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Hepatitis BPhase 1/2NCT02995005

Tenofovir in Early Pregnancy to Prevent Mother-to-child Transmission of Hepatitis B Virus

A Phase 1/2 study testing Tenofovir Disoproxil Fumarate in people with Hepatitis B, run by Johns Hopkins Bloomberg School of Public Health at 1 site in Thailand.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains the major mode of transmission in most high and intermediate HBV endemic areas, despite existing WHO immunoprophylaxis recommendations. Read more about this study

Who is it for?
Ages 16 to 49 years, women only
Conditions the study is for
Hepatitis B
What is being tested?
Tenofovir Disoproxil Fumarate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
98 participants
Where
1 siteThailand
Study dates
24 May 2018to 31 Jan 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 to 49 years
  • Women only
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Pregnant women aged 18 and over
  • HBsAg positive
  • In the 12th-20th week of pregnancy
  • Willing to take TDF daily during pregnancy
  • Providing written informed consent
  • Plans to deliver at Shoklo Malaria Research Unit (SMRU)
  • Able and willing to comply with study requirements

Who cannot join

  • Anti-HIV positive
  • Negative qualitative HBV DNA if HBeAg negative
  • On immunosuppressive therapy
  • Elevated creatinine
  • History of kidney disease
  • Short cervix
  • History of pregnancy complications or prior pre-term labor

Trial locations and contacts

1 site in 1 country.

Thailand1 site

  • Shoklo Malaria Research Unit

    Mae Sot

Other trials in Thailand

About this study

Official title: Prevention of Mother-to-child Transmission of Hepatitis B Virus: a One Arm, Open Label Intervention Study to Estimate the Optimal Timing of Tenofovir (TDF) in Pregnancy

Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains the major mode of transmission in most high and intermediate HBV endemic areas, despite existing WHO immunoprophylaxis recommendations. This immunoprophylaxis regimen, if given optimally, can prevent 75-80% of HBV MTCT, but optimal implementation is difficult because it requires administering monovalent HBV vaccine and hepatitis B immunoglobulin (HBIg) within 24 hours of birth. Due to the barriers of giving HBIg, the World Health Organization (WHO) states, "…owing to concerns related to supply, safety and cost, the use of HBIg is not feasible in most settings." Clearly, global control of HBV transmission will require improved MTCT prevention. Therefore, the investigators hypothesize that treating HBV early in pregnancy will lead to undetectable HBV DNA levels at delivery and prevention of MTCT of HBV without HBIg; a concept that has already been proven with HIV. Tenofovir disoproxil fumarate (TDF), an approved anti-HBV drug, is promising to prevent MTCT of HBV due to its high potency against hepatitis B and its safety record in pregnant women. A randomized, controlled clinical trial (RCT) will be necessary to determine if TDF given to HBV-infected pregnant women early in pregnancy plus vaccine to the newborn can decrease MTCT of HBV without HBIg. However, before embarking on a RCT, several critical knowledge gaps need to be addressed including the ideal timing for TDF initiation. The purpose of this proposal is to address these knowledge gaps.

Read the detailed description

The investigators hypothesize that anti-HBV therapy given in the late first or early second trimester achieves undetectable HBV DNA at delivery in >=95% of pregnant women with chronic hepatitis B. The one-arm, open-label, interventional study aims: 1, To estimate the time to complete HBV DNA suppression (<100 IU/ml) in 170 HBV DNA positive women who start TDF in the late first or early second trimester; and to estimate the proportion of women with HBV DNA <100 IU/ml at delivery. 2, To address potential barriers to and the efficacy of implementing TDF in early pregnancy to prevent mother-to-child transmission of hepatitis B. The investigators will measure potential barriers to acceptability and effectiveness of this intervention: adherence, potential hepatitis B flares in mothers (safety), and the proportion of hepatitis B infections in the offspring at 1 year of age (efficacy).

Conditions
Hepatitis B
Being tested
Tenofovir Disoproxil Fumarate
Keywords
mother to child transmission, hepatitis B, tenofovir
Medical subject headings
Hepatitis B

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tenofovir Disoproxil FumarateDrug

    Also called Viread

    300 mg daily

Study groups in NCT02995005
Study groupRoleWhat they receive
Tenofovir Disoproxil FumarateExperimentalWomen early in pregnancy (end of first or beginning second trimester) will be treated with TDF to determine the efficacy of this strategy to bring >=95% of women to undetectable HBV DNA levels at delivery.
Receives: Drug: Tenofovir Disoproxil Fumarate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The time (from inclusion through delivery; up to 6 months) to HBV DNA suppression (<100 IU/ml)

    HBV DNA will be monitored every month

    Measured: Up to 9 months

  2. The proportion of women with undetectable HBV DNA at delivery

    HBV DNA will be monitored at delivery.

    Measured: At delivery

Secondary outcomes (5)

  1. Proportion of hepatitis B flares in mothers postpartum

    All women will continue on study for 3 months after stopping TDF to measure their alanine aminotransferase (ALT) and aspartate aminotransferase (AST) monthly to detect a flare, which will be defined as >5x baseline or >10x the upper limit of normal. If at the end of the 3 months, there has been no change in ALT and AST, then the mothers will be discharged from the study. If there is an increase in liver enzymes but not a true flare, they will be followed for an additional 3 months with monthly ALT testing.

    Measured: Monthly measured for 3 months after stopping TDF.

  2. The proportion of women who adhered to TDF treatment during the course of the study (from inclusion through 1 month after delivery; up to 7 months; drug levels)

    Measurement of tenofovir drug levels

    Measured: Up to 9 months

  3. The proportion of women who adhered to TDF treatment during the course of the study (from inclusion through 1 month after delivery; up to 7 months; drug accountability)

    Drug accountability using standard methods (subtracting the number of tablets left from the number of tablets distributed).

    Measured: Up to 9 months

  4. The proportion of women who adhered to TDF treatment during the course of the study (from inclusion through 1 month after delivery; up to 7 months; questionnaire)

    All women will be surveyed at monthly visits and at birth to measure adherence including actionable barriers.

    Measured: Up to 9 months

  5. The proportion of hepatitis B infections in the offspring at 1 year of age

    Testing for HBsAg in children between 2 and 12 months of age.

    Measured: Between month 2 and 12 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Dec 2016 (estimated)
  2. Study start24 May 2018
  3. Primary completion31 Jan 2023
  4. Study completion31 Jan 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Model description
Single group study.
Masking
None (open label)
Enrolment
98 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02995005
Sponsor's protocol ID
JHSPH-TDF
Status last verified
Oct 2022
First submitted
8 Dec 2016
Last updated
6 Feb 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The investigators are currently developing an individual participant data (IPD) sharing plan.

Publications

  • Lee WM. Hepatitis B virus infection. N Engl J Med. 1997 Dec 11;337(24):1733-45. doi: 10.1056/NEJM199712113372406. No abstract available.

    PubMed 9392700

  • Lavanchy D. Worldwide epidemiology of HBV infection, disease burden, and vaccine prevention. J Clin Virol. 2005 Dec;34 Suppl 1:S1-3. doi: 10.1016/s1386-6532(05)00384-7.

    PubMed 16461208

  • Ranger-Rogez S, Denis F. Hepatitis B mother--to--child transmission. Expert Rev Anti Infect Ther. 2004 Feb;2(1):133-45. doi: 10.1586/14787210.2.1.133.

    PubMed 15482178

  • Chang MH. Natural history of hepatitis B virus infection in children. J Gastroenterol Hepatol. 2000 May;15 Suppl:E16-9. doi: 10.1046/j.1440-1746.2000.02096.x.

    PubMed 10921376

  • Wen WH, Chang MH, Zhao LL, Ni YH, Hsu HY, Wu JF, Chen PJ, Chen DS, Chen HL. Mother-to-infant transmission of hepatitis B virus infection: significance of maternal viral load and strategies for intervention. J Hepatol. 2013 Jul;59(1):24-30. doi: 10.1016/j.jhep.2013.02.015. Epub 2013 Feb 26.

