Safety and Immunogenicity of Hecolin® in Healthy Pregnant Women

NCT05808166 | Recruiting Phase 2

• 1 other identifier: IVI_Hecolin_P001
• Study Type: interventional
• Target: 2,358
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hepatitis E Infection

Keywords

Hepatitis E infection; Hepatitis E virus; Hepatitis E vaccine; Hepatitis E in pregnancy

Outcome Measures

Primary Outcomes (2)

• 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.

  Throughout the study period, approximately 24 months.

• 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.

  4 weeks post second dose of Hecolin®

Secondary Outcomes (11)

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

  6 months of life in neonate/infant

• Proportion of immediate adverse events in pregnant and non-pregnant participants

  Within 30 minutes post each dose of vaccination.

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

  Within 7 days post each dose of vaccination.

• Proportion of unsolicited adverse events in pregnant and non-pregnant participants

  Within 28 days post each dose of vaccination.

• Immunogenicity in pregnant and non-pregnant participants

  4 weeks post second dose of vaccination.

Other Outcomes (7)

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

  throughout the study

• Immunogenicity in neonate/infant participants

  at delivery, infant age of 6 weeks and 6 months

• Immunogenicity in maternal blood and umbilical cord at delivery

  at time of delivery

Study Arms (3)

Pregnant participant receiving Hecolin®

EXPERIMENTAL

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)).

Pregnant participants receiving placebo

PLACEBO COMPARATOR

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

Non-Pregnant participants receiving Hecolin®

ACTIVE COMPARATOR

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

Hecolin® (Recombinant Hepatitis E Vaccine (Escherichia coli)). BIOLOGICAL

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.

Non-Pregnant participants receiving Hecolin®; Pregnant participant receiving Hecolin®

Isotonic Sodium Chloride injection OTHER

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

Pregnant participants receiving placebo

Eligibility Criteria

• Age: 16 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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
• Concomitantly enrolled or scheduled to be enrolled in another trial.

Sponsors & Collaborators

• International Vaccine Institute: lead
• Open Philanthropy: collaborator
• Bill and Melinda Gates Foundation: collaborator
• Thrasher Research Fund: collaborator

Study Sites (1)

The Aga Khan University

Karachi, Sindh, 74800, Pakistan

RECRUITING

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MeSH Terms

Interventions

hecolin; Sodium Chloride

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

Katerina Rok Song, M.D.

CONTACT

+82-2-881-1228; katerina.song@ivi.int

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2023
• First Posted: April 11, 2023
• Study Start: May 2, 2024
• Primary Completion: November 1, 2025
• Study Completion: April 1, 2026
• Last Updated: September 27, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)