration.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
nAb Evaluable Analysis Set - Authentic Virus

Reporting Groups

	Description
AZD7442: 600mg ONCE / 300mg Q3M	AZD7442 600 mg intramuscularly (IM) on Day 1 followed by 300 mg IM every 3 months (Q3M) for 12 months.
AZD7442: 1200 mg ONCE / 600mg Q6M	AZD7442 1200 mg intravenously (IV) on Day 1 followed by 600 mg IM every 6 months (Q6M) for 12 months.

Measured Values

	AZD7442: 600mg ONCE / 300mg Q3M	AZD7442: 1200 mg ONCE / 600mg Q6M
Number of Participants Analyzed [units:participants]	112	119
Changes from baseline in GMFRs values in SARSCoV- 2 nAbs (wild-type assay) [units: Fold rise] Geometric Mean (Standard Deviation)
Day 29 fold rise	6.87 (4.765)	16.79 (6.429)
Day 92 fold rise	4.32 (4.329)	10.53 (6.362)
Day 121 fold rise	6.53 (4.928)
Day 183 fold rise	5.29 (4.744)	5.43 (5.122)
Day 212 fold rise	4.09 (5.554)	5.28 (6.243)
Day 274 fold rise	1.96 (4.385)	3.08 (5.820)
Day 365 fold rise	9.97 (1.093)	2.00 (5.343)

No statistical analysis provided for Changes from baseline in GMFRs values in SARSCoV- 2 nAbs (wild-type assay)

7. Secondary Outcome Measure: Changes from baseline in GMFRs values in SARSCoV- 2 nAbs (pseudo neutralization assay) [ Time Frame: SARSCoV-2 nAbs (Pseudo Neutralization Assay) were assessed through the study at these specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early termination visit after the first IMP administration. ]

Measure Type	Secondary
Measure Name	Changes from baseline in GMFRs values in SARSCoV- 2 nAbs (pseudo neutralization assay)
Measure Description	To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442
Time Frame	SARSCoV-2 nAbs (Pseudo Neutralization Assay) were assessed through the study at these specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early termination visit after the first IMP administration.
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
nAb Evaluable Analysis Set - Pseudo Virus

Reporting Groups

	Description
AZD7442: 600mg ONCE / 300mg Q3M	AZD7442 600 mg intramuscularly (IM) on Day 1 followed by 300 mg IM every 3 months (Q3M) for 12 months.
AZD7442: 1200 mg ONCE / 600mg Q6M	AZD7442 1200 mg intravenously (IV) on Day 1 followed by 600 mg IM every 6 months (Q6M) for 12 months.

Measured Values

	AZD7442: 600mg ONCE / 300mg Q3M	AZD7442: 1200 mg ONCE / 600mg Q6M
Number of Participants Analyzed [units:participants]	112	119
Changes from baseline in GMFRs values in SARSCoV- 2 nAbs (pseudo neutralization assay) [units: Fold rise] Geometric Mean (Standard Deviation)
Day 29 fold rise	18.02 (7.081)	58.84 (8.473)
Day 92 fold rise	7.82 (7.270)	20.38 (8.068)
Day 121 fold rise	13.13 (8.439)
Day 183 fold rise	7.28 (6.954)	6.90 (7.185)
Day 212 fold rise	10.28 (6.969)	14.44 (7.457)
Day 274 fold rise	7.06 (6.133)	8.99 (8.271)
Day 365 fold rise	12.64 (1.251)	2.84 (8.353)

No statistical analysis provided for Changes from baseline in GMFRs values in SARSCoV- 2 nAbs (pseudo neutralization assay)

Serious Adverse Events

Time Frame	Safety data were recorded from the time of the first IMP administration throughout the study for an average safety follow up time of 48.85 weeks. This was shorter than the planned one of 105 weeks due to FDA’s request to halt dosing.
Additional Description	No text entered.

Reporting Groups

	Description
AZD7442: 600mg ONCE / 300mg Q3M	AZD7442 600 mg intramuscularly (IM) on Day 1 followed by 300 mg IM every 3 months (Q3M) for 12 months.
AZD7442: 1200 mg ONCE / 600mg Q6M	AZD7442 1200 mg intravenously (IV) on Day 1 followed by 600 mg IM every 6 months (Q6M) for 12 months.

