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Phase III Study of AZD7442 for Treatment of COVID-19 in Outpatient Adults (TACKLE)

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: NCT04723394
Recruitment Status : Active, not recruiting
First Posted : January 25, 2021
Last Update Posted : September 20, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
This Phase III study will assess whether AZD7442 (a combination of 2 mAbs) can safely treat outpatient adults with COVID-19 and prevent either severe COVID-19 or death.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: AZD7442 Drug: Placebo Phase 3

Detailed Description:

A novel coronavirus, SARS-CoV-2, first emerged in China in November 2019 causing cases of atypical pneumonia. As of 6 October 2020, the virus has spread to all corners of the globe, with over 35 million confirmed cases reported and more than one million associated deaths according to the WHO. The COVID-19 pandemic is causing major disruption to global healthcare systems with significant socioeconomic impacts. Effective interventions to prevent or treat COVID-19 remain few in number and clinical experience is limited.

There is an urgent need to rapidly evaluate treatments in the non-hospitalized setting to prevent progression and reduce serious complications of COVID-19, as well as its transmission.

As a response to the ongoing pandemic, AstraZeneca is developing mAbs to the SARS-CoV-2 spike 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 treat or prevent COVID-19. There are currently one ongoing Phase I study and two ongoing Phase III studies with AZD7442, in addition to this treatment study.

Enrollment of up to approximately 1700 participants is planned.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 910 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III Randomized, Double-blind, Placebo-controlled, Multicenter Study to Determine the Safety and Efficacy of AZD7442 for the Treatment of COVID-19 in Non-hospitalized Adults
Actual Study Start Date : January 28, 2021
Actual Primary Completion Date : August 21, 2021
Estimated Study Completion Date : October 21, 2022

Arm Intervention/treatment
Experimental: AZD7442
Up to approximately 1700 participants will be randomized in a 1:1 ratio. Arm 1 (n=up to approximately 850) will receive a single dose (× 2 IM injections) of 600 mg of AZD7442.
Drug: AZD7442
Single dose (× 2 separate IM injections) of 600 mg of AZD7442 or saline placebo on Day 1.
Other Name: Combination of 2 mAbs (AZD8895 and AZD1061)

Placebo Comparator: Placebo
Up to approximately 1700 participants will be randomized in a 1:1 ratio. Arm 2 (n=up to approximately 850) will receive saline placebo.
Drug: Placebo
Single dose (× 2 separate IM injections) of 600 mg of AZD7442 or saline placebo on Day 1.




Primary Outcome Measures :
  1. A composite of either severe COVID-19 or death from any cause through Day 29. [ Time Frame: Through Day 29 ]
    To estimate the efficacy of AZD7442 in the prevention of the composite endpoint of either severe COVID-19 or death from any cause through study Day 29.

  2. AEs, SAEs, and AESIs through end of study. [ Time Frame: Through Day 457 ]
    To evaluate safety and tolerability of a single IM dose of AZD7442 compared to placebo.


Secondary Outcome Measures :
  1. A composite of either death from any cause or hospitalization for COVID-19 complications or sequelae during the 168-day post-dose period (Day 1 to Day 169). [ Time Frame: Day 1 to Day 169 ]
    To estimate the efficacy of AZD7442 in the prevention of the composite endpoint of either death or hospitalization for COVID-19 complications or sequelae through Day 169.

  2. The incidence of participants with respiratory failure, defined as requirement for mechanical ventilation, ECMO, non-invasive ventilation, or high-flow nasal cannula oxygen delivery. [ Time Frame: Through Day 29 ]
    To determine if AZD7442 will prevent respiratory failure through study Day 29.

  3. COVID-19 symptom severity assessments based on symptom severity scores over time during the 28-day period from and including the day of the dose of AZD7442 or placebo. [ Time Frame: Through Day 29 ]
    To determine whether AZD7442 reduces participants' severity of participant-reported COVID-19 symptoms through Day 29.

