48 Participants Needed

Dolutegravir for Newborns Exposed to HIV

Recruiting at 18 trial locations
SB
Overseen BySarah Bradford, MPH
Age: Any Age
Sex: Any
Trial Phase: Phase 1
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Must be taking: ARV prophylaxis
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 5 JurisdictionsThis treatment is already approved in other countries

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that infants or breastfeeding mothers should not be receiving any disallowed medication, so it's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug Dolutegravir for newborns exposed to HIV?

Dolutegravir has been shown to be effective in managing HIV-1 infection in adolescents and adults, with studies indicating it works well even against some drug-resistant strains. It has been successfully used in children under 15 in Mozambique, showing good virological outcomes, which suggests it could be effective for newborns as well.12345

Is Dolutegravir safe for humans?

Dolutegravir is generally considered safe and well-tolerated in adults and children with HIV, with most reported side effects being mild and not serious. In a large study in Brazil, only 1.39% of people reported adverse reactions, mostly related to the stomach, nerves, and mood.26789

What makes the drug Dolutegravir unique for newborns exposed to HIV?

Dolutegravir is unique because it is a potent, once-daily HIV-1 integrase inhibitor that can be used in newborns, offering a new option for treating and preventing HIV transmission in this age group, where few antiretroviral drugs are available.345610

What is the purpose of this trial?

This study will test an anti-HIV drug (ARV) for newborn babies. The study will include a minimum of 36 and up to 108 mothers living with HIV and their newborn babies from Brazil, South Africa, Thailand, and the United States. Infants will be in the study for approximately 16 weeks (four months) after they are born. Mothers will not receive study drug and will exit the study after the Entry visit.

Research Team

DC

Diana Clarke, Pharm.D.

Principal Investigator

BMC/Dept. of Pharmacy

Eligibility Criteria

This trial is for newborn babies exposed to HIV-1, born at least 37 weeks into pregnancy and weighing at least 2 kg. They must be generally healthy with normal or slightly altered blood tests. Babies can participate if their mothers have confirmed HIV-1 but haven't taken Dolutegravir close to delivery. Mothers need legal capacity to consent.

Inclusion Criteria

My baby was born full-term and was not a twin or multiple.
My baby's birth weight was within the required range.
Mother is of legal age or circumstance to provide independent informed consent and is willing and able to provide written informed consent for her and permission for her infant's participation in this study
See 6 more

Exclusion Criteria

At entry, infant with a documented positive HIV nucleic acid test result
Mother or infant has any condition that, in the opinion of the site investigator or designee, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives
Known maternal-fetal blood group incompatibility
See 2 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Infants receive the study drug Dolutegravir to evaluate pharmacokinetics and safety

16 weeks
Regular visits for monitoring and drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Dolutegravir
Trial Overview The study tests the safety and dosage of an anti-HIV drug called Dolutegravir in two forms: oral suspension (0.5 mg/kg) and dispersible tablets (5 mg). It involves up to 108 mother-baby pairs from various countries, monitoring infants for about four months after birth.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Cohort 2Experimental Treatment2 Interventions
Cohort 2, Strata 2A and 2B, will be opened to accrual when the DTG dose and formulation to be administered for each stratum are established based on the PK and safety data from all Cohort 1 strata (Strata 1A and 1B, and 1C if applicable) and available data from other studies. * Stratum 2A (DTG-naïve): Infants with no in utero exposure to maternal DTG (no exposure to DTG during the two weeks prior to delivery) * Stratum 2B (DTG-exposed): Infants with in utero exposure to maternal DTG (mothers who receive at least one dose of DTG within 72 hours prior to delivery)
Group II: Cohort 1Experimental Treatment2 Interventions
Cohort 1 will be opened first to accrual, with Strata 1A and 1B being opened concurrently, to evaluate the PK and safety of two single DTG liquid suspension doses for the relevant stratum. Stratum 1C will only be opened to accrual if PK and safety data from Strata 1A and 1B infants support administration of DTG 5 mg DT across all neonates, or only in neonates with a minimum birth weight. * Stratum 1A (DTG-naïve): Infants with no in utero exposure to maternal DTG (no exposure to DTG during the two weeks prior to delivery) * Stratum 1B (DTG-exposed): Infants with in utero exposure to maternal DTG (mothers who receive at least one dose of DTG within 72 hours prior to delivery) * Stratum 1C (DTG-naïve): Infants with no in utero exposure to maternal DTG (no exposure to DTG during the two weeks prior to delivery).

Dolutegravir is already approved in European Union, United States, Canada, Japan, Switzerland for the following indications:

🇪🇺
Approved in European Union as Tivicay for:
  • HIV-1 infection
🇺🇸
Approved in United States as Tivicay for:
  • HIV-1 infection
🇨🇦
Approved in Canada as Tivicay for:
  • HIV-1 infection
🇯🇵
Approved in Japan as Tivicay for:
  • HIV-1 infection
🇨🇭
Approved in Switzerland as Tivicay for:
  • HIV-1 infection

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials
3,361
Recruited
5,516,000+

ViiV Healthcare

Industry Sponsor

Trials
379
Recruited
479,000+
Founded
2009
Headquarters
London, England, UK
Known For
HIV Research
Top Products
- Tivicay (dolutegravir), - Triumeq (abacavir/dolutegravir/lamivudine), - Juluca (dolutegravir/rilpivirine), - Apretude (cabotegravir)
Dr. Harmony Garges profile image

Dr. Harmony Garges

ViiV Healthcare

Chief Medical Officer

MD

Deborah Waterhouse profile image

Deborah Waterhouse

ViiV Healthcare

Chief Executive Officer since 2017

Bachelor's degree in Business Administration

National Institute of Mental Health (NIMH)

Collaborator

Trials
3,007
Recruited
2,852,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials
2,103
Recruited
2,760,000+

Findings from Research

In a study of 3,347 children living with HIV in Mozambique, the introduction of dolutegravir (DTG) led to high viral suppression rates of 79.7% for newly initiated patients and 85.8% for those switching to DTG after at least 6 months.
Despite achieving over 80% viral suppression, more than one-third of the children experienced multiple changes in their anchor drug, highlighting challenges in treatment stability that may be linked to drug stockouts.
Virologic Outcomes and ARV Switch Profiles 2 Years After National Rollout of Dolutegravir to Children Less Than 15 Years in Southern Mozambique.Gill, MM., Herrera, N., Guilaze, R., et al.[2023]
In a multicenter phase I/II study involving pediatric participants aged 4 weeks to <18 years with HIV-1, treatment-emergent resistance to dolutegravir was observed in 8 participants, highlighting the need for monitoring resistance in highly treatment-experienced populations.
The study identified specific integrase resistance mutations (G118R and R263K) that reduced dolutegravir susceptibility and replication capacity, providing insights into the mechanisms of resistance that can inform future treatment strategies.
Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study.Vavro, C., Ruel, T., Wiznia, A., et al.[2022]
A physiologically based pharmacokinetic (PBPK) model successfully predicted the pharmacokinetics of dolutegravir in neonates, suggesting that a dosing regimen of 5 mg every 48 hours during the first 3 weeks of life could achieve effective plasma levels for treating and preventing HIV.
The model was validated using clinical data for other drugs, showing that the predicted exposure levels of dolutegravir are consistent with those observed in pediatric patients, indicating its potential safety and efficacy for neonatal use.
Prediction of dolutegravir pharmacokinetics and dose optimization in neonates via physiologically based pharmacokinetic (PBPK) modelling.Bunglawala, F., Rajoli, RKR., Mirochnick, M., et al.[2021]

References

Virologic Outcomes and ARV Switch Profiles 2 Years After National Rollout of Dolutegravir to Children Less Than 15 Years in Southern Mozambique. [2023]
Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. [2022]
Prediction of dolutegravir pharmacokinetics and dose optimization in neonates via physiologically based pharmacokinetic (PBPK) modelling. [2021]
Dolutegravir: a review of its use in the management of HIV-1 infection in adolescents and adults. [2022]
Efficacy and tolerance of dolutegravir-based combined ART in perinatally HIV-1-infected adolescents: a French multicentre retrospective study. [2020]
Dolutegravir: An Integrase Strand Transfer Inhibitor for the Treatment of Human Immunodeficiency Virus 1 in Adults. [2023]
Pharmacokinetics, safety, tolerability, and antiviral activity of dolutegravir dispersible tablets in infants and children with HIV-1 (IMPAACT P1093): results of an open-label, phase 1-2 trial. [2023]
Active Pharmacovigilance Project on the safety profile of Dolutegravir in Brazil. [2023]
Optimizing Dolutegravir Initiation in Neonates Using Population Pharmacokinetic Modeling and Simulation. [2023]
Population Pharmacokinetic Modeling of Dolutegravir to Optimize Pediatric Dosing in HIV-1-Infected Infants, Children, and Adolescents. [2023]
Unbiased ResultsWe believe in providing patients with all the options.
Your Data Stays Your DataWe only share your information with the clinical trials you're trying to access.
Verified Trials OnlyAll of our trials are run by licensed doctors, researchers, and healthcare companies.
Back to top
Terms of Service·Privacy Policy·Cookies·Security