Study will assess the safety, neutralizing activity and efficacy of AZD3152 in adults with conditions increasing risk of inadequate protective immune response after vaccination and thus are at high risk of developing severe COVID-19 - NOVELLA

Study identifier:AZ-RU-00002

ClinicalTrials.gov identifier:NCT06057064

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase II Randomized, Double-blind Study to Evaluate the Safety, Neutralizing Activity and Efficacy of AZD3152 for Pre-exposure Prophylaxis of COVID-19 in Participants having an Increased Risk for Inadequate Response to Active Immunization (NOVELLA)

Medical condition

COVID-19, SARS-CoV-2

Phase

Phase 2

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

116

Study type

Interventional

Age

18 Years - 99 Years

Date

Study Start Date: 29 Sept 2023

Primary Completion Date: 17 May 2024

Study Completion Date: 17 May 2024

Study design

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

Verification:

Verified 01 Apr 2025 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Moscow, Russian Federation, 125284

Location

Research Site

St Petersburg, Russian Federation, 197341

Location

Research Site

Moscow, Russian Federation, 142770

Location

Research Site

Moscow, Russian Federation, 123182

Location

Research Site

Moscow, Russian Federation, 115522

Location

Research Site

Moscow, Russian Federation, 115478

Arms	Assigned Interventions
Placebo Comparator: Placebo Single dose of Placebo IM (0.9% sodium chloride)	Biological/Vaccine: Biological: Placebo Single dose of Placebo IM (0.9% sodium chloride)
Experimental: AZD3152 Single dose of 300 mg IM	Biological/Vaccine: Biological: AZD3152 300 mg single dose of AZD3152 IM

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
[Not Specified]

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
[Not Specified]

Reporting Groups

	Description
AZD3152	AZD3152 300 mg
Placebo	Saline Placebo

Participant Flow: Overall Study

	AZD3152	Placebo
STARTED	87	29
COMPLETED	83	28
NOT COMPLETED	4	1
Death	2	0
Physician Decision	1	0
Withdrawal by Subject	1	1

Baseline Characteristics

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

Reporting Groups

	Description
AZD3152	AZD3152 300 mg
Placebo	Saline Placebo

Baseline Measures

	AZD3152	Placebo	Total
Number of Participants [units: Participants]	87	29	116
Age Continuous [units: Years] Mean ± Standard Deviation	55.6 ± 12.61	58.2 ± 11.78	56.2 ± 12.41
Sex: Female, Male [units: Participants]
Female	44	17	61
Male	43	12	55
Race/Ethnicity, Customized [units: Participants]
Hispanic or Latino	0	0	0
Not Hispanic or Latino	83	28	111
Missing	4	1	5
Race/Ethnicity, Customized [units: Participants]
White	86	29	115
Asian	1	0	1
Other	0	0	0
Not Reported	0	0	0
Previous COVID-19 vaccinations [units: Participants]	56	13	69
SARS-CoV-2 status at baseline [units: Participants]
Negative	87	29	116
Positive	0	0	0
Missing	0	0	0
Any COVID-19 comorbidities at baseline [units: Participants]
Yes	87	29	116
Missing	0	0	0
Any high risk for severe COVID-19 [units: Participants]
Yes	87	29	116
Missing	0	0	0
Height [units: cm] Mean ± Standard Deviation	171.0 ± 9.39	170.7 ± 8.80	170.9 ± 9.21
Baseline BMI [units: kg/m*2] Mean ± Standard Deviation	28.7 ± 6.08	27.8 ± 5.30	28.5 ± 5.89
Age, Customized [units: Participants]
>= 18 to <60 years	52	15	67
>=60 years	35	14	49

Outcome Measures

1. Primary Outcome Measure: The number and proportion of subjects with AEs, SAEs, MAAEs, AESIs. [ Time Frame: up to Day 181 ]

Measure Type	Primary
Measure Name	The number and proportion of subjects with AEs, SAEs, MAAEs, AESIs.
Measure Description	The safety profile will be evaluated using vital signs, laboratory data, electrocardiograms (ECGs), and adverse event data
Time Frame	up to Day 181
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 population

Reporting Groups

	Description
AZD3152	AZD3152 300 mg
Placebo	Saline Placebo

Measured Values

	AZD3152	Placebo
Number of Participants Analyzed [units:participants]	87	29
The number and proportion of subjects with AEs, SAEs, MAAEs, AESIs. [units: Participants]
Adverse Events	45	17
Serious Adverse Events	5	2
Medically Attended Adverse Events	14	7
Adverse Events of Special Interest	0	0

No statistical analysis provided for The number and proportion of subjects with AEs, SAEs, MAAEs, AESIs.