  4. Progression through Day 29 of one or more COVID-19-associated symptoms to a worse status than recorded in the participant-reported symptom diary at study entry, prior to start of AZD7442 or placebo. [ Time Frame: Through Day 29 ]
    To determine if AZD7442 reduces the progression of participant-reported COVID-19-associated symptoms through Day 29.

  5. Detection (detectable versus undetectable) from baseline of SARS-CoV-2 RNA from nasal swabs through Day 29. [ Time Frame: Through Day 29 ]
    To determine if AZD7442 reduces detection or levels of SARS-CoV-2 RNA in nasal swabs through Day 29.

  6. Level of SARS-CoV-2 RNA from nasal swabs through Day 29. [ Time Frame: Through Day 29 ]
    To determine if AZD7442 reduces levels of SARS-CoV-2 RNA in nasal swabs through Day 29.

  7. Change from baseline of SARS-CoV-2 RNA from nasal swabs through Day 29. [ Time Frame: Through Day 29 ]
    To determine if AZD7442 reduces levels of SARS-CoV-2 RNA in nasal swabs compared to baseline through Day 29.

  8. Time to return to usual (pre-COVID-19) health through Day 29. [ Time Frame: Through Day 29 ]
    To evaluate differences in symptom duration between the AZD7442 and placebo treatment groups through Day 29.

  9. Duration of fever through Day 29 defined as the last day in the participant-reported symptom diary on which a temperature greater than 100°F (37.8° C) was recorded or a potentially antipyretic drug, such as acetaminophen or ibuprofen, was taken. [ Time Frame: Through Day 29 ]
    To evaluate differences in symptom duration between the AZD7442 and placebo treatment groups through Day 29.

  10. Incidence of ADA to AZD7442 in serum over time. [ Time Frame: Through Day 457 ]
    To evaluate the ADA responses to AZD7442 in serum.

  11. Pharmacokinetics - Serum Concentration [ Time Frame: Through Day 457 ]
    To evaluate the single-dose PK of AZD7442.

  12. Pharmacokinetics - Maximum Serum Concentration [ Time Frame: Through Day 457 ]
    To evaluate the single-dose PK of AZD7442.

  13. Pharmacokinetics - Time to Maximum Serum Concentration [ Time Frame: Through Day 457 ]
    To evaluate the single-dose PK of AZD7442.

  14. Pharmacokinetics - Area under the plasma concentration-time curve to the last measurable time point [ Time Frame: Through Day 457 ]
    To evaluate the single-dose PK of AZD7442.

  15. Pharmacokinetics - Area under the plasma concentration-time curve extrapolated to infinity [ Time Frame: Through Day 457 ]
    To evaluate the single-dose PK of AZD7442.



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 and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Participant has a documented laboratory-confirmed SARS-CoV-2 infection, as determined by a molecular test (antigen or nucleic acid) from any respiratory tract specimen (eg, oropharyngeal, NP, or nasal swab, or saliva) collected ≤ 3 days prior to Day 1.
  2. WHO Clinical Progression Scale score > 1 and < 4.
  3. Participant must be dosed with IMP no more than 7 days from self-reported onset of COVID-19-related symptoms (mild to moderate COVID-19) or measured fever, defined as the self-reported date of first reported sign/symptom.
  4. One or more of the following signs/symptoms must be present within 24 hours prior to Day1: Cough, Sore throat, Shortness of breath or difficulty breathing at rest or with activity, Body pain or muscle pain/aches, Fatigue, Headache, Chills, Nasal obstruction or congestion, Nasal discharge, Nausea or vomiting, Diarrhea, New loss of taste or smell.
  5. Oxygenation saturation of ≥ 92% obtained at rest by study staff within 24 hours prior to Day 1 (unless participant regularly receives chronic supplementary oxygen for an underlying lung condition).
  6. Participant agrees not to participate in another clinical trial for the treatment of COVID-19 or SARS-CoV-2 during the study period until reaching hospitalization or 28 days after entry into the study (whichever is earliest).
  7. Participant must be ≥ 18 years of age, provide informed consent and is able to comply with study requirements/procedures.
  8. Male participants: Contraception for male participants is not required; however, to avoid the transfer of any fluids, all male participants must use a condom from Day 1 and agree to continue through 90 days following administration of IMP.
  9. Women of childbearing potential must use one highly effective form of birth control.

