UNC CCP RCT: Coronavirus Disease 2019 (COVID-19) Antibody Plasma Research Study in Hospitalized Patients

• Sponsor: University of North Carolina, Chapel Hill (Other)
• Overall Status: Completed
• CT.gov ID: NCT04524507
• Collaborator: (none)
• Enrollment: 56
• Location: 1
• Arms: 2
• Actual Duration (Months): 9.2
• Patients Per Site Per Month: 6.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Biological: High-titer Convalescent COVID-19 Plasma (CCP1); Biological: Standard-titer Convalescent COVID-19 plasma (CCP2)	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This study has 2 treatment arms and participants will be assigned/randomized to one arm: CCP1 - CCP tested for the presence of anti-SARS-CoV-2 antibodies and assigned high-titer CCP2 - CCP tested for the presence of anti-SARS-CoV-2 antibodies and assigned standard-titerThis study has 2 treatment arms and participants will be assigned/randomized to one arm:CCP1 - CCP tested for the presence of anti-SARS-CoV-2 antibodies and assigned high-titer CCP2 - CCP tested for the presence of anti-SARS-CoV-2 antibodies and assigned standard-titer
• Masking: Double (Participant, Investigator)
• Masking Description: This study is double-blinded so neither the participant nor the study team/investigators will know which plasma treatment (CCP1 or CCP2) that the participant is receiving.
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Aug 27, 2020
• Actual Primary Completion Date: Jan 4, 2021
• Actual Study Completion Date: Jun 4, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: High-Titer (CCP1) Within 8 days of COVID symptom onset and no more than 48 hours following hospitalization, participants will be randomized to and receive high-titer ABO-compatible convalescent COVID-19 plasma (CCP1) within 24 hours following random assignment.	Biological: High-titer Convalescent COVID-19 Plasma (CCP1); At least two units of CCP transfused 4-24 hours apart on Study Day 0. A third unit may be administered, if available.
Active Comparator: Standard-Titer (CCP2) Within 8 days of COVID symptom onset and no more than 48 hours following hospitalization, participants will be randomized to and receive standard-titer ABO-compatible convalescent COVID-19 plasma (CCP2) within 24 hours following random assignment.	Biological: Standard-titer Convalescent COVID-19 plasma (CCP2); At least two units of CCP transfused 4-24 hours apart on Study Day 0. A third unit may be administered, if available.

Outcome Measures

Primary Outcome Measures

1. Total Number of Serious Adverse Events (SAE) Through Study Day 14 [14 days]

   Total number of SAE among all participants through Day 14; Definition of SAE per protocol and will only be included if related to COVID-19 Convalescent Plasma (CCP): 1. Death; 2. Life-threatening (immediate risk of death); 3. Prolongation of existing hospitalization; 4. Persistent or significant disability or incapacity; OR 5. Important medical events that may not result in death, be life threatening, or require intervention or escalation of care may be considered a serious adverse event when, based upon appropriate medical judgment, they may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias, or convulsions that do not result in inpatient hospitalization.

2. Median Time to Hospital Discharge (or Discharge Equivalent) Following First Dose of CCP [up to 28 days]

   Median number of days to hospital discharge following first dose of CCP among all participants.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. 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.

2. ABO-compatible titered plasma is not available

3. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of North Carolina Health Care	Chapel Hill	North Carolina	United States	27514

Sponsors and Collaborators

• University of North Carolina, Chapel Hill

Investigators

• Principal Investigator: Luther A Bartelt, MD, UNC-Chapel Hill
• Principal Investigator: David M Margolis, MD, UNC-Chapel Hill

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 18, 2020

More Information

Publications

None provided.

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT04524507
• Other Study ID Numbers: 20-1544
• First Posted: Aug 24, 2020
• Last Update Posted: Dec 3, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of North Carolina, Chapel Hill: COVID-19; Coronavirus; Infection; SARS-CoV-2; Randomized; Hospitalized; Plasma; Neutralizing; Antibody
• Additional relevant MeSH terms: COVID-19; Coronavirus Infections

Study Results

Participant Flow

Arm/Group Title	High-Titer (CCP1)	Standard-Titer (CCP2)
Arm/Group Description	Within 10 days of COVID symptom onset and no more than 48 hours following hospitalization, participants will be randomized to and receive high-titer ABO-compatible convalescent COVID-19 plasma (CCP1) within 24 hours following random assignment. High-titer Convalescent COVID-19 Plasma (CCP1): At least two units of CCP transfused 4-24 hours apart on Study Day 0. A third unit may be administered, if available.	Within 10 days of COVID symptom onset and no more than 48 hours following hospitalization, participants will be randomized to and receive standard-titer ABO-compatible convalescent COVID-19 plasma (CCP2) within 24 hours following random assignment. Standard-titer Convalescent COVID-19 plasma (CCP2): At least two units of CCP transfused 4-24 hours apart on Study Day 0. A third unit may be administered, if available.
Period Title: Overall Study
STARTED	15	41
Received Intervention	14	41
Hospital Discharge	13	27
COMPLETED	9	18
NOT COMPLETED	6	23

Baseline Characteristics

Arm/Group Title	High-Titer (CCP1)	Standard-Titer (CCP2)	Total
Arm/Group Description	Within 10 days of COVID symptom onset and no more than 48 hours following hospitalization, participants will be randomized to and receive high-titer ABO-compatible convalescent COVID-19 plasma (CCP1) within 24 hours following random assignment. High-titer Convalescent COVID-19 Plasma (CCP1): At least two units of CCP transfused 4-24 hours apart on Study Day 0. A third unit may be administered, if available.	Within 10 days of COVID symptom onset and no more than 48 hours following hospitalization, participants will be randomized to and receive standard-titer ABO-compatible convalescent COVID-19 plasma (CCP2) within 24 hours following random assignment. Standard-titer Convalescent COVID-19 plasma (CCP2): At least two units of CCP transfused 4-24 hours apart on Study Day 0. A third unit may be administered, if available.	Total of all reporting groups
Overall Participants	15	41	56
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	57	62	61
Sex: Female, Male (Count of Participants)
Female	6 40%	14 34.1%	20 35.7%
Male	9 60%	27 65.9%	36 64.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 33.3%	13 31.7%	18 32.1%
Not Hispanic or Latino	10 66.7%	27 65.9%	37 66.1%
Unknown or Not Reported	0 0%	1 2.4%	1 1.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 2.4%	1 1.8%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 13.3%	12 29.3%	14 25%
White	8 53.3%	15 36.6%	23 41.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	5 33.3%	13 31.7%	18 32.1%
Region of Enrollment (Count of Participants)
United States	15 100%	41 100%	56 100%

Outcome Measures

1. Primary Outcome

Title	Total Number of Serious Adverse Events (SAE) Through Study Day 14
Description	Total number of SAE among all participants through Day 14; Definition of SAE per protocol and will only be included if related to COVID-19 Convalescent Plasma (CCP): 1. Death; 2. Life-threatening (immediate risk of death); 3. Prolongation of existing hospitalization; 4. Persistent or significant disability or incapacity; OR 5. Important medical events that may not result in death, be life threatening, or require intervention or escalation of care may be considered a serious adverse event when, based upon appropriate medical judgment, they may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias, or convulsions that do not result in inpatient hospitalization.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High-Titer (CCP1)	Standard-Titer (CCP2)
Arm/Group Description	Within 10 days of COVID symptom onset and no more than 48 hours following hospitalization, participants will be randomized to and receive high-titer ABO-compatible convalescent COVID-19 plasma (CCP1) within 24 hours following random assignment. High-titer Convalescent COVID-19 Plasma (CCP1): At least two units of CCP transfused 4-24 hours apart on Study Day 0. A third unit may be administered, if available.	Within 10 days of COVID symptom onset and no more than 48 hours following hospitalization, participants will be randomized to and receive standard-titer ABO-compatible convalescent COVID-19 plasma (CCP2) within 24 hours following random assignment. Standard-titer Convalescent COVID-19 plasma (CCP2): At least two units of CCP transfused 4-24 hours apart on Study Day 0. A third unit may be administered, if available.
Measure Participants	14	41
Number [Serious Adverse Events]	0	0

