Convalescent Plasma for Early Treatment of COVID-19

NCT04390503 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAT0052
• Study Type: interventional
• Target: 223
• Locations: 1 country
• Sites: 1

Brief Summary

This is a double-blinded, randomized control trial to assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma as early treatment. Participants will be randomized 2:1 to receive either convalescent plasma qualitatively positive for SARS-CoV-2 antibody ("anti-SARS-CoV-2 plasma") or control (albumin 5%). This study will investigate the potential of convalescent plasma (CP) to reduce severity of and/or help treat SARS-CoV-2 disease in patients with mild disease.

Conditions

SARS-CoV 2; COVID-19

Keywords

Coronavirus; COVID; Convalescent Plasma

Outcome Measures

Primary Outcomes (3)

• Number of Non-Hospitalized Participants

  Participants who were discharged from the hospital after receiving the study intervention.

  Up to 28 days

• Number of Hospitalized Participants Requiring Supplemental Oxygen

  Participants who remained hospitalized and required supplemental oxygen after receiving the study drug.

  Up to 28 days

• Number of Hospitalized Participants Requiring High-flow Oxygen Therapy or Noninvasive Mechanical Ventilation

  Participants who remained hospitalized and required high-flow oxygen therapy or noninvasive mechanical ventilation after receiving the study intervention.

  Up to 28 days

Secondary Outcomes (5)

• Number of In-hospital Mortalities

  Up to 28 days

• Rate of Measurable Anti-SARS-CoV-2 Titers

  Up to 90 days

• Rate of SARS-CoV-2 PCR Positivity

  Up to 28 days

• Duration of SARS-CoV-2 PCR Positivity

  Up to 28 days

• Levels of SARS-CoV-2 RNA

  Up to 28 days

Study Arms (2)

Convalescent Plasma (anti-SARS-CoV-2 plasma)

EXPERIMENTAL

Participants randomized to the experimental arm will receive 2 units (approximately 200 to 250 mL per unit, total 400-500mL) of convalescent plasma that was collected from a volunteer who recovered from COVID-19 disease.

Biological: Convalescent Plasma (anti-SARS-CoV-2 plasma)

Control (albumin 5%)

ACTIVE COMPARATOR

Participants randomized to the control arm will receive 2 units of 250 mL (500mL total) of albumin (human) 5% infusion. The albumin will be prepared in bags that are identical to the bags used for plasma. The similar appearance of albumin and plasma will facilitate maintaining the blinded status of subjects and most of the study staff.

Biological: Control (albumin 5%)

Interventions

Convalescent Plasma (anti-SARS-CoV-2 plasma) BIOLOGICAL

Convalescent Plasma that contains antibody titers against SARS-CoV-2.

Convalescent Plasma (anti-SARS-CoV-2 plasma)

Control (albumin 5%) BIOLOGICAL

Albumin (Human) 5% is a sterile aqueous solution for intravenous use containing the albumin component human plasma.

Control (albumin 5%)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be 18 years of age or older
• Recent close contact with a person with COVID-19, i.e. last close contact occurred within 7 days of anticipated infusion of study product. It is anticipated that most contacts will be household contacts with extensive interaction. All must meet the CDC criteria for close contacts. This includes healthcare workers at higher risk of developing severe disease.
• Recent self-reported or documented evidence of infection by nasal swab PCR that is positive for SARS-CoV-2, i.e., nasal sample was collected within 7 days or 10 days of anticipated infusion of study product for those who are asymptomatic or symptomatic, respectively.
• Evidence of infection by nasal swab PCR that is positive for SARS-CoV-2 at screening visit.
• May or may not be hospitalized.
• No symptoms or no more than 5 days of mild symptoms at the time of screening. Mild symptoms (rated by participant as mild and not interfering with normal daily activities) may include:
• Mild rhinorrhea
• Mild sore throat or throat irritation
• Mild nonproductive cough
• Mild fatigue (able to perform Activities of Daily Living (ADLs))
• Risk for severe COVID-19 based on a risk score of ≥ 1 Calculated Risk Score of ≥ 1 point, with risk factors based on Center for Disease Control and Prevention (CDC) description
• Age 65-74: 1 point
• Age ≥ 75: 2 points
• Known cardiovascular disease (including hypertension): 1 point
• Diabetes mellitus: 1 point

You may not qualify if:

