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

COVID-19 Clinical Trial

— TACKLE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04723394
• Other study ID #: D8851C00001
• Status: Completed
• Phase: Phase 3
• Start date: January 28, 2021
• Est. completion date: October 19, 2022

Study information

• Verified date: June 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 910
• Est. completion date: October 19, 2022
• Est. primary completion date: August 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• AZD7442
Single dose (× 2 separate IM injections) of 600 mg of AZD7442 or saline placebo on Day 1.
• Placebo
Single dose (× 2 separate IM injections) of 600 mg of AZD7442 or saline placebo on Day 1.

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Munro
Brazil	Research Site	Blumenau
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Ribeirão Preto
Brazil	Research Site	São Paulo
Brazil	Research Site	Sorocaba
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Kolin
Czechia	Research Site	Svitavy
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin - Friedrichshain
Germany	Research Site	Frankfurt
Germany	Research Site	Frankfurt/Main
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	Koblenz
Germany	Research Site	Köln
Germany	Research Site	Mainz
Germany	Research Site	München
Germany	Research Site	München-Pasing
Hungary	Research Site	Debrecen
Hungary	Research Site	Gyöngyös
Italy	Research Site	Guastalla
Italy	Research Site	Milano
Italy	Research Site	Piacenza
Italy	Research Site	Pisa
Italy	Research Site	Roma
Japan	Research Site	Chiba-shi
Japan	Research Site	Hachioji-shi
Japan	Research Site	Iruma-Gun
Japan	Research Site	Kyoto-shi
Japan	Research Site	Maebashi-shi
Japan	Research Site	Narita-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Shinagawa-ku
Japan	Research Site	Shinagawa-ku
Japan	Research Site	Shinjuku-ku
Mexico	Research Site	Chihuahua
Mexico	Research Site	Cuauhtemoc
Mexico	Research Site	Cuautitlan Izcalli
Mexico	Research Site	Ecatepec de Morelos
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mazatlán
Mexico	Research Site	Mérida
Mexico	Research Site	Monterrey
Mexico	Research Site	Tlalpan
Mexico	Research Site	Tlalpan
Peru	Research Site	Lima
Poland	Research Site	Rzeszów
Poland	Research Site	Wolomin
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Murmansk
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Spain	Research Site	Cabra
Spain	Research Site	Centelles (Barcelona)
Spain	Research Site	Girona
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Ukraine	Research Site	Dnipro
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kherson
United Kingdom	Research Site	Blackpool
United Kingdom	Research Site	Bracknell
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Connor Downs
United Kingdom	Research Site	Highgate
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	Preston
United Kingdom	Research Site	Rochdale
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chicago	Illinois
United States	Research Site	Columbus	Ohio
United States	Research Site	Cutler Bay	Florida
United States	Research Site	Dallas	Texas
United States	Research Site	Fargo	North Dakota
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Humble	Texas
United States	Research Site	Jasper	Alabama
United States	Research Site	La Vista	Nebraska
United States	Research Site	Lake Charles	Louisiana
United States	Research Site	Long Beach	California
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	New York	New York
United States	Research Site	Northridge	California
United States	Research Site	Pompano Beach	Florida
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Statesville	North Carolina
United States	Research Site	Tucson	Arizona
United States	Research Site	West Columbia	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Czechia,  Germany,  Hungary,  Italy,  Japan,  Mexico,  Peru,  Poland,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

References & Publications (15)

Ashraf-Kashani and Kumar 2017 Ashraf-Kashani N, Kumar R. High-flow nasal oxygen therapy. BJA Education. 2017;17:57-62.

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

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

Li F. Structure, Function, and Evolution of Coronavirus Spike Proteins. Annu Rev Virol. 2016 Sep 29;3(1):237-261. doi: 10.1146/annurev-virology-110615-042301. Epub 2016 Aug 25. — View Citation

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

Miettinen O, Nurminen M. Comparative analysis of two rates. Stat Med. 1985 Apr-Jun;4(2):213-26. doi: 10.1002/sim.4780040211. — View Citation

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)

Sharma S, Danckers M, Sanghavi DK, Chakraborty RK. High-Flow Nasal Cannula. 2023 Apr 6. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK526071/ — View Citation

Tamhane AC, Mehta CR, Liu L. Testing a primary and a secondary endpoint in a group sequential design. Biometrics. 2010 Dec;66(4):1174-84. doi: 10.1111/j.1541-0420.2010.01402.x. — View Citation

WHO 2020 WHO COVID-19 Dashboard. Available from: https://covid19.who.int

WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis. 2020 Aug;20(8):e192-e197. doi: 10.1016/S1473-3099(20)30483-7. Epub 2020 Jun 12. Erratum In: Lancet Infect Dis. 2020 Oct;20(10):e250. — View Citation

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. Erratum In: Nature. 2020 Dec;588(7836):E6. — View Citation

Zou G. A modified poisson regression approach to prospective studies with binary data. Am J Epidemiol. 2004 Apr 1;159(7):702-6. doi: 10.1093/aje/kwh090. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	A Composite of Either Severe COVID-19 or Death From Any Cause Through Day 29	Severe COVID-19 is characterized by a minimum of either pneumonia (fever, cough, tachypnea, or dyspnea, and lung infiltrates) or hypoxemia (SpO2 < 90% in room air and/or severe respiratory distress) and a WHO Clinical Progression Scale score of 5 or higher.	Baseline (Day 1) and Day 29
Secondary	A Composite of Death From Any Cause or Hospitalization for COVID-19 Complications or Sequelae Through Day 169	Death from Any Cause or Hospitalization for COVID-19 Complications or Sequelae through Day 169	Baseline (Day 1) and Day 169

External Links

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•   Redacted CSR Synopsis
•   Redacted SAP