PROVENT: Phase III Double-blind, Placebo-controlled Study of AZD7442 for Pre-exposure Prophylaxis of COVID-19 in Adult.

• Sponsor: AstraZeneca (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04625725
• Collaborator: Iqvia Pty Ltd (Industry)
• Enrollment: 5,197
• Locations: 86
• Arms: 4
• Anticipated Duration (Months): 36.3
• Patients Per Site: 60.4
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

This study will assess the safety and efficacy of a single dose of AZD7442(× 2 IM injections) compared to placebo for the prevention of COVID-19.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: AZD7442; Drug: Placebo	Phase 3

Detailed Description

SARS-CoV-2 is the causative agent of the ongoing COVID-19 pandemic that, as of 29 September 2020, has resulted in a high death toll to date. Unlike the majority of coronaviruses that cause mild disease in humans and animals, SARS-CoV-2 can replicate in the lower respiratory tract to cause acute respiratory distress syndrome and fatal pneumonia. Effective interventions to prevent or treat COVID-19 remain limited in number and clinical experience is limited. Clinical management is limited to supportive care, consequently overwhelming resources of healthcare systems around the world. As a response to the ongoing pandemic, AstraZeneca is developing mAbs to the SARS-CoV-2 S protein. The SARS-CoV-2 spike protein contains the virus's RBD, which enables the virus to bind to receptors on human cells. By targeting this region of the virus's spike protein, antibodies can block the virus's attachment to human cells, and, therefore, is expected to block infection. Amino acid substitutions have been introduced into the antibodies to both extend their half-lives, which should prolong their potential prophylactic benefit, and decrease Fc effector function in order to decrease the potential risk of antibody-dependent enhancement of disease. AZD7442, a combination of 2 of these mAbs (AZD8895 and AZD1061), is being evaluated for administration to prevent and/or treat COVID-19. There is currently one completed and 2 ongoing Phase I studies with AZD7442.

-The Provent repeat dose open-label sub-study is initiated to assess the safety, PK and immunogenicity of repeat doses of AZD7442 in participants currently enrolled in the Provent study who may benefit from repeat dose of AZD7442.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5197 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase III Randomized, Double-blind, Placebo-controlled, Multi-center Study in Adults to Determine the Safety and Efficacy of AZD7442, a Combination Product of Two Monoclonal Antibodies (AZD8895 and AZD1061), for Pre-exposure Prophylaxis of COVID-19.
• Actual Study Start Date: Nov 21, 2020
• Actual Primary Completion Date: May 5, 2021
• Anticipated Study Completion Date: Nov 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZD7442 Approximately 5150 participants will be randomized in a 2:1 ratio • Arm 1 (n=approximately 3433) will receive a single dose (× 2IM injections) of 300 mg of AZD7442	Drug: AZD7442; Single dose (× 2IM injections) of 300 mg of AZD7442 on parent study Day 1. Single dose (× 2IM injections) of 300 mg of AZD7442 on sub-study Day 1. Single dose (× 2IM injections) of 300 mg of AZD7442 on sub-study Day 183.; Other Names: Combination of 2mAbs(AZD8895 and AZD1061)
Placebo Comparator: Placebo Approximately 5150 participants will be randomized in a 2:1 ratio • Arm 2 (n=approximately 1717) will receive saline placebo	Drug: Placebo; Single dose (× 2IM injections) of saline placebo on parent study Day 1.
Experimental: Sub-study AZD7442 Arm 1 Approximately 500 participants will receive AZD7442 in the repeat dose sub-study. -Sub-study Arm 1 (~ 12 month repeat dose interval): Participants who received AZD7442 300 mg IM on Day 1 of the parent study will receive a second dose of AZD7442 300mg IM on sub-study Day 1.	Drug: AZD7442; Single dose (× 2IM injections) of 300 mg of AZD7442 on parent study Day 1. Single dose (× 2IM injections) of 300 mg of AZD7442 on sub-study Day 1. Single dose (× 2IM injections) of 300 mg of AZD7442 on sub-study Day 183.; Other Names: Combination of 2mAbs(AZD8895 and AZD1061)
Experimental: Sub-study AZD7442 Arm 2 Approximately 500 participants will receive AZD7442 in the repeat dose sub-study. -Sub-study Arm 2(~ 6 month repeat dose interval): Participants who received placebo on Day 1 of the parent study will receive their first dose of AZD7442 300mg IM on sub-study Day1 followed by a second dose on sub-study Day 183.	Drug: AZD7442; Single dose (× 2IM injections) of 300 mg of AZD7442 on parent study Day 1. Single dose (× 2IM injections) of 300 mg of AZD7442 on sub-study Day 1. Single dose (× 2IM injections) of 300 mg of AZD7442 on sub-study Day 183.; Other Names: Combination of 2mAbs(AZD8895 and AZD1061)

Outcome Measures

Primary Outcome Measures

1. The incidence of the first case of SARS CoV-2 RT PCR positive symptomatic illness [Day 183]

   To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of COVID-19 prior to Day 183

2. AEs, SAEs, MAAEs, and AESIs post dose of IMP [Day 457]

   To assess the safety and tolerability of a single IM dose of AZD7442 compared to placebo

Secondary Outcome Measures

1. The incidence of participants who have a post-treatment response (negative at baseline to positive at any time post-baseline) for SARS-CoV-2 nucleocapsid antibodies. [1 year]

   To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of SARS-CoV-2 infection

2. The incidence of SARS-CoV-2 RT-PCR-positive severe or critical symptomatic illness occurring after dosing with IMP [1 year]

   To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of severe or critical symptomatic COVID-19

3. The incidence of COVID-19-related Emergency Department visits occurring after dosing with IMP [1 year]

   To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of COVID-19-related Emergency Department visits

4. Serum AZD7442 concentrations, PK parameters if data permit. [Day 457]

   To assess the pharmacokinetics of AZD7442 administered as a single dose of 300 mg IM

5. Incidence of ADA to AZD7442 in serum. [Day 457]

   To evaluate ADA responses to AZD7442 in serum

Other Outcome Measures

1. Sub-study Primary Endpoint: AEs, SAEs, MAAEs and AESIs post repeat dose of IMP. [Day 457 for Group 1 and Day 639 for Group 2]

   To evaluate the safety and tolerability of repeat doses of AZD7442 300 mg IM.

2. Sub-study Secondary Endpoint: Serum AZD7442 concentrations after repeat dosing PK parameters if data permit after repeat dosing. [Day 457 for Group 1 and Day 639 for Group 2]

   To evaluate the PK of repeat doses of AZD7442 300 mg IM

3. Sub-study Secondary Endpoint: Incidence of ADA to repeat doses of AZD7442 in serum [Day 457 for Group 1 and Day 639 for Group 2]

   To evaluate ADA responses to repeat doses of AZD7442 300 mg IM in serum

4. Sub-study Secondary Endpoint: Post dose GMTs and GMFRs from baseline values after a repeat IM dose in SARS-CoV-2 nAbs (wild-type assay or pseudo-neutralization assay) [Day 457 for Group 1 and Day 639 for Group 2]

   To determine anti-SARS-CoV-2 nAb level in serum following repeat doses of AZD7442 300mg IM.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. ≥ 18 years of age at the time of signing the informed consent

2. Can benefit from passive immunization with antibodies

3. Medically stable

4. Negative result from point of care SARS-CoV-2 serology testing at screening

5. Contraceptive used by women of child bearing potential, condom used by men

6. Able to understand and comply with study requirements/procedures based on the assessment of the investigator

Sub-study Inclusion criteria which are additional to those in parent study are as follows:

• The participant has been randomized, dosed, and is ongoing in the PROVENT parent study and is 12±2 months post first dose of blinded IMP.

• If one or more of the following apply:

1. Immunocompromised and/or may be at increased risk for an inadequate immune response to a COVID-19 vaccine.

2. In the opinion of the Investigator, are at increased risk and would benefit from a repeat dose of AZD7442.

• Documented negative SARS-CoV-2 RT-PCR test collected ≤ 3 days prior to sub-study Day 1 or a negative rapid SARS-CoV-2 antigen test at screening.

Exclusion Criteria:

1. Significant infection or other acute illness, including fever >100°F (>37.8°C) on the day prior to or day of randomization.

2. History of laboratory-confirmed SARS-CoV-2 infection or any positive SARS-CoV-2 result based on available data at screening.

3. History of infection with severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS).

4. Known history of allergy or reaction to any component of the study drug formulation.

5. Previous hypersensitivity, infusion-related reaction, or severe adverse reaction following administration of a mAb.

6. Any prior receipt of investigational or licensed vaccine or other mAb/biologic indicated for the prevention of SARS-CoV-2 or COVID-19 or expected receipt during the period of study follow-up.

7. Bleeding disorder or prior history of significant bleeding or bruising following IM injections or venepuncture.

8. 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.

9. 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

10. Currently pregnant or breastfeeding.

11. Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 30 days prior to randomization.

12. 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.

13. 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.

Sub-study Exclusion criteria are as follows:

1. Patient have received a COVID-19 vaccination ≤ 14 days before sub-study Day1 or plan to receive a COVID-19 vaccination ≤ 14 days after sub-study Day1. (Such participants can subsequently be included in the study once they have reached >14 days after their last dose of vaccine).

