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Trial registered on ANZCTR


Registration number
ACTRN12619000419167
Ethics application status
Approved
Date submitted
21/02/2019
Date registered
14/03/2019
Date last updated
9/07/2021
Date data sharing statement initially provided
14/03/2019
Date results information initially provided
9/07/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
Tenofovir Alafenamide (TAF) Breast Milk Pharmacokinetics (PK) study
Scientific title
Breast Milk Pharmacokinetics of Vemlidy® (Tenofovir Alafenamide: TAF) After its use
in the Prevention of Mother-to-Child Transmission in the Setting of Hepatitis B Virus (HBV) infection
Secondary ID [1] 297476 0
IN-AU-320-5429
Universal Trial Number (UTN)
U1111-1229-0205
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
hepatitis B infection 311667 0
Condition category
Condition code
Infection 310290 310290 0 0
Other infectious diseases
Oral and Gastrointestinal 310291 310291 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Breastfeeding mothers will receive tenofovir alafenamide (TAF; 25mg oral tablet taken once per day) for a minimum of 4 weeks prior to the pharmacokinetics visit day. Participants will be instructed to take their tablet in the morning (8am-9am) and to document the time it is taken in a pill diary. TAF will be provided for a maximum of 20 weeks.
The PK visit day will take place 2-12 weeks post-partum. Maternal blood (MB), breast milk (BM) and infant urine sample will be collected after a clinical review including h physical examination, TAF adherence check, and AE check. MB and BM sampling will take place at the following time points: pre-dose, 0.5hrs post-dose, 1-1.5hrs post-dose, 2.5-3.5hrs post-dose, 5-6hrs post-dose, 8hrs post-dose, and 24hrs post-dose.
Intervention code [1] 313728 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 319183 0
Composite primary outcome determining the breast milk (BM), maternal blood (MB), and infant urine (IU) concentration and pharmacokinetics (PK) of tenofovir alafenamide (TAF) and tenofovir (TFV) in breast-feeding women on a stable dose of TAF. PK parameters being assessed are T1/2, Tmax, AUC, Cmax.
Timepoint [1] 319183 0
PK visit day, which is to occur after a minimum of 4 weeks treatment with TAF. Sampling will take place at the following time points: pre-dose, 0.5hrs post-dose, 1-1.5hrs post-dose, 2.5-3.5hrs post-dose, 5-6hrs post-dose, 8hrs post-dose, and 24hrs post-dose.
Secondary outcome [1] 367212 0
Safety and tolerability of TAF in breastfeeding mothers and their infants. Determined by monitoring maternal and infant obstetric outcomes, physical assessment and standard clinical and laboratory testing.
Timepoint [1] 367212 0
Monitored throughout TAF treatment.
Secondary outcome [2] 367213 0
Concentration of TAF in maternal blood cells as determined by liquid chromatography/mass spectrometry.
Timepoint [2] 367213 0
PK visit day. Sampling will take place at the following time points: pre-dose, 0.5hrs post-dose, 1-1.5hrs post-dose, 2.5-3.5hrs post-dose, 5-6hrs post-dose, 8hrs post-dose, and 24hrs post-dose.
Secondary outcome [3] 368080 0
Concentration of TFV in maternal blood cells as determined by liquid chromatography/mass spectrometry.
Timepoint [3] 368080 0
PK visit day. Sampling will take place at the following time points: pre-dose, 0.5hrs post-dose, 1-1.5hrs post-dose, 2.5-3.5hrs post-dose, 5-6hrs post-dose, 8hrs post-dose, and 24hrs post-dose.
Secondary outcome [4] 368175 0
Concentration of TAF in breast milk cells as determined by liquid chromatography/mass spectrometry.
Timepoint [4] 368175 0
PK visit day. Sampling will take place at the following time points: pre-dose, 0.5hrs post-dose, 1-1.5hrs post-dose, 2.5-3.5hrs post-dose, 5-6hrs post-dose, 8hrs post-dose, and 24hrs post-dose.
Secondary outcome [5] 368176 0
Concentration of TFV in breast milk cells as determined by liquid chromatography/mass spectrometry.
Timepoint [5] 368176 0
PK visit day. Sampling will take place at the following time points: pre-dose, 0.5hrs post-dose, 1-1.5hrs post-dose, 2.5-3.5hrs post-dose, 5-6hrs post-dose, 8hrs post-dose, and 24hrs post-dose.

