Clinical trial NCT04524507: Coronavirus Disease 2019 (COVID-19) Antibody Plasma Research Study in Hospitalized Patients
Official title: IGHID 12021 - A Randomized, Phase II Study Comparing the Efficacy and Safety of Standard Versus High-Titer Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibody Plasma in Hospitalized Patients With COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Keywords: COVID-19
Coronavirus
Infection
SARS-CoV-2
Randomized
Hospitalized
Plasma
Neutralizing
Antibody
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
First posted: 2020-08-24
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study has 2 treatment arms and participants will be assigned/randomized to one arm:

1. CCP1 - CCP tested for the presence of anti-SARS-CoV-2 antibodies and assigned high-titer
2. CCP2 - CCP tested for the presence of anti-SARS-CoV-2 antibodies and assigned standard-titer
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to find out if CCP is safe and to determine the safest and most effective level of anti-viral antibody when given to people admitted to the hospital with confirmed COVID-19 infection. Participants enrolled on this study will be transfused with 2 units of CCP through an IV. These units will be given one at a time 4 to 24 hours apart. Participants will be randomized to receive either 2 units with standard antibody levels as recommended by the FDA or 2 units with an antibody level higher than that recommended by the FDA. This study is experimental and CCP is investigational and has not been approved by the FDA for the treatment of COVID-19. The CCP is collected per FDA guidelines from persons recovered from COVID-19 infection. The plasma contains antibodies and possibly other properties that inhibit the virus. The investigators do not know if the level of antibodies present in the CCP will make a difference in how the participant's body is able to fight the infection and hope to learn that in this study.

Detailed description: This randomized, double-blinded, phase 2 trial will assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with less than 8 days of symptoms. Eligible participants will receive institutional-guided standard-of-care (SOC) and ABO-compatible convalescent COVID-19 plasma (CCP). The CCP units will be tested for the presence of anti-SARS-CoV-2 antibodies and pre-assigned as high-titer (CCP1) or standard-titer (CCP2) in a 1:1 randomization. Participants and clinical investigators will be blinded to the CCP titer group identities.

The investigators plan to enroll approximately 56 participants (28 in each group) at UNC-Chapel Hill. Participants will be randomized within 48 hours of admission to a COVID service and will receive convalescent plasma within 24 hours of randomization. At least two units of CCP will be transfused 4-24 hours apart on study Day 0. If available, a third unit may be administered. All participants will undergo a series of safety and efficacy assessments pre-, during, and post-transfusion. Samples for research will be collected on Day 0 through Day 28, unless previously discharged. Additionally, after discharge, participants can provide longitudinal samples collected at 1, 3, and 6-month timepoints after the infusion.

Eligibility criteria: Inclusion Criteria:

1. Age at least 18 years
2. Ability and willingness of participant or Legally Authorized Representative (LAR) to give written informed consent.
3. Laboratory confirmed diagnosis of infection with SARS-CoV-2 by PCR
4. Hospitalized for COVID-19 with one or more respiratory or gastrointestinal (GI) symptoms:

   * COVID-19 associated respiratory symptoms include but are not limited to: cough, shortness of breath, difficulty breathing, or sore throat
   * COVID-19 associated GI symptoms include but are not limited to: loss of taste, loss of sense of smell, diarrhea, nausea, or vomiting,

Note: Respiratory and GI symptoms other than those listed above, must be noted as acceptable and signed by study PI or designee.

Exclusion Criteria:

1. Receipt of pooled immunoglobulin in past 30 days
2. Current or prior enrollment in a SARS-CoV-2 antibody or T-cell therapeutic study.

   Note: Patients enrolled on other randomized controlled trials of pharmaceutical and/or non-pharmaceutical interventions for COVID and meeting eligibility criteria will not be excluded, as determined by study PI (or designee) on a case-by-case basis and as allowed by eligibility criteria of the other trials.
3. Contraindication to transfusion or history of prior reactions to transfusion blood products. This may include religious or cultural objections to receiving blood products and transfusions.
4. ABO-compatible titered plasma is not available
5. \> 10 days from noted COVID-related subjective or objective fever at randomization. Patients without subjective or objective fever, \> 10 days from symptom onset as determined by study PI.

Primary outcomes:
measure: Total Number of Serious Adverse Events (SAE) Through Study Day 14
timeFrame: 14 days
measure: Median Time to Hospital Discharge (or Discharge Equivalent) Following First Dose of CCP
timeFrame: up to 28 days
Secondary outcomes:
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina Health Care
state: North Carolina
Study officials:
affiliation: UNC-Chapel Hill
name: Luther A Bartelt, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UNC-Chapel Hill
name: David M Margolis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bartelt LA, Markmann AJ, Nelson B, Keys J, Root H, Henderson HI, Kuruc J, Baker C, Bhowmik DR, Hou YJ, Premkumar L, Cornaby C, Schmitz JL, Weiss S, Park Y, Baric R, de Silva AM, Lachiewicz A, Napravnik S, van Duin D, Margolis DM. Outcomes of Convalescent Plasma with Defined High versus Lower Neutralizing Antibody Titers against SARS-CoV-2 among Hospitalized Patients: CoronaVirus Inactivating Plasma (CoVIP) Study. mBio. 2022 Oct 26;13(5):e0175122. doi: 10.1128/mbio.01751-22. Epub 2022 Sep 22.