Doravirine Dose Optimisation in Pregnancy

HIV Clinical Trial

— DoraDO  

Official title:

Doravirine Dose Optimisation in Pregnancy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05630638
• Other study ID #: UoL001707
• Status: Recruiting
• Phase: Phase 4
• Start date: October 10, 2023
• Est. completion date: February 2026

Study information

• Verified date: November 2023
• Source: University of Liverpool
• Contact: Helen Reynolds
• Phone: + 44 151 794 5553
• Email: dorado[@]liverpool.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 76
• Est. completion date: February 2026
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 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 upper limit of normal (ULN) or ALT > 3xULN and bilirubin >2xULN (with > 35 % direct bilirubin)

• 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 Liverpool Drug Interactions website (hiv-druginteractions.org)

• Participants with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption cannot take DOR as the tablet contains lactose monohydrate

• Clinical depression or clinical judgment suggests increased risk of suicidality

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• Doravirine
Fixed dose combination of doravirine, lamivudine and tenofovir disoproxil
• Dolutegravir
Fixed dose combination of dolutegravir, lamivudine and tenofovir disoproxil

Locations

Country	Name	City	State
South Africa	Desmond Tutu Health Foundation	Cape Town

Sponsors (3)

Lead Sponsor	Collaborator
University of Liverpool	Desmond Tutu Health Foundation, Liverpool School of Tropical Medicine

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Viral dynamics in the genital tract of mothers	Assessment of viral load in the genital tract	Baseline and 32 to 36 weeks gestation
Other	PK in the genital tract of mothers	Assessment of drug concentrations in the genital tract	Baseline and 32 to 36 weeks gestation
Other	PK of DOR in breastmilk, breastfed infants and in the genital tract	Assessment of drug concentrations in non-plasma compartments	Delivery, 6 weeks postpartum and 24 weeks postpartum
Other	Prevalence or emergence of HIV drug resistance by determining HIV mutations	Assessment of drug resistance tests	Baseline to 24 weeks postpartum
Primary	AUC of doravirine in pregnant women	Pharmacokinetic parameters of doravirine in pregnancy - AUC	24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum
Primary	Cmax of doravirine in pregnant women	Pharmacokinetic parameters of doravirine in pregnancy - Cmax	24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum
Primary	Cmin of doravirine in pregnant women	Pharmacokinetic parameters of doravirine in pregnancy - Cmin	24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum
Primary	CL/F of doravirine in pregnant women	Pharmacokinetic parameters of doravirine in pregnancy - CL/F	24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum
Secondary	To assess the number of treatment related adverse events by DAIDS v2.1	Safety and tolerability of doravirine in mothers and neonates	Until study completion, a maximum of 13 months
Secondary	To determine the concentration of doravirine in breastmilk, in breastfed infants, in genital tract, cord blood	Pharmacokinetics of doravirine in various compartments	24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum
Secondary	To assess maternal viral load responses	Viral load assessment	Delivery and 6 months postpartum
Secondary	To determine infant transmissions in the first 6 months of life using HIV viral load	Assessment of perinatal transmission using HIV viral load	Delivery until 6 months postpartum
Secondary	To assess the prevalence or emergence of HIV drug resistance by determining HIV mutations	Assessment of drug resistance tests	Until study completion, a maximum of 13 months