Clinical trial NCT03343431: Antiviral Prophylaxis and Infant Vaccination to Prevent Perinatal Hepatitis B Infection
Official title: A Maternal Short Course of Tenofovir Disoproxil Fumarate and Infant Vaccine to Prevent Mother-to-child Transmission of Hepatitis B Virus
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hepatitis B
Pregnancy
Keywords: Hepatitis B
Hepatitis B eAg
Pregnancy
Lead sponsor: Institut de Recherche pour le Developpement
Sponsor class: OTHER_GOV
Collaborators: name: Chiang Mai University
name: Ministry of Health, Thailand
name: Ministry of Health, Lao PDR
First posted: 2017-11-17
Enrollment: 504
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All participants receive the intervention
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Infant hepatitis B infection status
timeFrame: Six months of age
Secondary outcomes:
measure: Maternal HBV DNA changes
timeFrame: From enrollment until end of study treatment scheduled 2 months after delivery
measure: Infant levels of anti-HBs antibodies
timeFrame: At 1, 2, 4, 6, and 12 months of age
measure: HBV infection status in all infants regardless of maternal response to study treatment
timeFrame: At 6 months of age
measure: Serious adverse events
timeFrame: From enrollment until 12 months postpartum
measure: Serious adverse events
timeFrame: From birth until 12 months of age
measure: Preterm live births
timeFrame: Delivery
measure: Low birth weight
timeFrame: Delivery
measure: Active or previous transient infection in children
timeFrame: At 18 months of age
Other outcomes:
Locations:
city: Champasak
country: Lao People's Democratic Republic
facility: Champasak Hospital
city: Luang Prabang
country: Lao People's Democratic Republic
facility: Luang Prabang Provincial Hospital
city: Savannakhet
country: Lao People's Democratic Republic
facility: Savannakhet Provincial hospital
city: Sayaboury
country: Lao People's Democratic Republic
facility: Sayaboury Hospital
city: Vientiane
country: Lao People's Democratic Republic
facility: 103 Hospital
city: Vientiane
country: Lao People's Democratic Republic
facility: Mahosot Hospital
city: Vientiane
country: Lao People's Democratic Republic
facility: Mother and Newborn Hospital
city: Vientiane
country: Lao People's Democratic Republic
facility: Setthathirath Hospital
city: Chiang Kham
country: Thailand
facility: Chiang Kham Hospital
state: Phayao
city: Bangkok
country: Thailand
facility: Nopparat Rajathanee Hospital
city: Chanthaburi
country: Thailand
facility: Prapokklao Hospital
city: Chiang Mai
country: Thailand
facility: Health Promotion Center Region 1
city: Chiang Mai
country: Thailand
facility: Nakornping Hospital
city: Chiang Rai
country: Thailand
facility: Chiangrai Prachanukroh Hospital
city: Chon Buri
country: Thailand
facility: Chonburi Hospital
city: Chon Buri
country: Thailand
facility: Banglamung Hospital
city: Lampang
country: Thailand
facility: Lampang Hospital
city: Lamphun
country: Thailand
facility: Lamphun Hospital
city: Samut Prakan
country: Thailand
facility: Samutprakarn Hospital
city: Samut Sakhon
country: Thailand
facility: Samutsakhon Hospital
Study officials:
affiliation: Chiang Mai University
name: Gonzague Jourdain, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: