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Hepatitis E InfectionPhase 2NCT05808166

Safety and Immunogenicity of Hecolin® in Healthy Pregnant Women

A Phase 2 study testing Hecolin® (Recombinant Hepatitis E Vaccine (Escherichia coli)). and Isotonic Sodium Chloride injection in people with Hepatitis E Infection, run by International Vaccine Institute at 1 site in Pakistan.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 16 to 45 years, women onlyHealthy volunteers can take part
Conditions the study is for
Hepatitis E Infection
What is being tested?
Hecolin® (Recombinant Hepatitis E Vaccine (Escherichia coli)). and Isotonic Sodium Chloride injection
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
2,358 participants
Where
1 sitePakistan
Study dates
2 May 2024to Apr 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 to 45 years
  • Women only
  • Healthy volunteers accepted
  • Child, Adult

Who may be able to join

  • In order to be eligible to participate in this study, a pregnant/non-pregnant woman must meet all of the following criteria:
  • Pregnant women only:
  • Healthy women 16-45 years of age who are between 14 0/7 and 34 6/7 weeks gestation1 on the day of planned vaccination with an uncomplicated, singleton pregnancy, who are at no known increased risk for complications for herself and her infant.
  • Individual willing to provide written informed consent for herself and her infant to participate in the study.
  • Individual who can be followed up during the study period and can comply with the study requirements.
  • Individual and fetus in good health as determined by the outcome of medical history, physical examination, obstetric history, prenatal care (by ultrasound and other prenatal assessment subject to gestational age), vital signs, laboratory evaluations at screening and the clinical judgment of the investigator.
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  • Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  • Non-pregnant women only:
  • Healthy women 16-45 years of age.
  • Individual willing to provide written informed consent to participate in the study.
  • Individual who can be followed up during the study period and can comply with the study requirements.
  • Individual in good health as determined by the outcome of medical history, physical examination, vital signs, laboratory evaluations at screening and the clinical judgment of the investigator.
  • Individuals who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  • Females of childbearing potential with negative urinary pregnancy test on the day of screening.
  • Females of childbearing potential who are using an effective birth control method2 for at least 4 weeks before the screening and up to 4 weeks after the last vaccination.

Who cannot join

  • A pregnant/non-pregnant woman who meets any of the following criteria will be excluded from participation in this study:
  • Has received any hepatitis E vaccine in the past.
  • Febrile illness (axillary temperature ≥ 38.5°C) or acute illness within 3 days prior to the study vaccination.
  • Known history or allergy to study vaccine components and/or excipients or other medications, or any other allergies or medical history deemed by the investigator to increase the risk of an adverse event if they were to participate in the trial (e.g., Guillain-Barre Syndrome).
  • Major congenital abnormalities which in the opinion of investigator may affect the participant's participation in the study.
  • Known history of immune function disorders including immunodeficiency diseases (known HIV infection or other immune function disorders) and lupus.
Show all 25Show fewer
  • Chronic use of systemic steroids (>2 mg/kg/day or >20 mg/day prednisone equivalent for periods exceeding 10 days), cytotoxic or other immunosuppressive drugs within past 6 weeks.
  • Any abnormality or chronic disease which in the opinion of the investigator might be detrimental for the safety of the participant and interfere with the assessment of the study objectives.
  • Behavioral or cognitive impairment, or chronic substance abuse, or psychiatric disease or neural disorders, that, in the opinion of the investigator, could interfere with the participant's ability to participate in the trial.
  • History of splenectomy.
  • Past history of thrombocytopenia and/or thrombosis, myocarditis or pericarditis or any other significant cardiac condition.
  • With a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time resulting in contraindication for IM injections/blood extractions. (Those who receive low dose aspirin (less than 100mg/day) are not excluded)
  • Receipt of blood or blood-derived products in the past 3 months.
  • Receipt of other vaccines from 4 weeks prior to test vaccination or planned to receive any vaccine within 4 weeks of last dose of study vaccine
  • As per Investigator's medical judgement, an individual could be excluded from the study in spite of meeting all inclusion/exclusion criteria mentioned above.
  • Concomitantly enrolled or scheduled to be enrolled in another trial.
  • Research staff involved with the clinical study or family/household members of research staff.
  • Body mass index (BMI) of ≥ 40, at the time of the screening visit.
  • Pregnant women only:
  • 1. Plans to terminate her pregnancy. Pregnancy complications (in the current pregnancy) such as preterm labor, gestational diabetes, hypertension (blood pressure (BP) > 140/90 in the presence of proteinuria or BP > 150/100 with or without proteinuria), or currently on an antihypertensive therapy, or pre-eclampsia, or evidence of intrauterine growth restriction.
  • 3. Prior stillbirth or neonatal death, or multiple (≥ 3) spontaneous abortions. 4. Prior preterm delivery ≤ 34 weeks gestation or having ongoing intervention (medical/surgical) in current pregnancy to prevent preterm birth.
  • 5. Previous infant with a known genetic disorder or major congenital anomaly. 6. History of major gynecologic or major abdominal surgery (previous Caesarean section is not an exclusion) 7. Current pregnancy results from in vitro fertilization (IVF). 8. Current pregnancy results from rape or incest. 9. Plans to release the neonate for adoption or the neonate to be a ward of the state.
  • 10. Greater than 5 prior deliveries
  • Non-pregnant women only:
  • 1. Pregnant or plan to be pregnant during the study period.

