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Safety of Tenofovir Disoproxil Fumarate (TDF) and Emtricitabine/TDF in HIV Infected Pregnant Women and Their Infants

28 oktober 2021 bijgewerkt door: National Institute of Allergy and Infectious Diseases (NIAID)

A Phase I Study of the Safety, Tolerance, and Pharmacokinetics of Tenofovir Disoproxil Fumarate (TDF) and the Combination of TDF Plus Emtricitabine in HIV-1 Infected Pregnant Women and Their Infants

Most infants infected with HIV through mother-to-child transmission (MTCT, or perinatal transmission) become infected during labor and delivery. The purpose of this study is to test the safety and tolerability of a single dose of tenofovir disoproxil fumarate (TDF) or emtricitabine/TDF (FTC/TDF) given at the time of labor to HIV infected pregnant women and to their newborn infants.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

The majority of perinatally infected infants are infected during the labor and delivery process, but recent studies suggest that additional factors, such as postexposure prophylaxis, are likely to be involved in the prevention of MTCT of HIV. It is possible that antiretroviral dosing only during labor and short-term dosing to newly born infants would be sufficiently effective to prevent MTCT of HIV. TDF is a nucleoside reverse transcriptase inhibitor that has demonstrated significant effectiveness in preventing MTCT of simian immunodeficiency virus (SIV) in a primate model of HIV. FTC/TDF is a combination of two NRTIs being studied because this combination has the potential to prevent MTCT, while protecting the mother from developing resistance that may develop with single drug therapy. This study will evaluate the safety, tolerance, and pharmacokinetics (PK) of single doses of TDF and FTC/TDF in both HIV infected pregnant women and their newborn infants.

Cohort 1 is now closed. Each participant in Cohort 1 received a single 600 mg oral dose of TDF at the start of active labor or 4 hours prior to C-section, with concurrent administration of standard intravenous zidovudine (ZDV) prophylaxis and/or other antiretrovirals prescribed by her physician. The infants from Cohort 1 received only the standard 6 weeks of oral ZDV prophylaxis postpartum. PK blood samples were taken from mothers at predose and 1, 2, 4, 8, 12, and 24 hours postdose and at the time of delivery; PK blood samples were taken from infants at 12, 24, and 36 hours after birth.

Pregnant women with HIV infection entering this study will be assigned to Cohort 2, as all infants in Cohort 1 have completed the 6 to 8 week study visit and all Cohort 1 data have been reviewed. Mothers in Cohort 2 will receive a single dose of 900 mg of TDF combined with 600 mg emtricitabine, along with standard ZDV prophylaxis and/or other antiretrovirals prescribed by her physician. Infants will receive a single dose of TDF at 4 mg/kg combined with 3 mg/kg emtricitabine as soon as possible after delivery and within 6 hours of age as well as the standard 6 weeks of oral ZDV prophylaxis after birth. Blood samples from mothers and infants will be taken as for Cohort 1.

Mothers will be followed for 12 weeks postpartum or for 2 years after giving birth if viral resistance to TDF or FTC/TDF is demonstrated at Weeks 1, 6, or 12. In addition to the PK studies, blood collection will occur around the time of delivery, at screening, study entry, at delivery, and after delivery at various times up to Week 12. Physical exams will be done at screening, study entry, at delivery, and after delivery at various times up to Week 8. Infants will be followed until age 2. Blood will be collected and physical exams will be done at birth and at various times up to Week 96. Mothers are encouraged to coenroll in PACTG P1025, Pharmacokinetic Study of Anti-HIV Drugs During Pregnancy.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

66

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Puerto Rico
      • San Juan, Puerto Rico
        • San Juan City Hosp. PR NICHD CRS
  • Verenigde Staten
    • District of Columbia
      • Washington, District of Columbia, Verenigde Staten, 20010
        • Children's National Med. Ctr. Washington DC NICHD CRS
      • Washington, District of Columbia, Verenigde Staten, 20010
        • Washington Hosp. Ctr. NICHD CRS
    • Florida
      • Miami, Florida, Verenigde Staten, 33136
        • Univ. of Miami Ped. Perinatal HIV/AIDS CRS
    • Illinois
      • Chicago, Illinois, Verenigde Staten, 60608
        • Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program
    • Michigan
      • Detroit, Michigan, Verenigde Staten, 48201
        • Children's Hospital of Michigan NICHD CRS
    • New Jersey
      • Newark, New Jersey, Verenigde Staten, 07101-1709
        • NJ Med. School CRS
    • New York
      • Bronx, New York, Verenigde Staten, 10457
        • Bronx-Lebanon Hosp. IMPAACT CRS
      • New York, New York, Verenigde Staten, 10016
        • Nyu Ny Nichd Crs
    • Pennsylvania
      • Philadelphia, Pennsylvania, Verenigde Staten, 19102-1192
        • Hahnemann Univ. Hosp.
    • Tennessee
      • Memphis, Tennessee, Verenigde Staten
        • Regional Med. Ctr. at Memphis
      • Memphis, Tennessee, Verenigde Staten
        • St. Jude/UTHSC CRS

