Anti COVID 19 Hyperimmune Intravenous Immunoglobulin (C-IVIG) Therapy for Severe COVID-19 Patients

Study Overview
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Brief Summary
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Severe ill Patients will be enrolled in the study (n=310) after duly filled consent forms. Recipients will be divided into 2 group, each group contain 155 patients to compare Safety and efficacy of patients in Clinical Trial phase II/III. One Group will receive 0.15g/kg single dose of anti COVID 19 intravenously immunoglobulin (C-IVIG) develop from convalescent plasma of recovered patients from COVID 19, along with Standard of care. The Comparator group will only receive standard of Care

Detailed Description
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The 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 it to prepare IVIG formulation to treat severe and critically ill COVID-19 patients. Phase I/II trial was completed and showed potential safety and efficacy of the drug Anti COVID-19 intravenous immunoglobulin (C-IVIG) in severe and critical patients with COVID-19. This trial's aim is to investigate the safety and efficacy of passive immunization in severe COVID-19 patients in phase II/III. The trial will be a randomized, single-blinded, superiority trial, through parallel-group design. The participant will either receive C-IVIG with Standard of care or receive only Standard of care. The study will consist of 310 participants of which 155 will receive a single dose of C-IVIG (0.15g/kg) with the standard of care and 155 will receive only the standard of care. Standard of care is standard hospital care which includes airway support, anti-viral medication, antibiotics, fluid resuscitation, hemodynamic support, steroids, painkillers, and antipyretics. Randomized test patients will receive a single dose of C-IVIG in the following two dosage groups: Group 1 (Test): Severe COVID-19 patients: Single dose of 0.15g/Kg with standard hospital care Group 2 (Comparator): Severe COVID-19 patients: only standard hospital care only

Official Title
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Phase II/III Clinical Trial Study to Evaluate Efficacy and Safety of Anti COVID 19 Intravenous Immunoglobulin (C-IVIG) Therapy for Severe COVID-19 Patients

Conditions
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Covid19

Intervention / Treatment
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* Biological: Anti COVID 19 Intravenous Immunoglobulin (C-IVIG)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Above 18 years of age Have positive COVID PCR on nasopharyngeal and/or oropharyngeal swabs classified as severe* COVID-19 according to WHO guideline (5L-15L of oxygen requirement on FM, NRM) Consent given by the patient or first degree relative Exclusion Criteria: Critical COVID-19 patients [ non-invasive ventilation (HFNC, BiPAP, CPAP) and invasive ventilation], Pregnant females Previous allergic reaction to immunoglobulin treatment Known case of any autoimmune disorder Chronic kidney disease 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: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>The Control group will be receive Standard of care only | |
| Experimental: C-IVIG<br>The intervention group will receive the single dose of C-IVIG (0.15g/kg) with Standard of Care | Biological: Anti COVID 19 Intravenous Immunoglobulin (C-IVIG)<br>* Intervention arm will receive single dose of 0.15g/kg C-IVIG. This will be infused within period of 16 hours intravenously. Additionally, all participants will receive same standard care. Standard Care as per hospital protocol, which may include: Airway support, Anti-Viral medication, Antibiotics, Fluid Resuscitation, Hemodynamic Support, Steroids, Painkillers, Anti-Pyretics, anti coagulant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28 day Mortality | All cause mortality of participants will be monitored for 28 days to asses the safety and efficacy of C-IVIG | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immediate and serious adverse event during hospital Stay | Immediate adverse event (within 24 hours) and serious adverse event (throughout the hospital stay) which will be observed | 28 days | 
| Clinical Status of follow-up days according to 7-Catergory Ordinal Scale | Clinical Status of follow-up days according to 7-Catergory Ordinal Scale Not hospitalized and no limitations of activities Not hospitalized, with limitation of activities, home oxygen requirement, or both Hospitalized, not requiring supplemental oxygen Hospitalized, requiring any supplemental oxygen Hospitalized, requiring noninvasive ventilation or use of high-flow oxygen devices Hospitalized, receiving invasive mechanical ventilation Death | 28 days | 
| change in C-Reactive Protein (CRP) levels | Change in C-Reactive protein (CRP) levels form enrollment (baseline) till 3 days followup to monitor inflammation | 5 Days | 
| change in interleukin 6 (IL-6) | Change in IL-6 levels form enrollment (baseline) till 3 days followup | 5 days | 
| change in anti-SARS-CoV-2 antibody levels | Change in IL-6 levels form enrollment (baseline) till 3 days followup by quantitive method | 5 days | 
| change in Horowitz idex | The Horowitz index is a ratio used to assess lung function in patients during Hospital stay | 28 days | 
| change in radiological findings | Change in any radiological after receive single Dose of C-IVIG | 5 days | 

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