Clinical trial NCT04432272: ANTIBODY-LEVEL BASED ANALYSIS OF COVID-19 CONVALESCENT SERUM (ABACCuS)
Official title: ANTIBODY-LEVEL BASED ANALYSIS OF COVID-19 CONVALESCENT SERUM (ABACCuS)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID-19
Severe Acute Respiratory Syndrome (SARS)
Coronavirus Infections
Keywords: therapeutic treatment
COVID-19 convalescent plasma
anti-SARS-CoV-2 antibody
IgA
IgG
COVID-19 pandemic
Lead sponsor: William Beaumont Hospitals
Sponsor class: OTHER
First posted: 2020-06-16
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, single health system, non-randomized, open-label study.
Primary purpose: TREATMENT

Brief summary: The goal of this study is to evaluate the safety and effectiveness of Coronavirus-90 (COVID-19) convalescent plasma for the treatment of COVID-19. Plasma is the liquid part of blood that is left when all the blood cells have been removed. Convalescent means it is taken from people who were infected with COVID-19 and recovered. The use of this blood product to treat COVID-19 is investigational, which means the U.S. Food and Drug Administration has not yet approved it to be sold commercially. This is a human blood product collected by licensed blood banks. Donors of COVID-19 convalescent plasma must meet all standard blood donor criteria and must also meet all criteria set by the FDA for being a donor of COVID-19 convalescent plasma.

A total of 500 patients will take part in the study at 8 hospitals within Beaumont. Similar studies are being done at other centers, but they are not directly related to this study.

Participants will be assigned to a study group depending on how sick they are.

* Group A: Those who require more than 6 liters (L) of supplemental oxygen but are not on a ventilator
* Group B: Those who require a ventilator to preserve their life.

Both groups will receive one unit (approximately 200ml or just under 1 cup) of COVID convalescent plasma. The transfusion will be given over about 30 minutes via an IV. Blood samples will be taken prior to and one hour after the transfusion to measure participant antibodies against Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) and a nasopharyngeal swab (deep in the nostril) will be taken to test for presence of the SARS-CoV-2 virus. One hour after the transfusion a blood sample will be taken to measure antibody levels to determine if the plasma caused the antibody level to rise. Similarly, blood samples will be taken to measure antibodies against SARS-CoV-2 and a nasopharyngeal swab will be taken to test for presence of the SARS-CoV-2 virus 1, 3 and every 7 days after the transfusion while the participant is in the hospital The participant's final health status will be determined on day 28. Hospital records will be monitored for 90 days after discharge to determine if the participant is readmitted to the hospital.

Detailed description: This trial will evaluate the efficacy and safety of SARS-CoV-2 convalescent plasma as treatment for confirmed COVID-19 respiratory disease (as defined in the inclusion criteria). Participants in both group A and group B will receive COVID-19 convalescent plasma. Group A will include hospitalized COVID-19 patients ages ≥18 years with respiratory symptoms, requiring \>6 L of oxygen to maintain O2 saturation \>92%. Patient may not require intubation, and may be admitted for no longer than 14 days. Group B will include hospitalized COVID-19 patients ages ≥18 years requiring intubation. Patients may be enrolled in group A within 14 days of admission to the hospital and may be enrolled in group B at any time after intubation. A total of 300 eligible subjects with significant oxygen requirements and 200 eligible subjects who require intubation will be included in the study. They will receive convalescent plasma from either a patient who has recovered from COVID-19 or from an asymptomatic carrier with confirmed Immunoglobulin-G (IgG) antibodies against SARS-CoV-2. Subjects will not be randomized. The amount of anti-SARS-CoV-2 IgG and Immunoglobulin-A (IgA) antibodies in any unit of plasma will not be known when the unit is assigned to the patient. This will allow us to examine the relationship between the amount of anti-SARS-CoV-2 antibody and outcomes. Analysis will be based on measurement of optical density of the IgG level in the unit of plasma the patient is randomly supplied by the blood bank. While investigators and patients will be aware the patient is receiving a unit of COVID-19 convalescent plasma, both the investigators and the patients will be blinded to the antibody content of that unit.

COVID-19 convalescent plasma (1 unit; \~200mL) will be produced by a blood bank licensed to produce plasma using standard screening and safety procedures. The product may be procured from patients who have: 1) been symptom free for 14 days and screen negative via nasopharyngeal swab or 2) symptom free for at least 28 days or 3) individuals who have never had symptoms of COVID-19 but were found to have elevated anti-SARS-CoV-2 IgG by a serology test deemed to be of acceptable quality and fitting the current guidance by the FDA.

Participants at the eight Michigan hospitals comprising the Beaumont Health system may be eligible to participate. Study oversight and coordination will occur centrally, from the Infectious Disease Research Department at Beaumont's Royal Oak campus.

Eligibility criteria: Inclusion Criteria:

* Subjects must be 18 years of age or older.
* Hospitalized with confirmed COVID-19 infection via COVID-19 SARS-CoV-2 Reverse-transcription polymerase chain reaction (RT-PCR) testing.
* Symptoms consistent with COVID-19 infection (fever, acute onset cough, shortness of breath) at time of screening.
* Patient requires \>6 L nasal cannula oxygen (Group A) or intubated (Group B).
* Patient (or their legal authorized representative) is willing and able to provide written informed consent and comply with all protocol requirements.

Exclusion Criteria:

* For patients in Group A admitted for \>14 days
* Female subjects with positive pregnancy test, breastfeeding, or planning to become --pregnant or breastfeed during the study period.
* Receipt of pooled immunoglobulin in past 30 days.
* Contraindication to transfusion or history of prior reactions to transfusion blood products.
* Patients currently undergoing cancer treatment or those who are presently immunocompromised.
* Patient who in the opinion of the investigator will not be a good study candidate.

Primary outcomes:
measure: Avoidance of Intubation at 28 Days (Group A)
timeFrame: 28 days
measure: Mortality (Group B)
timeFrame: 28 days
Secondary outcomes:
measure: Cardio-circulatory Arrest
timeFrame: 28 days
measure: Patient Outcome at 28 Days
timeFrame: 28 days
measure: Renal Failure
timeFrame: 28 days
measure: Liver Failure
timeFrame: 28 days
measure: Cytokine Storm
timeFrame: 28 days
measure: Respiratory Support
timeFrame: 28 days
measure: Vasopressor Medication Support
timeFrame: 28 days
measure: Length of ICU Length of Stay
timeFrame: 28 days
measure: Intensive Care Unit (ICU) Mortality
timeFrame: 28 days
measure: Hospital Length of Stay
timeFrame: 28 days
measure: Ventilator Free Days
timeFrame: 28 days
measure: Intubation Duration
timeFrame: 28 days
measure: Readmission
timeFrame: 90 days
measure: Serum Anti-SARS-CoV-2 IgG
timeFrame: During hospitalization, a maximum of 28 days
measure: SARS-CoV-2 RNA
timeFrame: During hospitalization, a maximum of 28 days
measure: Mortality (Group A)
timeFrame: 28 days
measure: Time From Transfusion to End of Ventilator Support (Group B)
timeFrame: During hospitalization, a maximum of 28 days
Other outcomes:
Locations:
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
Study officials:
affiliation: Beaumont Health
name: Matthew Sims, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: