Clinical Trials

MainTitle

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

This study is currently recruiting participants. (see Contacts and Locations)

Verified March 2020 by National Institute of Allergy and Infectious Diseases (NIAID)

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)


Information provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier
NCT03208231

First received: June 30, 2017
Last updated: March 20, 2020
Last Verified: March 2020
History of Changes
Purpose

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

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
Study Start Date: May 8, 2018
Estimated Study Completion Date: July 1, 2021
Estimated Primary Completion Date: October 31, 2020 (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

  1. 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

Eligibility

Ages Eligible for Study: up to 12 Weeks  
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

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03208231

Locations

United States, California
University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program Recruiting
La Jolla, California, United States, 92093-0672
Contact: Megan Loughran, B.A.    858-534-9218    meloughran@ucsd.edu
Usc La Nichd Crs Recruiting
Los Angeles, California, United States, 90089
Contact: Eva A. Operskalski, Ph.D.    323-865-1554    eva@usc.edu
David Geffen School of Medicine at UCLA NICHD CRS 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, Colorado
Univ. of Colorado Denver NICHD CRS Recruiting
Aurora, Colorado, United States, 80045
Contact: Emily Barr, C.P.N.P., C.N.M., M.S.N.    720-777-6752    emily.barr@childrenscolorado.org
United States, Florida
South Florida CDTC Ft Lauderdale NICHD CRS Recruiting
Fort Lauderdale, Florida, United States, 33316
Contact: Feiona Heaven    954-728-1054    fheaven@browardhealth.org
United States, Maryland
Johns Hopkins Univ. Baltimore NICHD CRS Recruiting
Baltimore, Maryland, United States, 21287
Contact: Aleisha Collinson-Streng, R.N., A.C.R.N.    443-801-7301    acolli14@jhmi.edu
Botswana
Gaborone CRS Recruiting
Gaborone, South-East District, Botswana
Contact: Tebogo J. Kakhu    267-3931353    tkakhu@bhp.org.bw
Molepolole CRS Recruiting
Gaborone, Botswana
Contact: Unoda A. Chakalisa, MBBCh    267-3910388    uchakalisa@bhp.org.bw
Brazil
Hospital Federal dos Servidores do Estado NICHD CRS Recruiting
Rio de Janeiro, Brazil, 20221-903
Contact: Leon C. Sidi, M.D.    55-21-22330018    leon@diphse.com.br
Hosp. Geral De Nova Igaucu Brazil NICHD CRS Recruiting
Rio De Janeiro, Brazil, 26030
Contact: Gisely G. Falco    55-21-26676059    gisely.falco@gmail.com
Haiti
Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS Recruiting
Port-au-Prince, Haiti, HT-6110
Contact: Cynthia Riviere, M.D.    509-22222241    criviere@gheskio.org
Malawi
Malawi CRS Recruiting
Lilongwe, Central, Malawi
Contact: Thokozani N. Makuhunga    1-265-1755056    tmakuhunga@unclilongwe.org
Blantyre CRS Recruiting
Blantyre, Malawi
Contact: Dumisile Huwa    265-1811885    dhuwa@jhu.medcol.mw
South Africa
Soweto IMPAACT CRS Recruiting
Johannesburg, Gauteng, South Africa, 1862
Contact: Nastassja Ramsagar    27-11-9899858    choonilaln@phru.co.za
Wits RHI Shandukani Research Centre CRS Recruiting
Johannesburg, Gauteng, South Africa, 2001
Contact: Hermien Gous, Pharm.D.    27-11-3585500 ext 5502    hgous@wrhi.ac.za
Umlazi CRS Recruiting
Durban, Kwa Zulu Natal, South Africa, 4066
Contact: Vani Govender    27-31-2601998    Chettyv1@ukzn.ac.za
Famcru Crs Recruiting
Tygerberg, Western Cape Province, South Africa, 7505
Contact: Joan Coetzee    27-21-9384157    joan@sun.ac.za
Zimbabwe
Harare Family Care CRS Recruiting
Harare, Zimbabwe
Contact: Sukunena J. Maturure, RGN    263-712437682    smaturure@uzchs-ctrc.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

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  
Study First Received: June 30, 2017  
Last Updated: March 20, 2020  

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

Additional relevant MeSH terms:
HIV Infections
Anti-Retroviral Agents
Antibodies
Antibodies, Monoclonal

ClinicalTrials.gov processed this data on March 27, 2020
This information is provided by ClinicalTrials.gov.