Convalescent Plasma (PC) and Human Intravenous Anti-COVID-19 Immunoglobulin (IV Anti COVID-19 IgG) in Patients Hospitalized for COVID-19.

Coronavirus Disease 2019 (COVID-19) Clinical Trial

Official title:

A Randomized, Multicenter Clinical Trial to Evaluate the Efficacy and Safety of the Use of Convalescent Plasma (PC) and Human Intravenous Anti COVID-19 Immunoglobulin (IV Anti COVID-19 IgG) in Patients Hospitalized for COVID-19.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04395170
• Other study ID #: LFCOLCOVID-19-001
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: September 2020
• Est. completion date: June 2021

Study information

• Verified date: July 2020
• Source: Lifefactors Zona Franca, SAS
• Contact: Santiago Jaramillo
• Phone: +573128092776
• Email: sjaramillo[@]lifefactors.co
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A randomized, open-label, multicenter, three-arm clinical trial to study the efficacy and safety of passive immunotherapy (convalescent plasma and anti-COVID-19 human immunoglobulin) compared to the standard treatment in Colombia.

Description:

The study population will be patients (≥18 years) hospitalized by COVID-19 but still with an early form of the disease (in states 1-3 of the ordinal scale) who do not require mechanical ventilation (invasive or non-invasive) and who can give their consent informed.

All the participants will receive non-specific supportive treatment for COVID-19 such as oxygen, IV liquid or corticosteroids. Additionally, they will be randomized to one of the following arms:

Experimental arm 1: Plasma with inactivation/reduction of pathogens from convalescent patients with COVID-19 and who at the same time receive support therapy, in the 200 - 250 mL scheme, on days 1 and 3 of the intervention.

Experimental arm: Anti-COVID-19 human immunoglobulin produced by Lifefactors Zona Franca S.A.S, intravenous at a dose of immunoglobulin 10% IgG solution (10% mL vial) for:

Patient of 50 Kg or more, a dose of 50 mL will be applied on days 1 and 3 of treatment.

Patients of less than 50 Kg, the dose will be 1 mL / Kg, will be applied on days 1 and 3 of treatment.

This arm will be included once available. The supply of anti-COVID-19 human immunoglobulin produced by LifeFactors will be carried out once the national regulatory agency (Invima) grants authorization and/or the regulatory requirements for the production of medications are met.

Control arm: Standard (specific) therapy for COVID-19 according to the suggested pharmacological recommendations of the Colombian Association of Infectious Diseases - ACIN. This therapy is subject to changes that are determined by the Colombian Health Regulatory Authorities.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 75
• Est. completion date: June 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Obtaining the informed written consent before carrying out the study procedures, by the patients.

2. Adult patients =18 years at the time of recruitment for the study.

3. Patients with laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction on nasal/oropharyngeal swabs or any other relevant specimen <72 hours before randomization.

4. Patients requiring hospitalization for COVID-19 without mechanical ventilation (invasive or non-invasive, including an oxygen mask with reserve bag) and at least one of the following:

1. Radiographic evidence of pulmonary infiltrates by images (chest radiography, computed tomography, etc.),

2. Clinical evaluation (evidence of rales/crackles on examination) and oxygen saturation = 94% in ambient air requiring supplemental oxygen.

5. Patient with no more than 72 hours (3 days) of hospitalization prior to the administration of PC treatment (except the days after initial hospital admission for other reasons and prior to COVID-19 infection).

6. Patients who do not have more than 10 days between the onset of symptoms (fever or cough) and the day of administration of treatment or the demonstration of the absence of anti-SARS-CoV-2 antibodies (patients with more than 10 days of symptoms they can only be included if a negative antibody result has been confirmed).

Exclusion Criteria:

1. Patient in a state of pregnancy.

2. Require mechanical ventilation (invasive or non-invasive, including oxygen mask with reserve bag) on examination.

3. Participation in any other clinical trial of an experimental treatment for COVID-19.

4. At the discretion of the clinical team, progression to death is imminent and inevitable within the next 24 hours, regardless of the provision of treatments.

5. Any incompatibility or allergy to the administration of plasma of human origin.

6. Severe chronic kidney disease in stage 4 or requiring dialysis (that is, glomerular filtration rate <30).

7. Any condition that in the investigator's opinion limits participation in the study.

Related Conditions & MeSH terms

• Coronavirus Disease 2019 (COVID-19)
• Coronavirus Infections

Intervention

Biological:
• COVID-19 convalescent plasma
Plasma from convalescent patients with COVID-19 and at the same time receiving supportive therapy, with inactivation / reduction of pathogens, in the scheme of two doses of 200 - 250 mL administered on days 1 and 3 of the intervention.
• Anti-COVID-19 human immunoglobulin
Anti-COVID-19 human immunoglobulin produced by Lifefactors Zona Franca S.A.S, intravenously at a dose of immunoglobulin 10% IgG solution (10% mL vial) for: Patient of 50 Kg or more, a dose of 50 mL, administered on days 1 and 3 of treatment. Patient under 50 Kg, the dose will be 1 mL / Kg, administered on days 1 and 3 of treatment. The supply of anti-COVID-19 human immunoglobulin produced by Lifefactors Zona Franca S.A.S included once it has been authorized by INVIMA and/or the regulatory requirements in force for the production of drugs are met.

