A B C D E F G H I J K L M N O P Q R S T U V W X Y Z All
Parikh, Devang
- Safety and Efficacy of COVID-19 Hyperimmune Globulin (HIG) Solution in the Treatment of Active COVID-19 infection- Findings from a Prospective, Randomized, Controlled, Multi-Centric Trial
Authors
1 Senior Manager, Clinical Development & Medical Affairs, Intas Pharmaceuticals Ltd., IN
2 Senior Vice President, Medical Affairs, Intas Pharmaceuticals Ltd., IN
3 Senior General Manager, Medical Services, Lambda Therapeutics Research Ltd., IN
4 Assistant General Manager, Medical Affairs, Intas Pharmaceuticals Ltd., IN
5 Associate Vice President, Biostatistics & Programming. Lambda Therapeutics Research Ltd., IN
6 Senior Vice President, Plasma Operations, Intas Pharmaceuticals Ltd., IN
Source
The Indian Practitioner, Vol 74, No 11 (2021), Pagination: 15-22Abstract
Background: COVID-19 hyper-immune globulin (HIG) solution is a human plasma-derived, highly-purified, concentrated, virus-inactivated preparation of neutralizing antibodies (NAbs) against COVID-19.
Material & Methods: This was a randomized, two-arm, controlled, multi-center trial to evaluate the efficacy and safety of COVID-19 HIG in patients who were hospitalized with moderate-severe COVID-19 infection.
Results: A total of 60 patients were randomized (30 in each arm). Overall, COVID-19 HIG was well-tolerated without any serious treatment-emergent adverse event or tolerability issue. The mean change in ordinal scale by day 8 was 1.7 ± 1.61 in the test arm vs. 2.0 ± 1.68 in the control arm (mITT; p=0.367). Early and high NAbs were observed in the test arm compared to the control arm.
More patients had negative RT-PCR by day 3 for the test arm vs. the control arm (mITT: 46.67% in test vs. 37.93% in control). The median time to be RT-PCR negative was 5.5 days for the test arm vs. 8.0 days for the control arm for PP population. Patients receiving COVID-19 HIG showed early improvement (reduction) in the biomarkers (CRP, IL-6, and D-dimer).
Conclusion: COVID-19 HIG was found to be safe and well-tolerated. Early and high NAbs were achieved in COVID-19 HIG recipients qualifying the product as a suitable treatment option, particularly in an immunocompromised state. It should be given early in infection to mitigate progression to severe disease. It should also be evaluated for post-exposure prophylaxis as well as for prevention (where a vaccine is not suitable or effective). HIG should be evaluated in the pediatric population as well.
Clinical Trial registration number: CTRI/2020/09/027903
Keywords
Convalescent Plasma, COVID-19, Hyperimmune Globulin, Neutralizing Antibodies, Plasma-Derived Product, SARS-CoV-2.
References
- Keller MA, Stiehm ER. Passive immunity in prevention and treatment of infectious diseases. Clin Microbiol Rev. 2000;13(4):602-614.
- World Health Organization. WHO Coronavirus (COVID-19) Dashboard. Cited 2021 May 16. Available from: https://covid19.who.int/.
- Salzberger B, Buder F, Lampl B. Ehrenstein B, Hitzenbichler F, Holzmann T, et al. Epidemiology of SARS-CoV-2. Infection. 2021;49:233–239 DOI: 10.1007/s15010-020-01531-3.
- U.S. Food and Drug Administration: FDA Issues Emergency Use Authorization for Convalescent Plasma as Potential Promising COVID–19 Treatment. FDA NEWS Release. Cited 2021 Sep 7. Available from https://www.fda. gov/news-events/press-announcements/fda-issues-emergencyuse-authorization-convalescent-plasma-potentialpromisingcovid-19-treatment.
- Rojas M, Rodríguez Y, Monsalve DM, Acosta-Ampudia Y, Camacho B, Gallo JE, et al. Convalescent plasma in Covid-19: Possible mechanisms of action. Autoimmun Reviews. 2020;19(7):02554.
- Gharebaghi N, Nejadrahim R, Mousavi SJ, Sadat-Ebrahimi SR, Hajizadeh R. The use of intravenous immunoglobulin gamma for the treatment of severe coronavirus disease 2019: a randomized placebo-controlled double-blind clinical trial. BMC Infect Dis.2020;20:786.
- Safety, PK and PD of Kamada Anti-SARS-CoV-2 in COVID-19. Clinicaltrials.gov. Cited 2021 June 3. Available from https://clinicaltrials.gov/ct2/show/NCT04550325.
- Nguyen AA, Habiballah SB, Platt CD, Geha RS, Chou JS, McDonald DR. Immunoglobulins in the treatment of COVID-19 infection: Proceed with caution!. Clin Immunol. 2020;216:108459.
