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Evaluate the efficacy of treatment with high-titer Anti- SARS-CoV-2 plasma versus control (SARS-CoV-2 non-immune plasma) in subjects exposed to Coronavirus disease (COVID-19) at day 28.
This randomized, controlled, double-blinded phase 2 trial will assess the efficacy and safety of Anti- SARS-CoV-2 convalescent plasma as prophylaxis following exposure to COVID-19 (as defined in the inclusion criteria). Adults 18 years of age and older with high risk exposure as defined by CDC may participate. A total of 500 eligible subjects will be randomized in a 1:1 ratio to receive either high titer anti-SARS-CoV-2 plasma or control (SARS-CoV-2 non-immune plasma).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High titer anti-SARS-CoV-2 plasma | Experimental | Participants with High titer anti-SARS-CoV-2 plasma. |
|
| SARS-CoV-2 non-immune plasma | Active Comparator | Participants with SARS-CoV-2 non-immune plasma. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Anti- SARS-CoV-2 Plasma | Biological | SARS-CoV-2 convalescent plasma (1 unit; ~200-250 mL collected by pheresis from a volunteer who recovered from COVID-19 disease and has SARS-CoV-2 antibody titers ≥ 1:320 |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of Treatment at Day 28 as Assessed by Number of Participants Who Develop SARS-Cov-2 Infection | Comparison of proportions of cumulative incidence of development of SARS-Cov-2 infection (symptoms compatible with infection and/or + molecular testing) regardless of disease severity, following high-titer Anti- SARS-CoV-2 plasma versus control (SARS-CoV-2 non-immune plasma) in subjects exposed to COVID-19. | Day 28 |
| Safety of Treatment With High-titer Anti- SARS-CoV-2 Plasma Versus Control as Assessed by Number of Participants With "Serious Adverse Events" | Number of participants with serious adverse events categorized as either severe infusion reactions or Acute Respiratory Distress Syndrome during the study period. | Up to Day 28 |
| Safety of Treatment With High-titer Anti- SARS-CoV-2 Plasma Versus Control as Assessed by Cumulative Incidence of Grade 3 and 4 Adverse Events | Cumulative incidence of grade 3 and 4 adverse events during the study period evaluated as events per 100 person-years will be used to assess safety of the intervention. | Up to Day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Severe Disease | Number of participants with severe disease between the anti-SARS-CoV-2 convalescent plasma and control groups. Severity of disease will be measured using the number of participants with any of the disease severity categories below:
|
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Inclusion Criteria
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Shmuel Shoham, MD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35294 | United States | ||
| Center for American Indian Health - Whiteriver Office |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35579509 | Derived | Shoham S, Bloch EM, Casadevall A, Hanley D, Lau B, Gebo K, Cachay E, Kassaye SG, Paxton JH, Gerber J, Levine AC, Naeim A, Currier J, Patel B, Allen ES, Anjan S, Appel L, Baksh S, Blair PW, Bowen A, Broderick P, Caputo CA, Cluzet V, Cordisco ME, Cruser D, Ehrhardt S, Forthal D, Fukuta Y, Gawad AL, Gniadek T, Hammel J, Huaman MA, Jabs DA, Jedlicka A, Karlen N, Klein S, Laeyendecker O, Lane K, McBee N, Meisenberg B, Merlo C, Mosnaim G, Park HS, Pekosz A, Petrini J, Rausch W, Shade DM, Shapiro JR, Singleton JR, Sutcliffe C, Thomas DL, Yarava A, Zand M, Zenilman JM, Tobian AAR, Sullivan DJ. Transfusing Convalescent Plasma as Post-Exposure Prophylaxis Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Double-Blinded, Phase 2 Randomized, Controlled Trial. Clin Infect Dis. 2023 Feb 8;76(3):e477-e486. doi: 10.1093/cid/ciac372. | |
| 34931202 |
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Sharing is governed by Johns Hopkins University Institutional Guidelines
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| ID | Title | Description |
|---|---|---|
| FG000 | High Titer Anti-SARS-CoV-2 Plasma | Participants with High titer anti-SARS-CoV-2 plasma. Anti- SARS-CoV-2 Plasma: SARS-CoV-2 convalescent plasma (1 unit; ~200-250 mL collected by pheresis from a volunteer who recovered from COVID-19 disease and has SARS-CoV-2 antibody titers ≥ 1:320 |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 23, 2020 | Apr 19, 2022 |
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1:1 ratio
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| SARS-CoV-2 non-immune Plasma | Biological | Normal human plasma collected prior to December 2019 |
