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Trial registered on ANZCTR


Registration number
ACTRN12619000054112p
Ethics application status
Submitted, not yet approved
Date submitted
11/01/2019
Date registered
15/01/2019
Date last updated
16/01/2019
Date data sharing statement initially provided
15/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of therapy for hepatitis C in pregnancy
Scientific title
A pharmacokinetic (PK) study of directly acting antiviral therapy for hepatitis C in pregnancy
Secondary ID [1] 297037 0
None
Universal Trial Number (UTN)
U1111-1226-1356
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C 311022 0
Pregnancy 311023 0
Condition category
Condition code
Infection 309668 309668 0 0
Other infectious diseases
Reproductive Health and Childbirth 309712 309712 0 0
Normal pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pregnant women will be treated with Sofosbuvir (SOF) 400mg and Velpatasvir (VEL) 100mg tablet orally, once daily for 12 weeks starting between 22 and 24 weeks gestation. Adherence to the intervention will be only be monitored by asking the woman if she has missed any tablets and the number missed.
Intervention code [1] 313316 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 318640 0
The inactive Sofosbuvir metabolite GS-331007 will be measured pre and post dose to determine pharmacokinetics (Tmax, AUC, T1/2 and Cmin) by serum assay.
Timepoint [1] 318640 0
Systemic exposure to sofosbuvir will be assessed at three gestational time points (between 25+0 weeks gestation and 26+5 weeks gestation; between 29+0 and 30+6 weeks gestation; and between 33+0 and 34+6 weeks gestation).
Primary outcome [2] 318682 0
Velpatasvir will be measured pre and post dose to determine pharmacokinetics (Tmax, AUC, T1/2 and Cmin) by serum assay.
Timepoint [2] 318682 0
Systemic exposure to velpatasvir will be assessed at three gestational time points (between 25+0 weeks gestation and 26+5 weeks gestation; between 29+0 and 30+6 weeks gestation; and between 33+0 and 34+6 weeks gestation).
Secondary outcome [1] 365559 0
A sustained virological response (SVR) as assessed by a HCV RT-PCR of maternal serum.
Timepoint [1] 365559 0
12 weeks post end of treatment
Secondary outcome [2] 365560 0
Perinatal HCV transmission as assessed by a HCV RT-PCR of neonatal serum.
Timepoint [2] 365560 0
6 months of age of the child

Eligibility
Key inclusion criteria
Pregnant women mono-infected with hepatitis C, able to provide written, informed consent, will need to be able to provide contact details, have any HCV genotype with a detectable HCV RNA viral load at screening >1000 IU/ml, a gestational age of 22 weeks at enrollment and a singleton pregnancy with no known fetal anomalies (as confirmed on routine 18-22 week ultrasound).
Minimum age
18 Years
Maximum age
45 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Women will be excluded from the study if they have previously had treatment for HCV with a NS5A inhibitor, use of any medications contraindicated with SOF/VEL, have a history of cirrhosis, have any significant uncontrolled active or chronic cardiovascular, renal, or liver disease, haematological, neurological, immunological or infectious disease (other than HCV), have a high risk of preterm birth (defined as a history of preterm birth at less than 34 weeks or a shortened cervical length of less than 20 millimeters).

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
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
This study proposes to recruit 10 participants. This study is primarily to analyse PK. Although endpoints such as maternal cure and perinatal transmission will be included, these are not the primary endpoints and the study is therefore not powered to analyse these.

Recruitment
Recruitment status
Not yet recruiting
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)
VIC
Recruitment hospital [1] 12861 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [2] 12862 0
Sunshine Hospital - St Albans
Recruitment postcode(s) [1] 25337 0
3168 - Clayton
Recruitment postcode(s) [2] 25338 0
3021 - St Albans

Funding & Sponsors
Funding source category [1] 301606 0
Commercial sector/Industry
Name [1] 301606 0
Gilead Sciences PTY Ltd
Address [1] 301606 0
Level 6, 417 St Kilda Road
Melbourne Victoria
Australia 3004
Country [1] 301606 0
Australia
Primary sponsor type
Hospital
Name
Monash Health
Address
Monash Health
246 Clayton Road
Clayton
Victoria 3168
Country
Australia
Secondary sponsor category [1] 301309 0
Individual
Name [1] 301309 0
Associate Professor Michelle Giles
Address [1] 301309 0
Department of Obstetrics and Gynaecology
Monash University
Monash Medical Centre
246 Clayton Road
Clayton
Victoria 3168
Country [1] 301309 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 302334 0
Monash Health Human Research and Ethics Committee
Ethics committee address [1] 302334 0
Monash Medical Centre
246 Clayton Road
Clayton
Victoria 3168
Ethics committee country [1] 302334 0
Australia
Date submitted for ethics approval [1] 302334 0
29/11/2018
Approval date [1] 302334 0
Ethics approval number [1] 302334 0

Summary
Brief summary
Sofosbuvir and Velpatasvir (SOF/VEL) are new antiviral drugs recently registered and listed in Australia for the treatment of hepatitis C (HCV). These medications are highly effective, orally administered, well tolerated and work against all the different genotypes of Hepatitis C. In preclinical evaluations in animals they have been shown to be safe during pregnancy. This study will evaluate the safety and pharmacokinetics of antenatal SOF/VEL treatment given for 12 weeks during the second and third trimester. If proven to be effective, antenatal treatment of HCV with SOF/VEL will prevent transmission of HCV to the baby, community transmission of HCV and maternal HCV-related liver disease . It will also reduce the maternal anxiety and stigma of potential transmission.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89858 0
A/Prof Michelle Giles
Address 89858 0
Department of Obstetrics and Gynaecology
Monash University
Monash Medical Centre
246 Clayton Road
Clayton
Victoria 3168
Country 89858 0
Australia
Phone 89858 0
+61 390765581
Fax 89858 0
Email 89858 0
michelle.giles@monash.edu
Contact person for public queries
Name 89859 0
A/Prof Michelle Giles
Address 89859 0
Department of Obstetrics and Gynaecology
Monash University
Monash Medical Centre
246 Clayton Road
Clayton
Victoria 3168
Country 89859 0
Australia
Phone 89859 0
+61 390765581
Fax 89859 0
Email 89859 0
michelle.giles@monash.edu
Contact person for scientific queries
Name 89860 0
A/Prof Michelle Giles
Address 89860 0
Department of Obstetrics and Gynaecology
Monash University
Monash Medical Centre
246 Clayton Road
Clayton
Victoria 3168
Country 89860 0
Australia
Phone 89860 0
+61 390765581
Fax 89860 0
Email 89860 0
michelle.giles@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD will not be shared outside of the study investigator team. De-identified, aggregated results will be shared with the financial sponsor of the study.
What supporting documents are/will be available?
No other documents available
Summary results
No Results