Serious Adverse Events

AZD7442: 600mg ONCE / 300mg Q3M

AZD7442: 1200 mg ONCE / 600mg Q6M

Total, serious adverse events

# participants affected / at risk

13/124 (10.48%)

10/124 (8.06%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

1/124 (0.81%)

# events

Infections and infestations

Abscess limb¹,^†

# participants affected / at risk

0/124 (0.00%)

1/124 (0.81%)

# events

Infections and infestations

Covid-19¹,^†

# participants affected / at risk

0/124 (0.00%)

1/124 (0.81%)

# events

Infections and infestations

Diverticulitis¹,^†

# participants affected / at risk

1/124 (0.81%)

0/124 (0.00%)

# events

Infections and infestations

Escherichia pyelonephritis¹,^†

# participants affected / at risk

1/124 (0.81%)

0/124 (0.00%)

# events

Infections and infestations

Escherichia sepsis¹,^†

# participants affected / at risk

1/124 (0.81%)

0/124 (0.00%)

# events

Infections and infestations

Escherichia urinary tract infection¹,^†

# participants affected / at risk

1/124 (0.81%)

0/124 (0.00%)

# events

Infections and infestations

Gastroenteritis norovirus¹,^†

# participants affected / at risk

0/124 (0.00%)

1/124 (0.81%)

# events

Cardiac disorders

Acute myocardial infarction¹,^†

# participants affected / at risk

1/124 (0.81%)

0/124 (0.00%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

2/124 (1.61%)

1/124 (0.81%)

# events

Infections and infestations

Pneumonia bacterial¹,^†

# participants affected / at risk

0/124 (0.00%)

2/124 (1.61%)

# events

Infections and infestations

Pulmonary sepsis¹,^†

# participants affected / at risk

1/124 (0.81%)

0/124 (0.00%)

# events

Infections and infestations

Sepsis¹,^†

# participants affected / at risk

0/124 (0.00%)

1/124 (0.81%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

0/124 (0.00%)

1/124 (0.81%)

# events

Infections and infestations

Urinary tract infection bacterial¹,^†

# participants affected / at risk

0/124 (0.00%)

1/124 (0.81%)

# events

Cardiac disorders

Angina pectoris¹,^†

# participants affected / at risk

1/124 (0.81%)

0/124 (0.00%)

# events

Injury, poisoning and procedural complications

Gastrointestinal anastomotic stenosis¹,^†

# participants affected / at risk

0/124 (0.00%)

1/124 (0.81%)

# events

Injury, poisoning and procedural complications

Subdural haematoma¹,^†

# participants affected / at risk

1/124 (0.81%)

0/124 (0.00%)

# events

Cardiac disorders

Angina unstable¹,^†

# participants affected / at risk

1/124 (0.81%)

0/124 (0.00%)

# events

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

0/124 (0.00%)

1/124 (0.81%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Anal squamous cell carcinoma¹,^†

# participants affected / at risk

1/124 (0.81%)

0/124 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Metastases to spine¹,^†

# participants affected / at risk

0/124 (0.00%)

1/124 (0.81%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Myelodysplastic syndrome¹,^†

# participants affected / at risk

1/124 (0.81%)

0/124 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Pituitary tumour benign¹,^†

# participants affected / at risk

0/124 (0.00%)

1/124 (0.81%)

# events

Nervous system disorders

Focal dyscognitive seizures¹,^†

# participants affected / at risk

0/124 (0.00%)

1/124 (0.81%)

# events

Nervous system disorders

Syncope¹,^†

# participants affected / at risk

1/124 (0.81%)

0/124 (0.00%)

# events

Nervous system disorders

Uraemic encephalopathy¹,^†

# participants affected / at risk

0/124 (0.00%)

1/124 (0.81%)

# events

Renal and urinary disorders

Acute kidney injury¹,^†

# participants affected / at risk

1/124 (0.81%)

# events

Renal and urinary disorders

Hydronephrosis¹,^†

# participants affected / at risk

1/124 (0.81%)

0/124 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure¹,^†

# participants affected / at risk

0/124 (0.00%)

2/124 (1.61%)

