Doravirine Dose Optimisation in Pregnancy

Last updated: December 4, 2024
Sponsor: University of Liverpool
Overall Status: Active - Recruiting

Phase

4

Condition

Hiv

Treatment

Dolutegravir

Doravirine

Clinical Study ID

NCT05630638
UoL001707
  • Ages > 18
  • Female

Study Summary

A randomised, open label, controlled PK standard of care vs doravirine plus 2 nucleoside reverse transcriptase inhibitors backbone in pregnant women initiating combination antiretroviral therapy in the second trimester of pregnancy.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Women ≥ 18 years old

  • Ability to give informed consent prior to participation

  • Willing and able to comply with all study requirements

  • HIV positive

  • Pregnant (initiating cART ≥ 12 weeks and < 26 weeks gestation)

  • Intention to breastfeed postpartum

Exclusion

Exclusion Criteria:

  • Received any cART in preceding 6 months

  • Chronic hepatitis B (HBV) infection with clinical evidence of transaminitis

  • Elevations in serum levels of alanine aminotransferase (ALT) > 5 times the upperlimit of normal (ULN) or ALT > 3xULN and bilirubin >2xULN (with > 35 % directbilirubin)

  • Previous documented failure of an NNRTI-containing cART regimen

  • Previous history of hypersensitivity to any ARV

  • Concomitant medication which are inducers of SoC and DOR metabolism (e.g.rifampicin, anti-epileptic agents, rifabutin, St John's Wort, mitotane,enzalutamide, lumacaftor). Contraindicated medications can be found on LiverpoolDrug Interactions website (hiv-druginteractions.org)

  • Participants with rare hereditary problems of galactose intolerance, total lactasedeficiency or glucose-galactose malabsorption cannot take DOR as the tablet containslactose monohydrate

  • Clinical depression or clinical judgment suggests increased risk of suicidality

Study Design

Total Participants: 76
Treatment Group(s): 2
Primary Treatment: Dolutegravir
Phase: 4
Study Start date:
October 10, 2023
Estimated Completion Date:
February 28, 2026

Study Description

Women diagnosed HIV positive in the second trimester of pregnancy in South Africa will be enrolled and randomised 1:1 to receive standard of care or doravirine plus 2 NRTI backbone. Participants will receive study treatment until delivery and up to 28 weeks postpartum, with a maximum total of 14 months of study treatment. Given the high prevalence of NNRTI resistance, alternative ARV treatment options are essential. Doravirine is licenced for the treatment of HIV-1 in adults in North America and Europe. Whilst the efficacy and safety of doravirine has been established in non-pregnant adults, there are no adequate human data available to establish whether DOR poses a risk to pregnancy outcomes. It is important to have data on the safety and pharmacokinetics of the drug during pregnancy and in particularly the third trimester of pregnancy in order to support its use. The hypothesis for this study is that pregnancy influences the pharmacokinetics of doravirine when initiated in the second trimester.

Connect with a study center

  • Desmond Tutu Health Foundation

    Cape Town,
    South Africa

    Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.