Clinical trial NCT04397757: COVID-19 Convalescent Plasma for the Treatment of Hospitalized Patients With Pneumonia Caused by SARS-CoV-2.
Official title: An Open-Label, Controlled, Phase 1, Safety and Exploratory Efficacy Study of Convalescent Plasma for Severely Ill, Hospitalized Participants With COVID-19 Pneumonia Caused by SARS-CoV-2.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: COVID-19
Keywords: Convalescent plasma
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2020-05-21
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized 1:1 to receive either convalescent plasma on Study Day 1 in addition to standard care or standard care alone.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to see if this plasma can be safely used in humans with COVID-19 and to see if it improves patients' health as compared to not using it in patients with pneumonia caused by SARS-CoV-2.

Detailed description: This open-label, randomized, controlled, phase 1 trial will assess the safety and efficacy of convalescent plasma in severely ill, hospitalized participants with pneumonia due to COVID-19. This study will enroll adults 18 years old and older, including pregnant women.

A total of 80 eligible participants will be randomized to receive either 2 units of convalescent plasma collected from ABO-compatible donors who have recovered from COVID-19 and standard of care (treatment arm) or standard of care alone (control arm). Participants in the treatment arm will receive 2 units of convalescent plasma on Study Day 1 in addition to standard of care.

Participants will be assessed on study Day 1 (pre-dose), 30 minutes after each unit of plasma, on all Study Days while hospitalized, and Study Days 15, 22, 29, and 60. All participants will undergo a series of safety and efficacy, assessments. Blood samples will be collected on Days 1 (prior to plasma administration), 3, 8, 15, 29, and 60. Oropharyngeal or endotracheal samples will be collected on Days 1 (prior to plasma administration), 3, 5, 8, 11, and 15.

Eligibility criteria: Inclusion Criteria:

1. Adult ≥18 years of age
2. Laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other authorized or approved assay in any specimen collected within 72 hours prior to enrollment.

   Note - An exception must be requested to the Sponsor if ≥72 hours since positive test.
3. Hospitalized in participating facility.
4. Documentation of pneumonia with radiographic evidence of infiltrates by imaging (e.g., chest x-ray or CT scan).
5. Abnormal respiratory status that is judged worse than baseline by the investigator and as documented at any point within 24 hours prior to randomization, consistent with ordinal scale levels 5, 6 or 7, specifically defined as:

   * Room air saturation of oxygen (SaO2) \< 93%, OR
   * Requiring supplemental oxygen, OR
   * Tachypnea with respiratory rate ≥30
6. Patient or proxy is willing and able to provide written informed consent and comply with all protocol requirements

Exclusion Criteria:

1. Contraindication to transfusion (e.g., severe volume overload, history of severe allergic reaction to blood products), as judged by the investigator.
2. Clinical suspicion that the etiology of acute illness (acute decompensation) is primarily due to a condition other than COVID-19
3. Receipt of other investigational therapy as a part of another clinical trial. Note: investigational therapies used as part of clinical care, (eg, remdesivir, hydroxychloroquine) are permissible.

Primary outcomes:
measure: Participants With Serious Adverse Events.
timeFrame: Up to Study Day 29
measure: Clinical Severity Score
timeFrame: Up to Study Day 29
Secondary outcomes:
measure: Clinical Status Assessment, Time to Recovery
timeFrame: Up to Study Day 29
measure: National Early Warning Score (NEWS) Clinical Status Assessment
timeFrame: Up to Study Day 29
measure: Oxygenation
timeFrame: Daily while hospitalized and up to Study Day 29
measure: Incidence of New Oxygenation Use up to Day 29
timeFrame: From enrollment to Day 29.
measure: Duration of New Oxygen Use up to Day 29
timeFrame: From enrollment to Day 29.
measure: Non-invasive Ventilation/High Flow Oxygen Days up to Day 29
timeFrame: Daily while in hospital to Study Day 29.
measure: Number of Participants With at Least One Day on Non-invasive Ventilation/High Flow Oxygen up to Day 29
timeFrame: Daily while in hospital until Study Day 29
measure: Duration of Non-invasive Ventilation/High Flow Oxygen up to Day 29
timeFrame: Daily while in hospital to Study Day 29.
measure: Ventilator/ECMO Days to Day 29
timeFrame: Daily while in hospital to Study Day 29
measure: New Mechanical Ventilation or ECMO Use
timeFrame: From enrollment to Day 29.
measure: Duration of New Mechanical Ventilation or ECMO
timeFrame: Daily while in hospital to Study Day 29
measure: Duration of Hospitalization
timeFrame: To Study Day 29
measure: Mortality
timeFrame: 28 days from Study Day 1
measure: Number of Subjects With SAEs Through Day 29
timeFrame: Through Study Day 29
measure: Number of Subjects With at Least One Grade 3 and Grade 4 Clinical and/or Laboratory Adverse Events Through Day 29
timeFrame: Through Study Day 29
measure: Changes in WBC With Differential Through Day 29
timeFrame: Through Day 29
measure: Changes in Hemoglobin Measurement Through Day 29
timeFrame: Through Day 29
measure: Changes in Platelets Measurement Through Day 29
timeFrame: Through Day 29.
measure: Changes in Creatinine Measurement Through Day 29
timeFrame: Through Day 29.
measure: Changes in Glucose Measurement Through Day 29
timeFrame: Through Day 29.
measure: Changes in Total Bilirubin Measurement Through Day 29
timeFrame: Through Day 29
measure: Changes in ALT Measurement Through Day 29
timeFrame: Through Day 29
measure: Changes in AST Measurement Through Day 29
timeFrame: Through Day 29.
measure: Changes in PT Measurement Laboratory Through Day 29
timeFrame: Through Day 29.
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Katharine J. Bar
role: PRINCIPAL_INVESTIGATOR
References:
citation: Herman JD, Wang C, Burke JS, Zur Y, Compere H, Kang J, Macvicar R, Taylor S, Shin S, Frank I, Siegel D, Tebas P, Choi GH, Shaw PA, Yoon H, Pirofski LA, Julg BD, Bar KJ, Lauffenburger D, Alter G. Nucleocapsid-specific antibody function is associated with therapeutic benefits from COVID-19 convalescent plasma therapy. Cell Rep Med. 2022 Nov 15;3(11):100811. doi: 10.1016/j.xcrm.2022.100811. Epub 2022 Oct 24.
citation: Bar KJ, Shaw PA, Choi GH, Aqui N, Fesnak A, Yang JB, Soto-Calderon H, Grajales L, Starr J, Andronov M, Mastellone M, Amonu C, Feret G, DeMarshall M, Buchanan M, Caturla M, Gordon J, Wanicur A, Monroy MA, Mampe F, Lindemuth E, Gouma S, Mullin AM, Barilla H, Pronina A, Irwin L, Thomas R, Eichinger RA, Demuth F, Luning Prak ET, Pascual JL, Short WR, Elovitz MA, Baron J, Meyer NJ, Degnan KO, Frank I, Hensley SE, Siegel DL, Tebas P. A randomized controlled study of convalescent plasma for individuals hospitalized with COVID-19 pneumonia. J Clin Invest. 2021 Dec 15;131(24):e155114. doi: 10.1172/JCI155114.