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Dual bNAb Treatment in Children

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03707977
Recruitment Status : Completed
First Posted : October 16, 2018
Results First Posted : February 14, 2023
Last Update Posted : February 14, 2023
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Description
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Brief Summary:
The purpose of this study is to evaluate the impact of two broadly neutralizing antibodies, VRC01LS and 10-1074, on the maintenance of HIV suppression in a cohort of early-treated children in Botswana.

Condition or disease Intervention/treatment Phase
HIV Infection Drug: ART Biological: VRC01LS Biological: 10-1074 Phase 1 Phase 2

Detailed Description:

This study will evaluate the impact of two broadly neutralizing antibodies, VRC01LS and 10-1074, on the maintenance of HIV suppression in a cohort of early-treated children in Botswana.

The primary objectives are as follows:

  1. To conduct an interventional clinical trial to determine the safety, pharmacokinetics, dosing and antiviral efficacy of up to 24 weeks of maintenance VRC01LS and 10-1074 immunotherapy in early-treated HIV-1 infected children in Botswana.
  2. To evaluate effects of treatment with VRC01LS and 10-1074 on the size and cellular composition of residual viral reservoirs.
  3. To investigate the influence of VRC01LS and 10-1074 treatment on the magnitude and quality of antiviral innate and adaptive immune responses.

The study includes 4 steps: the pharmacokinetics (PK) Step, Step 1, Step 2, and Step 3. In the PK Step, antiretroviral treatment (ART) is continued and 12 study participants will undergo safety and PK testing, 6 for each bNAb used in the study (10-1074 and VRC01LS). In Step 1, ART is continued and dual bNAb treatment occurs, with PK confirmation of dual bNAb dosing for the first 6 participants in Step 1. In Step 2, ART is withdrawn and dual bNAb maintenance treatment occurs. In Step 3, dual bNAbs will be discontinued and participants will be re-started on ART.

Participants will be in the study for a minimum of 56 weeks, and a maximum of 98 weeks for those who start in the PK step and continue through the study.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Clinical Trial to Evaluate the Impact of Broadly Neutralizing Antibodies VRC01LS and 10-1074 on Maintenance of HIV Suppression in a Cohort of Early-Treated Children in Botswana (Dual bNAb Treatment in Children)
Actual Study Start Date : June 17, 2019
Actual Primary Completion Date : December 3, 2021
Actual Study Completion Date : December 3, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arms and Interventions
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Arm Intervention/treatment
Experimental: Group PK-A: ART + VRC01LS
In the PK Step, participants will continue ART and receive VRC01LS at Weeks 0, 4, and 8 as a single intravenous (IV) dose (30 mg/kg load then 10 mg/kg maintenance).
 Drug: ART
ART will not be provided by the study. Participants will continue to receive their ART regimen they were receiving prior to enrolling in the study.

Biological: VRC01LS
Administered by intravenous (IV) infusion
Experimental: Group PK-B: ART + 10-1074
In the PK Step, participants will continue ART and receive 10-1074 at Weeks 0, 4, and 8 as a single IV dose (30 mg/kg).
 Drug: ART
ART will not be provided by the study. Participants will continue to receive their ART regimen they were receiving prior to enrolling in the study.

Biological: 10-1074
Administered by intravenous (IV) infusion
Experimental: Steps 1-3 Participants (ART + 10-1074 + VRC01LS)
In Step 1, eligible participants will continue to receive ART and will receive both 10-1074 and VRC01LS at Weeks 0, 4, and 8. Following a recommendation from the study team and Safety Monitoring Committee (SMC) to increase the maintenance dosing based on the PK Step, a VRC01LS loading dose of 30 mg/kg will be given at the start of Step 1, followed by 15 mg/kg dosing at each 4-weekly visit, and 10-1074 dosing will be at 30 mg/kg at each 4-weekly visit. In Step 2, participants with ongoing viral suppression throughout Step 1 will undergo withdrawal of ART and will continue maintenance 10-1074 (30 mg/kg) and VRC01LS (15 mg/kg) treatment for up to 24 weeks. In Step 3, both 10-1074 and VRC01LS will be discontinued and ART will be re-started.
 Drug: ART
ART will not be provided by the study. Participants will continue to receive their ART regimen they were receiving prior to enrolling in the study.

Biological: VRC01LS
Administered by intravenous (IV) infusion

Biological: 10-1074
Administered by intravenous (IV) infusion


Outcome Measures
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Primary Outcome Measures :
  1. Frequency of Treatment-associated Adverse Events (AEs) [Number of Participants With Treatment-associated Adverse Event(s) of Any Grade] [ Time Frame: Measured until 30 days after study completion for each participant ]
  2. Severity of Treatment-associated AEs (Number of Participants With Grade 3 or Higher Related AEs) [ Time Frame: Measured until 30 days after study completion for each participant ]
    Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table). The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5 with Grade 1 indicating a mild event, Grade 2 indicating a moderate event, Grade 3 indicating a severe event, Grade 4 indicating a potentially life-threatening event, and Grade 5 indicating death.