    PubMed 23485519

  • Chien YC, Jan CF, Kuo HS, Chen CJ. Nationwide hepatitis B vaccination program in Taiwan: effectiveness in the 20 years after it was launched. Epidemiol Rev. 2006;28:126-35. doi: 10.1093/epirev/mxj010. Epub 2006 Jun 16.

    PubMed 16782778

  • Xu H, Zeng T, Liu JY, Lei Y, Zhong S, Sheng YJ, Zhou Z, Ren H. Measures to reduce mother-to-child transmission of Hepatitis B virus in China: a meta-analysis. Dig Dis Sci. 2014 Feb;59(2):242-58. doi: 10.1007/s10620-013-2918-0. Epub 2013 Nov 6.

    PubMed 24193353

  • Xu DZ, Yan YP, Choi BC, Xu JQ, Men K, Zhang JX, Liu ZH, Wang FS. Risk factors and mechanism of transplacental transmission of hepatitis B virus: a case-control study. J Med Virol. 2002 May;67(1):20-6. doi: 10.1002/jmv.2187.

    PubMed 11920813

  • Shao ZJ, Zhang L, Xu JQ, Xu DZ, Men K, Zhang JX, Cui HC, Yan YP. Mother-to-infant transmission of hepatitis B virus: a Chinese experience. J Med Virol. 2011 May;83(5):791-5. doi: 10.1002/jmv.22043. Epub 2011 Feb 25.

    PubMed 21360547

  • Chen DS. Hepatitis B vaccination: The key towards elimination and eradication of hepatitis B. J Hepatol. 2009 Apr;50(4):805-16. doi: 10.1016/j.jhep.2009.01.002. Epub 2009 Feb 3.

    PubMed 19231008

  • Wiseman E, Fraser MA, Holden S, Glass A, Kidson BL, Heron LG, Maley MW, Ayres A, Locarnini SA, Levy MT. Perinatal transmission of hepatitis B virus: an Australian experience. Med J Aust. 2009 May 4;190(9):489-92. doi: 10.5694/j.1326-5377.2009.tb02524.x.

    PubMed 19413519

  • Tran TT. Management of hepatitis B in pregnancy: weighing the options. Cleve Clin J Med. 2009 May;76 Suppl 3:S25-9. doi: 10.3949/ccjm.76.s3.06.

    PubMed 19465706

  • del Canho R, Grosheide PM, Mazel JA, Heijtink RA, Hop WC, Gerards LJ, de Gast GC, Fetter WP, Zwijneberg J, Schalm SW. Ten-year neonatal hepatitis B vaccination program, The Netherlands, 1982-1992: protective efficacy and long-term immunogenicity. Vaccine. 1997 Oct;15(15):1624-30. doi: 10.1016/s0264-410x(97)00080-7.

    PubMed 9364693

  • Read JS. Prevention of mother-to-child transmission of HIV: antiretroviral strategies. Clin Perinatol. 2010 Dec;37(4):765-76, viii. doi: 10.1016/j.clp.2010.08.007.

    PubMed 21078449

  • Warszawski J, Tubiana R, Le Chenadec J, Blanche S, Teglas JP, Dollfus C, Faye A, Burgard M, Rouzioux C, Mandelbrot L; ANRS French Perinatal Cohort. Mother-to-child HIV transmission despite antiretroviral therapy in the ANRS French Perinatal Cohort. AIDS. 2008 Jan 11;22(2):289-99. doi: 10.1097/QAD.0b013e3282f3d63c.

    PubMed 18097232

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tenofovir Disoproxil Fumarate in people with Hepatitis B, run by Johns Hopkins Bloomberg School of Public Health at 1 site in Thailand.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The time (from inclusion through delivery; up to 6 months) to HBV DNA suppression (<100 IU/ml) (time frame: Up to 9 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02995005, which also lists 46 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2023.

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