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

Covid19 Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04891172
• Other study ID #: C-IVIG-02
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: August 1, 2021
• Est. completion date: December 2, 2022

Study information

• Verified date: August 2022
• Source: Dow University of Health Sciences
• Contact: Shaukat Ali, PhD
• Phone: +92-3363010185
• Email: ali.shaukat[@]duhs.edu.pk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 310
• Est. completion date: December 2, 2022
• Est. primary completion date: December 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Biological:
• Anti COVID 19 Intravenous Immunoglobulin (C-IVIG)
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

Locations

Country	Name	City	State
Pakistan	Dow University of Health Sciences	Karachi	Sindh

Sponsors (2)

Lead Sponsor	Collaborator
Dow University of Health Sciences	Higher Education Commission (Pakistan)

Country where clinical trial is conducted

Pakistan, 

References & Publications (4)

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. — View 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. — View 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. Update in: Cochrane Database Syst Rev. 2021 May 20;5:CD013600. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	change in interleukin 6 (IL-6)	Change in IL-6 levels form enrollment (baseline) till 3 days followup	5 days
Secondary	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
Secondary	change in Horowitz idex	The Horowitz index is a ratio used to assess lung function in patients during Hospital stay	28 days
Secondary	change in radiological findings	Change in any radiological after receive single Dose of C-IVIG	5 days