• Receipt of any blood product in past 120 days.
• Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the principal investigator, would affect subject safety and/or compliance.
• Confirmed or self-reported presumed COVID-19, with symptoms that began more than 5 days prior to enrollment, and SARS-CoV-2 PCR positive sample that was collected more than 7 days prior to anticipated infusion for an asymptomatic participant or more than 10 days prior to anticipated infusion for a patient with mild symptoms at screening.
• Symptoms consistent with COVID---19 infection that are more than mild (as defined above) at time of screening.
• Symptoms consistent with COVID---19 infection that are more than mild at time of screening.
• History of allergic reaction to transfusion blood products
• Inability to complete infusion of the product within 48 hours after randomization.
• Resident of a long term or skilled nursing facility
• Known prior diagnosis of immunoglobulin A (IgA) deficiency
• Oxygen saturation that is \< 95% at the screening visit
• On supplemental oxygen at time of enrollment
• Participation in another clinical trial of anti-viral agent(s) for COVID-19
• Receipt of any COVID-19 vaccine, either as part of a clinical research trial or through routine service delivery.

Sponsors & Collaborators

• Andrew Eisenberger: lead

Study Sites (1)

National Institute of Infectious Diseases Evandro Chagas (INI)

Rio de Janeiro, 21040-900, Brazil

Location

Related Publications (7)

• Arabi YM, Hajeer AH, Luke T, Raviprakash K, Balkhy H, Johani S, Al-Dawood A, Al-Qahtani S, Al-Omari A, Al-Hameed F, Hayden FG, Fowler R, Bouchama A, Shindo N, Al-Khairy K, Carson G, Taha Y, Sadat M, Alahmadi M. Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia. Emerg Infect Dis. 2016 Sep;22(9):1554-61. doi: 10.3201/eid2209.151164.

  PMID: 27532807 BACKGROUND

• Casadevall A, Dadachova E, Pirofski LA. Passive antibody therapy for infectious diseases. Nat Rev Microbiol. 2004 Sep;2(9):695-703. doi: 10.1038/nrmicro974.

  PMID: 15372080 BACKGROUND

• Casadevall A, Pirofski LA. Antibody-mediated regulation of cellular immunity and the inflammatory response. Trends Immunol. 2003 Sep;24(9):474-8. doi: 10.1016/s1471-4906(03)00228-x. No abstract available.

  PMID: 12967670 BACKGROUND

• Casadevall A, Scharff MD. Serum therapy revisited: animal models of infection and development of passive antibody therapy. Antimicrob Agents Chemother. 1994 Aug;38(8):1695-702. doi: 10.1128/AAC.38.8.1695. No abstract available.

  PMID: 7985997 BACKGROUND

• Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, Ng MH, Chan P, Wong KC, Leung CB, Cheng G. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005 Jan;24(1):44-6. doi: 10.1007/s10096-004-1271-9.

  PMID: 15616839 BACKGROUND

• Crowe JE Jr, Firestone CY, Murphy BR. Passively acquired antibodies suppress humoral but not cell-mediated immunity in mice immunized with live attenuated respiratory syncytial virus vaccines. J Immunol. 2001 Oct 1;167(7):3910-8. doi: 10.4049/jimmunol.167.7.3910.

  PMID: 11564809 BACKGROUND

• Gunn BM, Yu WH, Karim MM, Brannan JM, Herbert AS, Wec AZ, Halfmann PJ, Fusco ML, Schendel SL, Gangavarapu K, Krause T, Qiu X, He S, Das J, Suscovich TJ, Lai J, Chandran K, Zeitlin L, Crowe JE Jr, Lauffenburger D, Kawaoka Y, Kobinger GP, Andersen KG, Dye JM, Saphire EO, Alter G. A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus. Cell Host Microbe. 2018 Aug 8;24(2):221-233.e5. doi: 10.1016/j.chom.2018.07.009.

  PMID: 30092199 BACKGROUND

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Jessica Justman, MD
• Organization: Columbia University

jj2158@cumc.columbia.edu

212-342-0537

Study Officials

• Jessica Justman, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: A total of 150 eligible subjects will be randomized in a 2:1 ratio to receive either convalescent plasma qualitatively positive for SARS-CoV-2 antibody (anti-SARS-CoV-2 plasma) or control (albumin 5%)

Study Record Dates

• First Submitted: May 14, 2020
• First Posted: May 15, 2020
• Study Start: March 12, 2021
• Primary Completion: January 6, 2022
• Study Completion: January 6, 2022
• Last Updated: August 28, 2024
• Results First Posted: August 28, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)