Clinical trial NCT04625725: Phase III Double-blind, Placebo-controlled Study of AZD7442 for Pre-exposure Prophylaxis of COVID-19 in Adult.
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Keywords: Pre-exposure Prophylaxis of COVID-19
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Iqvia Pty Ltd
First posted: 2020-11-12
Enrollment: 5197
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With First Case of SARS-CoV-2 RT-PCR-positive Symptomatic Illness
timeFrame: 165 Days for primary analysis, 183 days for final analysis
measure: AEs, SAEs, MAAEs, and AESIs Post Dose of IMP
timeFrame: 457 Days, Final analysis
Secondary outcomes:
measure: 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.
timeFrame: 366 days
measure: The Incidence of SARS-CoV-2 RT-PCR-positive Severe or Critical Symptomatic Illness Occurring After Dosing With IMP
timeFrame: 366 Days
measure: The Incidence of COVID-19-related Emergency Department Visits Occurring After Dosing With IMP
timeFrame: 366 days
measure: Serum AZD7442 Concentrations, PK Parameters if Data Permit.
timeFrame: 457 days
measure: Incidence of ADA to AZD7442 in Serum
timeFrame: 457 days
Other outcomes:
measure: AEs, SAEs, MAAEs, and AESIs Post Dose of IMP at Time of Primary Efficacy Analysis
timeFrame: 165 Days
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Tempe
country: United States
facility: Research Site
state: Arizona
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Cerritos
country: United States
facility: Research Site
state: California
city: Fresno
country: United States
facility: Research Site
state: California
city: Garden Grove
country: United States
facility: Research Site
state: California
city: Huntington Beach
country: United States
facility: Research Site
state: California
city: Lancaster
country: United States
facility: Research Site
state: California
city: Modesto
country: United States
facility: Research Site
state: California
city: Victorville
country: United States
facility: Research Site
state: California
city: Westminster
country: United States
facility: Research Site
state: California
city: Hartford
country: United States
facility: Research Site
state: Connecticut
city: Middlebury
country: United States
facility: Research Site
state: Connecticut
city: Clearwater
country: United States
facility: Research Site
state: Florida
city: Coral Springs
country: United States
facility: Research Site
state: Florida
city: Hollywood
country: United States
facility: Research Site
state: Florida
city: Lauderdale Lakes
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Ormond Beach
country: United States
facility: Research Site
state: Florida
city: Pompano Beach
country: United States
facility: Research Site
state: Florida
city: Wesley Chapel
country: United States
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state: Florida
city: West Palm Beach
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Columbus
country: United States
facility: Research Site
state: Georgia
city: Conyers
country: United States
facility: Research Site
state: Georgia
city: Marietta
country: United States
facility: Research Site
state: Georgia
city: Honolulu
country: United States
facility: Research Site
state: Hawaii
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Hazel Crest
country: United States
facility: Research Site
state: Illinois
city: Quincy
country: United States
facility: Research Site
state: Illinois
city: Evansville
country: United States
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state: Indiana
city: Noblesville
country: United States
facility: Research Site
state: Indiana
city: Wichita
country: United States
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state: Kansas
city: Wichita
country: United States
facility: Research Site
state: Kansas
city: Minneapolis
country: United States
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state: Minnesota
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Omaha
country: United States
facility: Research Site
state: Nebraska
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Bronx
country: United States
facility: Research Site
state: New York
city: Jamaica
country: United States
facility: Research Site
state: New York
city: Ridgewood
country: United States
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state: New York
city: Greensboro
country: United States
facility: Research Site
state: North Carolina
city: Columbus
country: United States
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state: Ohio
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Summerville
country: United States
facility: Research Site
state: South Carolina
city: Rapid City
country: United States
facility: Research Site
state: South Dakota
city: Austin
country: United States
facility: Research Site
state: Texas
city: El Paso
country: United States
facility: Research Site
state: Texas
city: El Paso
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Shenandoah
country: United States
facility: Research Site
state: Texas
city: Sugar Land
country: United States
facility: Research Site
state: Texas
city: Layton
country: United States
facility: Research Site
state: Utah
city: Alexandria
country: United States
facility: Research Site
state: Virginia
city: Chesapeake
country: United States
facility: Research Site
state: Virginia
city: Tacoma
country: United States
facility: Research Site
state: Washington
city: Alken
country: Belgium
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Gozée
country: Belgium
facility: Research Site
city: Namur
country: Belgium
facility: Research Site
city: Wetteren
country: Belgium
facility: Research Site
city: Clermont-Ferrand cedex
country: France
facility: Research Site
city: Dijon cedex
country: France
facility: Research Site
city: La Roche S/ Yon Cedex 9
country: France
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Limoges cedex
country: France
facility: Research Site
city: Nantes Cedex 1
country: France
facility: Research Site
city: Paris cedex 10
country: France
facility: Research Site
city: Paris cedex 14
country: France
facility: Research Site
city: Saint Etienne Cedex 2
country: France
facility: Research Site
city: Tours cedex 9
country: France
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Marbella (Málaga)
country: Spain
facility: Research Site
city: Pozuelo de Alarcón
country: Spain
facility: Research Site
city: Bournemouth
country: United Kingdom
facility: Research Site
city: Enfield
country: United Kingdom
facility: Research Site
city: Hayle
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Preston
country: United Kingdom
facility: Research Site
city: Rochdale
country: United Kingdom
facility: Research Site
city: Salford
country: United Kingdom
facility: Research Site
city: Torpoint
country: United Kingdom
facility: Research Site
city: Wakefield
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Myron Levin, MD
role: PRINCIPAL_INVESTIGATOR
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