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

28 octobre 2021 mis à jour par: 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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

66

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Femelle

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: La prévention
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur actif: 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.
Médicament: Emtricitabine/Tenofovir disoproxil fumarate
900 mg of TDF combined with 600 mg emtricitabine
Médicament: Tenofovir disoproxil fumarate
600 mg oral dose of TDF
Comparateur actif: 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.
Médicament: Emtricitabine/Tenofovir disoproxil fumarate
900 mg of TDF combined with 600 mg emtricitabine
Médicament: Tenofovir disoproxil fumarate
600 mg oral dose of TDF

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Délai
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
Délai: Throughout study
Throughout study

Mesures de résultats secondaires

Mesure des résultats
Délai
Maternal viral load
Délai: 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
Délai: at Weeks 1, 6, and 12 postpartum
at Weeks 1, 6, and 12 postpartum
infant HIV DNA PCR
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborateurs

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

Les enquêteurs

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

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 mars 2004

Achèvement primaire (Réel)

1 mars 2010

Achèvement de l'étude (Réel)

1 mars 2011

Dates d'inscription aux études

Première soumission

3 février 2004

Première soumission répondant aux critères de contrôle qualité

5 février 2004

Première publication (Estimation)

6 février 2004

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

1 novembre 2021

Dernière mise à jour soumise répondant aux critères de contrôle qualité

28 octobre 2021

Dernière vérification

1 octobre 2021

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • P394
  • 10034 (Identificateur de registre: DAIDS ES)
  • PACTG 394
  • IMPAACT 394

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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