|
| Up to 28 days |
| Whiteriver |
| Arizona |
| 85941 |
| United States |
| University of California, San Diego | La Jolla | California | 92093 | United States |
| University of California, Los Angeles | Los Angeles | California | 90095 | United States |
| University of California, Irvine Health | Orange | California | 92868 | United States |
| Western Connecticut Health Network, Danbury Hospital | Danbury | Connecticut | 06810 | United States |
| Western Connecticut Health Netowrk, Norwalk Hospital | Norwalk | Connecticut | 06856 | United States |
| MedStar Georgetown University Hospital | Washington D.C. | District of Columbia | 20007 | United States |
| University of Miami | Coral Gables | Florida | 33124 | United States |
| University of Miami Clinical Translational Research Site | Miami | Florida | 33136 | United States |
| NorthShore University HealthSystem | Evanston | Illinois | 60201 | United States |
| Anne Arundel Medical Center | Annapolis | Maryland | 21401 | United States |
| The Johns Hopkins University | Baltimore | Maryland | 21205 | United States |
| University of Massachusetts Worcester | Worcester | Massachusetts | 01655 | United States |
| Wayne State University | Detroit | Michigan | 48202 | United States |
| University of New Mexico Health Sciences Center | Albuquerque | New Mexico | 87131 | United States |
| Center for American Indian Health - Gallup Office | Gallup | New Mexico | 87301 | United States |
| Center for American Indian Health - Shiprock Office | Shiprock | New Mexico | 87420 | United States |
| Vassar Brothers Medical Center | Poughkeepsie | New York | 12601 | United States |
| University of Rochester | Rochester | New York | 14642 | United States |
| University of Cincinnati Medical Center | Cincinnati | Ohio | 45219 | United States |
| Lifespan/BrownUniversity (Rhode Island Hospital) | Providence | Rhode Island | 02903 | United States |
| Baylor College of Medicine | Houston | Texas | 77030 | United States |
| University of Texas Health Science Center at Houston | Houston | Texas | 77030 | United States |
| The University of Utah | Salt Lake City | Utah | 84132 | United States |
| Derived |
| Shoham S, Bloch EM, Casadevall A, Hanley D, Lau B, Gebo K, Cachay E, Kassaye SG, Paxton JH, Gerber J, Levine AC, Currier J, Patel B, Allen ES, Anjan S, Appel L, Baksh S, Blair PW, Bowen A, Broderick P, Caputo CA, Cluzet V, Cordisco ME, Cruser D, Ehrhardt S, Forthal D, Fukuta Y, Gawad AL, Gniadek T, Hammel J, Huaman MA, Jabs DA, Jedlicka A, Karlen N, Klein S, Laeyendecker O, Lane K, McBee N, Meisenberg B, Merlo C, Mosnaim G, Park HS, Pekosz A, Petrini J, Rausch W, Shade DM, Shapiro JR, Singleton JR, Sutcliffe C, Thomas DL, Yarava A, Zand M, Zenilman JM, Tobian AAR, Sullivan D. Randomized controlled trial transfusing convalescent plasma as post-exposure prophylaxis against SARS-CoV-2 infection. medRxiv [Preprint]. 2021 Dec 14:2021.12.13.21267611. doi: 10.1101/2021.12.13.21267611. |
| SARS-CoV-2 Non-immune Plasma |
Participants with SARS-CoV-2 non-immune plasma. SARS-CoV-2 non-immune Plasma: Normal human plasma collected prior to December 2019 |
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | High Titer Anti-SARS-CoV-2 Plasma | Participants with High titer anti-SARS-CoV-2 plasma. Anti- SARS-CoV-2 Plasma: SARS-CoV-2 convalescent plasma (1 unit; ~200-250 mL collected by pheresis from a volunteer who recovered from COVID-19 disease and has SARS-CoV-2 antibody titers ≥ 1:320 |
| BG001 | SARS-CoV-2 Non-immune Plasma | Participants with SARS-CoV-2 non-immune plasma. SARS-CoV-2 non-immune Plasma: Normal human plasma collected prior to December 2019 |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Age, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| BMI | Body Mass Index (BMI) of participants (Kg/m^2). | Count of Participants | Participants |
| |||||||||||||||
| Number of people in household | Count of Participants | Participants |
| ||||||||||||||||
| Number of household COVID-19 positives | Count of Participants | Participants |
| ||||||||||||||||
| Median time from last exposure to transfusion | Median | Inter-Quartile Range | hours |
| |||||||||||||||
| Days from last exposure to transfusion | Count of Participants | Participants |
| ||||||||||||||||
| Cancer Status | Count of Participants | Participants |
| ||||||||||||||||
| Cardiac condition | Count of Participants | Participants |
| ||||||||||||||||
| Immunologic condition | Count of Participants | Participants |
| ||||||||||||||||
