Safety and Immunogenicity of Hecolin® in Healthy Pregnant Women

Summary

This is a phase II randomized, observer-blinded, placebo-controlled study with 3 arms enrolling a total of 2,358 participants. The arms are composed of Arm 1, pregnant participants receiving Hecolin® (N=1,104) with immunogenicity subset (n=150), Arm 2, pregnant participants receiving placebo (N=1,104) with immunogenicity subset (n=150), and Arm 3, non-pregnant participants receiving Hecolin® (N=150) of which all participants in this arm will be included in the immunogenicity subset.

Timeline

Start

2024-05-02

Primary completion

2025-11

Completion

2026-04

Publications

• Results Bonhoeffer J, Kochhar S, Hirschfeld S, Heath PT, Jones CE, Bauwens J, Honrado A, Heininger U, Munoz FM, Eckert L, Steinhoff M, Black S, Padula M, Sturkenboom M, Buttery J, Pless R, Zuber P; GAIA project participants. Global alignment of immunization safety assessment in pregnancy - The GAIA project. Vaccine. 2016 Dec 1;34(49):5993-5997. doi: 10.1016/j.vaccine.2016.07.006. Epub 2016 Oct 14.
• Results Madhi SA, Polack FP, Piedra PA, Munoz FM, Trenholme AA, Simoes EAF, Swamy GK, Agrawal S, Ahmed K, August A, Baqui AH, Calvert A, Chen J, Cho I, Cotton MF, Cutland CL, Englund JA, Fix A, Gonik B, Hammitt L, Heath PT, de Jesus JN, Jones CE, Khalil A, Kimberlin DW, Libster R, Llapur CJ, Lucero M, Perez Marc G, Marshall HS, Masenya MS, Martinon-Torres F, Meece JK, Nolan TM, Osman A, Perrett KP, Plested JS, Richmond PC, Snape MD, Shakib JH, Shinde V, Stoney T, Thomas DN, Tita AT, Varner MW, Vatish M, Vrbicky K, Wen J, Zaman K, Zar HJ, Glenn GM, Fries LF; Prepare Study Group. Respiratory Syncytial Virus Vaccination during Pregnancy and Effects in Infants. N Engl J Med. 2020 Jul 30;383(5):426-439. doi: 10.1056/NEJMoa1908380.
• Results Rein DB, Stevens GA, Theaker J, Wittenborn JS, Wiersma ST. The global burden of hepatitis E virus genotypes 1 and 2 in 2005. Hepatology. 2012 Apr;55(4):988-97. doi: 10.1002/hep.25505.
• Results Beniwal M, Kumar A, Kar P, Jilani N, Sharma JB. Prevalence and severity of acute viral hepatitis and fulminant hepatitis during pregnancy: a prospective study from north India. Indian J Med Microbiol. 2003 Jul-Sep;21(3):184-5.
• Results Kumar RM, Uduman S, Rana S, Kochiyil JK, Usmani A, Thomas L. Sero-prevalence and mother-to-infant transmission of hepatitis E virus among pregnant women in the United Arab Emirates. Eur J Obstet Gynecol Reprod Biol. 2001 Dec 10;100(1):9-15. doi: 10.1016/s0301-2115(01)00448-1.
• Results Medhat A, el-Sharkawy MM, Shaaban MM, Makhlouf MM, Ghaneima SE. Acute viral hepatitis in pregnancy. Int J Gynaecol Obstet. 1993 Jan;40(1):25-31. doi: 10.1016/0020-7292(93)90768-r.
• Results Patra S, Kumar A, Trivedi SS, Puri M, Sarin SK. Maternal and fetal outcomes in pregnant women with acute hepatitis E virus infection. Ann Intern Med. 2007 Jul 3;147(1):28-33. doi: 10.7326/0003-4819-147-1-200707030-00005.
• Results Nelson KE, Heaney CD, Labrique AB, Kmush BL, Krain LJ. Hepatitis E: prevention and treatment. Curr Opin Infect Dis. 2016 Oct;29(5):478-85. doi: 10.1097/QCO.0000000000000294.
• Results Aggarwal R. Clinical presentation of hepatitis E. Virus Res. 2011 Oct;161(1):15-22. doi: 10.1016/j.virusres.2011.03.017. Epub 2011 Mar 31.
• Results Kamar N, Lhomme S, Abravanel F, Cointault O, Esposito L, Cardeau-Desangles I, Del Bello A, Dorr G, Lavayssiere L, Nogier MB, Guitard J, Ribes D, Goin AL, Broue P, Metsu D, Saune K, Rostaing L, Izopet J. An Early Viral Response Predicts the Virological Response to Ribavirin in Hepatitis E Virus Organ Transplant Patients. Transplantation. 2015 Oct;99(10):2124-31. doi: 10.1097/TP.0000000000000850.
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• Results Iqbal M, Ahmed A, Qamar A, Dixon K, Duncan JF, Islam NU, Rauf A, Bryan JP, Malik IA, Legters LJ. An outbreak of enterically transmitted non-A, non-B hepatitis in Pakistan. Am J Trop Med Hyg. 1989 Apr;40(4):438-43. doi: 10.4269/ajtmh.1989.40.438.
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• Results Jin H, Zhao Y, Zhang X, Wang B, Liu P. Case-fatality risk of pregnant women with acute viral hepatitis type E: a systematic review and meta-analysis. Epidemiol Infect. 2016 Jul;144(10):2098-106. doi: 10.1017/S0950268816000418. Epub 2016 Mar 4.
• Results Hakim MS, Wang W, Bramer WM, Geng J, Huang F, de Man RA, Peppelenbosch MP, Pan Q. The global burden of hepatitis E outbreaks: a systematic review. Liver Int. 2017 Jan;37(1):19-31. doi: 10.1111/liv.13237. Epub 2016 Sep 9.
• Results Scott RM, Kmush BL, Norkye K, Hada M, Shrestha MP, Vaughn DW, Myint KSA, Endy TP, Shrestha SK, Innis BL. Historical Analysis of the Risk of Hepatitis E and Its Complications in Pregnant Women in Nepal, 1996-1998. Am J Trop Med Hyg. 2021 Jun 14;105(2):440-448. doi: 10.4269/ajtmh.20-1007.
• Results Gurley ES, Halder AK, Streatfield PK, Sazzad HM, Huda TM, Hossain MJ, Luby SP. Estimating the burden of maternal and neonatal deaths associated with jaundice in Bangladesh: possible role of hepatitis E infection. Am J Public Health. 2012 Dec;102(12):2248-54. doi: 10.2105/AJPH.2012.300749. Epub 2012 Oct 18.
• Results Labrique AB, Sikder SS, Krain LJ, West KP Jr, Christian P, Rashid M, Nelson KE. Hepatitis E, a vaccine-preventable cause of maternal deaths. Emerg Infect Dis. 2012 Sep;18(9):1401-4. doi: 10.3201/eid1809.120241.
• Results Khuroo MS. Hepatitis E and Pregnancy: An Unholy Alliance Unmasked from Kashmir, India. Viruses. 2021 Jul 9;13(7):1329. doi: 10.3390/v13071329.
• Results Bigna JJ, Modiyinji AF, Nansseu JR, Amougou MA, Nola M, Kenmoe S, Temfack E, Njouom R. Burden of hepatitis E virus infection in pregnancy and maternofoetal outcomes: a systematic review and meta-analysis. BMC Pregnancy Childbirth. 2020 Jul 28;20(1):426. doi: 10.1186/s12884-020-03116-2.
• Results Puri M, Patra S, Singh P, Malhotra N, Trivedi SS, Sharma S, Kumar A, Sarin SK. Factors influencing occurrence of postpartum haemorrhage in pregnant women with hepatitis E infection and deranged coagulation profile. Obstet Med. 2011 Sep;4(3):108-12. doi: 10.1258/om.2011.110031. Epub 2011 Aug 23.
• Results Krain LJ, Atwell JE, Nelson KE, Labrique AB. Fetal and neonatal health consequences of vertically transmitted hepatitis E virus infection. Am J Trop Med Hyg. 2014 Feb;90(2):365-70. doi: 10.4269/ajtmh.13-0265. Epub 2014 Jan 13.
• Results Khuroo MS, Kamili S, Khuroo MS. Clinical course and duration of viremia in vertically transmitted hepatitis E virus (HEV) infection in babies born to HEV-infected mothers. J Viral Hepat. 2009 Jul;16(7):519-23. doi: 10.1111/j.1365-2893.2009.01101.x. Epub 2009 Feb 17.
• Results Sharma S, Kumar A, Kar P, Agarwal S, Ramji S, Husain SA, Prasad S, Sharma S. Risk factors for vertical transmission of hepatitis E virus infection. J Viral Hepat. 2017 Nov;24(11):1067-1075. doi: 10.1111/jvh.12730. Epub 2017 Jul 12.
• Results Berglov A, Hallager S, Weis N. Hepatitis E during pregnancy: Maternal and foetal case-fatality rates and adverse outcomes-A systematic review. J Viral Hepat. 2019 Nov;26(11):1240-1248. doi: 10.1111/jvh.13129. Epub 2019 Jun 14.
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• Results Ratho RK, Thakur V, Arya S, Singh MP, Suri V, Das A. Placenta as a site of HEV replication and inflammatory cytokines modulating the immunopathogenesis of HEV in pregnant women. J Med Virol. 2022 Jul;94(7):3457-3463. doi: 10.1002/jmv.27699. Epub 2022 Mar 24.
• Results Gouilly J, Chen Q, Siewiera J, Cartron G, Levy C, Dubois M, Al-Daccak R, Izopet J, Jabrane-Ferrat N, El Costa H. Genotype specific pathogenicity of hepatitis E virus at the human maternal-fetal interface. Nat Commun. 2018 Nov 12;9(1):4748. doi: 10.1038/s41467-018-07200-2.
• Results Zaman K, Dudman S, Stene-Johansen K, Qadri F, Yunus M, Sandbu S, Gurley ES, Overbo J, Julin CH, Dembinski JL, Nahar Q, Rahman A, Bhuiyan TR, Rahman M, Haque W, Khan J, Aziz A, Khanam M, Streatfield PK, Clemens JD. HEV study protocol : design of a cluster-randomised, blinded trial to assess the safety, immunogenicity and effectiveness of the hepatitis E vaccine HEV 239 (Hecolin) in women of childbearing age in rural Bangladesh. BMJ Open. 2020 Jan 19;10(1):e033702. doi: 10.1136/bmjopen-2019-033702.
• Results Wu T, Zhu FC, Huang SJ, Zhang XF, Wang ZZ, Zhang J, Xia NS. Safety of the hepatitis E vaccine for pregnant women: a preliminary analysis. Hepatology. 2012 Jun;55(6):2038. doi: 10.1002/hep.25522. No abstract available.
• Results Zhu FC, Zhang J, Zhang XF, Zhou C, Wang ZZ, Huang SJ, Wang H, Yang CL, Jiang HM, Cai JP, Wang YJ, Ai X, Hu YM, Tang Q, Yao X, Yan Q, Xian YL, Wu T, Li YM, Miao J, Ng MH, Shih JW, Xia NS. Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet. 2010 Sep 11;376(9744):895-902. doi: 10.1016/S0140-6736(10)61030-6. Epub 2010 Aug 20.
• Results Qiao YL, Wu T, Li RC, Hu YM, Wei LH, Li CG, Chen W, Huang SJ, Zhao FH, Li MQ, Pan QJ, Zhang X, Li Q, Hong Y, Zhao C, Zhang WH, Li YP, Chu K, Li M, Jiang YF, Li J, Zhao H, Lin ZJ, Cui XL, Liu WY, Li CH, Guo DP, Ke LD, Wu X, Tang J, Gao GQ, Li BY, Zhao B, Zheng FX, Dai CH, Guo M, Zhao J, Su YY, Wang JZ, Zhu FC, Li SW, Pan HR, Li YM, Zhang J, Xia NS. Efficacy, Safety, and Immunogenicity of an Escherichia coli-Produced Bivalent Human Papillomavirus Vaccine: An Interim Analysis of a Randomized Clinical Trial. J Natl Cancer Inst. 2020 Feb 1;112(2):145-153. doi: 10.1093/jnci/djz074.