Trial locations and contacts

1 site in 1 country.

Katerina Rok Song, M.D. contact

+82-2-881-1228

katerina.song@ivi.int

Pakistan1 site, 1 recruiting

  • The Aga Khan University

    Karachi, Sindh, 74800

    Imran Nisar, Assistant Professor, +92 21 3486 4354, imran.nisar@aku.edu

    Recruiting

Other trials in Pakistan

About this study

Official title: A Phase II, Randomized, Observer-blinded, Placebo Controlled Trial to Evaluate the Safety and Immunogenicity of Hecolin® in Healthy Pregnant Women Between Gestational Age 14-34 Weeks and Non-Pregnant Women of 16-45 Years Old.

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.

Read the detailed description

Hecolin® is licensed in China and Pakistan indicated to be used for prevention of hepatitis E in healthy adult. The primary goal of this clinical trial is to establish the safety and immunogenicity of Hecolin® during pregnancy. As secondary and exploratory objectives, infant immune response through passive immunization of infants achieved through transplacental transfer of maternal IgG antibodies from the pregnant mother who has received Hecolin® in the second or third trimester will be evaluated.

Hecolin® follows a 3-dose schedule (0-1-6 months). For Arm 1 and 2, pregnant participants will receive 2 doses of Hecolin® or placebo at a 4 weeks interval and the third dose will be administered postpartum, approximately 20 weeks after the second dose. The neonates from these Arms will be followed for 24 weeks after birth. For Arm 3, non-pregnant participants will receive Hecolin® at 0-1-6 months schedule.

After each dose of IP injection to pregnant/non-pregnant participants, immediate AE (30 minutes post injection), solicited AE (7 days post injection), unsolicited AE (28 days post injection) and AESI/SAE (during the whole study period) will be collected.

For the immunogenicity subset, the participants' blood will be drawn before and 4 weeks post each dose of IP injection. At delivery, maternal blood will be drawn. Breast milk samples will be taken at delivery, 6 weeks, and 24 weekss after delivery.

All infant AESI/SAE will be collected throughout the study period and developmental assessment will be performed at age of 6 weeks, and 24 weeks. Blood will be drawn from infant immunogenicity subset at the same time points, umbilical cord blood (neonate blood will be collected if cord blood is not available for collection) at delivery, venous blood at age of 6 weeks and 24 weeks.

Being tested
Hecolin® (Recombinant Hepatitis E Vaccine (Escherichia coli))., Isotonic Sodium Chloride injection
Keywords
Hepatitis E infection, Hepatitis E virus, Hepatitis E vaccine, Hepatitis E in pregnancy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hecolin® (Recombinant Hepatitis E Vaccine (Escherichia coli)).Biological

    Also called 26 kDa protein (239 amino acids, aa368 to aa606) encoded by ORF2 of the HEV1 (Chinese HEV strain, genotype 1) and is expressed in Escherichia coli as a non-fusion protein.

    Hecolin® will be administered 2 doses administered 4 weeks apart during pregnancy and 1 dose administered after delivery at least 20 weeks following the second dose for the pregnant participants (arm 1), and 0, 1 and 6 months for the non-pregnant participant (arm 3).

  • Isotonic Sodium Chloride injectionOther

    Also called Sterile 0.9% sodium chloride

    Placebo will be administered 2 doses administered 4 weeks apart during pregnancy and 1 dose administered after delivery at least 20 weeks following the second dose for the pregnant participants (arm 2)

Study groups in NCT05808166
Study groupRoleWhat they receive
Pregnant participant receiving Hecolin®Experimental1 (N=1,104): Pregnant participants receiving Hecolin® (n=150 immunogenicity subset). For Arm 1, pregnant participants will receive 2 doses of Hecolin® at a 4 weeks interval and the third dose will be administered postpartum, approximately 20 weeks after the second dose.
Receives: Biological: Hecolin® (Recombinant Hepatitis E Vaccine (Escherichia coli)).
Pregnant participants receiving placeboPlacebo comparatorArm 2 (N=1,104): Pregnant participants receiving placebo (n= 150 immunogenicity subset). For Arm 2, pregnant participants will receive 2 doses of placebo at a 4 weeks interval and the third dose will be administered postpartum, approximately 20 weeks after the second dose.
Receives: Other: Isotonic Sodium Chloride injection
Non-Pregnant participants receiving Hecolin®Active comparatorArm 3 (N=150): Non-Pregnant participants receiving Hecolin® (n= 150 immunogenicity subset). For Arm 3, non-pregnant participants will receive Hecolin® at 0-1-6 months schedule.
Receives: Biological: Hecolin® (Recombinant Hepatitis E Vaccine (Escherichia coli)).

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of pregnancy-related AESI and SAE from vaccination in pregnant participant.

    • Proportion of pregnancy-related AESI from the vaccination throughout the entire study in pregnant participants.
    • Proportion of SAE from the vaccination throughout the entire study in pregnant participants.

    Measured: Throughout the study period, approximately 24 months.

  2. Immunogenicity in pregnant and non-pregnant participants

    GMC of anti-HEV IgG at 4 weeks post second dose of Hecolin® administered 4 weeks apart in pregnant women and non-pregnant women.

    Measured: 4 weeks post second dose of Hecolin®

Secondary outcomes (11)

  1. Proportion of AESIs and SAE in neonate/infant participants.

    • Proportion of neonatal/infant AESIs.
    • Proportion of SAE through the 6 months of life in neonate/infant.

    Measured: 6 months of life in neonate/infant

  2. Proportion of immediate adverse events in pregnant and non-pregnant participants

    Proportion of immediate adverse events within 30 minutes post each dose of vaccination in pregnant and non-pregnant participants.

    Measured: Within 30 minutes post each dose of vaccination.

  3. Proportion of Solicited local and system adverse events in pregnant and non-pregnant participants

    Proportion of solicited local and systemic adverse events within 7 days post each dose of vaccination in pregnant and non-pregnant participants.

    Measured: Within 7 days post each dose of vaccination.

  4. Proportion of unsolicited adverse events in pregnant and non-pregnant participants

    Proportion of unsolicited adverse events within 28 days post each dose of vaccination in pregnant and non-pregnant participants.

    Measured: Within 28 days post each dose of vaccination.

  5. Immunogenicity in pregnant and non-pregnant participants

    SCR (antibody response greater than four times or more increase of anti-HEV IgG in paired sera) at 4 weeks post second dose of Hecolin® administered 4 weeks apart in pregnant and non-pregnant participants.

    Measured: 4 weeks post second dose of vaccination.

  6. Immunogenicity in pregnant and non-pregnant participants

    GMC of anti-HEV IgG at 4 weeks post third dose of Hecolin® (2 doses in pregnancy and 1 dose after delivery) in pregnant and non-pregnant participants.

    Measured: 4 weeks post third dose of vaccination.

  7. Immunogenicity in pregnant and non-pregnant participants

    SCR (antibody response greater than four times or more increase of anti-HEV IgG in paired sera) at 4 weeks post third dose of Hecolin® (2 doses in pregnancy and 1 dose after delivery) in pregnant and non-pregnant participants.

    Measured: 4 weeks post third dose of vaccination.

  8. Immunogenicity in pregnant and non-pregnant participants

    GMC of anti-HEV IgG at 4 weeks post first dose of Hecolin® in pregnant and non-pregnant participants.

    Measured: 4 weeks post first dose of vaccination.

  9. Immunogenicity in pregnant and non-pregnant participants

    SCR (antibody response greater than four times or more increase of anti-HEV IgG in paired sera) at 4 weeks post first dose of Hecolin® in pregnant and non-pregnant participants.

    Measured: 4 weeks post first dose of vaccination.

  10. Immunogenicity in pregnant and non-pregnant participants

    GMC of anti-HEV IgG at 4 weeks post second dose of Hecolin® in pregnant participants of GA 14-27 weeks (second trimester) and 28-34 weeks (third trimester) and non-pregnant participants as measured by anti HEV IgG ELISA.

    Measured: 4 weeks post second dose of vaccination.

  11. Immunogenicity in pregnant and non-pregnant participants

    SCR (antibody response greater than four times or more increase of anti-HEV IgG in paired sera) at 4 weeks post second dose of Hecolin® in pregnant participants of GA 14-27 weeks (second trimester) and 28-34 weeks (third trimester) and non-pregnant participants.

    Measured: 4 weeks post second dose of vaccination.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Apr 2023
  2. Study start2 May 2024
  3. Primary completionNov 2025 (estimated)
  4. Study completionApr 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
2,358 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05808166
Sponsor's protocol ID
IVI_Hecolin_P001
Status last verified
Sep 2024
First submitted
7 Mar 2023
Last updated
27 Sep 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 27751641

  • 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.

    PubMed 32726529

  • 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.

    PubMed 22121109

  • 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.

    PubMed 17643015

  • 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.

    PubMed 11728649

  • 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.

    PubMed 8094346

  • 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.

    PubMed 17606958

  • 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.

    PubMed 27454402

  • 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.

    PubMed 21458513

  • 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.

    PubMed 26214817

  • Khuroo MS, Kamili S. Aetiology, clinical course and outcome of sporadic acute viral hepatitis in pregnancy. J Viral Hepat. 2003 Jan;10(1):61-9. doi: 10.1046/j.1365-2893.2003.00398.x.

    PubMed 12558914

  • Holla RP, Ahmad I, Ahmad Z, Jameel S. Molecular virology of hepatitis E virus. Semin Liver Dis. 2013 Feb;33(1):3-14. doi: 10.1055/s-0033-1338110. Epub 2013 Apr 5.

    PubMed 23564385

  • Mori Y, Matsuura Y. Structure of hepatitis E viral particle. Virus Res. 2011 Oct;161(1):59-64. doi: 10.1016/j.virusres.2011.03.015. Epub 2011 Apr 1.

    PubMed 21440590

  • 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.

    PubMed 2496611

  • Butt AS, Sharif F. Viral Hepatitis in Pakistan: Past, Present, and Future. Euroasian J Hepatogastroenterol. 2016 Jan-Jun;6(1):70-81. doi: 10.5005/jp-journals-10018-1172. Epub 2016 Jul 9.

    PubMed 29201731

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Hecolin® (Recombinant Hepatitis E Vaccine (Escherichia coli)). and Isotonic Sodium Chloride injection in people with Hepatitis E Infection, run by International Vaccine Institute at 1 site in Pakistan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 27 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Katerina Rok Song, M.D. (+82-2-881-1228, katerina.song@ivi.int), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of pregnancy-related AESI and SAE from vaccination in pregnant participant. (time frame: Throughout the study period, approximately 24 months.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05808166, which also lists 46 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2024.

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