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HIV InfectionsPhase 1/2NCT03208231

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

A Phase 1/2 study testing VRC01 and Combination Antiretroviral Therapy (cART) in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study was to evaluate the safety and antiviral activity to promote clearance of HIV-1 infected cells of VRC01 in infants with HIV beginning combination antiretroviral therapy (cART). Read more about this study

Who is it for?
Ages 0 to 12 weeks
Conditions the study is for
HIV Infections
What is being tested?
VRC01 and Combination Antiretroviral Therapy (cART)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
7 sitesin 4 countries
Study dates
6 Aug 2018to 11 Feb 2021
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 0 to 12 weeks
  • All sexes
  • No healthy volunteers
  • Child

Infant Inclusion Criteria:

  • Weigh at least 2500 grams
  • Confirmed HIV-1 infection
  • The following laboratory values at screening:
  • Cluster of differentiation 4 (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
  • First dose of initial combination antiretroviral therapy (cART) regimen taken on the day of randomization or within 14 days prior to the day of randomization
  • Expected to be available for 48 weeks of follow-up at study entry
  • Parent or legal guardian willing and able to provide written informed consent for infant participation in the study
  • Parent or legal guardian willing and able to complete reactogenicity memory aids for study purposes, based on parent/guardian report.

Infant Exclusion Criteria:

  • Infant or infant's mother received exclusionary active or passive HIV-specific immunotherapy
  • Initiated a combination of three or more antiretrovirals, all at or above recommended treatment doses, within 48 hours of birth
  • Received within 30 days prior to study entry, or was 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 was permitted
  • 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
  • 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 (maternal study participation was not required for infant study participation):

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

  • Mother was willing and able to provide independent written informed consent for blood collection and storage for virology and immunology investigations
  • Mother had no documented or suspected condition that, in the opinion of the site investigator or designee, would make blood collection unsafe

Trial locations and contacts

7 sites in 4 countries.

7 sites in 4 countries

Botswana2 sites

  • Gaborone CRS

    Gaborone, South-East District

  • Molepolole CRS

    Molepolole, Kweneng District

Other trials in Botswana

Brazil2 sites

  • Hosp. Geral De Nova Igaucu Brazil NICHD CRS

    Rio de Janeiro

  • Hospital Federal dos Servidores do Estado NICHD CRS

    Rio de Janeiro

Other trials in Brazil

Malawi2 sites

  • Blantyre CRS

    Blantyre

  • Malawi CRS

    Lilongwe, Central Region

Other trials in Malawi

Zimbabwe1 site

  • Harare Family Care CRS

    Harare

Other trials in Zimbabwe

About this study

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

The purpose of this study was to evaluate the safety and antiviral activity to promote clearance of HIV-1 infected cells of VRC01 in infants with HIV beginning combination antiretroviral therapy (cART).

Read the detailed description

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

All infants were required to have initiated cART within 14 days before or at study entry. Infants were randomly assigned to either receive VRC01 (VRC01, Arm 1) or not receive VRC01 (No-VRC01, Arm 2). Randomization was stratified by whether the initial cART regimen included an integrase inhibitor.

Infants in the VRC01 arm received VRC01 injections at study entry (Week 0) and Weeks 2, 6, and 10. Infants in the No-VRC01 arm received no study product.

Infants attended study visits at Weeks 1, 2, 3, 6, 7, 10, 11, 14, 16, 20, 24, 36, and 48. Visits included physical examinations, blood and urine collection.

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

The study was closed to enrollment prematurely on March 19, 2020 due to the outbreak of coronavirus disease 2019 (COVID-19) and after enrolling 61 of the targeted 68 infants.

Conditions
HIV Infections
Being tested
VRC01, Combination Antiretroviral Therapy (cART)
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VRC01Biological

    Also called VRC-HIVMAB060-00-AB

    40 mg/kg of VRC01 administered by subcutaneous injection.