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• Results Li SW, Zhang J, He ZQ, Gu Y, Liu RS, Lin J, Chen YX, Ng MH, Xia NS. Mutational analysis of essential interactions involved in the assembly of hepatitis E virus capsid. J Biol Chem. 2005 Feb 4;280(5):3400-6. doi: 10.1074/jbc.M410361200. Epub 2004 Nov 22.
• Results Wei M, Zhang X, Yu H, Tang ZM, Wang K, Li Z, Zheng Z, Li S, Zhang J, Xia N, Zhao Q. Bacteria expressed hepatitis E virus capsid proteins maintain virion-like epitopes. Vaccine. 2014 May 19;32(24):2859-65. doi: 10.1016/j.vaccine.2014.02.025. Epub 2014 Mar 22.
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• Results Zhang J, Liu CB, Li RC, Li YM, Zheng YJ, Li YP, Luo D, Pan BB, Nong Y, Ge SX, Xiong JH, Shih JW, Ng MH, Xia NS. Randomized-controlled phase II clinical trial of a bacterially expressed recombinant hepatitis E vaccine. Vaccine. 2009 Mar 13;27(12):1869-74. doi: 10.1016/j.vaccine.2008.12.061. Epub 2009 Jan 23.
• Results Zhang J, Zhang XF, Huang SJ, Wu T, Hu YM, Wang ZZ, Wang H, Jiang HM, Wang YJ, Yan Q, Guo M, Liu XH, Li JX, Yang CL, Tang Q, Jiang RJ, Pan HR, Li YM, Shih JW, Ng MH, Zhu FC, Xia NS. Long-term efficacy of a hepatitis E vaccine. N Engl J Med. 2015 Mar 5;372(10):914-22. doi: 10.1056/NEJMoa1406011.
• Results Tavares Da Silva F, Gonik B, McMillan M, Keech C, Dellicour S, Bhange S, Tila M, Harper DM, Woods C, Kawai AT, Kochhar S, Munoz FM; Brighton Collaboration Stillbirth Working Group. Stillbirth: Case definition and guidelines for data collection, analysis, and presentation of maternal immunization safety data. Vaccine. 2016 Dec 1;34(49):6057-6068. doi: 10.1016/j.vaccine.2016.03.044. Epub 2016 Jul 16. No abstract available.
• Results Pathirana J, Munoz FM, Abbing-Karahagopian V, Bhat N, Harris T, Kapoor A, Keene DL, Mangili A, Padula MA, Pande SL, Pool V, Pourmalek F, Varricchio F, Kochhar S, Cutland CL; Brighton Collaboration Neonatal Death Working Group. Neonatal death: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. 2016 Dec 1;34(49):6027-6037. doi: 10.1016/j.vaccine.2016.03.040. Epub 2016 Jul 19.
• Results Jones CE, Munoz FM, Kochhar S, Vergnano S, Cutland CL, Steinhoff M, Black S, Heininger U, Bonhoeffer J, Heath PT. Guidance for the collection of case report form variables to assess safety in clinical trials of vaccines in pregnancy. Vaccine. 2016 Dec 1;34(49):6007-6014. doi: 10.1016/j.vaccine.2016.07.007. Epub 2016 Oct 25.
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• Results Stout MJ, Busam R, Macones GA, Tuuli MG. Spontaneous and indicated preterm birth subtypes: interobserver agreement and accuracy of classification. Am J Obstet Gynecol. 2014 Nov;211(5):530.e1-4. doi: 10.1016/j.ajog.2014.05.023. Epub 2014 May 17.
• Results Fulton TR, Narayanan D, Bonhoeffer J, Ortiz JR, Lambach P, Omer SB. A systematic review of adverse events following immunization during pregnancy and the newborn period. Vaccine. 2015 Nov 25;33(47):6453-65. doi: 10.1016/j.vaccine.2015.08.043. Epub 2015 Sep 26.

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