2. Primary Outcome

Title	Median Time to Hospital Discharge (or Discharge Equivalent) Following First Dose of CCP
Description	Median number of days to hospital discharge following first dose of CCP among all participants.
Time Frame	up to 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High-Titer (CCP1)	Standard-Titer (CCP2)
Arm/Group Description	Within 10 days of COVID symptom onset and no more than 48 hours following hospitalization, participants will be randomized to and receive high-titer ABO-compatible convalescent COVID-19 plasma (CCP1) within 24 hours following random assignment. High-titer Convalescent COVID-19 Plasma (CCP1): At least two units of CCP transfused 4-24 hours apart on Study Day 0. A third unit may be administered, if available.	Within 10 days of COVID symptom onset and no more than 48 hours following hospitalization, participants will be randomized to and receive standard-titer ABO-compatible convalescent COVID-19 plasma (CCP2) within 24 hours following random assignment. Standard-titer Convalescent COVID-19 plasma (CCP2): At least two units of CCP transfused 4-24 hours apart on Study Day 0. A third unit may be administered, if available.
Measure Participants	14	41
Median (95% Confidence Interval) [Days]	5	7

Adverse Events

Time Frame	From the time participants received the study intervention through Day 28.
Arm/Group Title	High-Titer (CCP1)		Standard-Titer (CCP2)
Arm/Group Description	Within 10 days of COVID symptom onset and no more than 48 hours following hospitalization, participants will be randomized to and receive high-titer ABO-compatible convalescent COVID-19 plasma (CCP1) within 24 hours following random assignment. High-titer Convalescent COVID-19 Plasma (CCP1): At least two units of CCP transfused 4-24 hours apart on Study Day 0. A third unit may be administered, if available.		Within 10 days of COVID symptom onset and no more than 48 hours following hospitalization, participants will be randomized to and receive standard-titer ABO-compatible convalescent COVID-19 plasma (CCP2) within 24 hours following random assignment. Standard-titer Convalescent COVID-19 plasma (CCP2): At least two units of CCP transfused 4-24 hours apart on Study Day 0. A third unit may be administered, if available.
All Cause Mortality
	High-Titer (CCP1)		Standard-Titer (CCP2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/14 (14.3%)		10/41 (24.4%)
Serious Adverse Events
	High-Titer (CCP1)		Standard-Titer (CCP2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/14 (14.3%)		15/41 (36.6%)
Cardiac disorders
Cardiac arrest	1/14 (7.1%)	1	0/41 (0%)	0
Gastrointestinal disorders
Gastrointestinal hemorrhage	0/14 (0%)	0	1/41 (2.4%)	1
Investigations
Alanine aminotransferase increased	0/14 (0%)	0	1/41 (2.4%)	1
Aspartate aminotransferase increased	0/14 (0%)	0	1/41 (2.4%)	1
Blood bilirubin increased	0/14 (0%)	0	1/41 (2.4%)	1
Lymphocyte count decreased	0/14 (0%)	0	2/41 (4.9%)	2
Platelet count decreased	0/14 (0%)	0	1/41 (2.4%)	1
Metabolism and nutrition disorders
Hyperkalemia	0/14 (0%)	0	1/41 (2.4%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/14 (7.1%)	1	10/41 (24.4%)	13
