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Antiviral Prophylaxis and Infant Vaccination to Prevent Perinatal Hepatitis B Infection

Primary Purpose

Hepatitis B, Pregnancy

Status

Active

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Anti-HBV antiviral prophylaxis

About this trial

This is an interventional prevention trial for Hepatitis B focused on measuring Hepatitis B, Hepatitis B eAg, Pregnancy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Outcomes

Primary Outcome Measures

Infant hepatitis B infection status

HBsAg positive confirmed by PCR detection of HBV DNA.

Secondary Outcome Measures

Maternal HBV DNA changes

Description of the effect of tenofovir disoproxil fumarate on maternal HBV DNA levels

Infant levels of anti-HBs antibodies

Levels of anti-HBs antibodies in infants in the absence of HBIg administration at birth

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

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

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

Preterm live births

Proportion of neonates born alive before 37 weeks of pregnancy

Low birth weight

Proportion of neonates born alive with birth weight of 2,499 g or less, regardless of gestational age

Active or previous transient infection in children

Detection of anti-HBc antibodies among all infants

Full Information

NCT ID

NCT03343431

First Posted

November 6, 2017

Last Updated

May 23, 2022

Sponsor

Institut de Recherche pour le Developpement

Collaborators

Chiang Mai University, Ministry of Health, Thailand, Ministry of Health, Lao PDR

1. Study Identification

Unique Protocol Identification Number

NCT03343431

Brief Title

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

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

August 2, 2018 (Actual)

Primary Completion Date

July 31, 2022 (Anticipated)

Study Completion Date

December 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Institut de Recherche pour le Developpement

Collaborators

Chiang Mai University, Ministry of Health, Thailand, Ministry of Health, Lao PDR

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis B, Pregnancy

Keywords

Hepatitis B, Hepatitis B eAg, Pregnancy

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Model Description

All participants receive the intervention

Masking

None (Open Label)

Allocation

N/A

Enrollment

504 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Anti-HBV antiviral prophylaxis

Other Intervention Name(s)

tenofovir disoproxil fumarate

Intervention Description

Tenofovir disoproxil fumarate (TDF), one 300 mg tablet once a day from 28 weeks' gestation through two months postpartum

Primary Outcome Measure Information:

Title

Infant hepatitis B infection status

Description

HBsAg positive confirmed by PCR detection of HBV DNA.

Time Frame

Six months of age

Secondary Outcome Measure Information:

Title

Maternal HBV DNA changes

Description

Description of the effect of tenofovir disoproxil fumarate on maternal HBV DNA levels

Time Frame

From enrollment until end of study treatment scheduled 2 months after delivery

Title

Infant levels of anti-HBs antibodies

Description

Levels of anti-HBs antibodies in infants in the absence of HBIg administration at birth

Time Frame

At 1, 2, 4, 6, and 12 months of age

Title

HBV infection status in all infants regardless of maternal response to study treatment

Description

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

Time Frame

At 6 months of age

Title

Serious adverse events

Description

Occurrence of maternal serious adverse events (ICH SAEs) including DAIDS grade 4 signs and symptoms regardless of their relatedness to the study treatment

Time Frame

From enrollment until 12 months postpartum

Title

Serious adverse events

Description

Occurrence of infant serious adverse events (ICH SAEs) including DAIDS grade 4 signs and symptoms regardless of their relatedness to the study treatment

Time Frame

From birth until 12 months of age

Title

Preterm live births

Description

Proportion of neonates born alive before 37 weeks of pregnancy

Time Frame

Delivery

Title

Low birth weight

Description

Proportion of neonates born alive with birth weight of 2,499 g or less, regardless of gestational age

Time Frame

Delivery

Title

Active or previous transient infection in children

Description

Detection of anti-HBc antibodies among all infants

Time Frame

At 18 months of age

10. Eligibility

Sex

Female

Gender Based

Yes

Gender Eligibility Description

Pregnant women

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gonzague Jourdain, MD, PhD

Organizational Affiliation

Institut de Recherche pour l e Développement

Official's Role

Principal Investigator

Facility Information:

Facility Name

Champasak Hospital

City

Champasak

Country