Doravirine Dose Optimisation in Pregnancy

NCT05630638 | Recruiting Phase 4 DMC

• 1 other identifier: UoL001707
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV

Keywords

Pregnancy

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (5)

• To assess the number of treatment related adverse events by DAIDS v2.1

  Until study completion, a maximum of 13 months

• To determine the concentration of doravirine in breastmilk, in breastfed infants, in genital tract, cord blood

  24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum

• To assess maternal viral load responses

  Delivery and 6 months postpartum

• To determine infant transmissions in the first 6 months of life using HIV viral load

  Delivery until 6 months postpartum

• To assess the prevalence or emergence of HIV drug resistance by determining HIV mutations

  Until study completion, a maximum of 13 months

Other Outcomes (4)

• Viral dynamics in the genital tract of mothers

  Baseline and 32 to 36 weeks gestation

• PK in the genital tract of mothers

  Baseline and 32 to 36 weeks gestation

• PK of DOR in breastmilk, breastfed infants and in the genital tract

  Delivery, 6 weeks postpartum and 24 weeks postpartum

Study Arms (2)

Delstrigo

EXPERIMENTAL

doravirine/lamivudine/tenofovir disoproxil 100 mg/ 300 mg/ 245 mg film coated tablets, dosed 1 tablet once daily for the duration of the study

Drug: Doravirine

Standard of care

ACTIVE COMPARATOR

dolutegravir/lamivudine/tenofovir disoproxil 50 mg/300 mg/245 mg film coated tablets, dosed 1 tablet once daily for the duration of the study

Drug: Dolutegravir

Interventions

Doravirine DRUG

Fixed dose combination of doravirine, lamivudine and tenofovir disoproxil

Also known as: Delstrigo

Delstrigo

Dolutegravir DRUG

Fixed dose combination of dolutegravir, lamivudine and tenofovir disoproxil

Also known as: TLD

Standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Desmond Tutu Health Foundation: collaborator
• University of Liverpool: lead
• Liverpool School of Tropical Medicine: collaborator

Study Sites (1)

Desmond Tutu Health Foundation

Cape Town, South Africa

RECRUITING

MeSH Terms

Interventions

doravirine; dolutegravir

Study Officials

• Saye Khoo

  University of Liverpool

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Helen Reynolds

CONTACT

+ 44 151 794 5553; dorado@liverpool.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2022
• First Posted: November 29, 2022
• Study Start: October 10, 2023
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: After study analysis has completed and manuscript is published for at least 5 years afterwards.
• Access Criteria: By reasonable request to the investigators.

Locations

ZA (1)