  3. Proportion of Children Who Maintain HIV-1 Plasma RNA Less Than 400 Copies/mL, After Initiating VRC01LS and 10-1074 Infusions and Stopping ART [ Time Frame: Measured through Week 24 of Step 2 ]
    Based on laboratory evaluations

  4. Proportion of Children Who Maintain HIV-1 Plasma RNA Less Than 40 Copies/mL, After Initiating VRC01LS and 10-1074 Infusions and Stopping ART [ Time Frame: Measured through Week 24 of Step 2 ]
    Based on laboratory evaluations


Secondary Outcome Measures :
  1. VRC01LS or 10-1074 Concentrations in Plasma [ Time Frame: Measured through Week 12 (PK Step) ]
    Median pre-dose trough (28 days post previous dose) based on laboratory evaluations

  2. Median Trough Concentration of VRC01LS or 10-1074 in Plasma 28 Days After the Third Dose [ Time Frame: Measured through Week 12 (PK Step) ]
    Based on laboratory evaluations

  3. VRC01LS and 10-1074 Concentrations in Plasma for Each Time Point [ Time Frame: Measured through Week 32 following Step 1 entry ]
    Based on laboratory evaluations

  4. Proportion of Children With Trough VRC01LS and 10-1074 Concentrations Below Defined Trough Ranges [ Time Frame: Measured through Week 32 following Step 1 entry ]
    Based on laboratory evaluations

  5. Height Z-scores of Virally Suppressed Children Receiving bNAbs [ Time Frame: Measured through Week 24 (Step 3) ]
    World Health Organization (WHO) standardized Z-scores will be evaluated for changes over time: WHO Length/height-for-age z-score (0-19 yrs), Change from Step 1, Day 0 to Step 3, Week 24. A z-score of 0 corresponds to the population mean. Scores above 0 indicate a participant's height is above the mean, while a score below 0 indicates a participant's height is below the mean. A positive change in z-score corresponds to a higher z-score at the second timepoint compared to the first.

  6. Weight Z-scores of Virally Suppressed Children Receiving bNAbs [ Time Frame: Measured through Week 24 (Step 3) ]
    WHO standardized Z-scores will be evaluated for changes over time: WHO Weight-for-age z-score (0-10 yrs), Change from Step 1, Day 0 to Step 3, Week 24. A z-score of 0 corresponds to the population mean. Scores above 0 indicate a participant's weight is above the mean, while a score below 0 indicates a participant's weight is below the mean. A positive change in z-score corresponds to a higher z-score at the second timepoint compared to the first.


Eligibility Criteria
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Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   96 Weeks to 7 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for PK Step*:

  • On ART for at least 96 weeks
  • Greater than or equal to 96 weeks and less than 5 years of age at enrollment
  • HIV RNA less than 40 copies/mL for at least 24 weeks prior to entry
  • Ability to remain in close study follow-up for at least 12 weeks
  • Willingness to receive IV infusions of bNAbs

  • Willingness to provide signed informed consent (by the parent/guardian)

    • *It is anticipated that all children in PK Step will be from Early Infant Treatment (EIT) Study (NCT02369406); however, up to 4 HIV+ children outside the PK Study (age range 2-5 years) may participate in the PK Step if otherwise eligible and if EIT children are unavailable.

Inclusion Criteria for Entry into Step 1 (followed by participation in Steps 2-3):

  • EIT Study participant (NCT02369406)
  • On ART for at least 96 weeks
  • Greater than or equal to 96 weeks and less than 7 years of age at enrollment
  • HIV RNA less than 40 copies/mL for at least 24 weeks prior to entry
  • Ability to remain in close study follow-up for at least 56 weeks
  • Willingness to receive IV infusions of bNAbs
  • Willingness to provide signed informed consent (by the parent/guardian)

Exclusion Criteria:

  • Medical condition making survival for at least 32 weeks unlikely
  • Active tuberculosis or malignancy
  • Actively breastfeeding
  • Previous receipt of VRC01/VRC01LS or 10-1074 (except during the PK Step)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03707977


Locations
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Botswana
Francistown Non-Network CRS
Francistown, Botswana
Botswana Harvard AIDS Institute Partnership CRS Non-Network
Gaborone, Botswana
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Roger Shapiro, MD, MPH Harvard School of Public Health (HSPH)
Principal Investigator: Daniel Kuritzkes, MD Brigham and Women's Hospital
Principal Investigator: Mathias Lichterfeld, MD, PhD Brigham and Women's Hospital/Massachusetts General Hospital
  Study Documents (Full-Text)

Documents provided by National Institute of Allergy and Infectious Diseases (NIAID):
Study Protocol  [PDF] July 19, 2021
Statistical Analysis Plan  [PDF] September 27, 2022
Informed Consent Form: PK Step  [PDF] December 20, 2018
Informed Consent Form: Steps 1 to 3  [PDF] May 19, 2020

More Information
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Publications of Results:

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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03707977    
Other Study ID Numbers: Tatelo Study
38551 ( Registry Identifier: DAIDS-ES Registry Number )
First Posted: October 16, 2018    Key Record Dates
Results First Posted: February 14, 2023
Last Update Posted: February 14, 2023
Last Verified: January 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
broadly neutralizing antibodies
HIV suppression
Additional relevant MeSH terms:
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HIV Infections
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