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Vrouw

Beschrijving

Inclusion Criteria for Mothers:

  • HIV infected
  • 34 weeks or more (third trimester) into pregnancy at study screening
  • Have access to a participating AIDS clinical trial unit (ACTU) and are willing to be followed at location for the duration of the study

Exclusion Criteria for Mothers:

  • Prior treatment with TDF, including coformulated drugs that contain TDF, during current pregnancy
  • Active opportunistic infection and/or serious bacterial infection at time of study entry
  • Certain abnormal laboratory values at study screening
  • Chronic malabsorption or chronic diarrhea
  • Certain medical or obstetrical complications during the current pregnancy
  • Fetal abnormalities as measured by ultrasound screening performed at 18 weeks into pregnancy or later
  • Intend to breastfeed
  • Current alcohol abuse or use of illicit substances
  • Participation in any other therapeutic or vaccine perinatal treatment trial during the current pregnancy, unless given permission by the protocol chairs
  • Require certain medications

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Preventie
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Actieve vergelijker: 1
Each participant in Cohort 1 received a single 600 mg oral dose of TDF at the start of active labor or 4 hours prior to C-section, with concurrent administration of standard intravenous zidovudine (ZDV) prophylaxis and/or other antiretrovirals prescribed by her physician. The infants from Cohort 1 received only the standard 6 weeks of oral ZDV prophylaxis postpartum.
Geneesmiddel: Emtricitabine/Tenofovir disoproxil fumarate
900 mg of TDF combined with 600 mg emtricitabine
Geneesmiddel: Tenofovir disoproxil fumarate
600 mg oral dose of TDF
Actieve vergelijker: 2
Mothers in Cohort 2 will receive a single dose of 900 mg of TDF combined with 600 mg emtricitabine, along with standard ZDV prophylaxis and/or other antiretrovirals prescribed by her physician. Infants will receive a single dose of TDF at 4 mg/kg combined with 3 mg/kg emtricitabine as soon as possible after delivery and within 6 hours of age as well as the standard 6 weeks of oral ZDV prophylaxis after birth.
Geneesmiddel: Emtricitabine/Tenofovir disoproxil fumarate
900 mg of TDF combined with 600 mg emtricitabine
Geneesmiddel: Tenofovir disoproxil fumarate
600 mg oral dose of TDF

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
Adverse experiences with a severity of Grade 3 or 4 and adverse pregnancy outcomes that cannot be directly attributed to a cause besides study treatment
Tijdsspanne: Throughout study
Throughout study

Secundaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
Maternal viral load
Tijdsspanne: during active labor and 24 to 48 hours, 7 days, 6 to 8 weeks, and 12 weeks postpartum
during active labor and 24 to 48 hours, 7 days, 6 to 8 weeks, and 12 weeks postpartum
viral resistance to emtricitabine/tenofovir disoproxil fumarate using bulk sequencing
Tijdsspanne: at Weeks 1, 6, and 12 postpartum
at Weeks 1, 6, and 12 postpartum
infant HIV DNA PCR
Tijdsspanne: at 24 to 48 hours, 6 to 8 weeks, 4 months, and 6 months of life
at 24 to 48 hours, 6 to 8 weeks, 4 months, and 6 months of life

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Medewerkers

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
International Maternal Pediatric Adolescent AIDS Clinical Trials Group

Onderzoekers

  • Studie stoel: Patricia M. Flynn, MD, Department of Infectious Disease, St. Jude's Children's Research Hospital
  • Studie stoel: Arlene D. Bardeguez, MD, MPH, FACOG, Obstetrics, Gynecology, and Women's Health, University of Medicine and Dentistry of New Jersey

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 maart 2004

Primaire voltooiing (Werkelijk)

1 maart 2010

Studie voltooiing (Werkelijk)

1 maart 2011

Studieregistratiedata

Eerst ingediend

3 februari 2004

Eerst ingediend dat voldeed aan de QC-criteria

5 februari 2004

Eerst geplaatst (Schatting)

6 februari 2004

Updates van studierecords

Laatste update geplaatst (Werkelijk)

1 november 2021

Laatste update ingediend die voldeed aan QC-criteria

28 oktober 2021

Laatst geverifieerd

1 oktober 2021

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • P394
  • 10034 (Register-ID: DAIDS ES)
  • PACTG 394
  • IMPAACT 394

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