2. Patient have two or more untreated cardiac risk factors or suspected unstable cardiac disease.

3. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35215
2	Research Site	Tempe	Arizona	United States	85284
3	Research Site	Little Rock	Arkansas	United States	72205
4	Research Site	Cerritos	California	United States	90703
5	Research Site	Fresno	California	United States	93720
6	Research Site	Garden Grove	California	United States	92844
7	Research Site	Huntington Beach	California	United States	92647
8	Research Site	Lancaster	California	United States	93534
9	Research Site	Modesto	California	United States	95350
10	Research Site	Victorville	California	United States	92394
11	Research Site	Westminster	California	United States	92683
12	Research Site	Hartford	Connecticut	United States	06112
13	Research Site	Middlebury	Connecticut	United States	06762
14	Research Site	Clearwater	Florida	United States	33756
15	Research Site	Coral Springs	Florida	United States	33071
16	Research Site	Hollywood	Florida	United States	33024
17	Research Site	Lauderdale Lakes	Florida	United States	33313
18	Research Site	Miami	Florida	United States	33125
19	Research Site	Ormond Beach	Florida	United States	32174
20	Research Site	Pompano Beach	Florida	United States	33064
21	Research Site	Wesley Chapel	Florida	United States	33545
22	Research Site	West Palm Beach	Florida	United States	33409
23	Research Site	Atlanta	Georgia	United States	30328
24	Research Site	Columbus	Georgia	United States	31904
25	Research Site	Conyers	Georgia	United States	30094
26	Research Site	Chicago	Illinois	United States	60607
27	Research Site	Hazel Crest	Illinois	United States	60429
28	Research Site	Quincy	Illinois	United States	62301
29	Research Site	Evansville	Indiana	United States	47714
30	Research Site	Noblesville	Indiana	United States	46060
31	Research Site	Wichita	Kansas	United States	67205
32	Research Site	Wichita	Kansas	United States	67214
33	Research Site	Minneapolis	Minnesota	United States	55404
34	Research Site	Minneapolis	Minnesota	United States	55435
35	Research Site	Saint Louis	Missouri	United States	63141
36	Research Site	Omaha	Nebraska	United States	68134
37	Research Site	Las Vegas	Nevada	United States	89128
38	Research Site	Albuquerque	New Mexico	United States	87109
39	Research Site	Bronx	New York	United States	10461
40	Research Site	Jamaica	New York	United States	11432
41	Research Site	Ridgewood	New York	United States	11385
42	Research Site	Greensboro	North Carolina	United States	27410
43	Research Site	Columbus	Ohio	United States	43213
44	Research Site	Oklahoma City	Oklahoma	United States	73104
45	Research Site	Summerville	South Carolina	United States	29485
46	Research Site	Rapid City	South Dakota	United States	57701
47	Research Site	Austin	Texas	United States	78751
48	Research Site	El Paso	Texas	United States	79925
49	Research Site	El Paso	Texas	United States	79935
50	Research Site	Houston	Texas	United States	77054
51	Research Site	San Antonio	Texas	United States	78215
52	Research Site	San Antonio	Texas	United States	78251
53	Research Site	Shenandoah	Texas	United States	77384
54	Research Site	Sugar Land	Texas	United States	77479
55	Research Site	Layton	Utah	United States	84041
56	Research Site	Alexandria	Virginia	United States	22304
57	Research Site	Chesapeake	Virginia	United States	23320
58	Research Site	Alken		Belgium	3570
59	Research Site	Bruxelles		Belgium	1000
60	Research Site	Gozée		Belgium	6534
61	Research Site	Namur		Belgium	5101
62	Research Site	Wetteren		Belgium	9230
63	Research Site	Clermont-Ferrand cedex		France	63003
64	Research Site	Dijon cedex		France	21079
65	Research Site	La Roche S/ Yon Cedex 9		France	85925
66	Research Site	Lille		France	59037
67	Research Site	Limoges cedex		France	87000
68	Research Site	Nantes Cedex 1		France	44093
69	Research Site	Paris cedex 10		France	75475
70	Research Site	Paris cedex 14		France	75679
71	Research Site	Saint Etienne Cedex 2		France	42055
72	Research Site	Tours cedex 9		France	37044
73	Research Site	Barcelona		Spain	08036
74	Research Site	Madrid		Spain	28034
75	Research Site	Madrid		Spain	28040
76	Research Site	Marbella (Málaga)		Spain	29603
77	Research Site	Pozuelo de Alarcón		Spain	28223
78	Research Site	Bournemouth		United Kingdom	BH7 7DW
79	Research Site	Enfield		United Kingdom	EN3 4GS
80	Research Site	Hayle		United Kingdom	TR27 5DT
81	Research Site	London		United Kingdom	WC1N 3BG
82	Research Site	Preston		United Kingdom	PR1 6YA
83	Research Site	Rochdale		United Kingdom	OL11 4AU
84	Research Site	Salford		United Kingdom	M6 8HD
85	Research Site	Torpoint		United Kingdom	PL11 2TB
86	Research Site	Wakefield		United Kingdom	WF1 5RH

