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Plasma for Early Treatment in Non-hospitalised Mild or Moderate COVID-19 Patients

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ClinicalTrials.gov Identifier: NCT04621123
Recruitment Status : Recruiting
First Posted : November 9, 2020
Last Update Posted : November 9, 2020
Sponsor:
Collaborators:
Germans Trias i Pujol Hospital
IrsiCaixa
Banc de Sang i Teixits
Grifols Biologicals, LLC
Information provided by (Responsible Party):
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Brief Summary:

This is a prospective, randomized (1:1), double blind study of Convalescent anti-SARS-CoV-2 MBT Plasma (also known as convalescent plasma) plus standard medical treatment (SMT) versus placebo plus SMT in mild or moderate COVID-19 patients who are non-hospitalised. Subjects with confirmed infection by SARS-CoV-2 will receive SMT plus a total of 200-250 mL of convalescent plasma that has been pathogen-inactivated using MBT or placebo.

Approximately 474 individuals will be randomized (1:1) with an interim analysis after the first 60 subjects (30 in each arm).

The sample size will be re-assessed upon interim analysis. Approximately 135 individuals from selected study sites will be included in the substudy to assess the immune response and the methods of sampling.

This is a prospective, randomized (1:1), double blind study of Convalescent anti-SARS-CoV-2 MBT Plasma (also known as convalescent plasma) plus standard medical treatment (SMT) versus placebo plus SMT in mild or moderate COVID-19 patients who are non-hospitalised. Subjects with confirmed infection by SARS-CoV-2 will receive SMT plus a total of 200-250 mL of convalescent plasma that has been pathogen-inactivated using MBT or placebo.

Approximately 474 individuals will be randomized (1:1) with an interim analysis after the first 60 subjects (30 in each arm).

The sample size will be re-assessed upon interim analysis. Approximately 135 individuals from selected study sites will be included in the substudy to assess the immune response and the methods of sampling.

The investigational product will be administered by IV infusion at baseline. Participants will continue their standard medical treatment (SMT) for SARS-CoV-2 infection as prescribed by their regular physician. If applicable, SMT may be modified during the study, depending on personal requirements, the severity and progression of the disease, and need for hospitalization.

Subjects' participation (from inclusion/baseline visit to the end-of-study visit) will be up to 60 days.


Condition or disease Intervention/treatment Phase
SARS-CoV-2 Infection Safety and Efficacy Biological: Convalescent anti-SARS-CoV-2 MBT plasma Other: Control Group Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 474 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Prospective, randomized (1:1), double blind study of Convalescent anti-SARS-CoV-2 MBT Plasma (also known as convalescent plasma) plus standard medical treatment (SMT) versus placebo plus SMT in mild or moderate COVID-19 patients who are non-hospitalised. Subjects will be followed up to 60 days after infusion
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Convalescent Methylene Blue Treated (MBT) Plasma for Early Treatment in Non-hospitalised Mild or Moderate COVID-19 Patients: a Randomized Double Blind Study (COnV-ert)
Actual Study Start Date : October 30, 2020
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : October 2021

Arm Intervention/treatment
Experimental: Experimental group
Subjects randomized to convalescent anti-SARS-CoV-2 MBT plasma plus SMT will receive one infusion of 200 to 250 ml of ABO-compatible convalescent plasma obtained from a convalescent donor.
Biological: Convalescent anti-SARS-CoV-2 MBT plasma
Subjects randomized to combination convalescent anti-SARS-CoV-2 MBT plasma plus SMT will undergo an ABO compatibility test and will receive a single infusion of 200 to 250 ml of ABO-compatible convalescent plasma

Placebo Comparator: Control Group
Subjects randomized to placebo plus SMT will receive one infusion of 200 to 250 ml of sterile saline solution 0.9%.
Other: Control Group
Subjects randomized to placebo plus SMT will receive one infusion of 200 to 250 ml of sterile saline solution 0.9%.
Other Name: Sterile saline solution 0.9%




Primary Outcome Measures :
  1. Hospitalization rate (safety and efficacy) [ Time Frame: Day 28 ]
    Assess the therapeutic potential of early administration of convalescent MBT plasma in reducing the rate of hospitalization in non-hospitalised mild or moderate COVID-19 patients.

  2. SARS-CoV-2 viral load (safety and efficacy) [ Time Frame: Day 7 ]
    Assess the therapeutic potential of early administration of convalescent MBT plasma in reducing SARS-CoV-2 viral load at day 7, measured by quantitative RT-PCR (RT-qPCR) in non-hospitalised mild or moderate COVID-19 patients.


Secondary Outcome Measures :
  1. COVID-19 WHO Clinical progression scale score (safety and efficacy) [ Time Frame: Day 60 ]

    Change in COVID-19 World Health Organization WHO Clinical progression scale score to assess hospitalization rate (i.e. who reach a score ≥4).

    • Minimum to maximum scores below:
    • Score 0 (uninfected) - Uninfected; no viral RNA detected
    • Score 1 (ambulatory mild disease) - Asymptomatic; viral RNA detected
    • Score 2 (ambulatory mild disease) - Symptomatic; independent
    • Score 3 (ambulatory mild disease) - Symptomatic; assistance needed
    • Score 4 (hospitalised: moderate disease) - Hospitalised; no oxygen therapy
    • Score 5 (hospitalised: moderate disease) - Hospitalised; oxygen by mask or nasal prongs
    • Score 6 (hospitalised: severe diseases) - Hospitalised; oxygen by NIV or high flow
    • Score 7 (hospitalised: severe diseases) - Intubation Score 8 (hospitalised: severe diseases) - Mechanical ventilation pO2/FiO2 <150 (SpO2/FiO2 <200) or vasopressors
    • and mechanical ventilation, pO2/FiO2 ≥150 or SpO2/FiO2 ≥200

  2. COVID-19 symptoms severity score (safety and efficacy) [ Time Frame: Day 14 ]

    Change in COVID-19 symptoms severity score, assessed with the COVID-19 daily self-score tool (FLU- patient-reported outcome measure (FLU-PRO©) PLUS instrument), certified-Spanish translation. COVID-19 daily self-score tool to assess symptom severity across six body systems: nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic. Data on the presence/absence of symptoms, symptom profiles, and change over time.

    Items 1-27 are Likert scale questions to score symptom severity (rated 0-4): 0=not at all;4=very much. Items 28-32 are also Likert scale questions (rated 0-4) measuring frequency of specific daily symptoms: 0=never or 0 times;4=always or 4 times. Items 33 and 34 measure the presence/absence of COVID-19 specific symptoms: 0=no;1=yes. Total maximum score of FLU-PRO© PLUS 134


  3. Resolution of symptoms (safety and efficacy) [ Time Frame: Day 28 ]
    Time to complete resolution of symptoms

  4. Death rate (safety and efficacy) [ Time Frame: Day 60 ]
    Death rate

  5. Adverse events (AE) (safety and efficacy) Adverse events (AE) Adverse events (AE) [ Time Frame: Day 28 ]
    Proportion of patients with adverse events (AE) and proportion of grade ≥4 AE, based on the FDA Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers scale

  6. Ferritin (safety and efficacy) [ Time Frame: Baseline and Day 7 ]
    Change in inflammatory prognostic markers (ferritin)

  7. Prealbumin (safety and efficacy) [ Time Frame: Baseline and Day 7 ]
    Change in inflammatory prognostic markers (prealbumin)

  8. Interleukin 6 (IL-6) (safety and efficacy) [ Time Frame: Baseline and Day 7 ]
    Change in inflammatory prognostic markers (Interleukin 6 (IL-6))

  9. D-dimer (safety and efficacy) [ Time Frame: Baseline and Day 7 ]
    Change in inflammatory prognostic markers (D-dimer)

  10. C reactive protein (CRP) (safety and efficacy) [ Time Frame: Baseline and Day 7 ]
    Change in inflammatory prognostic markers (C reactive protein (CRP))

  11. Leukocyte count (safety and efficacy) [ Time Frame: Baseline and Day 7 ]
    Change in inflammatory prognostic markers (Leukocyte count)

  12. Lymphocyte count (safety and efficacy) [ Time Frame: Baseline and Day 7 ]
    Change in inflammatory prognostic markers (Lymphocyte count)

  13. Absolute neutralization titers against SARS-CoV-2 in plasma (safety and efficacy) [ Time Frame: Baseline and Day 7 ]
    Intergroup comparison of absolute neutralization titers against SARS-CoV-2 in plasma in a subgroup of 135 participants

  14. Titers of neutralizing antibodies against SARS-CoV-2 in plasma (safety and efficacy) [ Time Frame: Baseline and Day 60 ]
    Change in titers of neutralizing antibodies against SARS-CoV-2 in plasma in a subgroup of 135 participants

