This study has been transitioned to CTIS with ID 2024-515487-31-00 check the CTIS register for the current data. The primary objective of this study is to describe the pharmacokinetics of antiretroviral agents, for which no or limited available…
ID
Source
Brief title
Condition
- Viral infectious disorders
- Pregnancy, labour, delivery and postpartum conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacokinetics (AUC, Cmax, Cmin) of the agents under study in the second,
third trimester of pregnancy related to the pharmacokinetics (AUC, Cmax, Cmin)
at 4-6 weeks after delivery.
Secondary outcome
Viral load of the pregnant female at screening, week 20, 33 of pregnancy and at
4-6 weeks post-partum.
Viral infection of the neonate.
Transfer of antiretrovirals to breast milk (milk to blood ratio)
Background summary
Due to the potential for pregnancy-induced changes in the pharmacokinetics of
medication, one cannot assume that the currently licensed doses of the
medication to be tested under this protocol lead to adequate exposure in an
HIV-infected pregnant woman. For the agents under study no or limited
pharmacokinetic data during pregnancy are available.
Recently women living with HIV are given the option to breastfeed their
children, under certain circumstances. For most antiretrovirals passage into
breastmilk is unknown. Therefore, if a mother decides to breastfeed and is
using at least one of the compounds mentioned in appendix 1, we will collect
breastmilk, maternal plasma and infant plasma (for cabotegravir/rilpivirine
regimen only) at at least one visit they have to report to the hospital for
viral load checks (generally done monthly during breastfeeding period).
The rationale for the current study is to evaluate the pharmacokinetics of
agents with unknown (or unclear) pharmacokinetic profiles during pregnancy when
their use is indicated in pregnant women by the treating physician.
Study objective
This study has been transitioned to CTIS with ID 2024-515487-31-00 check the CTIS register for the current data.
The primary objective of this study is to describe the pharmacokinetics of
antiretroviral agents, for which no or limited available pharmacokinetic data
during pregnancy is available, in the 2nd, 3rd trimester of pregnant
HIV-infected women and at 4-6 weeks post-partum.
In addition, the pharmacokinetics will be determined in the infant as well in
case of post-exposure prophylaxis with one of the agents tested.
To describe breastmilk transfer in case of breastfeeding and assess exposure
in child if breastfeeding.
Secondary objective of this study is to describe the safety of the
antiretroviral agents during pregnancy and the efficacy in terms of viral load
response of the mother and prevention of mother to child transmission.
Study design
This is a non-randomized, open-label, parallel-group, multi-center phase-IV
study in HIV-infected pregnant women recruited from HIV treatment centers in
Europe.
Patients treated with one or more of the agents listed below during pregnancy
will be screened and the PK evaluation will take place in Week 33 of the
pregnancy, representing the 2nd, 3rd trimester and between 4 and 6 weeks
post-partum (if medication use continues after delivery). Patients will use a
HAART regimen containing one or more of the agents mentioned below continuously
during pregnancy (at least two weeks prior to the first PK evaluation). Safety
and antiviral efficacy (including MTCT) will be evaluated too.
Agents under study:
raltegravir QD, tenofovir alafenamide fumarate, dolutegravir, bictegravir
(new), doravirine (new), etravirine, enfuvirtide, fosamprenavir, etravirine,
maraviroc, efavirenz, rilpivirine, abacavir, atazanavir, emtricitabine,
tenofovir (TDF), tirpanavir, indinavir, (cobicistat boosted darunavir and
elvitegravir arms have been closed).
Study burden and risks
Adverse effects of the HIV medication administered (the patients have to use
this medication to treat their HIV-infection, this medication is not provided
for this study).
The needles used for blood collection can induce pain or discomfort at the
injection site. Qualified personell will peform the blood sampling.
The patients are not treated with different medication for this study (the
regimen is not adapted). They will be admitted to the hospital two days for
blood collections. The total volume of blood collected is not large (max 140
mL). Future treatment of HIV-infected pregnant females will be better.
The same applies for neonates. The maximum blood volume collected from neonates
will be 12 mL.
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
1. HIV-infected as documented by positive HIV antibody test and confirmed by
Western Blot.
2. Subject is at least 18 years of age at screening.
3. Subject is able and willing to sign the Informed Consent Form prior to
screening evaluations.
4. Treated with an HAART regimen containing at least one agent which is
mentioned in Appendix 1; this agent has been taken for at least 2 weeks before
the day of first PK curve evaluation.
5. Duration of pregnancy not longer than 33 weeks at the day of screening
6. Subject is able to adhere to food intake recommendations.
Exclusion criteria
1. Relevant history or current condition that might interfere with drug
absorption, distribution, metabolism or excretion.
2. Inability to understand the nature and extent of the study and the
procedures required.
3. Presence of grade III/IV anemia (i.e. Hb <4.6 mmol/L or <7.4 g/dL)
4. Using oral cabotegravir/rilpivirine.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-515487-31-00 |
| EudraCT | EUCTR2008-006158-16-NL |
| CCMO | NL26028.091.08 |