Eligibility
Key inclusion criteria
- Pregnant women with HBV and high viral load (greater than or equal to 6 log10 IU/ml)
- Aged 18 years or older at the time of Screening
- Taking antiviral therapy for the prevention of mother to child transmission (MTCT) of HBV
- Willing to take 25mg of TAF routinely, ideally commenced at 28-32 weeks of gestation and continued to 12 weeks post-partum OR Willing to take TAF postpartum switching from routine tenofovir disoproxil fumurate (TDF) during pregnancy.
- Pregnant women presenting later than 32 weeks gestation (including post-partum) can be included, but TAF must have been commenced no less than 4 weeks prior to the PK study visit
- Pregnant women already taking TDF for the prevention of MTCT can be included if willing to switch to TAF either during the pregnancy or after delivery, (PK study will be performed after a minimum of 4 weeks on TAF which is a sufficient time period for full washout of any TFV present attributable to TDF).
- Willing to participate in PK study (over 24 hours) between 2-12 weeks post-partum, in a totally breast fed infant a minimum of 4 weeks after commencing TAF.
- Willingness to give informed consent and willingness to participate and comply with the study.
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Nucleos(t)ide analogue therapy within prior 6 months except for TDF
- Significant co-morbidities including advanced liver disease and systemic disease
- Any concomitant regular medications except iron or folate for pregnancy

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint(s)
Pharmacokinetics
Statistical methods / analysis
Summary statistics will be provided for quantitative variables. Linear regression correlations will be used to compare drug levels in breast milk and plasma.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 13219 0
Liverpool Hospital - Liverpool
Recruitment postcode(s) [1] 25776 0
2170 - Liverpool
Recruitment outside Australia
Country [1] 21298 0
New Zealand
State/province [1] 21298 0
Auckland

Funding & Sponsors
Funding source category [1] 302044 0
Other
Name [1] 302044 0
Gilead Sciences, Inc.
Address [1] 302044 0
333 Lakeside Drive
Foster City, CA 94404
Country [1] 302044 0
United States of America
Primary sponsor type
Government body
Name
South Western Sydney Local Health District
Address
Administration Building, Eastern Campus, Liverpool Hospital, Cnr Elizabeth & Goulburn Streets, Liverpool, NSW, 2170, Australia
Country
Australia
Secondary sponsor category [1] 301852 0
Government body
Name [1] 301852 0
Auckland District Health Board
Address [1] 301852 0
Level 1, Building 37,
2 Park Road, Grafton,
Auckland, 1023
New Zealand
Country [1] 301852 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302727 0
South Western Sydney Local Health District HREC
Ethics committee address [1] 302727 0
Research and Ethics Office, Level 2, UNSW Clinical School,
Liverpool Hospital, Elizabeth Street, NSW, 2170
Ethics committee country [1] 302727 0
Australia
Date submitted for ethics approval [1] 302727 0
22/11/2018
Approval date [1] 302727 0
14/01/2019
Ethics approval number [1] 302727 0
2018/ETH00570

Summary
Brief summary
Pharmacokinetics (metabolism) of tenofovir alafenamide (TAF) used in HBV-infected women that are breast feeding. Both analogues of tenofovir, differing only by their side chains, TAF has been demonstrated to be safer than tenofovir disoproxil fumurate (TDF), especially in patients with osteopaenia or osteoporosis, thus TAF is likely to be also superior to TDF for pregnant and breast feeding women. Women in this study may choose to take TAF in pregnancy or only postpartum whilst breast feeding. The study will be a one day pharmacokinetic study. There is no registration data on TAF or TDF in pregnancy, but both are allowable and TAF has superior pharmacology to TDF. TDF has been available for ten years and post-registration safety data for TDF are excellent. This project will determine if TAF is detectable in breast milk, maternal blood and infant urine.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91178 0
A/Prof Miriam Levy
Address 91178 0
Department of Gastroenterology and Hepatology, Liverpool Hospital, Elizabeth Street, Liverpool, NSW, 2170
Country 91178 0
Australia
Phone 91178 0
+61 287384085
Fax 91178 0
Email 91178 0
miriam.levy@health.nsw.gov.au
Contact person for public queries
Name 91179 0
A/Prof Miriam Levy
Address 91179 0
Department of Gastroenterology and Hepatology, Liverpool Hospital, Elizabeth Street, Liverpool, NSW, 2170
Country 91179 0
Australia
Phone 91179 0
+61 287384085
Fax 91179 0
Email 91179 0
miriam.levy@health.nsw.gov.au
Contact person for scientific queries
Name 91180 0
A/Prof Miriam Levy
Address 91180 0
Department of Gastroenterology and Hepatology, Liverpool Hospital, Elizabeth Street, Liverpool, NSW, 2170
Country 91180 0
Australia
Phone 91180 0
+61 287384085
Fax 91180 0
Email 91180 0
miriam.levy@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary