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

NCT03208231 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: IMPAACT 200820735
• Study Type: interventional
• Target: 61
• Locations: 4 countries
• Sites: 7

Brief 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).

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (2)

• 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.

  From Week 0 to Week 14

• 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.

  Week 0 and Week 14

Secondary Outcomes (4)

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

  Weeks 2, 6, 10, 14, and 16

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

  Weeks 2, 6, 10, 14, and 16

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

  Weeks 2, 6, 10, 14, 16

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

  Weeks 2, 6, 10, 14, 16

Study Arms (2)

VRC01 (Arm 1)

EXPERIMENTAL

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

Biological: VRC01; Drug: Combination Antiretroviral Therapy (cART)

No-VRC01 (Arm 2)

ACTIVE COMPARATOR

Infants did not receive VRC01.

Drug: Combination Antiretroviral Therapy (cART)

Interventions

VRC01 BIOLOGICAL

40 mg/kg of VRC01 administered by subcutaneous injection.

Also known as: VRC-HIVMAB060-00-AB

VRC01 (Arm 1)

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).

No-VRC01 (Arm 2); VRC01 (Arm 1)

Eligibility Criteria

• Age: 0 Weeks - 12 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (7)

Molepolole CRS

Molepolole, Kweneng District, Botswana

Location

Gaborone CRS

Gaborone, South-East District, Botswana

Location

Hosp. Geral De Nova Igaucu Brazil NICHD CRS

Rio de Janeiro, Brazil

Location

Hospital Federal dos Servidores do Estado NICHD CRS

Rio de Janeiro, Brazil

Location

Malawi CRS

Lilongwe, Central Region, Malawi

Location

Blantyre CRS

Blantyre, Malawi

Location

Harare Family Care CRS

Harare, Zimbabwe

Location

Related Publications (1)

• 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.

  BACKGROUND

Related Links

• Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (AE) Grading Table, Corrected Version 2.1, dated July 2017.
• Manual for Expedited Reporting of Adverse Events (EAE) to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

MeSH Terms

Conditions

HIV Infections

Interventions

VRC01 monoclonal antibody; Antiretroviral Therapy, Highly Active

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Drug Therapy, Combination; Drug Therapy; Therapeutics

Limitations and Caveats

Accrual into the study was terminated early due to the outbreak of coronavirus disease 2019 (COVID-19), with 60 evaluable infants out of the targeted 68.

Results Point of Contact

• Title: IMPAACT Clinicaltrials.gov Coordinator
• Organization: Family Health International (FHI 360)

IMPAACT.ctgov@fstrf.org

(919) 405-1429

Study Officials

• Elizabeth (Betsy) McFarland, MD

  University of Colorado School of Medicine

  STUDY CHAIR

• Alka Khaitan, MD

  Indiana University School of Medicine

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2017
• First Posted: July 5, 2017
• Study Start: August 6, 2018
• Primary Completion: June 16, 2020
• Study Completion: February 11, 2021
• Last Updated: May 24, 2023
• Results First Posted: May 24, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.
• Access Criteria: * With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT Network. * For what types of analyses? To achieve aims in the proposal approved by the IMPAACT Network. * By what mechanism will data be made available? Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https://www.impaactnetwork.org/studies/submit-research-proposal. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data."

Locations

MA (2); ZI (1); BR (2); BO (2)