SARS-CoV-2 Antibodies Based IVIG Therapy for COVID-19 Patients

Study Overview
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Brief Summary
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Severe and critically ill patients will be enrolled in the study (50 patients) after duly filled consent forms. Recipients shall be divided in to 5 groups with 10 patients per group to compare clinical efficacy and safety of patients in clinical phase I/phase II study. Each group shall receive particular single dose of Intravenously administered Immunoglobulins (IVIG) developed from convalescent plasma of recovered COVID-19 individual , an experimental drug along with standard treatment except for control group which will receive standard treatment only.

Detailed Description
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Passive immunization using intravenous immunoglobulins (IVIG) has been tested for treating previous viral outbreaks and holds the potential to save lives in the current crisis. Recently researchers from China reported satisfactory recovery of critically ill Corona Virus Disease 2019 (COVID 19) patients when high dose intravenous immunoglobulin (IVIG) were administered. Research team at Dow University of Health Sciences has purified immunoglobulin (both SARS-CoV 2 antibodies and existing antibodies) from convalescent plasma of COVID19 individuals and pooled to prepared IVIG formulation to treat severe and critically ill COVID-19 patients. To evaluate safety of the formulation animal (rats) safety trials and survival of all the animals were observed. It is intended to assess safety and efficacy of experimental the IVIG treatment in severe and critically ill COVID 19 patients through phase I/phase II randomized single blinded clinical trial with fifty study participants. FDA outlined criteria for passive immunization using convalescent plasma, which will be used for recruiting participants in the study.

Official Title
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Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) Antibodies Based Intravenous Immunoglobulin (IVIG) Therapy for Severe and Critically Ill COVID-19 Patients

