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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04625725
Recruitment Status : Active, not recruiting
First Posted : November 12, 2020
Last Update Posted : February 3, 2022
Sponsor:
Collaborator:
Iqvia Pty Ltd
Information provided by (Responsible Party):
AstraZeneca

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.

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Study Type : Interventional  (Clinical Trial)
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 : November 21, 2020
Actual Primary Completion Date : May 5, 2021
Estimated Study Completion Date : November 30, 2023

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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 Name: Combination of 2mAbs(AZD8895 and AZD1061)




Primary Outcome Measures :
  1. The incidence of the first case of SARS CoV-2 RT PCR positive symptomatic illness [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04625725


Locations
Show Show 86 study locations
Sponsors and Collaborators
AstraZeneca
Iqvia Pty Ltd
Investigators
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Principal Investigator: Myron Levin, MD AstraZeneca
Publications:
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.
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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04625725    
Other Study ID Numbers: D8850C00002
First Posted: November 12, 2020    Key Record Dates
Last Update Posted: February 3, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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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:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases