Doravirine Dose Optimisation in Pregnancy

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• AUC of doravirine in pregnant women [Срок оценки: 24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum]
• Cmax of doravirine in pregnant women [Срок оценки: 24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum]
• Cmin of doravirine in pregnant women [Срок оценки: 24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum]
• CL/F of doravirine in pregnant women [Срок оценки: 24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum]

Вторичные конечные точки (5)

• To assess the number of treatment related adverse events by DAIDS v2.1 [Срок оценки: Until study completion, a maximum of 13 months]
• To determine the concentration of doravirine in breastmilk, in breastfed infants, in genital tract, cord blood [Срок оценки: 24 to 28 weeks gestation, 32 to 36 weeks gestation, 6 weeks postpartum]
• To assess maternal viral load responses [Срок оценки: Delivery and 6 months postpartum]
• To determine infant transmissions in the first 6 months of life using HIV viral load [Срок оценки: Delivery until 6 months postpartum]
• To assess the prevalence or emergence of HIV drug resistance by determining HIV mutations [Срок оценки: Until study completion, a maximum of 13 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

ЮАР · 1 центр

• Desmond Tutu Health Foundation — Cape Town

Идентификаторы

NCT: NCT05630638 · UoL001707

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