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
Phase: PHASE2
Conditions: Covid19
Sponsor: Dow University of Health Sciences

Study Protocol 
Title: “Phase II/III Clinical Trial study to evaluate efficacy and Safety of C-IVIG therapy in Severe 
COVID-19 Patients”. 
 
NCT04891172 
 
Date: October 4, 2022 
 

 
Contents 
Title: “Phase II/III Clinical Trial study to evaluate efficacy and Safety of C-IVIG therapy in Severe COVID- 
19 Patients” ............................................................................................................................................... 1 
STUDY PROTOCOL ......................................................................................................................................... 3 
General Information ..................................................................................................................................... 3 
Title: “Phase II/III Clinical Trial study to evaluate efficacy and Safety of C-IVIG therapy in Severe COVID- 
19 Patients” ............................................................................................................................................... 3 
Principal and Co-Prinicipal Investigators................................................................................................... 3 
Trial Sites ................................................................................................................................................... 3 
Background Information ............................................................................................................................... 3 
Objective ....................................................................................................................................................... 3 
Trial Design .................................................................................................................................................... 3 
Participants ........................................................................................................................................... 4 
Intervention and comparator ............................................................................................................... 4 
Selection and Withdrawal of Subjects .......................................................................................................... 4 
Plasma collection from donors (recovered COVID-19 individuals): ...................................................... 4 
Administration of C-IVIG in respective doses by medical experts in selected recipient ....................... 5 
DECODING PROCEDURES FOR BLINDED TRIALS ............................................. Error! Bookmark not defined. 

STUDY PROTOCOL 
 
General Information: 
Title: “Phase II/III Clinical Trial study to evaluate efficacy and Safety of C-IVIG therapy in Severe 
COVID-19 Patients”. 
 
Principal and Co-Prinicipal Investigators 
Principal Investigator: Dr. Shaukat Ali 
Co- Principal Investigator: Dr. Shobha Luxmi 
Co- Principal Investigator: Abdul Samad Khan 
Co-Principal Investigator: Dr. Muneeba Ahsan Sayeed 
Trial Sites 
Dow University of Health Sciences (Ojha Campus), Karachi, Sindh 
Sindh Infectious Disease Hospital and Research Center, Karachi, Sindh 
PAF hospital Faisal Base, Karachi, Sindh 
Background Information: 
Anti-COVID19 Intravenous immunoglobulin (C-IVIg) is a mixture of IgG, IgA, IgM and Albumin derived 
from recovered COVID1-19 participant via Caprylic acid process. Anti-COVID19 Intravenous 
immunoglobulin (C-IVIg) Contain a total amount of protein 46±3.7g/L in which upto 80% is IgG, 4.0% is 
IgM, IgA is 15.8% and Albumin is <0.4. Anti-COVID19 C-IVIG is used in the treatment COVID 19 severe 
and critical patients. The dosage form is Liquid and route of administration is intravenous. The indication 
to given C-IVIG is PCR positive COVID 19. In non-clinical studies C-IVIG has been observed Safety and in 
phase I trial shown remarkable results in Safety as well as efficacy at Dow University Hospital, Karachi. 
28 day mortality have been reduced markedly which were given single dose of C-IVIG intravenously with 
Standard of Care when compared to Control with Standard of care. It has been observe that in 28 day 
patient monitoring did not report any drug related serious adverse event like organ damage, disability or 
permanent damage. 
 
Objective 
The aim of this trial is to investigate the safety and clinical efficacy of passive immunization therapy 
through Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG: 5% liquid formulation), on 
severe COVID-19 patients. 
 
Trial Design 
This is a phase II/III multi-centred, randomized controlled, single-blinded, superiority trial, through 
parallel-group design. Participants will be randomized either to receive C-IVIG and standard care or only 
standard care (1:1). 

Participants 
Consenting patients above 18 years that are classified by the treating physician as severe i.e. showing 
symptoms of COVID-19 pneumonia, dyspnea, respiratory rate ≥30/min, blood oxygen saturation ≤90%, 
PaO2/FiO2 <300, and lung infiltrates as seen on CXR/HRCT> 50% (on ≤15 Liters supplemental oxygen). 
Critical COVID-19 patients (patients requiring mechanical ventilation) and patients given 
immunomodulatory drug (Tociluzumab) are excluded from study. Patients with reported IgA deficiency, 
autoimmune disorder, thromboembolic disorder, and allergic reaction to immunoglobulin treatment 
were excluded from study. Similarly, pregnant females, patients requiring two or more inotropic agents 
to maintain blood pressure and patients with chronic kidney injury/failure, were also excluded from the 
study. 
Intervention and comparator 
The study consists of intervention comprising of two groups with each group containing 155 participants. 
All participants will receive standard hospital care which includes airway support, anti-viral medication, 
antibiotics, fluid resuscitation, hemodynamic support, steroids, painkillers, and anti-pyretic. Randomized 
test patients will receive single dose of C-IVIG in 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 receive standard hospital care 
Selection and Withdrawal of Subjects 
Plasma collection from donors (recovered COVID-19 individuals): 
Selection of donor according to World Health Organization (WHO) and Federal Drug Agency (FDA) 
guidelines 
 
 
Inclusion Criteria for Donor 
Exclusion criteria for Donor 
a. Submitted signed consent. 
b. Eligible to donate blood. 
c. Negative for HIV, HBV, HCV, syphilis and 
malarial parasite. 
d. Complete resolution of symptoms at least 14 
e. days prior to donation 
f. 
Defined SARS-CoV-2 neutralizing antibody 
activity 
a. Pre-existing condition Contra indicative for 
donating blood (HIV, viral hepatitis, 
tuberculosis, syphilis, oncological conditions, 
malaria). 
b. Bleeding tendency. 
c. Anemia. 
d. Fever of unknown origin 
 
Plasma Collection 
300-1000 ml plasma will be collected from consenting COVID-19 recovered patients (two weeks 
after resolution of symptoms) using plasmapheresis technique. Plasmapheresis is a technique 
where using a machine the blood components are separated, keeping the required component, 
in this case plasma, and returning other components like RBCs. Plasma will be stored according 

to WHO guidelines. Aliquot of plasma will be screened for syphilis, malarial parasite HIV, HBV, 
HCV, and COVID–19 by Nucleic Acid Test (NAT). The screened stored plasma qualifying safety 
criteria will be pooled and fractionated to obtain Anti-COVID hyperimmune immunoglobulin. 
Administration of C-IVIG in respective doses by medical experts in selected recipient 
Recipient criteria 
Inclusion criteria for Recipient 
Exclusion criteria for Recipient 
1. Above 18 years of age 
2. Have positive COVID PCR on 
nasopharyngeal and/or oropharyngeal 
swabs 
3. classified as severe* COVID-19 according to 
WHO guideline 
4. Consent given by the patient or first 
degree relative 
a. Critical COVID-19 patients 
b. Pregnant females 
c. Previous allergic reaction to 
immunoglobulin treatment 
d. Patient given immunomodulatory drug 
(e.g. tociluzumab) 
e. Patient requiring 2 inotropic agents to 
maintain blood pressures 
f. 
Known case of any autoimmune disorder 
g. Chronic kidney disease 
h. Known case of thromboembolic disorder 
i. 
Aseptic meningitis 
*Severe COVID-19 is defined by one or more of the following: dyspnea, respiratory frequency 
≥30/min, blood oxygen saturation ≤90%, PaO2/FiO2 ratio <300, lung infiltrates as seen through 
CXR/HRCT >50% (On ≤15 Liters supplemental oxygen)