2. Secondary Outcome Measure: Geometric mean titer (GMT) and geometric mean fold rise (GMFRs) [ Time Frame: up to Day 181 ]

Measure Type	Secondary
Measure Name	Geometric mean titer (GMT) and geometric mean fold rise (GMFRs)
Measure Description	NAbs response will be evaluated based on nAbs titer to the SARS-CoV-2 emerging dominant variant(s) circulating during the course of the study in RU local laboratory
Time Frame	up to Day 181
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.
SARS-CoV-2 nAb Set

Reporting Groups

	Description
AZD3152	AZD3152 300 mg
Placebo	Saline Placebo

Measured Values

	AZD3152	Placebo
Number of Participants Analyzed [units:participants]	87	29
Geometric mean titer (GMT) and geometric mean fold rise (GMFRs) [units: Serum dilution] Geometric Mean (Standard Deviation)
Baseline	12.0 (3.22)	9.8 (2.50)
Visit 2. Day 8 GMT	67.7 (2.02)	11.3 (2.76)
Visit 2. Day 8 GMFRs	5.63 (2.663)	1.16 (1.941)
Visit 3. Day 15 GMT	70.9 (1.96)	12.1 (2.89)
Visit 3. Day 15 GMFRs	5.84 (2.491)	1.24 (2.247)
Visit 4. Day 29 GMT	64.3 (2.05)	12.6 (2.67)
Visit 4. Day 29 GMFRs	4.71 (2.295)	1.33 (2.014)
Visit 5. Day 91 GMT	37.6 (2.24)	9.1 (2.25)
Visit 5. Day 91 GMFRs	2.81 (2.653)	1.10 (1.986)
Visit 6. Day 181 GMT	22.4 (2.71)	13.4 (2.76)
Visit 6. Day 181 GMFRs	1.71 (2.565)	1.55 (2.462)

No statistical analysis provided for Geometric mean titer (GMT) and geometric mean fold rise (GMFRs)

3. Secondary Outcome Measure: Incidence of a post-treatment symptomatic COVID-19 case [ Time Frame: up to Day 181 ]

Measure Type	Secondary
Measure Name	Incidence of a post-treatment symptomatic COVID-19 case
Measure Description	Incidence of a post-treatment symptomatic COVID-19 case (negative RT-PCR at baseline to positive RT-PCR or positive antigen test at any time up to 6 months AND symptoms specified in the modified WHO definition of symptomatic COVID-19).
Time Frame	up to Day 181
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.
Full analysis set

Reporting Groups

	Description
AZD3152	AZD3152 300 mg
Placebo	Saline Placebo

Measured Values

	AZD3152	Placebo
Number of Participants Analyzed [units:participants]	87	29
Incidence of a post-treatment symptomatic COVID-19 case [units: Participants]	4	2

No statistical analysis provided for Incidence of a post-treatment symptomatic COVID-19 case

Serious Adverse Events

Time Frame	AEs, MAAE, AESI will be collected from the time of study intervention administration throughout the study, up to and including the last visit. SAEs will be recorded from the time of signing of the ICF throughout the study, up to and including the last visit.
Additional Description	No text entered.

Reporting Groups

	Description
AZD3152	AZD3152 300 mg
Placebo	Saline Placebo

Serious Adverse Events

AZD3152

Placebo

Total, serious adverse events

# participants affected / at risk

5/87 (5.75%)

2/29 (6.90%)

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

2/87 (2.30%)

1/29 (3.45%)

# events

Infections and infestations

Bacteriuria¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Infections and infestations

COVID-19¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Infections and infestations

Necrotising ulcerative gingivostomatitis¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Injury, poisoning and procedural complications

Radius fracture¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

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

Malignant neoplasm progression¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 26.1
2	Term from vocabulary,

Other Adverse Events

Time Frame	AEs, MAAE, AESI will be collected from the time of study intervention administration throughout the study, up to and including the last visit. SAEs will be recorded from the time of signing of the ICF throughout the study, up to and including the last visit.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
AZD3152	AZD3152 300 mg
Placebo	Saline Placebo

Other Adverse Events

AZD3152

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

45/87 (51.72%)

17/29 (58.62%)

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

3/87 (3.45%)

0/29 (0.00%)

# events

Blood and lymphatic system disorders

Leukopenia¹,^†

# participants affected / at risk

2/87 (2.30%)

0/29 (0.00%)

# events

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

0/87 (0.00%)

2/29 (6.90%)

# events

Blood and lymphatic system disorders

Febrile neutropenia¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Blood and lymphatic system disorders

Neutrophilia¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Blood and lymphatic system disorders

