Clinical trial NCT04390503: Convalescent Plasma for Early Treatment of COVID-19
Official title: A Phase 2 Randomized, Double-blinded Trial to Evaluate the Efficacy and Safety of Human Anti-SARS-CoV-2 Plasma for Early Treatment of COVID-19
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: SARS-CoV 2
COVID-19
Keywords: Coronavirus
COVID
Convalescent Plasma
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2020-05-15
Enrollment: 223
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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%)
Primary purpose: TREATMENT

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.

Detailed description: There are no approved therapies for Coronavirus disease 2019 (COVID-19), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Exposure to viruses results in an adaptive immune response that commonly include antibodies with neutralization activity. Plasma from subjects who have recovered from viral infections has been used to both prevent or treat disease. Notable examples of the successful use of convalescent plasma (CP) include influenza, measles, Argentine hemorrhagic fever, Middle East respiratory syndrome (MERS), Ebola and severe acute respiratory syndrome (SARS). In recent work in China, an open label safety trial of CP in patients with COVID-19 suggested a substantive benefit.

Eligibility criteria: Inclusion Criteria:

* 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.

OR

* 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
  * Pulmonary disease (COPD, moderate to severe asthma, current smoking or other): 1 point
  * Morbid obesity: 1 point
  * Immunocompromised state: 1 point Received a bone marrow or solid organ transplant at any time, received chemotherapy for a malignancy within the past 6 months, has an acquired or congenital immunodeficiency, currently receiving immunosuppressive or immune modulating medications, HIV with non-suppressed viral load and/or cluster of differentiation 4 (CD4+) T cell count \<200 cells/mL).

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Number of Non-Hospitalized Participants
timeFrame: Up to 28 days
measure: Number of Hospitalized Participants Requiring Supplemental Oxygen
timeFrame: Up to 28 days
measure: Number of Hospitalized Participants Requiring High-flow Oxygen Therapy or Noninvasive Mechanical Ventilation
timeFrame: Up to 28 days
Secondary outcomes:
measure: Number of In-hospital Mortalities
timeFrame: Up to 28 days
measure: Rate of Measurable Anti-SARS-CoV-2 Titers
timeFrame: Up to 90 days
measure: Rate of SARS-CoV-2 PCR Positivity
timeFrame: Up to 28 days
measure: Duration of SARS-CoV-2 PCR Positivity
timeFrame: Up to 28 days
measure: Levels of SARS-CoV-2 RNA
timeFrame: Up to 28 days
Other outcomes:
Locations:
city: Rio de Janeiro
country: Brazil
facility: National Institute of Infectious Diseases Evandro Chagas (INI)
Study officials:
affiliation: Columbia University
name: Jessica Justman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.