Drug:
• Standard (specific) therapy for COVID-19
Standard therapy for COVID-19 according to the recommended pharmacological recommendations of the Colombian Association of Infectious Diseases - ACIN. This therapy is subject to changes that are defined by the Colombian Health Regulatory Authorities. To date, these therapies may include remdesivir, chloroquine, hydroxychloroquine, azithromycin.

Locations

Country	Name	City	State
Colombia	LifeFactors Zona Franca SAS	Medellín	Antioquia

Sponsors (1)

Lead Sponsor	Collaborator
Lifefactors Zona Franca, SAS

Country where clinical trial is conducted

Colombia, 

References & Publications (14)

Cancer Institute N. Common Terminology Criteria for Adverse Events (CTCAE) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 [Internet]. 2017. Available from: https://www.meddra.org/

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. — View Citation

Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, Zhou M, Chen L, Meng S, Hu Y, Peng C, Yuan M, Huang J, Wang Z, Yu J, Gao X, Wang D, Yu X, Li L, Zhang J, Wu X, Li B, Xu Y, Chen W, Peng Y, Hu Y, Lin L, Liu X, Huang S, Zhou Z, Zhang L, Wang Y, Zhang Z, Deng K, Xia — View Citation

FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency | FDA [Internet]. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-guidance-conduct-clinical-trials-medical-

Francis F, Hall M, Surg, Gaines A. Early use of convalescent serum in influenza. Mil Surg. 1920;47:177-9.

Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, Makki S, Rooney KD, Nguyen-Van-Tam JS, Beck CR; Convalescent Plasma Study Group. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe — View Citation

Redden WR. Treatment of Influenza-Pneumonia by Use of Convalescent Human Serum. Bost Med Surg J. 1919 Dec 11;181(24):688-91.

rice H, Genereux M, Sinclair C. Hyperimmune Immunoglobulin G. In: Production of Plasma Proteins for Therapeutic Use [Internet]. Hoboken, NJ, USA: John Wiley & Sons, Inc.; 2012.

Soo YO, Cheng Y, Wong R, Hui DS, Lee CK, Tsang KK, Ng MH, Chan P, Cheng G, Sung JJ. Retrospective comparison of convalescent plasma with continuing high-dose methylprednisolone treatment in SARS patients. Clin Microbiol Infect. 2004 Jul;10(7):676-8. — View Citation

Use of Convalescent Whole Blood or Plasma Collected from Patients Recovered from Ebola Virus Disease for Transfusion, as an Empirical Treatment during Outbreaks Interim Guidance for National Health Authorities and Blood Transfusion Services Use of Convale

van Griensven J, Edwards T, Baize S; Ebola-Tx Consortium. Efficacy of Convalescent Plasma in Relation to Dose of Ebola Virus Antibodies. N Engl J Med. 2016 Dec 8;375(23):2307-2309. doi: 10.1056/NEJMc1609116. Epub 2016 Nov 14. — View Citation

Vargas M, Segura Á, Wu YW, Herrera M, Chou ML, Villalta M, León G, Burnouf T. Human plasma-derived immunoglobulin G fractionated by an aqueous two-phase system, caprylic acid precipitation, and membrane chromatography has a high purity level and is free o — View Citation

Wong VW, Dai D, Wu AK, Sung JJ. Treatment of severe acute respiratory syndrome with convalescent plasma. Hong Kong Med J. 2003 Jun;9(3):199-201. — View Citation

Zingher A, Mortimer P. Convalescent whole blood, plasma and serum in the prophylaxis of measles: JAMA, 12 April, 1926; 1180-1187. Rev Med Virol. 2005 Nov-Dec;15(6):407-18; discussion 418-21. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Admission to ICU and/or mechanical ventilation	Admission to the intensive care unit with the requirement of mechanical ventilation (invasive or non-invasive) due to Acute Respiratory Distress Syndrome by COVID-19.	One year
Secondary	Length of hospital stay	Time in the hospital from admission to discharge or death.	One year
Secondary	Neutralizing antibody (IgG) titers against COVID-19	Neutralizing antibody (IgG) titers against COVID-19	One year
Secondary	Safety - Adverse events	Non-serious adverse events (NSAEs) and serious adverse events (SAEs)	One year
Secondary	Death	Overall mortality	One year