Clinical trial NCT04891172: Anti COVID 19 Hyperimmune Intravenous Immunoglobulin (C-IVIG) Therapy for Severe COVID-19 Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Covid19
Keywords: COVID19 (Corona Virus Disease-2019)
SARS-CoV-2 (Severe Acute respiratory syndrome Coronavirus 2)
Passive immunization
Intravenous Immunoglobulin (IVIG)
Pooled Convalescent Plasma
Severe ill COVID-19 patients
Antibody
Anti COVID 19 Antibodies
Anti SARS CoV 2 Antibodies
Lead sponsor: Dow University of Health Sciences
Sponsor class: OTHER
Collaborators: name: Higher Education Commission (Pakistan)
First posted: 2021-05-18
Enrollment: 310
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: Inclusion Criteria:

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 (5L-15L of oxygen requirement on FM, NRM)
4. Consent given by the patient or first degree relative

Exclusion Criteria:

1. Critical COVID-19 patients \[ non-invasive ventilation (HFNC, BiPAP, CPAP) and invasive ventilation\],
2. Pregnant females
3. Previous allergic reaction to immunoglobulin treatment
4. Known case of any autoimmune disorder
5. Chronic kidney disease
6. Known case of thromboembolic disorder
7. Aseptic meningitis

Primary outcomes:
measure: 28 day Mortality
timeFrame: 28 days
Secondary outcomes:
measure: Immediate and serious adverse event during hospital Stay
timeFrame: 28 days
measure: Clinical Status of follow-up days according to 7-Catergory Ordinal Scale
timeFrame: 28 days
measure: change in C-Reactive Protein (CRP) levels
timeFrame: 5 Days
measure: change in interleukin 6 (IL-6)
timeFrame: 5 days
measure: change in anti-SARS-CoV-2 antibody levels
timeFrame: 5 days
measure: change in Horowitz idex
timeFrame: 28 days
measure: change in radiological findings
timeFrame: 5 days
Other outcomes:
Locations:
city: Karachi
country: Pakistan
facility: Dow University of Health Sciences
state: Sindh
Study officials:
affiliation: Dow University of Health Sciences, Principal Dow College of Biotechnology
name: Shaukat Ali, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ali S, Luxmi S, Anjum F, Muhaymin SM, Uddin SM, Ali A, Ali MR, Tauheed S, Khan M, Bajwa M, Baig SU, Shalim E, Ahmed I, Khan AS, Quraishy S. Hyperimmune anti-COVID-19 IVIG (C-IVIG) Therapy for Passive Immunization of Severe and Critically Ill COVID-19 Patients: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Nov 2;21(1):905. doi: 10.1186/s13063-020-04839-5.
citation: Ali S, Uddin SM, Ali A, Anjum F, Ali R, Shalim E, Khan M, Ahmed I, M Muhaymin S, Bukhari U, Luxmi S, Khan AS, Quraishy S. Production of hyperimmune anti-SARS-CoV-2 intravenous immunoglobulin from pooled COVID-19 convalescent plasma. Immunotherapy. 2021 Apr;13(5):397-407. doi: 10.2217/imt-2020-0263. Epub 2021 Feb 9.
citation: Xie Y, Cao S, Dong H, Li Q, Chen E, Zhang W, Yang L, Fu S, Wang R. Effect of regular intravenous immunoglobulin therapy on prognosis of severe pneumonia in patients with COVID-19. J Infect. 2020 Aug;81(2):318-356. doi: 10.1016/j.jinf.2020.03.044. Epub 2020 Apr 10. No abstract available.
citation: Chai KL, Valk SJ, Piechotta V, Kimber C, Monsef I, Doree C, Wood EM, Lamikanra AA, Roberts DJ, McQuilten Z, So-Osman C, Estcourt LJ, Skoetz N. Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review. Cochrane Database Syst Rev. 2020 Oct 12;10:CD013600. doi: 10.1002/14651858.CD013600.pub3.
citation: Ali S, Shalim E, Farhan F, Anjum F, Ali A, Uddin SM, Shahab F, Haider M, Ahmed I, Ali MR, Khan S, Rao S, Guriro K, Elahi S, Ali M, Mushtaq T, Sayeed MA, Muhaymin SM, Luxmi S, Saifullah, Qureshi S. Phase II/III trial of hyperimmune anti-COVID-19 intravenous immunoglobulin (C-IVIG) therapy in severe COVID-19 patients: study protocol for a randomized controlled trial. Trials. 2022 Nov 8;23(1):932. doi: 10.1186/s13063-022-06860-2.