Sponsors and Collaborators

• AstraZeneca
• Iqvia Pty Ltd

Investigators

• Principal Investigator: Myron Levin, MD, AstraZeneca

Study Documents (Full-Text)

None provided.

More Information

Publications

• Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeño J, Faivre-Finn C, Reck M, Vansteenkiste J, Spigel DR, Wadsworth C, Melillo G, Taboada M, Dennis PA, Özgüroğlu M; PACIFIC Investigators. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med. 2018 Dec 13;379(24):2342-2350. doi: 10.1056/NEJMoa1809697. Epub 2018 Sep 25.
• CDC. (Centers for Disease Control and Prevention). Coronavirus Disease 2019 (COVID-19), Symptoms of Coronavrus. https://www.cdc.gov/coronavirus/2019-ncov/symptomstesting/symptoms.html. Published 2020. Accessed 01 July 2020.
• Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol. 2020 Apr;5(4):536-544. doi: 10.1038/s41564-020-0695-z. Epub 2020 Mar 2.
• Domachowske JB, Khan AA, Esser MT, Jensen K, Takas T, Villafana T, Dubovsky F, Griffin MP. Safety, Tolerability and Pharmacokinetics of MEDI8897, an Extended Half-life Single-dose Respiratory Syncytial Virus Prefusion F-targeting Monoclonal Antibody Administered as a Single Dose to Healthy Preterm Infants. Pediatr Infect Dis J. 2018 Sep;37(9):886-892. doi: 10.1097/INF.0000000000001916.
• Furer V, Rondaan C, Heijstek MW, Agmon-Levin N, van Assen S, Bijl M, Breedveld FC, D'Amelio R, Dougados M, Kapetanovic MC, van Laar JM, de Thurah A, Landewé RB, Molto A, Müller-Ladner U, Schreiber K, Smolar L, Walker J, Warnatz K, Wulffraat NM, Elkayam O. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2020 Jan;79(1):39-52. doi: 10.1136/annrheumdis-2019-215882. Epub 2019 Aug 14.
• Griffin MP, Khan AA, Esser MT, Jensen K, Takas T, Kankam MK, Villafana T, Dubovsky F. Safety, Tolerability, and Pharmacokinetics of MEDI8897, the Respiratory Syncytial Virus Prefusion F-Targeting Monoclonal Antibody with an Extended Half-Life, in Healthy Adults. Antimicrob Agents Chemother. 2017 Feb 23;61(3). pii: e01714-16. doi: 10.1128/AAC.01714-16. Print 2017 Mar.
• Griffin MP, Yuan Y, Takas T, Domachowske JB, Madhi SA, Manzoni P, Simões EAF, Esser MT, Khan AA, Dubovsky F, Villafana T, DeVincenzo JP; Nirsevimab Study Group. Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants. N Engl J Med. 2020 Jul 30;383(5):415-425. doi: 10.1056/NEJMoa1913556. Erratum in: N Engl J Med. 2020 Aug 13;383(7):698.
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• Wagner A, Weinberger B. Vaccines to Prevent Infectious Diseases in the Older Population: Immunological Challenges and Future Perspectives. Front Immunol. 2020 Apr 23;11:717. doi: 10.3389/fimmu.2020.00717. eCollection 2020. Review.
• WHO. WHO Coronavirus Disease (COVID-19) Dashboard. 2020a.
• WHO. WHO R&D Blueprint COVID-19 Therapeutic Trial Synopsis Draft 18 February 2020. https://www.who.int/blueprint/priority-diseases/key-action/COVID19_Treatment_Trial_Design_Master_Protocol_synopsis_Final_18022020.pdf. Published 2020b. Accessed 25 September 2020.
• Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar;579(7798):270-273. doi: 10.1038/s41586-020-2012-7. Epub 2020 Feb 3.
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• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT04625725
• Other Study ID Numbers: D8850C00002
• First Posted: Nov 12, 2020
• Last Update Posted: Feb 3, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by AstraZeneca: Pre-exposure Prophylaxis of COVID-19
• Additional relevant MeSH terms: COVID-19

Study Results

No Results Posted as of Feb 3, 2022