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Evaluating the Safety and Antiviral Activity of Monoclonal Antibody VRC01 in HIV-Infected Infants Receiving Combination Antiretroviral Therapy

This study is not yet open for participant recruitment.
Verified October 2017 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
ClinicalTrials.gov Identifier:
NCT03208231
First Posted: July 5, 2017
Last Update Posted: November 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
  Purpose
The purpose of this study is to evaluate the safety and antiviral activity of VRC01 in HIV-1-infected infants beginning combination antiretroviral therapy (cART).

Condition Intervention Phase
HIV Infections Biological: VRC01 Drug: Combination Antiretroviral Therapy (cART) Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Multisite, Randomized, Controlled Study of Monoclonal Antibody VRC01 With Combination Antiretroviral Therapy to Promote Clearance of HIV-1-Infected Cells in Infants

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Frequency of Grade 3 or higher adverse events (AEs) [ Time Frame: Measured through Week 14 ]
    Including reactogenicity outcomes, abnormal laboratory test results, signs, symptoms, and diagnoses

  • Change of HIV-1 DNA concentration in peripheral blood mononuclear cells (PBMCs) from baseline (Week 0) to Week 14 [ Time Frame: Measured through Week 14 ]
    Based on laboratory evaluations


Secondary Outcome Measures:
  • Pharmacokinetic (PK) parameters of VRC01 in the plasma at Weeks 2, 6, 10, 14, and 16 (Arm 1 only) [ Time Frame: Measured through Week 16 ]
    VRC01 concentrations will be presented for each time point and the frequency of achieving trough concentrations greater than 20 and 50 mcg/mL will be calculated.


Estimated Enrollment: 68
Anticipated Study Start Date: January 2018
Estimated Study Completion Date: January 2020
Estimated Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: VRC01
Participants will receive VRC01 at Weeks 0, 2, 6, and 10.
Biological: VRC01
40 mg/kg of VRC01 will be administered by subcutaneous injection.
Other Name: VRC-HIVMAB060-00-AB
Drug: Combination Antiretroviral Therapy (cART)
All infants will receive non-study provided cART. Each infant's cART regimen will be selected by his or her primary care provider and supplied through non-study sources (i.e., ARVs will not be provided through the study).
Placebo Comparator: Arm 2: No study treatment
Participants will not receive the study treatment.
Drug: Combination Antiretroviral Therapy (cART)
All infants will receive non-study provided cART. Each infant's cART regimen will be selected by his or her primary care provider and supplied through non-study sources (i.e., ARVs will not be provided through the study).

Detailed Description:

VRC01 is an experimental human immunoglobulin G1 (IgG1) monoclonal antibody. The purpose of this study is to evaluate the safety and antiviral activity of VRC01 in HIV-1-infected infants initiating cART within 12 weeks of birth.

The infants will be randomly assigned to either receive VRC01 (Arm 1) or not receive VRC01 (Arm 2). Infants in Arm 1 will receive VRC01 at study entry (Week 0) and Weeks 2, 6, and 10. Infants in Arm 2 will receive no study product.

Participants will attend study visits at Weeks 1, 2, 3, 6, 7, 10, 11, 14, 16, 20, 24, 36, and 48. Visits will include physical examinations, blood and urine collection, and specimen collection.

Infants' mothers may optionally be enrolled in the study for one-time specimen collection for exploratory evaluations. Maternal study participation is not required for infant study participation.

Study duration is approximately two years. Accrual is expected to require approximately one year, and each infant will complete 48 weeks of follow-up.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 12 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Infant Inclusion Criteria:

All the criteria listed below must be met in order for infants to be included in this study.

  • Parent or legal guardian is willing and able to provide written informed consent for infant participation in the study, including collection and storage of biological specimens for exploratory virology and immunology investigations.
  • Infant is within 12 weeks (84 days) of birth at study entry.
  • Infant weighs at least 2500 g at study entry.
  • Infant has confirmed HIV-1 infection based on positive results from two samples (whole blood or plasma) collected at different time points using the following methods:

    • One HIV DNA polymerase chain reaction (PCR)
    • One quantitative HIV RNA PCR (above the limit of detection of the assay)
    • One qualitative HIV RNA PCR
    • One total HIV nucleic acid test
    • At least one of the two samples must be tested in a Clinical Laboratory Improvement Amendments (CLIA)-certified (U.S. sites) or DAIDS Virology Quality Assurance program (VQA)-certified (non-U.S. sites) laboratory. For tests performed in other (non-certified) settings, adequate source documentation including the date of specimen collection, date of testing, test performed, and test result must be available.
  • Infant has the following laboratory values at screening (with samples collected for testing within 30 days prior to entry):