  • Combination Antiretroviral Therapy (cART)Drug

    All infants received non-study provided cART selected by their primary care provider and supplied through non-study sources (i.e., cART not provided through the study).

Study groups in NCT03208231
Study groupRoleWhat they receive
VRC01 (Arm 1)ExperimentalInfants received VRC01 subcutaneous injections (40 mg/kg) at Weeks 0, 2, 6, and 10.
Receives: Biological: VRC01; Drug: Combination Antiretroviral Therapy (cART)
No-VRC01 (Arm 2)Active comparatorInfants did not receive VRC01.
Receives: Drug: Combination Antiretroviral Therapy (cART)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Infants Experiencing at Least One Grade 3 or Higher Adverse Event (AE)

    Includes reactogenicity outcomes, abnormal laboratory test results, signs, symptoms, and diagnoses. Adverse event severity grading was based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. Two-sided exact 95% Clopper-Pearson confidence intervals were calculated.

    Measured: From Week 0 to Week 14

  2. Change in HIV-1 DNA Concentration in Peripheral Blood Mononuclear Cells (PBMCs) From Week 0 to Week 14

    Mean changes (Week 14 - Week 0) were calculated on log10-transformed HIV-1 DNA concentration. Values below the assay detection limit were set to half the lower assay limit of 4.09 copies/million PBMCs. Values above the detection limit were set to the upper limit of 10,000 copies/million PBMCs.

    Measured: Week 0 and Week 14

Secondary outcomes (4)

  1. Median Pre-dose VRC01 Concentrations in the Plasma (VRC01 Arm Only)

    Median (mcg/ml) pre-dose VRC01 concentrations in the plasma (VRC01 Arm only)

    Measured: Weeks 2, 6, 10, 14, and 16

  2. Geometric Mean of Pre-dose VRC01 Concentrations in the Plasma (VRC01 Arm Only)

    Geometric mean (mcg/ml) of pre-dose VRC01 concentrations with 90% confidence intervals

    Measured: Weeks 2, 6, 10, 14, and 16

  3. Percentage of Infants With Pre-dose VRC01 Concentrations >= 20 mcg/ml in the Plasma (VRC01 Arm Only)

    Percentage of infants with pre-dose VRC01 concentrations >= 20 mcg/ml in the plasma (VRC01 Arm only)

    Measured: Weeks 2, 6, 10, 14, 16

  4. Percentage of Infants With Pre-dose VRC01 Concentrations >= 50 mcg/ml in the Plasma (VRC01 Arm Only)

    Percentage of infants with pre-dose VRC01 concentrations >= 50 mcg/ml in the plasma (VRC01 Arm only)

    Measured: Weeks 2, 6, 10, 14, 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jul 2017
  2. Study start6 Aug 2018
  3. Primary completion16 Jun 2020
  4. Study completion11 Feb 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03208231
Sponsor's protocol ID
IMPAACT 2008
Other IDs
20735
Status last verified
Apr 2023
First submitted
30 Jun 2017
Last updated
24 May 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data that underlie results in the publication, after deidentification.

Publications

  • Khaitan A, Lindsey J, Capparelli E, Tierney C, Coletti A, Perlowski C, Cotton MF, Yin DE, Majji S, Moye J, Spiegel H, Harding P, Costello D, Krotje C, Gama L, Persaud D, McFarland EJ, on behalf of the IMPAACT 2008 Protocol Team. Phase I/II Study of monoclonal antibody VRC01 with early antiretroviral therapy to promote clearance of HIV-1 infected cells in infants (IMPAACT 2008). Oral presentation at 24th International AIDS Conference, July 2022.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing VRC01 and Combination Antiretroviral Therapy (cART) in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Botswana, Brazil, Malawi, Zimbabwe. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Infants Experiencing at Least One Grade 3 or Higher Adverse Event (AE) (time frame: From Week 0 to Week 14). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03208231, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2023.

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