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

NCT ID: NCT04723394

Last Updated: 2023-07-05

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

910 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-28

Study Completion Date

2022-10-19

Brief Summary

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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.

Detailed Description

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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.

Conditions

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COVID-19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

AZD7442

Intervention Type DRUG

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

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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AZD7442

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Other Intervention Names

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Combination of 2 mAbs (AZD8895 and AZD1061)

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Jasper, Alabama, United States

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Tucson, Arizona, United States

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Long Beach, California, United States

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Northridge, California, United States

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Cutler Bay, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Pompano Beach, Florida, United States

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Chicago, Illinois, United States

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Lake Charles, Louisiana, United States

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St Louis, Missouri, United States

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La Vista, Nebraska, United States

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New York, New York, United States

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Charlotte, North Carolina, United States

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Charlotte, North Carolina, United States

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Statesville, North Carolina, United States

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Fargo, North Dakota, United States

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Columbus, Ohio, United States

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West Columbia, South Carolina, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Houston, Texas, United States

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Humble, Texas, United States

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Munro, , Argentina

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Blumenau, , Brazil

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Porto Alegre, , Brazil

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Ribeirão Preto, , Brazil

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São Paulo, , Brazil

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Sorocaba, , Brazil

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Hradec Králové, , Czechia

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Kolín, , Czechia

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Svitavy, , Czechia

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Berlin, , Germany

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Berlin, , Germany

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Cologne, , Germany

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Frankfurt, , Germany

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Frankfurt am Main, , Germany

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Friedrichshain, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Koblenz, , Germany

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Mainz, , Germany

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München, , Germany

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München-Pasing, , Germany

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Debrecen, , Hungary

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Gyöngyös, , Hungary

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Guastalla, , Italy

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Milan, , Italy

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Piacenza, , Italy

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Pisa, , Italy

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Roma, , Italy

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Chiba, , Japan

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Hachioji-shi, , Japan

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Iruma-Gun, , Japan

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Kyoto, , Japan

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Maebashi, , Japan

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Narita-shi, , Japan

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Sendai, , Japan

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Shinagawa-ku, , Japan

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Shinagawa-ku, , Japan

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Shinjuku-ku, , Japan

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Chihuahua City, , Mexico

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Cuauhtémoc, , Mexico

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Cuautitlán Izcalli, , Mexico

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Ecatepec de Morelos, , Mexico

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Guadalajara, , Mexico

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Guadalajara, , Mexico

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Mazatlán, , Mexico

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Mérida, , Mexico

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Monterrey, , Mexico

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Tlalpan, , Mexico

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Tlalpan, , Mexico

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Lima, , Peru

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Rzeszów, , Poland

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Wołomin, , Poland

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Moscow, , Russia

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Murmansk, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Cabra, , Spain

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Centelles (Barcelona), , Spain

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Girona, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Dnipro, , Ukraine

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Ivano-Frankivsk, , Ukraine

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Kherson, , Ukraine

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Blackpool, , United Kingdom

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Bracknell, , United Kingdom

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Bristol, , United Kingdom

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Cambridge, , United Kingdom

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Connor Downs, , United Kingdom

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Highgate, , United Kingdom

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Leicester, , United Kingdom

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Preston, , United Kingdom

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Rochdale, , United Kingdom

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Countries

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United States Argentina Brazil Czechia Germany Hungary Italy Japan Mexico Peru Poland Russia Spain Ukraine United Kingdom

References

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

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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

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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.

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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.

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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

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Hobbs FDR, Montgomery H, Padilla F, Simon-Campos JA, Arbetter D, Seegobin S, Kiazand A, Streicher K, Martinez-Alier N, Cohen TS, Esser MT. Safety, Efficacy and Pharmacokinetics of AZD7442 (Tixagevimab/Cilgavimab) for Treatment of Mild-to-Moderate COVID-19: 15-Month Final Analysis of the TACKLE Trial. Infect Dis Ther. 2024 Mar;13(3):521-533. doi: 10.1007/s40121-024-00931-4. Epub 2024 Feb 25.

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Hobbs FDR, Montgomery H, Padilla F, Simon-Campos JA, Kim K, Arbetter D, Padilla KW, Reddy VP, Seegobin S, Streicher K, Templeton A, Viani RM, Johnsson E, Koh GCKW, Esser MT. Outpatient Treatment with AZD7442 (Tixagevimab/Cilgavimab) Prevented COVID-19 Hospitalizations over 6 Months and Reduced Symptom Progression in the TACKLE Randomized Trial. Infect Dis Ther. 2023 Sep;12(9):2269-2287. doi: 10.1007/s40121-023-00861-7. Epub 2023 Sep 26.

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Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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D8851C00001

Identifier Type: -

Identifier Source: org_study_id

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