Conditions
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COVID-19

Intervention / Treatment
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* Biological: SARS-CoV-2 antibody based IVIG therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Above 18 years of age Have positive SARS-CoV-2 PCR on nasopharyngeal and/or oropharyngeal swabs Admitted in isolation ward and ICU of institutes affiliated with DUHS have severe or critical COVID 19 as judged by the treating physician Consent given by the patient or first degree relative Exclusion Criteria: Pregnancy Previous allergic reaction to immunoglobulin treatment Ig A deficiency Patient requiring 2 inotropic agents to maintain blood pressures Known case of any autoimmune disorder Acute kidney injury or chronic renal failure Known case of thromboembolic disorder Aseptic meningitis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Standard care only n = 10 patients. | |
| Experimental: IVIG dose: 0.15 g/kg<br>Standard Care + Single dose of 0.20 g/Kg anti-COVID-19 IVIG (experimental drug prepared at DUHS) n= 10 patients | Biological: SARS-CoV-2 antibody based IVIG therapy<br>* Patient groups will receive IVIG prepared from pooled convalescent plasma from recovered COVID-19 patients. This will be administered sequentially and in varying dosages, infused over a period of 12 hours, intravenously.Additionally, all treatment groups will receive same standard care as control group. Standard Care as per hospital protocol, which may include: Airway support, Anti-Viral medication, Antibiotics, Fluid Resuscitation, Hemodynamic Support, Steroids, Painkillers, Anti-Pyretics<br>|
| Experimental: IVIG dose: 0.20 g/kg<br>Standard Care + Single dose of 0.25 g/Kg anti-COVID19 IVIG (experimental drug prepared at DUHS) n= 10 patients | Biological: SARS-CoV-2 antibody based IVIG therapy<br>* Patient groups will receive IVIG prepared from pooled convalescent plasma from recovered COVID-19 patients. This will be administered sequentially and in varying dosages, infused over a period of 12 hours, intravenously.Additionally, all treatment groups will receive same standard care as control group. Standard Care as per hospital protocol, which may include: Airway support, Anti-Viral medication, Antibiotics, Fluid Resuscitation, Hemodynamic Support, Steroids, Painkillers, Anti-Pyretics<br>|
| Experimental: IVIG dose: 0.25 g/kg<br>Standard Care + Single dose of 0.30 g/Kg anti-COVID19 IVIG (experimental drug prepared at DUHS) n= 10 patients | Biological: SARS-CoV-2 antibody based IVIG therapy<br>* Patient groups will receive IVIG prepared from pooled convalescent plasma from recovered COVID-19 patients. This will be administered sequentially and in varying dosages, infused over a period of 12 hours, intravenously.Additionally, all treatment groups will receive same standard care as control group. Standard Care as per hospital protocol, which may include: Airway support, Anti-Viral medication, Antibiotics, Fluid Resuscitation, Hemodynamic Support, Steroids, Painkillers, Anti-Pyretics<br>|
| Experimental: IVIG dose: 0.30 g/kg<br>Standard Care + Single dose of 0.35 g/Kg anti-COVID19 IVIG (experimental drug prepared at DUHS) n= 10 patients | Biological: SARS-CoV-2 antibody based IVIG therapy<br>* Patient groups will receive IVIG prepared from pooled convalescent plasma from recovered COVID-19 patients. This will be administered sequentially and in varying dosages, infused over a period of 12 hours, intravenously.Additionally, all treatment groups will receive same standard care as control group. Standard Care as per hospital protocol, which may include: Airway support, Anti-Viral medication, Antibiotics, Fluid Resuscitation, Hemodynamic Support, Steroids, Painkillers, Anti-Pyretics<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28 Days mortality | All cause mortality of participants will be monitored for 28 days to assess the safety and efficacy of IVIG treatment. | 28 days | 
| Requirement of supplemental oxygen support | Number of days required for invasive or non-invasive oxygen supply during hospital stay as per oxygen saturation status of patient | 28 days | 
| Number of days on assisted ventilation | Number of days a participant will be requiring assisted ventilation both invasive and noninvasive | 28 days | 
| Days to step down | Shifting from ICU to ward | 28 days | 
| Days to Hospital Discharge | Duration from day of enrollment in study to Day of hospital discharge | 28 days | 
| Adverse events during hospital stay | Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI) | 28 days | 
| Change in C-Reactive Protein (CRP) levels | Change in C-Reactive Protein (CRP) levels from baseline will be used to monitor inflammation | 28 days | 
| Change in neutrophil lymphocyte ratio | change in neutrophil lymphocyte ratio from baseline will be used to monitor inflammation | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Ferritin levels | change in Ferritin level from baseline will be used to monitor inflammation and immune dysregulation | 28 days | 
| Change in lactate dehydrogenase (LDH) levels | change in LDH from baseline will be used to monitor infections and tissue health | 28 days | 
| Change in radiological (X-ray) findings | Any change seen in radiological chest X-ray findings | 28 days | 
| Days to negative SARS-CoV-2 Polymerase Chain Reaction (PCR) test | Time taken for participant to receive negative COVID-19 PCR test | 28 days | 
| Anti-SARS-CoV-2 Antibody | Anti-SARS-CoV-2 antibody titre from blood measured by semi-qualitative method | 28 days | 
| Change in fever | Change in body temperature from baseline will be used to monitor safety and efficacy | 28 days | 
| Change in Sodium levels | Change in electrolytes (Sodium) seen in participants | 28 days | 
| Change in Potassium levels | Change in electrolytes (Potassium) seen in participants | 28 days | 
| Change in Chloride levels | Change in electrolytes (Chloride) seen in participants | 28 days | 
| Change in Bicarbonate levels | Change in electrolytes (Bicarbonate) seen in participants | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Passive Immunization, COVID19 ( Corona Virus Disease -2019), SARS-CoV-2 (Severe Acute respiratory syndrome Coronavirus 2), Intravenous Immunoglobulin (IVIG), Pooled convalescent Plasma, Critically ill COVID-19 patients, Severe COVID-19 patients, Antibody