Acute respiratory distress syndrome	0/14 (0%)	0	3/41 (7.3%)	4
Acute respiratory distress	0/14 (0%)	0	1/41 (2.4%)	1
Other (Not Including Serious) Adverse Events
	High-Titer (CCP1)		Standard-Titer (CCP2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/14 (92.9%)		38/41 (92.7%)
Blood and lymphatic system disorders
Anemia	0/14 (0%)	0	14/41 (34.1%)	18
Eosinophilia	1/14 (7.1%)	1	0/41 (0%)	0
Leukopenia	1/14 (7.1%)	1	3/41 (7.3%)	3
Thrombocytopenia	0/14 (0%)	0	2/41 (4.9%)	3
Cardiac disorders
Acute myocardial infarction	1/14 (7.1%)	1	0/41 (0%)	0
Atrial fibrillation	0/14 (0%)	0	4/41 (9.8%)	4
Bradycardia	1/14 (7.1%)	1	2/41 (4.9%)	2
Sinus tachycardia	1/14 (7.1%)	1	1/41 (2.4%)	1
Gastrointestinal disorders
Vomiting	0/14 (0%)	0	2/41 (4.9%)	2
Infections and infestations
Bacteremia	0/14 (0%)	0	3/41 (7.3%)	3
Pneumonia	1/14 (7.1%)	1	4/41 (9.8%)	5
Pneumonia staphylococcal	0/14 (0%)	0	3/41 (7.3%)	4
Escherichia urinary tract infection	1/14 (7.1%)	1	0/41 (0%)	0
Pneumonia bacterial	1/14 (7.1%)	1	2/41 (4.9%)	2
Investigations
Activated partial thromboplastin time prolonged	1/14 (7.1%)	1	4/41 (9.8%)	7
Alanine aminotransferase increased	7/14 (50%)	8	14/41 (34.1%)	18
Aspartate aminotransferase increased	4/14 (28.6%)	5	7/41 (17.1%)	8
Blood albumin decreased	1/14 (7.1%)	1	5/41 (12.2%)	5
Blood bicarbonate decreased	0/14 (0%)	0	3/41 (7.3%)	3
Blood bilirubin increased	0/14 (0%)	0	6/41 (14.6%)	8
Blood creatinine increased	2/14 (14.3%)	2	4/41 (9.8%)	4
Blood potassium decreased	1/14 (7.1%)	1	0/41 (0%)	0
Blood pressure increased	0/14 (0%)	0	4/41 (9.8%)	5
Hemoglobin decreased	1/14 (7.1%)	1	0/41 (0%)	0
International normalized ratio increased	0/14 (0%)	0	7/41 (17.1%)	9
Lymphocyte count decreased	2/14 (14.3%)	2	11/41 (26.8%)	13
Neutrophil count decreased	1/14 (7.1%)	1	2/41 (4.9%)	2
Platelet count decreased	1/14 (7.1%)	1	1/41 (2.4%)	3
White blood cell count decreased	0/14 (0%)	0	3/41 (7.3%)	3
Ejection fraction decreased	1/14 (7.1%)	1	0/41 (0%)	0
Blood alkaline phosphatase increased	1/14 (7.1%)	1	4/41 (9.8%)	4
Metabolism and nutrition disorders
Hyperglycemia	2/14 (14.3%)	2	7/41 (17.1%)	7
Hyperkalemia	1/14 (7.1%)	2	10/41 (24.4%)	11
Hypernatremia	1/14 (7.1%)	1	7/41 (17.1%)	7
Hyperphosphatemia	0/14 (0%)	0	2/41 (4.9%)	2
Hypoalbuminemia	3/14 (21.4%)	4	11/41 (26.8%)	13
Hypocalcemia	0/14 (0%)	0	2/41 (4.9%)	2
Hypoglycemia	0/14 (0%)	0	4/41 (9.8%)	4
Hypokalemia	1/14 (7.1%)	1	4/41 (9.8%)	4
Hyponatremia	4/14 (28.6%)	4	9/41 (22%)	9
Hypophosphatemia	2/14 (14.3%)	2	2/41 (4.9%)	2
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	1/14 (7.1%)	1	0/41 (0%)	0
Psychiatric disorders
Confusional state	1/14 (7.1%)	1	0/41 (0%)	0
Delirium	2/14 (14.3%)	2	0/41 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/14 (7.1%)	1	1/41 (2.4%)	1
Pneumothorax	1/14 (7.1%)	1	0/41 (0%)	0
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/14 (7.1%)	1	0/41 (0%)	0
Vascular disorders
Hypertension	0/14 (0%)	0	7/41 (17.1%)	11
Hypotension	0/14 (0%)	0	3/41 (7.3%)	3
Venous occlusion	1/14 (7.1%)	1	0/41 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.