Summary

at La Jolla, California and other locations
study started
estimated completion:

Description

Summary

The purpose of this study is to assess the safety and pharmacokinetics (PK) of two monoclonal antibodies, VRC01 and VRC01LS, in HIV-exposed infants who are at increased risk of mother-to-child HIV transmission.

Official Title

Open-Label, Dose-Escalating, Phase I Study to Determine Safety and Pharmacokinetic Parameters of Subcutaneous (SC) VRC01 and VRC01LS, Potent Anti-HIV Neutralizing Monoclonal Antibodies, in HIV-1-Exposed Infants

Details

VRC01 and VRC01LS are anti-HIV neutralizing monoclonal antibodies that may help prevent mother-to-child transmission of HIV. This study will enroll HIV-infected mothers who are at increased risk of passing HIV on to their children. The purpose of this study is to assess the safety and PK of VRC01 and VRC01LS in HIV-exposed infants.

This study will enroll mother-infant pairs into four groups. Infants enrolled in Dose Group 1 and Dose Group 2 will receive a single VRC01 injection less than 72 hours after birth. Infants in Dose Group 3 will receive a VRC01 injection less than 5 days after birth. They will then receive additional VRC01 injections monthly for at least 6 months and no more than 18 months while breastfeeding. Infants will enroll into one of two cohorts in Dose Group 4: Cohort 1 (non-breastfeeding) or Cohort 2 (breastfeeding). Infants in Cohort 1 will receive a single VRC01LS injection less than 72 hours after birth. Infants in Cohort 2 will receive an initial VRC01LS injection less than 5 days after birth, and a second VRC01LS injection at Week 12 if they are still breastfeeding.

The mothers will not receive any VRC01 or VRC01LS injections. At study entry, all mothers will undergo a medical history review and a blood collection. Infants in Dose Groups 1 and 2 will attend several study visits through Week 48. Infants in Dose Group 3 and 4 will attend several study visits through Week 96. Visits will include a medical history review, physical examination, blood collection, and oral fluid collection.

Keywords

HIV Infections Antibodies Antibodies, Monoclonal VRC01 VRC01LS

Eligibility

Maternal Inclusion Criteria:

  • Documentation of HIV infection. Documentation of HIV-1 infection is defined as positive results from two samples collected at different time points. All samples tested must be whole blood, serum, or plasma. For this protocol, the results for sample #2 may be pending at the time of enrollment. Results documented in the clinical record from past testing may be used to satisfy the criteria for documentation of HIV-1 infection. More information on this criterion can be found in the protocol.
  • Greater than or equal to 18 years of age
  • Able and willing to provide signed informed consent for herself and her infant

Maternal Exclusion Criteria:

  • Prior participation in any HIV-1 vaccine trial
  • Receipt of any other active or passive HIV immunotherapy or investigational product during this pregnancy. (Note that administration of Food and Drug Administration[FDA]-approved antiretroviral [ARV] drugs when used to treat disease or prevent mother-to-child transmission are not considered investigational.)
  • Documented or suspected serious medical illness or immediate life threatening condition (other than HIV infection) in the mother that may interfere with the ability to complete study requirements, as judged by the examining clinician

Infant Inclusion Criteria:

  • Born to an HIV-1-infected woman who meets all maternal inclusion/exclusion criteria listed above
  • Gestational age, by best obstetrical, ultrasound, or infant exam, greater than or equal to 36 weeks
  • Birth weight greater than or equal to 2.0 kg
  • Allowable infant age at the time of enrollment is dependent on the Dose Group and

Cohort:

  • Dose Group 4 (Cohort 1): Less than 72 hours of age, and anticipated availability to receive VRC01 immunization at less than 72 hours after birth.
  • Dose Group 4 (Cohort 2): Less than or equal to 5 days of age, and anticipated availability to receive VRC01 immunization no more than 5 days after birth.
  • At increased risk of HIV acquisition defined as documentation of one or more of the following risk factors:
  • Dose Group 4 (Cohort 1), only:
  • Mother received no ART during pregnancy or mother began or reinitiated ART (after an interruption of greater than 14 days), during the third trimester of pregnancy; or
  • Mother with any detectable viral replication (HIV RNA above the limit of detection) at last measurement prior to delivery determined within 30 days of delivery; or
  • Prolonged rupture of membranes (greater than 12 hours); or
  • Mother with documented* 2-class resistant HIV infection, which may include historical documentation of lack of response
  • Women who have a documented history of virologic failure while on NNRTIs but who had no resistance testing at the time of viral failure will be considered to have NNRTI documented resistance.
  • Dose Group 4 (Cohort 2), only (African sites):
  • Mother intends to breastfeed

Infant Exclusion Criteria:

  • Receipt of any other active or passive HIV immunotherapy or investigational product other than the study vaccine (Note: Infant prophylaxis with any licensed ARV drugs clinically prescribed to prevent mother-to-child HIV transmission are not considered investigational.)
  • Receipt of or anticipated need for blood products, immunoglobulin, or immunosuppressive therapy. This includes infants who require hepatitis B immunoglobulin (HBIG) but does not require exclusion of infants who receive hepatitis B vaccine in the newborn period.
  • Documented or suspected serious medical illness, serious congenital anomaly, or immediate life threatening condition in the infant that may interfere with the ability to complete study requirements, as judged by the examining clinician
  • Any requirement for supplemental oxygen beyond 24 hours of life or requiring supplemental oxygen at the time of the VRC01 dose
  • Baseline laboratory results:
  • Hemoglobin less than 12.0 g/dL
  • Platelet count less than 100,000 cells/mm3

  • Absolute neutrophil count: for infants less than or equal to 24 hours old, less than 4,000 cells/mm3; for infants greater than 24 hours old, less than 1,250 cells/mm3

  • Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT])greater than or equal to 1.25 times upper limit of age adjusted normal
  • Dose Group 4 (Cohort 1), only: Infant is breastfeeding at time of enrollment or mother has indicated an intention to initiate breastfeeding. Note: if a child is breastfed prior to known maternal diagnosis (in the case of a woman diagnosed in the intrapartum period), the child is still eligible as long as breastfeeding is stopped by the time the child is enrolled and there is no plan to resume breast milk feeding.

Locations

  • University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program not yet accepting patients
    La Jolla California 92093-0672 United States
  • Usc La Nichd Crs not yet accepting patients
    Los Angeles California 90089 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
ID
NCT02256631
Phase
Phase 1
Study Type
Interventional
Last Updated