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.
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
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
Brazil2 sites
Hosp. Geral De Nova Igaucu Brazil NICHD CRS
Rio de Janeiro
Hospital Federal dos Servidores do Estado NICHD CRS
Rio de Janeiro
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 group | Role | What they receive |
|---|---|---|
| VRC01 (Arm 1) | Experimental | Infants 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 comparator | Infants 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.
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
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)
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
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
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
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.
- First posted5 Jul 2017
- Study start6 Aug 2018
- Primary completion16 Jun 2020
- Study completion11 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Elizabeth (Betsy) McFarland, MD, Study chair, University of Colorado School of MedicineAlka Khaitan, MD, Study chair, Indiana University
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
- Results posted
- Yes, on ClinicalTrials.gov
- 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.