  15. SARS-CoV-2 viral load of self-collected middle turbinate (MT) swab and saliva samples compared to nasopharyngeal swabs collected by a healthcare worker (safety and efficacy) [ Time Frame: Baseline and Day 7 ]

    Agreement and SARS-CoV-2 viral load of self-collected middle turbinate (MT) swab and saliva samples compared to nasopharyngeal swabs collected by a healthcare worker in a subgroup of 135 participants

    Outcome 18: Secondary Outcome Measure:


  16. Reduction of SARS-CoV-2 viral load (safety and efficacy) [ Time Frame: Baseline and Day 28 ]
    Reduction of SARS-CoV-2 viral load in nasopharyngeal swabs at day 28 after start of treatment, as determined by RT-qPCR



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 1. Adult male or female individuals of ≥50 years old.
  2. 2. In women of childbearing potential1, negative pregnancy test at inclusion/baseline.
  3. 3. Has confirmed SARS-CoV-2 infection as determined by PCR or validated antigen rapid diagnostic test2 from nasopharyngeal swabs ≤5 days prior to inclusion/baseline visit.
  4. 4. Symptomatic with mild or moderate COVID-19 with symptoms onset date ≤ 7 days prior to inclusion/baseline visit.

    1. a. Mild COVID-19: Individuals who have any of the common signs and/or symptoms of COVID-19 (i.e., fever, cough, sore throat, malaise, headache, muscle pain) without shortness of breath, dyspnoea, or abnormal chest imaging.
    2. Moderate COVID-19: Individuals who have evidence of lower respiratory disease by clinical assessment or imaging and a saturation of oxygen (SpO2) ≥94% on room air at sea level.
  5. 5. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.
  6. 6. Has understood the information provided and capable of giving informed consent.

1 A woman will be considered of childbearing potential if not permanently sterilized nor postmenopausal. Permanent sterilization methods include tubal ligation, hysterectomy and bilateral oophorectomy. Postmenopausal is defined as 12 months with no menses without an alternative medical cause.

2 PanbioTM COVID-19 Ag Rapid Test (Abbott), STANDARDTM Q COVID-19 Ag Test (Roche) or any other CE marketed test for SARS-CoV-2 Ag detection.

Exclusion Criteria:

  1. If female, pregnant, breastfeeding, or planning a pregnancy during the study.
  2. Severe or critical COVID-19:

    1. Severe COVID-19: respiratory frequency >30 breaths per minute, SpO2 <94% on room air at sea level, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mmHg, or lung infiltrates >50%.
    2. Critical COVID-19: respiratory failure, septic shock, and/or multiple organ dysfunction.
  3. Current hospital admission for any cause.
  4. History of previous confirmed SARS-CoV-2 infection.
  5. History of significantly abnormal liver function (Child Pugh C).
  6. History of chronic kidney disease (CKD) ≥ stage 4, or need of dialysis treatment.
  7. Any pre-existing condition that increases risk of thrombosis.
  8. History of allergic reactions to blood or plasma products or methylene blue.
  9. Known IgA deficiency with anti-IgA antibodies.
  10. Medical conditions for which 250 ml of intravenous fluid is considered dangerous (i.e., decompensated heart failure or renal failure with fluid overload).
  11. Inability to consent and/or comply with study requirements, in the opinion of the investigator.
  12. Currently participating or planning to participate in any interventional study for the treatment of COVID-19 or SARS-CoV-2 infection until day 60.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04621123


Contacts
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Contact: Oriol Mitjà Villar, PhD, MD 934978849 omitja@flsida.org

Locations
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Spain
Germans Trias i Pujol Hospital Recruiting
Badalona, Barcelona, Spain, 08916
Contact: ORIOL Mitjà Villar, MD,Phd    934978849    omitja@flsida.org   
Principal Investigator: ORIOL Mitjà Villar, MD,PhD         
Sponsors and Collaborators
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Germans Trias i Pujol Hospital
IrsiCaixa
Banc de Sang i Teixits
Grifols Biologicals, LLC
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Responsible Party: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
ClinicalTrials.gov Identifier: NCT04621123    
Other Study ID Numbers: COnV-ert
First Posted: November 9, 2020    Key Record Dates
Last Update Posted: November 9, 2020
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia:
Convalescent anti-SARS-CoV-2 MBT Plasma
Convalescent plasma
SARS-CoV-2
Safety
Efficacy