Antiviral Prophylaxis and Infant Vaccination to Prevent Perinatal Hepatitis B Infection

Pregnancy Clinical Trial

Official title:

A Maternal Short Course of Tenofovir Disoproxil Fumarate and Infant Vaccine to Prevent Mother-to-child Transmission of Hepatitis B Virus

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03343431
• Other study ID #: iTAP-2
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 2, 2018
• Est. completion date: January 31, 2025

Study information

• Verified date: June 2024
• Source: Institut de Recherche pour le Developpement
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Most new hepatitis B virus (HBV) infections are acquired perinatally. In this study, pregnant women with HBsAg and HBeAg will receive tenofovir disoproxil fumarate during the last trimester of pregnancy and for two months following delivery. Their infants will receive hepatitis B (HB) immunization, starting with a first dose soon after birth. We hypothesize that the risk of mother-to-child transmission of HBV will be lower than 2%. The results of the study will help define policy to manage HBV infected pregnant women to prevent perinatal transmission.

Description:

This is a prospective multi-center, multi-country (Thailand and Lao PDR), open-label, single arm clinical trial in HBsAg and HBeAg positive pregnant women (from 28 weeks until one year postpartum) and their infants (until 18 months of age). Pregnant women with HBsAg and HBeAg will receive tenofovir disoproxil fumarate 300 mg once daily from 28 weeks of pregnancy until two months postpartum. Their infants will receive hepatitis B (HB) immunization, starting with the first dose soon after birth.

The study aims to show that substituting maternal antiviral treatment for infant HBIg can be favorably considered in settings where HBIg plus vaccine has been used as well as in settings where only vaccine is used. A significant improvement over the standard HBIg + vaccine strategy would be that adding an antiviral strategy results in less than 2% transmission. A total of 499 women and their infants will be enrolled in public hospitals in Thailand and Lao PDR.

The study will be monitored by a Data and Safety Monitoring Board (DSMB) at least annually.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 504
• Est. completion date: January 31, 2025
• Est. primary completion date: January 13, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pregnancy

• Age =18 years

• Negative HIV antibody test during current pregnancy

• Positive HBsAg test during current pregnancy

• Positive HBeAg using a rapid test during current pregnancy

• Absence of clinical symptoms of liver disease

• Gestational age of 28 weeks (+/- 7 days) based on the obstetrician judgment guided by the review of the date of last menstruation period.

• Willing and able to provide written informed consent

• Agreeing to bring her infants(s) at the planned study visits at one of the study site until the last visit (18 months after birth) and to inform the site investigators if plans to move to another place and not be able to return to the clinic

• Understand the need for adequate infant immunization for her infant(s) and accept that blood draws will be performed to determine the infant HBV infection status

Exclusion Criteria:

• Receipt of anti-HBV antivirals at any time during the last 9 months

• Known liver cirrhosis or evidence of hepatocellular carcinoma

• Creatinine clearance <50 ml/min, calculated using the Cockcroft-Gault formula

• Confirmed dipstick proteinuria >1+ (>30 mg/dL) or normoglycemic glycosuria

• Evidence of pre-existing fetal anomalies incompatible with life

• Any concomitant condition or treatment that, in the view of the clinical site investigator, would contraindicate participation or compromise adherence to treatment and satisfactory follow up in the study.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Pregnancy

Intervention

Drug:
• Anti-HBV antiviral prophylaxis
Tenofovir disoproxil fumarate (TDF), one 300 mg tablet once a day from 28 weeks' gestation through two months postpartum

Locations

Country	Name	City	State
Lao People's Democratic Republic	Champasak Hospital	Champasak
Lao People's Democratic Republic	Luang Prabang Provincial Hospital	Luang Prabang
Lao People's Democratic Republic	Savannakhet Provincial hospital	Savannakhet
Lao People's Democratic Republic	Sayaboury Hospital	Sayaboury
Lao People's Democratic Republic	103 Hospital	Vientiane
Lao People's Democratic Republic	Mahosot Hospital	Vientiane
Lao People's Democratic Republic	Mother and Newborn Hospital	Vientiane
Lao People's Democratic Republic	Setthathirath Hospital	Vientiane
Thailand	Nopparat Rajathanee Hospital	Bangkok
Thailand	Prapokklao Hospital	Chanthaburi
Thailand	Chiang Kham Hospital	Chiang Kham	Phayao
Thailand	Health Promotion Center Region 1	Chiang Mai
Thailand	Nakornping Hospital	Chiang Mai
Thailand	Chiangrai Prachanukroh Hospital	Chiang Rai
Thailand	Banglamung Hospital	Chon Buri
Thailand	Chonburi Hospital	Chon Buri
Thailand	Lampang Hospital	Lampang
Thailand	Lamphun Hospital	Lamphun
Thailand	Samutprakarn Hospital	Samut Prakan
Thailand	Samutsakhon Hospital	Samut Sakhon

Sponsors (4)

Lead Sponsor	Collaborator
Institut de Recherche pour le Developpement	Chiang Mai University, Ministry of Health, Lao PDR, Ministry of Health, Thailand

Countries where clinical trial is conducted

Lao People's Democratic Republic,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Infant hepatitis B infection status	HBsAg positive confirmed by PCR detection of HBV DNA.	Six months of age
Secondary	Maternal HBV DNA changes	Description of the effect of tenofovir disoproxil fumarate on maternal HBV DNA levels	From enrollment until end of study treatment scheduled 2 months after delivery
Secondary	Infant levels of anti-HBs antibodies	Levels of anti-HBs antibodies in infants in the absence of HBIg administration at birth	At 1, 2, 4, 6, and 12 months of age
Secondary	HBV infection status in all infants regardless of maternal response to study treatment	HBsAg positive confirmed by PCR detection of HBV DNA in all infants, i.e. including those born to women with unsatisfactory virological response to study treatment	At 6 months of age
Secondary	Serious adverse events	Occurrence of maternal serious adverse events (ICH SAEs) including DAIDS grade 4 signs and symptoms regardless of their relatedness to the study treatment	From enrollment until 12 months postpartum
Secondary	Serious adverse events	Occurrence of infant serious adverse events (ICH SAEs) including DAIDS grade 4 signs and symptoms regardless of their relatedness to the study treatment	From birth until 12 months of age
Secondary	Preterm live births	Proportion of neonates born alive before 37 weeks of pregnancy	Delivery
Secondary	Low birth weight	Proportion of neonates born alive with birth weight of 2,499 g or less, regardless of gestational age	Delivery
Secondary	Active or previous transient infection in children	Detection of anti-HBc antibodies among all infants	At 18 months of age