- Arabi YM, Arifi AA, Balkhy HH, Najm H, Aldawood AS, Ghabashi A, et al. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med. 2014;160(6):389–97.
- De Alwis R, Chen S, Gan ES, Ooi EE. Impact of immune enhancement on Covid-19 polyclonal hyperimmune globulin therapy and vaccine development. EBioMedicine. 2020;55:02768.
- Vandeberg P, Cruz M, Diez JM, Merritt WK, Santos B, Trukawinski S, et al. Production of anti-SARS-CoV-2 hyperimmune globulin from convalescent plasma. Transfusion. 2021;61:1705-1709.
- Ali S, Uddin SM, Ali A, Anjum F, Ali R, Shalim E, et al. Production of hyperimmune anti-SARS-CoV-2 intravenous immunoglobulin from pooled COVID-19 convalescent plasma. Immunotherapy. 2021;13(5):397-407.
- U.S. Food and Drug Administration. Coronavirus (COVID-19) Update: FDA Authorizes Monoclonal Antibodies for Treatment of COVID-19. 2020. Cited 2021 June 8. Available from https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fdaauthorizesmonoclonal-antibodies-treatment-covid-19.
- Cipla: Roche receives EUA India investigational antibody cocktail casirivimabImdevimab covid. Cited 2021 June 8. Available from https://www.cipla.com/press-releasesstatements/ roche-receives-EUA-India-investigational-antibodycocktail-casirivimab-Imdevimab-covid.
- Verma S, Dolia S, Pawar A, Ray S. SARS-CoV-2 HyperImmunoglobulin: Purification and Characterization from Human Convalescent Plasma. BioProcess Int. 2021;19(4).
- Blake P, Wadhwa D. 2020 Year in Review: The impact of COVID-19 in 12 charts. World Bank Blogs. 2020. Cited 2021 June 8. Available from https://blogs.worldbank.org/ voices/2020-year-review-impact-covid-19-12-charts
- Goyal A, Cardozo-Ojeda EF, Schiffer JT. Potency and timing of antiviral therapy as determinants of duration of SARS-CoV-2 shedding and intensity of inflammatory response. Science Advances 2020;6(47):eabc7112.
- Zheng S, Fan J, Yu F, Feng B, Lou B, Zou Q, et al. Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. BMJ. 2020;369:m1443.
- Keller MA, Stiehm ER. Passive Immunity in Prevention and Treatment of Infectious Diseases. Clin Microbiol Rev. 2000;13(4):602–614.
- U.S. Food and Drug Administration. Bratcher-Bowman N. Convalescent plasma emergency authorization. Mar 2021. Cited 2021 May 23. Available from https://www.fda.gov/media/141477/download.
- Liu L, Wang P, Nair MS, Yu J, Rapp M, Wang Q, et al. Potent neutralizing antibodies against multiple epitopes on SARSCoV2 spike. Nature. 2020;584:450-6.
- Data on file. Intas Pharmaceuticals Ltd. 2020.
- da Costa C, Martins F, da Cunha L, Ratcliffe N, Cisne de Paula R, Castro H. COVID-19 and Hyperimmune sera: A feasible plan B to fight against coronavirus, Int Immunopharmacol. 2021;90:107220.
- Chen J, Gao K, Wang R, Wei G. Revealing the threat of emerging SARS-CoV-2 mutations to antibody therapies. BioRxiv[Preprint]. 2021. DOI: 10.1101/2021.04.12.439473
- Barron E, Bakhai C, Kar P, Weaver A, Bradley D, Ismail H, et al. Associations of type 1 and type 2 diabetes with COVID-19-related mortality in England: a whole-population study. Lancet Diabetes Endocrinol. 2020;8:813-822.
- Xue J, Zheng J, Shang X, Qin E, Zhao P, He Y, et al. Risk factors for prolonged viral clearance in adult patients with COVID-19 in Beijing, China: A prospective observational study. Int Immunopharmacol. 2020;89:107031.
- Fajnzylber J, Regan J, Coxen K, Corry H, Wong C, Rosenthal A, et al. SARS-CoV-2 viral load is associated with increased disease severity and mortality. Nat Commun2020;11:5493.
- Ali S, Uddin SM, Shalim E, Sayeed MA, Anjum F, Saleem F, et al. Hyperimmune anti-COVID-19 IVIG (C-IVIG) treatment in severe and critical COVID-19 patients: A phase I/II randomized control trial. EClinicalMedicine. 2021;36:100926.
- Casadevall A, Dragotakes Q, Johnson PW, Senefeld JW, Klassen SA, Wright RS, et al. Convalescent Plasma Use in the United States was inversely correlated with COVID-19 Mortality: Did Plasma Hesitancy cost lives? MedRxiv[Preprint]. 2021. DOI: 10.1101/2021.04.07.21255089.