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Evaluating 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)

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ClinicalTrials.gov Identifier: NCT03707977
Recruitment Status : Not yet recruiting
First Posted : October 16, 2018
Last Update Posted : October 16, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

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 In Step 2, ART is withdrawn and dual bNAb maintenance treatment occurs.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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 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)
Estimated Study Start Date : January 2019
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : August 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

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. If dosing recommendations do not change based on the PK Step, a VRC01LS loading dose of 30 mg/kg will be given at the start of Step 1, followed by 10 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 (10 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




Primary Outcome Measures :
  1. Frequency of treatment-associated adverse events (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)

  2. Severity of treatment-associated 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)

  3. Proportion of children who maintain HIV-1 plasma RNA less than 400 copies/mL, after initiating VRC01LS and 10-1074 infusions [ Time Frame: Measured through Week 24 (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 [ Time Frame: Measured through Week 24 (Step 2) ]
    Based on laboratory evaluations


Secondary Outcome Measures :
  1. VRC01LS or 10-1074 concentrations in plasma for each time point [ Time Frame: Measured through Week 12 (PK Step) ]
    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 and compared with data from prior studies for children on continuous ART

  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 and compared with data from prior studies for children on continuous ART



Information from the National Library of Medicine

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Ages Eligible for Study:   96 Weeks to 5 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 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 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 30 weeks unlikely
  • Active tuberculosis or malignancy
  • Actively breastfeeding
  • Previous receipt of VRC01/VRC01LS or 10-1074

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


Contacts
Contact: Joseph Makhema, MD 267-390-2671 jmakhema@bhp.org.bw

Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Roger Shapiro, MD, MPH Harvard T.H. Chan School of Public Health
Principal Investigator: Daniel Kuritzkes, MD Brigham and Women's Hospital
Principal Investigator: Mathias Lichterfeld, MD, PhD Brigham and Women's Hospital/Massachusetts General Hospital

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

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:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Antibodies
Immunoglobulins
Antibodies, Blocking
Immunologic Factors
Physiological Effects of Drugs