# events

Respiratory, thoracic and mediastinal disorders

Asthma¹,^†

# participants affected / at risk

1/124 (0.81%)

0/124 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Hypoxia¹,^†

# participants affected / at risk

1/124 (0.81%)

0/124 (0.00%)

# events

Gastrointestinal disorders

Colitis ischaemic¹,^†

# participants affected / at risk

0/124 (0.00%)

1/124 (0.81%)

# events

Vascular disorders

Peripheral artery aneurysm¹,^†

# participants affected / at risk

1/124 (0.81%)

0/124 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 26.0

Other Adverse Events

Time Frame	Safety data were recorded from the time of the first IMP administration throughout the study for an average safety follow up time of 48.85 weeks. This was shorter than the planned one of 105 weeks due to FDA’s request to halt dosing.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	1%

Reporting Groups

	Description
AZD7442: 600mg ONCE / 300mg Q3M	AZD7442 600 mg intramuscularly (IM) on Day 1 followed by 300 mg IM every 3 months (Q3M) for 12 months.
AZD7442: 1200 mg ONCE / 600mg Q6M	AZD7442 1200 mg intravenously (IV) on Day 1 followed by 600 mg IM every 6 months (Q6M) for 12 months.

Other Adverse Events

AZD7442: 600mg ONCE / 300mg Q3M

AZD7442: 1200 mg ONCE / 600mg Q6M

Total, other (not including serious) adverse events

# participants affected / at risk

76/124 (61.29%)

58/124 (46.77%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

2/124 (1.61%)

4/124 (3.23%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

4/124 (3.23%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

3/124 (2.42%)

1/124 (0.81%)

# events

General disorders and administration site conditions

Chills¹,^†

# participants affected / at risk

2/124 (1.61%)

# events

General disorders and administration site conditions

Fatigue¹,^†

# participants affected / at risk

6/124 (4.84%)

5/124 (4.03%)

# events

General disorders and administration site conditions

Injection site pain¹,^†

# participants affected / at risk

2/124 (1.61%)

0/124 (0.00%)

# events

General disorders and administration site conditions

Injection site pruritus¹,^†

# participants affected / at risk

1/124 (0.81%)

3/124 (2.42%)

# events

General disorders and administration site conditions

Pain¹,^†

# participants affected / at risk

2/124 (1.61%)

1/124 (0.81%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

2/124 (1.61%)

1/124 (0.81%)

# events

Immune system disorders

Seasonal allergy¹,^†

# participants affected / at risk

2/124 (1.61%)

0/124 (0.00%)

# events

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

3/124 (2.42%)

2/124 (1.61%)

# events

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

5/124 (4.03%)

0/124 (0.00%)

# events

Infections and infestations

Covid-19¹,^†

# participants affected / at risk

10/124 (8.06%)

12/124 (9.68%)

# events

Infections and infestations

Cystitis¹,^†

# participants affected / at risk

2/124 (1.61%)

1/124 (0.81%)

# events

Infections and infestations

Diverticulitis¹,^†

# participants affected / at risk

2/124 (1.61%)

1/124 (0.81%)

# events

Infections and infestations

Herpes zoster¹,^†

# participants affected / at risk

3/124 (2.42%)

0/124 (0.00%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

11/124 (8.87%)

7/124 (5.65%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

0/124 (0.00%)

2/124 (1.61%)

# events

Infections and infestations

Respiratory tract infection viral¹,^†

# participants affected / at risk

3/124 (2.42%)

0/124 (0.00%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

3/124 (2.42%)

4/124 (3.23%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

7/124 (5.65%)

# events

Infections and infestations

Viral upper respiratory tract infection¹,^†

# participants affected / at risk

6/124 (4.84%)

# events

Injury, poisoning and procedural complications

Fall¹,^†

# participants affected / at risk

2/124 (1.61%)

3/124 (2.42%)

# events

Injury, poisoning and procedural complications

Skin laceration¹,^†

# participants affected / at risk

0/124 (0.00%)

2/124 (1.61%)

# events

Investigations

Blood pressure increased¹,^†

# participants affected / at risk

2/124 (1.61%)

1/124 (0.81%)

# events

Investigations

Blood thrombin increased¹,^†

# participants affected / at risk

1/124 (0.81%)

