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

Sponsor
AstraZeneca (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04723394
Collaborator
(none)
910
Enrollment
110
Locations
2
Arms
21
Anticipated Duration (Months)
8.3
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

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
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.

Study Design

Study Type:
Interventional
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 :
Jan 28, 2021
Actual Primary Completion Date :
Aug 21, 2021
Anticipated Study Completion Date :
Oct 28, 2022

Arms and Interventions

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 Names:
  • 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.

    Outcome Measures

    Primary Outcome Measures

    1. A composite of either severe COVID-19 or death from any cause through Day 29. [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. [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). [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. [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. [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. [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. [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. [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. [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. [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. [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. [Through Day 457]

      To evaluate the ADA responses to AZD7442 in serum.

    11. Pharmacokinetics - Serum Concentration [Through Day 457]

      To evaluate the single-dose PK of AZD7442.

    12. Pharmacokinetics - Maximum Serum Concentration [Through Day 457]

      To evaluate the single-dose PK of AZD7442.

    13. Pharmacokinetics - Time to Maximum Serum Concentration [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 [Through Day 457]

      To evaluate the single-dose PK of AZD7442.

    15. Pharmacokinetics - Area under the plasma concentration-time curve extrapolated to infinity [Through Day 457]

      To evaluate the single-dose PK of AZD7442.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Jasper Alabama United States 35501
    2 Research Site Tucson Arizona United States 85704
    3 Research Site Long Beach California United States 90806
    4 Research Site Northridge California United States 91324
    5 Research Site Cutler Bay Florida United States 33157
    6 Research Site Miami Florida United States 33125
    7 Research Site Miami Florida United States 33165
    8 Research Site Pompano Beach Florida United States 33064
    9 Research Site Chicago Illinois United States 60621
    10 Research Site Lake Charles Louisiana United States 70601
    11 Research Site Saint Louis Missouri United States 63141
    12 Research Site La Vista Nebraska United States 68128
    13 Research Site New York New York United States 10016
    14 Research Site Charlotte North Carolina United States 28208
    15 Research Site Charlotte North Carolina United States 28277
    16 Research Site Statesville North Carolina United States 28625
    17 Research Site Fargo North Dakota United States 58104
    18 Research Site Columbus Ohio United States 43213
    19 Research Site West Columbia South Carolina United States 29169
    20 Research Site Dallas Texas United States 75235
    21 Research Site Houston Texas United States 77027
    22 Research Site Houston Texas United States 77057
    23 Research Site Houston Texas United States 77093
    24 Research Site Humble Texas United States 77338
    25 Research Site Buenos Aires Argentina B7600FYW
    26 Research Site Buenos Aires Argentina C1039
    27 Research Site Buenos Aires Argentina C1430EGF
    28 Research Site Munro Argentina B1605FRE
    29 Research Site Blumenau Brazil 89030-101
    30 Research Site Porto Alegre Brazil 90430-001
    31 Research Site Ribeirão Preto Brazil 14051-140
    32 Research Site Sorocaba Brazil 18040-425
    33 Research Site São Paulo Brazil 01228-200
    34 Research Site Bilina Czechia 41801
    35 Research Site Hradec Kralove Czechia 500 02
    36 Research Site Kolin Czechia 280 02
    37 Research Site Ostrava Czechia 708 52
    38 Research Site Berlin - Friedrichshain Germany 10243
    39 Research Site Berlin Germany 10439
    40 Research Site Berlin Germany 10777
    41 Research Site Frankfurt/Main Germany 60389
    42 Research Site Frankfurt Germany 60596
    43 Research Site Hamburg Germany 20095
    44 Research Site Hannover Germany 30625
    45 Research Site Koblenz Germany 56068
    46 Research Site Köln Germany 50668
    47 Research Site Mainz Germany 55128
    48 Research Site München-Pasing Germany 81241
    49 Research Site München Germany 80336
    50 Research Site Budapest Hungary 1097
    51 Research Site Budapest Hungary 1126
    52 Research Site Debrecen Hungary 4031
    53 Research Site Gyöngyös Hungary 3200
    54 Research Site Nyíregyháza Hungary 4400
    55 Research Site Tatabánya Hungary 2800
    56 Research Site Bologna Italy 40138
    57 Research Site Guastalla Italy 42016
    58 Research Site Milano Italy 20127
    59 Research Site Milano Italy 20157
    60 Research Site Piacenza Italy 29121
    61 Research Site Pisa Italy 56124
    62 Research Site Roma Italy 00149
    63 Research Site Chiba-shi Japan 260-0852
    64 Research Site Hachioji-shi Japan 193-0998
    65 Research Site Iruma-Gun Japan 350-0495
    66 Research Site Kyoto-shi Japan 607-8062
    67 Research Site Maebashi-shi Japan 371-0811
    68 Research Site Narita-shi Japan 286-8520
    69 Research Site Sendai-shi Japan 983-8512
    70 Research Site Shinagawa-ku Japan 140-8522
    71 Research Site Shinagawa-ku Japan 142-8666
    72 Research Site Shinjuku-ku Japan 162-8655
    73 Research Site Chihuahua Mexico 31350
    74 Research Site Cuauhtemoc Mexico 06700
    75 Research Site Cuautitlan Izcalli Mexico 54750
    76 Research Site Ecatepec de Morelos Mexico 55450
    77 Research Site Guadalajara Mexico 44100
    78 Research Site Guadalajara Mexico 44200
    79 Research Site Mazatlán Mexico 82110
    80 Research Site Monterrey Mexico 64460
    81 Research Site Mérida Mexico 97070
    82 Research Site Tlalpan Mexico 14050
    83 Research Site Tlalpan Mexico 14080
    84 Research Site Lima Peru 15088
    85 Research Site Rzeszów Poland 35-326
    86 Research Site Wołomin Poland 05-200
    87 Research Site Moscow Russian Federation 143442
    88 Research Site Murmansk Russian Federation 183047
    89 Research Site Saint-Petersburg Russian Federation 192283
    90 Research Site Saint-Petersburg Russian Federation 196084
    91 Research Site Saint-Petersburg Russian Federation 197227
    92 Research Site Saint-Petersburg Russian Federation 199106
    93 Research Site Saint-Petersburg Russian Federation 199226
    94 Research Site Cabra Spain 14940
    95 Research Site Centelles (Barcelona) Spain 08540
    96 Research Site Girona Spain 17005
    97 Research Site Madrid Spain 28031
    98 Research Site Málaga Spain 29010
    99 Research Site Dnipro Ukraine 49102
    100 Research Site Ivano-Frankivsk Ukraine 76018
    101 Research Site Kherson Ukraine 73000
    102 Research Site Blackpool United Kingdom FY3 7EN
    103 Research Site Bracknell United Kingdom RG12 8WY
    104 Research Site Bristol United Kingdom BS8 2PU
    105 Research Site Cambridge United Kingdom CB2 2QQ
    106 Research Site Connor Downs United Kingdom TR27 5DT
    107 Research Site Highgate United Kingdom N19 5NF
    108 Research Site Leicester United Kingdom LE5 4LJ
    109 Research Site Preston United Kingdom PR2 9HT
    110 Research Site Rochdale United Kingdom OL11 4AU

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT04723394
    Other Study ID Numbers:
    • D8851C00001
    First Posted:
    Jan 25, 2021
    Last Update Posted:
    Jun 30, 2022
    Last Verified:
    Jun 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
    Treatment of COVID-19
    Additional relevant MeSH terms:
    COVID-19

    Study Results

    No Results Posted as of Jun 30, 2022