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

28. oktober 2021 opdateret af: 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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

66

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

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

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Kvinde

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Forebyggelse
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: 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.
Medicin: Emtricitabine/Tenofovir disoproxil fumarate
900 mg of TDF combined with 600 mg emtricitabine
Medicin: Tenofovir disoproxil fumarate
600 mg oral dose of TDF
Aktiv komparator: 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.
Medicin: Emtricitabine/Tenofovir disoproxil fumarate
900 mg of TDF combined with 600 mg emtricitabine
Medicin: Tenofovir disoproxil fumarate
600 mg oral dose of TDF

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
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
Tidsramme: Throughout study
Throughout study

Sekundære resultatmål

Resultatmål
Tidsramme
Maternal viral load
Tidsramme: 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
Tidsramme: at Weeks 1, 6, and 12 postpartum
at Weeks 1, 6, and 12 postpartum
infant HIV DNA PCR
Tidsramme: 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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Samarbejdspartnere

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

Efterforskere

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

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. marts 2004

Primær færdiggørelse (Faktiske)

1. marts 2010

Studieafslutning (Faktiske)

1. marts 2011

Datoer for studieregistrering

Først indsendt

3. februar 2004

Først indsendt, der opfyldte QC-kriterier

5. februar 2004

Først opslået (Skøn)

6. februar 2004

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

1. november 2021

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

28. oktober 2021

Sidst verificeret

1. oktober 2021

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • P394
  • 10034 (Registry Identifier: DAIDS ES)
  • PACTG 394
  • IMPAACT 394

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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