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RecruitingNCT05808166Updated Sep 27, 2024

Safety and Immunogenicity of Hecolin® in Healthy Pregnant Women

A Phase 2 interventional study of Hecolin® (Recombinant Hepatitis E Vaccine (Escherichia coli)). and Isotonic Sodium Chloride injection in Hepatitis E Infection, sponsored by International Vaccine Institute. Recruiting at 1 site in Pakistan. Open to female participants aged 16 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-09-27.

Sponsored by International Vaccine Institute · Phase 2, Interventional, and Prevention

From the registry’s dates

  • Primary completion was expected by Nov 2025, 1 year ago, but the record still lists the study as recruiting.
  • Started May 2024; still recruiting 2 years 6 months later.
Phase
Phase 2
Study type
Interventional
Enrollment
2,358
Allocation
Randomized
Ages
16 Years to 45 Years
Sex
Female
01

Study 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.

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.

02

Conditions studied

  • Hepatitis E Infection

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Keywords

  • Hepatitis E infection
  • Hepatitis E virus
  • Hepatitis E vaccine
  • Hepatitis E in pregnancy
03

In context

Hepatitis E

37 studies on the registry are indexed under Hepatitis E; 9 are open to participants now.

This study's planned enrollment of 2,358 is above the median of 330 across 26 interventional studies indexed under Hepatitis E.

Browse Hepatitis E studies →

Lead sponsor

International Vaccine Institute is the lead sponsor of 47 studies on the registry; 12 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
16 Years to 45 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

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:

  1. 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.
  2. Individual willing to provide written for herself and her infant to participate in the study.
  3. Individual who can be followed up during the study period and can comply with the study requirements.
  4. 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.
  5. Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Non-pregnant women only:

  1. Healthy women 16-45 years of age.
  2. Individual willing to provide written informed consent to participate in the study.
  3. Individual who can be followed up during the study period and can comply with the study requirements.
  4. 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.
  5. Individuals who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  6. Females of with negative urinary pregnancy test on the day of screening.
  7. Females of childbearing potential who are using an effective method2 for at least 4 weeks before the screening and up to 4 weeks after the last vaccination.

Exclusion criteria

Exclusion Criteria:

A pregnant/non-pregnant woman who meets any of the following criteria will be excluded from participation in this study:

  1. Has received any hepatitis E vaccine in the past.
  2. Febrile illness (axillary temperature ≥ 38.5°C) or acute illness within 3 days prior to the study vaccination.
  3. Known history or allergy to study vaccine components and/or 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).
  4. Major congenital abnormalities which in the opinion of investigator may affect the participant's participation in the study.
  5. Known history of immune function disorders including immunodeficiency diseases (known infection or other immune function disorders) and lupus.
  6. Chronic use of systemic (>2 mg/kg/day or >20 mg/day prednisone equivalent for periods exceeding 10 days), cytotoxic or other drugs within past 6 weeks.
  7. 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.
  8. 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.
  9. History of splenectomy.
  10. Past history of thrombocytopenia and/or thrombosis, myocarditis or pericarditis or any other significant cardiac condition.
  11. With a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time resulting in for IM injections/blood extractions. (Those who receive low dose aspirin (less than 100mg/day) are not excluded)
  12. Receipt of blood or blood-derived products in the past 3 months.
  13. 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
  14. As per Investigator's medical judgement, an individual could be excluded from the study in spite of meeting all inclusion/exclusion criteria mentioned above.
  15. Concomitantly enrolled or scheduled to be enrolled in another trial.
  16. Research staff involved with the clinical study or family/household members of research staff.
  17. (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.
  1. 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.
  1. 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.
  1. Greater than 5 prior deliveries

Non-pregnant women only:

  1. Pregnant or plan to be pregnant during the study period.
Terms in these criteria, in plain language(9)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Excipients

The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

BMI (body mass index)

Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.

What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.

05

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
2,358 participants (estimated)

Study arms

  • Experimental
    Pregnant participant receiving Hecolin®

    1 (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.

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

  • Placebo comparator
    Pregnant participants receiving placebo

    Arm 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.

    Other: Isotonic Sodium Chloride injection

  • Active comparator
    Non-Pregnant participants receiving Hecolin®

    Arm 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.

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

Interventions

  • BiologicalHecolin® (Recombinant Hepatitis E Vaccine (Escherichia coli)).

    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).

    Also known as: 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.

  • OtherIsotonic Sodium Chloride injection

    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)

    Also known as: Sterile 0.9% sodium chloride

06

What researchers measure

Primary outcomes

  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.

    Time frame: 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.

    Time frame: 4 weeks post second dose of Hecolin®

Secondary outcomes

  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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 4 weeks post second dose of vaccination.

Other outcomes

  1. Proportion of vaginal delivery, elective cesarian section and emergency cesarian section in pregnant participants.

    Time frame: throughout the study

  2. Immunogenicity in neonate/infant participants

    * GMC of anti-HEV IgG in neonates/infants at delivery and age of 6 weeks and 6 months. * Anti-HEV IgG Subclass

    Time frame: at delivery, infant age of 6 weeks and 6 months

  3. Immunogenicity in maternal blood and umbilical cord at delivery

    * GMC of anti-HEV IgG in maternal blood and umbilical cord at the time of delivery * Anti-HEV IgG Subclass

    Time frame: at time of delivery

  4. Immunogenicity in breastmilk

    * GMC of anti-HEV IgG in breastmilk at delivery and postpartum 6 weeks and 6 months. * Anti-HEV IgG Subclass

    Time frame: at delivery, 6 weeks and 6 months post partum

  5. Counts and proportion of laboratory confirmed Hepatitis E among pregnant recipients of Hecolin® and placebo and their infants during pregnancy and 6 months after birth.

    Time frame: throughout the study period, approximately 24 months

  6. Safety in seropositive and seronegative pregnant participants at baseline

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

    Time frame: throughout the study period, approximately 24 months

  7. Immunogenicity in seropositive and seronegative 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 depending on serostatus.

    Time frame: 4 weeks post third dose of vaccination.

07

Study locations

1 of 1 sites recruiting
08

References and documents

Publications

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Individual participant data

Plan to share: No

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Started May 2024 (actual). Primary completion is estimated for Nov 2025, 18 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered
Mar 7, 2023
First posted
Apr 11, 2023
StartActual
May 2, 2024
Primary completionEst.
Nov 2025
CompletionEst.
Apr 2026
Last update
Sep 27, 2024
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Sep 27, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05808166
Lead sponsor
International Vaccine Institute
Collaborators
Open Philanthropy, Bill and Melinda Gates Foundation, Thrasher Research Fund
Responsible party
Sponsor
First posted
Apr 11, 2023
Start date
May 2, 2024
Primary completion
Nov 2025 (estimated)
Completion
Apr 2026 (estimated)
Last update
Sep 27, 2024

Study contacts

Katerina Rok Song, M.D.
Contact
katerina.song@ivi.int
+82-2-881-1228

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Discussion

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