Thrombocytosis¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Eye disorders

Dry eye¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Eye disorders

Presbyopia¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

1/87 (1.15%)

1/29 (3.45%)

# events

Gastrointestinal disorders

Gastritis¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Gastrointestinal disorders

Mouth ulceration¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Gastrointestinal disorders

Pancreatitis chronic¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

General disorders

Asthenia¹,^†

# participants affected / at risk

1/87 (1.15%)

1/29 (3.45%)

# events

General disorders

Chest pain¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

General disorders

Injection site haematoma¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Hepatobiliary disorders

Non-alcoholic steatohepatitis¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Immune system disorders

Allergy to animal¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Infections and infestations

Respiratory tract infection¹,^†

# participants affected / at risk

9/87 (10.34%)

1/29 (3.45%)

# events

Infections and infestations

COVID-19¹,^†

# participants affected / at risk

4/87 (4.60%)

2/29 (6.90%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

3/87 (3.45%)

3/29 (10.34%)

# events

Infections and infestations

Pharyngitis¹,^†

# participants affected / at risk

3/87 (3.45%)

1/29 (3.45%)

# events

Infections and infestations

Acute sinusitis¹,^†

# participants affected / at risk

3/87 (3.45%)

0/29 (0.00%)

# events

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

2/87 (2.30%)

1/29 (3.45%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

1/87 (1.15%)

2/29 (6.90%)

# events

Infections and infestations

Oral herpes¹,^†

# participants affected / at risk

3/87 (3.45%)

0/29 (0.00%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

2/87 (2.30%)

1/29 (3.45%)

# events

Infections and infestations

Rhinitis¹,^†

# participants affected / at risk

3/87 (3.45%)

0/29 (0.00%)

# events

Infections and infestations

Bacteriuria¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Infections and infestations

Conjunctivitis¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Infections and infestations

Cystitis¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Infections and infestations

Necrotising ulcerative gingivostomatitis¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Infections and infestations

Oral candidiasis¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Infections and infestations

Otosalpingitis¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Infections and infestations

Periodontitis¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Infections and infestations

Sinusitis¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Infections and infestations

Tracheitis¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Infections and infestations

Vaginal infection¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Infections and infestations

Varicella²,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Injury, poisoning and procedural complications

Radius fracture¹,^†

# participants affected / at risk

0/87 (0.00%)

2/29 (6.90%)

# events

Injury, poisoning and procedural complications

Ankle fracture¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Injury, poisoning and procedural complications

Concussion¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Injury, poisoning and procedural complications

Postoperative wound complication¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Investigations

Blood pressure increased¹,^†

# participants affected / at risk

0/87 (0.00%)

2/29 (6.90%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Investigations

Aspartate aminotransferase increased¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Investigations

Bilirubin conjugated increased¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Investigations

Blood bilirubin increased¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Investigations

Blood urea increased¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Investigations

Gamma-glutamyltransferase increased¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Metabolism and nutrition disorders

Hyperlipidaemia¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Metabolism and nutrition disorders

Hypomagnesaemia¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Back disorder¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Osteoarthritis¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Psoriatic arthropathy¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Musculoskeletal and connective tissue disorders

Spinal osteoarthritis¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

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

Malignant neoplasm progression¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

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

Pancreatic cystadenoma¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

2/87 (2.30%)

0/29 (0.00%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

1/87 (1.15%)

1/29 (3.45%)

# events

Nervous system disorders

Cerebrovascular disorder¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Nervous system disorders

Hypoaesthesia¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Renal and urinary disorders

Renal cyst¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Reproductive system and breast disorders

Prostatitis¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease¹,^†

# participants affected / at risk

1/87 (1.15%)

1/29 (3.45%)

# events

Respiratory, thoracic and mediastinal disorders

Asthma¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

2/87 (2.30%)

0/29 (0.00%)

# events

Vascular disorders

Brachiocephalic arteriosclerosis¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Vascular disorders

Haematoma¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Vascular disorders

Hypertensive crisis¹,^†

# participants affected / at risk

0/87 (0.00%)

1/29 (3.45%)

# events

Vascular disorders

Hypotension¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

Vascular disorders

Pelvic venous thrombosis¹,^†

# participants affected / at risk

1/87 (1.15%)

0/29 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 26.1
2	Term from vocabulary, MedDRA
3	Term from vocabulary,

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

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
[Not Specified]

Results Point of Contact

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

Documents available

Redacted CSP
Download
Redacted CSR Synopsis
Download
Redacted SAP
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

Redacted CSP

Redacted CSR Synopsis

Redacted SAP

Trial Results Summaries