| Metabolic condition | Count of Participants | Participants |
| ||||||||||||||||
| Respiratory condition | Count of Participants | Participants |
| ||||||||||||||||
| Tobacco use status | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Efficacy of Treatment at Day 28 as Assessed by Number of Participants Who Develop SARS-Cov-2 Infection | Comparison of proportions of cumulative incidence of development of SARS-Cov-2 infection (symptoms compatible with infection and/or + molecular testing) regardless of disease severity, following high-titer Anti- SARS-CoV-2 plasma versus control (SARS-CoV-2 non-immune plasma) in subjects exposed to COVID-19. | Posted | Count of Participants | Participants | Day 28 |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Safety of Treatment With High-titer Anti- SARS-CoV-2 Plasma Versus Control as Assessed by Number of Participants With "Serious Adverse Events" | Number of participants with serious adverse events categorized as either severe infusion reactions or Acute Respiratory Distress Syndrome during the study period. | Posted | Count of Participants | Participants | Up to Day 28 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Safety of Treatment With High-titer Anti- SARS-CoV-2 Plasma Versus Control as Assessed by Cumulative Incidence of Grade 3 and 4 Adverse Events | Cumulative incidence of grade 3 and 4 adverse events during the study period evaluated as events per 100 person-years will be used to assess safety of the intervention. | Posted | Number | 95% Confidence Interval | Events per 100 person-years | Up to Day 28 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Severe Disease | Number of participants with severe disease between the anti-SARS-CoV-2 convalescent plasma and control groups. Severity of disease will be measured using the number of participants with any of the disease severity categories below:
| Posted | Count of Participants | Participants | Up to 28 days |
|
|
Within 28 days
Adverse events were evaluated among those transfused and not SARS Cov-2 positive at baseline. Adverse Events were monitored/assessed without regard to the specific Adverse Event Term.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | High Titer Anti-SARS-CoV-2 Plasma | Participants with High titer anti-SARS-CoV-2 plasma. Anti- SARS-CoV-2 Plasma: SARS-CoV-2 convalescent plasma (1 unit; ~200-250 mL collected by pheresis from a volunteer who recovered from COVID-19 disease and has SARS-CoV-2 antibody titers ≥ 1:320 | 0 | 81 | 4 | 81 | 24 | 81 |
| EG001 | SARS-CoV-2 Non-immune Plasma | Participants with SARS-CoV-2 non-immune plasma. SARS-CoV-2 non-immune Plasma: Normal human plasma collected prior to December 2019 | 0 | 87 | 14 | 87 | 44 | 87 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Severe transfusion reaction | Blood and lymphatic system disorders | MedDRA unspecified | Non-systematic Assessment |
| |
| Grade 3 or 4 adverse events | General disorders | MedDRA unspecified | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Non-serious adverse events | General disorders | MedDRA unspecified | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Shmuel Shoham | The Johns Hopkins University School of Medicine | 410-614-6431 | sshoham1@jhmi.edu |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 12, 2021 | Apr 6, 2022 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jan 13, 2021 | Apr 19, 2022 | ICF_002.pdf |
| ID | Term |
|---|---|
| D018352 | Coronavirus Infections |
| D003289 | Convalescence |
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| 35 - 44 years |
|
| 45 - 54 years |
|
| 55 - 64 years |
|
| >/=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| 18-24.9 |
|
| 25-29.9 |
|
| 30-34.9 |
|
| 35-39.9 |
|
| >/=40 |
|
| Missing |
|
| 2 |
|
| 3 |
|
| 4 |
|
| >/=5 |
|
| Missing |
|
| 2 |
|
| 3 |
|
| >/=4 |
|
| Missing |
|
| 1 |
|
| 2 |
|
| 3 |
|
| 4 |
|
| >/=5 |
|
| Missing |
|
| Not transfused |
|
| Active cancer on chemotherapy |
|
| Cancer in remission |
|
| Leukemia/Lymphoma |
|
| No cancer |
|
| Atrial fibrillation, on anticoagulant |
|
| Cardiomyopathy |
|
| Coronary artery disease |
|
| Myocardial infarction |
|
| No cardiac condition |
|
| Inflammatory bowel disease |
|
| HIV, on antiretroviral treatment |
|
| Psoriasis |
|
| Immunosuppression or on other immune modulator |
|
| No immunologic condition |
|
| Vitamin D deficiency |
|
| No metabolic condition |
|
| Chronic Bronchitis |
|
| Chronic sinusitis |
|
| Cough |
|
| Pulmonary fibrosis |
|
| Pulmonary hypertension |
|
| No respiratory condition |
|
| Past tobacco user |
|
| No tobacco use |
|
|
|
|
|
|