3/124 (2.42%)

# events

Investigations

C-reactive protein increased¹,^†

# participants affected / at risk

2/124 (1.61%)

# events

Investigations

Troponin increased¹,^†

# participants affected / at risk

1/124 (0.81%)

2/124 (1.61%)

# events

Metabolism and nutrition disorders

Diabetes mellitus¹,^†

# participants affected / at risk

3/124 (2.42%)

1/124 (0.81%)

# events

Metabolism and nutrition disorders

Hypoglycaemia¹,^†

# participants affected / at risk

2/124 (1.61%)

1/124 (0.81%)

# events

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

2/124 (1.61%)

1/124 (0.81%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

1/124 (0.81%)

2/124 (1.61%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

2/124 (1.61%)

# events

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

0/124 (0.00%)

4/124 (3.23%)

# events

Musculoskeletal and connective tissue disorders

Neck pain¹,^†

# participants affected / at risk

0/124 (0.00%)

2/124 (1.61%)

# events

Musculoskeletal and connective tissue disorders

Rheumatoid arthritis¹,^†

# participants affected / at risk

3/124 (2.42%)

2/124 (1.61%)

# events

Musculoskeletal and connective tissue disorders

Systemic lupus erythematosus¹,^†

# participants affected / at risk

2/124 (1.61%)

0/124 (0.00%)

# events

Cardiac disorders

Coronary artery disease¹,^†

# participants affected / at risk

2/124 (1.61%)

0/124 (0.00%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

7/124 (5.65%)

1/124 (0.81%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

8/124 (6.45%)

# events

Nervous system disorders

Migraine¹,^†

# participants affected / at risk

2/124 (1.61%)

1/124 (0.81%)

# events

Nervous system disorders

Sciatica¹,^†

# participants affected / at risk

2/124 (1.61%)

0/124 (0.00%)

# events

Renal and urinary disorders

Acute kidney injury¹,^†

# participants affected / at risk

1/124 (0.81%)

3/124 (2.42%)

# events

Renal and urinary disorders

End stage renal disease¹,^†

# participants affected / at risk

0/124 (0.00%)

2/124 (1.61%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

0/124 (0.00%)

2/124 (1.61%)

# events

Respiratory, thoracic and mediastinal disorders

Asthma¹,^†

# participants affected / at risk

2/124 (1.61%)

0/124 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Atelectasis¹,^†

# participants affected / at risk

2/124 (1.61%)

1/124 (0.81%)

# events

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease¹,^†

# participants affected / at risk

2/124 (1.61%)

1/124 (0.81%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

3/124 (2.42%)

5/124 (4.03%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

4/124 (3.23%)

# events

Respiratory, thoracic and mediastinal disorders

Nasal congestion¹,^†

# participants affected / at risk

2/124 (1.61%)

4/124 (3.23%)

# events

Respiratory, thoracic and mediastinal disorders

Oropharyngeal pain¹,^†

# participants affected / at risk

3/124 (2.42%)

5/124 (4.03%)

# events

Respiratory, thoracic and mediastinal disorders

Pleural effusion¹,^†

# participants affected / at risk

3/124 (2.42%)

0/124 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Respiratory tract congestion¹,^†

# participants affected / at risk

1/124 (0.81%)

3/124 (2.42%)

# events

Respiratory, thoracic and mediastinal disorders

Rhinorrhoea¹,^†

# participants affected / at risk

2/124 (1.61%)

6/124 (4.84%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

2/124 (1.61%)

0/124 (0.00%)

# events

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

4/124 (3.23%)

5/124 (4.03%)

# events

Vascular disorders

Hypotension¹,^†

# participants affected / at risk

2/124 (1.61%)

3/124 (2.42%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

2/124 (1.61%)

0/124 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 26.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Sponsor terminated the study after review of FDA's request to halt further dosing (30Mar2023) and subjects were terminated prior to 1 year dose given that AZD7442 is not active against >99% of the currently circulating SARS-CoV-2 variants in the USA, the benefit risk assessment may not be favorable.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

redacted SAP
Download
redacted CSP
Download
redacted CRS Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

redacted SAP

redacted CSP

redacted CRS Synopsis

Trial Results Summaries