Exclusion Criteria:

  1. History or current hospitalization for COVID-19.
  2. Current need for hospitalization/immediate medical attention in a clinic/emergency room service
  3. Previous hypersensitivity, infusion related reaction, or adverse reaction to any monoclonal antibodies or known allergy to components of the IMP or placebo.
  4. Receipt of any investigational or licensed vaccine for prevention of COVID-19 at any time prior to entry into this study or expected administration immediately after enrollment.
  5. Current requirement or anticipated impending need for mechanical ventilation.
  6. Any significant disease, disorder or finding that may increase risk to the participant that might affect his/her ability to participate in this study.
  7. Received convalescent COVID-19 plasma treatment any time prior to entry into this study.
  8. Receipt of systemic steroids (e.g., prednisone, dexamethasone) or inhaled steroids within 30 days prior to study entry, unless a stable dose is used for a chronic condition.
  9. Receipt of any IMP in the previous 90 days or 5 half lives (whichever is longer), or expected receipt of IMP during the study follow-up period, or concurrent participation in another interventional study.
  10. Pregnant or breastfeeding women.

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): NCT04723394


Locations
Show Show 116 study locations
Sponsors and Collaborators
AstraZeneca
Publications:
Ashraf-Kashani and Kumar 2017 Ashraf-Kashani N, Kumar R. High-flow nasal oxygen therapy. BJA Education. 2017;17:57-62.
Gou and Xi 2019 Gou J, Xi D. Hierarchical testing of a primary and a secondary endpoint in a group sequential design with different information times. Statistics in Biopharmaceutical Research. 2019;11(4):398-406, DOI: 10.1080/19466315.2018.1546613.
ICMRA 2020 International Coalition of Medicines Regulatory Authorities. Global regulatory workshop on COVID-19 therapeutics: agreement on acceptable endpoints for clinical trials. Published online July 2020. Retrieved from http://icmra.info/drupal/news/20july2020/summary
Sharma et al 2020 Sharma S, Danckers M, Sanghavi D, Chakraborty RK. High Flow Nasal Cannula. 2020 Jul 2. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. PMID: 30252327.
WHO 2020 WHO COVID-19 Dashboard. Available from: https://covid19.who.int
CDC, 2021 CDC, Investigating the Impact of COVID-19 during Pregnancy, available from https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/special-populations/pregnancy-data-on-covid-19/what-cdc-is-doing.html
CDC, Growth Charts CDC, Growth Charts, available from https://www.cdc.gov/growthcharts/clinical_charts.htm
Lilly BLAZE-1 2021 Lilly. Lilly's bamlanivimab and etesevimab together reduced hospitalizations and death in Phase 3 trial for early COVID-19. Published online 10 March 2021. Accessed 31 March 2021. https://investor.lilly.com/news-releases/news-release-details/lillys-bamlanivimab-and-etesevimab-together-reduced
Regeneron Pharmaceuticals, Inc. REGEN-COV Outpatient Trial 2021 Regeneron Pharmaceuticals, Inc. Phase 3 trial shows Regen-Cov™ (casirivimab with imdevimab) antibody cocktail reduced hospitalization or death by 70% in non-hospitalized Covid-19 patients. Published online 23 March 2021. Accessed 31 March 2021. https://investor.regeneron.com/news-releases/news-release-details/phase-3-trial-shows-regen-covtm-casirivimab-imdevimab-antibody#:~:text=This%20definitive%20Phase%203%20outcomes,71%25%20(2%2C400%20mg%20IV)

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04723394    
Other Study ID Numbers: D8851C00001
First Posted: January 25, 2021    Key Record Dates
Last Update Posted: September 20, 2021
Last Verified: September 2021
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.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

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:
Treatment 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