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

NCT ID: NCT03208231

Last Updated: 2023-05-24

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

61 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-08-06

Study Completion Date

2021-02-11

Brief Summary

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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).

Detailed Description

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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

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HIV Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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VRC01 (Arm 1)

Infants received VRC01 subcutaneous injections (40 mg/kg) at Weeks 0, 2, 6, and 10.

Group Type EXPERIMENTAL

VRC01

Intervention Type BIOLOGICAL

40 mg/kg of VRC01 administered by subcutaneous injection.

Combination Antiretroviral Therapy (cART)

Intervention Type 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).

No-VRC01 (Arm 2)

Infants did not receive VRC01.

Group Type ACTIVE_COMPARATOR

Combination Antiretroviral Therapy (cART)

Intervention Type 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).

Interventions

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VRC01

40 mg/kg of VRC01 administered by subcutaneous injection.

Intervention Type BIOLOGICAL

Combination Antiretroviral Therapy (cART)

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).

Intervention Type DRUG

Other Intervention Names

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VRC-HIVMAB060-00-AB

Eligibility Criteria

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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.


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

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
Minimum Eligible Age

0 Weeks

Maximum Eligible Age

12 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Elizabeth (Betsy) McFarland, MD

Role: STUDY_CHAIR

University of Colorado School of Medicine

Alka Khaitan, MD

Role: STUDY_CHAIR

Indiana University School of Medicine

Locations

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Molepolole CRS

Molepolole, Kweneng District, Botswana

Site Status

Gaborone CRS

Gaborone, South-East District, Botswana

Site Status

Hosp. Geral De Nova Igaucu Brazil NICHD CRS

Rio de Janeiro, , Brazil

Site Status

Hospital Federal dos Servidores do Estado NICHD CRS

Rio de Janeiro, , Brazil

Site Status

Malawi CRS

Lilongwe, Central Region, Malawi

Site Status

Blantyre CRS

Blantyre, , Malawi

Site Status

Harare Family Care CRS

Harare, , Zimbabwe

Site Status

Countries

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Botswana Brazil Malawi Zimbabwe

References

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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.

Reference Type BACKGROUND

Provided Documents

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Document Type: Study Protocol: Protocol Version 2.0

View Document

Document Type: Study Protocol: Letter of Amendment 1.0

View Document

Document Type: Study Protocol: Letter of Amendment 2.0

View Document

Document Type: Study Protocol: Protocol Clarification Memo 1.0

View Document

Document Type: Study Protocol: Protocol Clarification Memo 2.0

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

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https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables

Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (AE) Grading Table, Corrected Version 2.1, dated July 2017.

http://rsc.niaid.nih.gov/clinical-research-sites/manual-expedited-reporting-adverse-events-daids

Manual for Expedited Reporting of Adverse Events (EAE) to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

Other Identifiers

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20735

Identifier Type: REGISTRY

Identifier Source: secondary_id

IMPAACT 2008

Identifier Type: -

Identifier Source: org_study_id

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