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

NCT ID: NCT04521309

Last Updated: 2021-03-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-06-19

Study Completion Date

2021-02-08

Brief Summary

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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.

Detailed Description

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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.

Conditions

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COVID-19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Control

Standard care only n = 10 patients.

Group Type NO_INTERVENTION

No interventions assigned to this group

IVIG dose: 0.15 g/kg

Standard Care + Single dose of 0.20 g/Kg anti-COVID-19 IVIG (experimental drug prepared at DUHS) n= 10 patients

Group Type EXPERIMENTAL

SARS-CoV-2 antibody based IVIG therapy

Intervention Type BIOLOGICAL

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

IVIG dose: 0.20 g/kg

Standard Care + Single dose of 0.25 g/Kg anti-COVID19 IVIG (experimental drug prepared at DUHS) n= 10 patients

Group Type EXPERIMENTAL

SARS-CoV-2 antibody based IVIG therapy

Intervention Type BIOLOGICAL

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

IVIG dose: 0.25 g/kg

Standard Care + Single dose of 0.30 g/Kg anti-COVID19 IVIG (experimental drug prepared at DUHS) n= 10 patients

Group Type EXPERIMENTAL

SARS-CoV-2 antibody based IVIG therapy

Intervention Type BIOLOGICAL

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

IVIG dose: 0.30 g/kg

Standard Care + Single dose of 0.35 g/Kg anti-COVID19 IVIG (experimental drug prepared at DUHS) n= 10 patients

Group Type EXPERIMENTAL

SARS-CoV-2 antibody based IVIG therapy

Intervention Type BIOLOGICAL

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

Interventions

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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

Intervention Type BIOLOGICAL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Higher Education Commission (Pakistan)

OTHER

Sponsor Role collaborator

Dow University of Health Sciences

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dr.Shaukat Ali, PhD

Role: PRINCIPAL_INVESTIGATOR

Dow University of Health Sciences, Principal Dow College of Biotechnology

Locations

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Dow University of Health Sciences

Karachi, Sindh, Pakistan

Site Status

Countries

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Pakistan

References

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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. No abstract available.

Reference Type BACKGROUND
PMID: 32178711 (View on PubMed)

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. No abstract available.

Reference Type BACKGROUND
PMID: 32113510 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32219428 (View on PubMed)

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. doi: 10.1002/biot.200500037.

Reference Type BACKGROUND
PMID: 16892245 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18178525 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23450336 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25030060 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26618098 (View on PubMed)

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. doi: 10.1007/s10096-004-1271-9.

Reference Type BACKGROUND
PMID: 15616839 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 22578374 (View on PubMed)

Ali S, Uddin SM, Shalim E, Sayeed MA, Anjum F, Saleem F, Muhaymin SM, Ali A, Ali MR, Ahmed I, Mushtaq T, Khan S, Shahab F, Luxmi S, Kumar S, Arain H, Khan M, Khan AS, Mehmood H, Rasheed A, Jahangeer A, Baig S, Quraishy S. Hyperimmune anti-COVID-19 IVIG (C-IVIG) treatment in severe and critical COVID-19 patients: A phase I/II randomized control trial. EClinicalMedicine. 2021 Jun;36:100926. doi: 10.1016/j.eclinm.2021.100926. Epub 2021 Jun 4.

Reference Type DERIVED
PMID: 34109306 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33557591 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33138867 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Related Links

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https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance

World Health Organization (WHO) technical guidance on COVID-19

http://www.euro.who.int/__data/assets/pdf_file/0011/268787/Use-of-Convalescent-Whole-Blood-or-Plasma-Collected-from-Patients-Recovered-from-Ebola-Virus-Disease-for-Transfusion,-as-an-Empirical-Treatment-during-Outbreaks-Eng.pdf

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

Other Identifiers

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biotech001

Identifier Type: -

Identifier Source: org_study_id

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