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

COVID-19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04521309
• Other study ID #: biotech001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 19, 2020
• Est. completion date: February 8, 2021

Study information

• Verified date: March 2021
• Source: Dow University of Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: February 8, 2021
• Est. primary completion date: January 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Severe Acute Respiratory Syndrome

Intervention

Biological:
• SARS-CoV-2 antibody based IVIG therapy
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

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 (10)

Arabi Y, Balkhy H, Hajeer AH, Bouchama A, Hayden FG, Al-Omari A, Al-Hameed FM, Taha Y, Shindo N, Whitehead J, Merson L, AlJohani S, Al-Khairy K, Carson G, Luke TC, Hensley L, Al-Dawood A, Al-Qahtani S, Modjarrad K, Sadat M, Rohde G, Leport C, Fowler R. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol. Springerplus. 2015 Nov 19;4:709. doi: 10.1186/s40064-015-1490-9. eCollection 2015. — View Citation

Buchacher A, Iberer G. Purification of intravenous immunoglobulin G from human plasma--aspects of yield and virus safety. Biotechnol J. 2006 Feb;1(2):148-63. Review. — View Citation

Chen L, Xiong J, Bao L, Shi Y. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis. 2020 Apr;20(4):398-400. doi: 10.1016/S1473-3099(20)30141-9. Epub 2020 Feb 27. — View Citation

Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, Ng MH, Chan P, Wong KC, Leung CB, Cheng G. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005 Jan;24(1):44-6. — View Citation

Cunningham AC, Goh HP, Koh D. Treatment of COVID-19: old tricks for new challenges. Crit Care. 2020 Mar 16;24(1):91. doi: 10.1186/s13054-020-2818-6. — View Citation

Hughes RA, Donofrio P, Bril V, Dalakas MC, Deng C, Hanna K, Hartung HP, Latov N, Merkies IS, van Doorn PA; ICE Study Group. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial. Lancet Neurol. 2008 Feb;7(2):136-44. doi: 10.1016/S1474-4422(07)70329-0. Erratum in: Lancet Neurol. 2008 Sep;7(9):771. — View Citation

Hung IFN, To KKW, Lee CK, Lee KL, Yan WW, Chan K, Chan WM, Ngai CW, Law KI, Chow FL, Liu R, Lai KY, Lau CCY, Liu SH, Chan KH, Lin CK, Yuen KY. Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection. Chest. 2013 Aug;144(2):464-473. doi: 10.1378/chest.12-2907. — View Citation

Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, Makki S, Rooney KD, Nguyen-Van-Tam JS, Beck CR; Convalescent Plasma Study Group. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis. 2015 Jan 1;211(1):80-90. doi: 10.1093/infdis/jiu396. Epub 2014 Jul 16. Review. — View Citation

Pandey S, Vyas GN. Adverse effects of plasma transfusion. Transfusion. 2012 May;52 Suppl 1:65S-79S. doi: 10.1111/j.1537-2995.2012.03663.x. Review. — View Citation

Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, Wei J, Xiao H, Yang Y, Qu J, Qing L, Chen L, Xu Z, Peng L, Li Y, Zheng H, Chen F, Huang K, Jiang Y, Liu D, Zhang Z, Liu Y, Liu L. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020 Apr 28;323(16):1582-1589. doi: 10.1001/jama.2020.4783. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Number of days on assisted ventilation	Number of days a participant will be requiring assisted ventilation both invasive and noninvasive	28 days
Primary	Days to step down	Shifting from ICU to ward	28 days
Primary	Days to Hospital Discharge	Duration from day of enrollment in study to Day of hospital discharge	28 days
Primary	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
Primary	Change in C-Reactive Protein (CRP) levels	Change in C-Reactive Protein (CRP) levels from baseline will be used to monitor inflammation	28 days
Primary	Change in neutrophil lymphocyte ratio	change in neutrophil lymphocyte ratio from baseline will be used to monitor inflammation	28 days
Secondary	Change in Ferritin levels	change in Ferritin level from baseline will be used to monitor inflammation and immune dysregulation	28 days
Secondary	Change in lactate dehydrogenase (LDH) levels	change in LDH from baseline will be used to monitor infections and tissue health	28 days
Secondary	Change in radiological (X-ray) findings	Any change seen in radiological chest X-ray findings	28 days
Secondary	Days to negative SARS-CoV-2 Polymerase Chain Reaction (PCR) test	Time taken for participant to receive negative COVID-19 PCR test	28 days
Secondary	Anti-SARS-CoV-2 Antibody	Anti-SARS-CoV-2 antibody titre from blood measured by semi-qualitative method	28 days
Secondary	Change in fever	Change in body temperature from baseline will be used to monitor safety and efficacy	28 days
Secondary	Change in Sodium levels	Change in electrolytes (Sodium) seen in participants	28 days
Secondary	Change in Potassium levels	Change in electrolytes (Potassium) seen in participants	28 days
Secondary	Change in Chloride levels	Change in electrolytes (Chloride) seen in participants	28 days
Secondary	Change in Bicarbonate levels	Change in electrolytes (Bicarbonate) seen in participants	28 days

External Links

•   list of FDA approved Intravenously administrable Immune Globulin(IVIG) along Indications
•   News story of FDA approval for use of convalescent plasma for COVID-19 patients
•   U.S Food and Drug Administration (FDA) Recommendations for Investigational COVID-19 Convalescent Plasma
•   WHO guidelines for Use of Convalescent Whole Blood or Plasma Collected from Patients Recovered from Ebola Virus Disease for Transfusion, as an Empirical Treatment during Outbreaks
•   World Health Organization (WHO) technical guidance on COVID-19