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

28 ottobre 2021 aggiornato da: 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.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

66

Fase

  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

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

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Femmina

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Prevenzione
  • Assegnazione: Non randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore attivo: 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.
Droga: Emtricitabine/Tenofovir disoproxil fumarate
900 mg of TDF combined with 600 mg emtricitabine
Droga: Tenofovir disoproxil fumarate
600 mg oral dose of TDF
Comparatore attivo: 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.
Droga: Emtricitabine/Tenofovir disoproxil fumarate
900 mg of TDF combined with 600 mg emtricitabine
Droga: Tenofovir disoproxil fumarate
600 mg oral dose of TDF

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Lasso di tempo
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
Lasso di tempo: Throughout study
Throughout study

Misure di risultato secondarie

Misura del risultato
Lasso di tempo
Maternal viral load
Lasso di tempo: 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
Lasso di tempo: at Weeks 1, 6, and 12 postpartum
at Weeks 1, 6, and 12 postpartum
infant HIV DNA PCR
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaboratori

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

Investigatori

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

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 marzo 2004

Completamento primario (Effettivo)

1 marzo 2010

Completamento dello studio (Effettivo)

1 marzo 2011

Date di iscrizione allo studio

Primo inviato

3 febbraio 2004

Primo inviato che soddisfa i criteri di controllo qualità

5 febbraio 2004

Primo Inserito (Stima)

6 febbraio 2004

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

1 novembre 2021

Ultimo aggiornamento inviato che soddisfa i criteri QC

28 ottobre 2021

Ultimo verificato

1 ottobre 2021

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • P394
  • 10034 (Identificatore di registro: DAIDS ES)
  • PACTG 394
  • IMPAACT 394

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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