    • CD4 lymphocyte percentage greater than 15
    • Severity grade 1 or lower hemoglobin, platelet count, and absolute neutrophil count
    • Severity grade 1 or lower alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase
    • See Section 7.3 of the study protocol for guidance on severity grading.
  • Infant's initial combination antiretroviral therapy (cART) regimen has been selected and documented at study entry, prior to randomization, with the first dose taken on the day of randomization or within 14 days prior to the day of randomization.
  • Infant is expected to be available for 48 weeks of follow-up at study entry.
  • Parent or legal guardian is willing and able to complete reactogenicity memory aids for study purposes, based on parent/guardian report.

Infant Exclusion Criteria:

Infants must be excluded from the study if any of the following are identified at any time prior to randomization:

  • Infant or infant's mother received exclusionary active or passive HIV-specific immunotherapy, as follows:

    • Infant received any active or passive HIV-specific immunotherapy prior to study entry.
    • Infant's mother received any active HIV-specific immunotherapy prior to infant study entry.
    • Infant's mother received any passive HIV-specific immunotherapy within two years prior to infant study entry.
    • If infant's mother is breastfeeding: mother is planned to receive any active or passive HIV-specific immunotherapy at any time during infant study participation.
  • Infant initiated a combination of three or more ARVs, all at or above recommended treatment doses, within 48 hours of birth. Recommended treatment doses are as follows:

    • Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs): As per World Health Organization (WHO) or U.S. Department of Health and Human Services pediatric treatment guidelines
    • Nevirapine (NVP): At least 8 mg for infants weighing up to 2 kg, at least 12 mg for infants weighing more than 2 kg
    • Lopinavir/ritonavir (LPV/r): 300 mg/75 mg per m^2 of body surface area twice daily
    • All other ARVs: Consult with IMPAACT 2008 Clinical Management Committee (CMC)
    • Note: Regimens comprised of fewer than three ARVs, or of three ARVs with at least one ARV below the recommended treatment dose, are permitted, even if initiated within 48 hours of birth.
  • Infant received within 30 days prior to study entry, or is identified as requiring, any of the following:

    • Chronic (more than 14 days) systemic steroid treatment
    • Immunoglobulin treatment
    • Immunomodulators (interleukins, interferons, cyclosporin)
    • Cytotoxic chemotherapy
    • Treatment for active tuberculosis (TB) disease
    • Any investigational agent
    • Note: Treatment for latent TB infection is permitted.
  • Infant has any documented or suspected clinically significant medical illness, clinically significant congenital anomaly, or immediately life-threatening condition that, in the opinion of the site investigator or designee, would interfere with the infant's ability to comply with study requirements.
  • Infant has any other condition that, in the opinion of the site investigator or designee, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

Maternal Inclusion Criteria:

The mothers of enrolled infants will be asked to consent to blood collection and storage for this study. The following criteria must be met in order for mothers to undergo blood collection for this purpose:

  • Mother is willing and able to provide independent written informed consent for blood collection and storage for virology and immunology investigations.
  • Mother has no documented or suspected condition that, in the opinion of the site investigator or designee, would make blood collection unsafe.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03208231


Locations
United States, California
David Geffen School of Medicine at UCLA NICHD CRS Not yet recruiting
Los Angeles, California, United States, 90095-1752
Contact: Michele F. Carter, B.S., R.N.    310-206-6369    mfcarter@mednet.ucla.edu   
United States, Florida
South Florida CDTC Ft Lauderdale NICHD CRS Not yet recruiting
Fort Lauderdale, Florida, United States, 33316
Contact: Dayana Leon, L.P.N.    954-728-1054    dleon@browardhealth.org   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Study Chair: Elizabeth (Betsy) McFarland, MD University of Colorado School of Medicine
Study Chair: William Borkowsky, MD New York University
  More Information

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03208231     History of Changes
Other Study ID Numbers: IMPAACT 2008
20735 ( Registry Identifier: DAIDS-ES Registry Number )
First Submitted: June 30, 2017
First Posted: July 5, 2017
Last Update Posted: November 1, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs