The Tatelo Plus Study

NCT ID: NCT06508749

Last Updated: 2025-06-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-11
• Study Completion Date: 2028-04-21

Brief Summary

The purpose of this study is to advance pediatric HIV treatment and cure research by evaluating the impact of a combination of three anti-HIV-1 broadly neutralizing antibodies (bNAbs) or analytic treatment interruption (ATI) on viral reservoir, immune function, and maintenance of HIV suppression in early-treated children.

Conditions

HIV; HIV Infections

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group 1-Step 1a Entry

Receiving PGDM1400LS first

Step 1a includes a single-agent safety lead-in period for PGDM1400LS (Group 1), followed by three bNAbs administered on a rotating schedule while participants continue to receive ART. A pharmacokinetic assessment will be conducted for the three bNAbs.

Group Type: EXPERIMENTAL

PGDM1400LS

Intervention Type: DRUG

IV Antibody Infusion based on subject's weight

VRC07-523LS

Intervention Type: DRUG

IV Antibody Infusion based on subject's weight

PGT121.414.LS

Intervention Type: DRUG

IV Antibody Infusion based on subject's weight

ART Regimen prior to enrolling in Step 1a

Intervention Type: DRUG

Antiviral drugs are not study product. However, participants will continue to receive the ART regimen they were receiving prior to enrolling in the study during Step 1a.

Group 2-Step 1a Entry

Receiving PGT121.414.LS first

Step 1a includes a single-agent safety lead-in period for PGT121.414.LS (Group 2), followed by three bNAbs administered on a rotating schedule while participants continue to receive ART. A pharmacokinetic assessment will be conducted for the three bNAbs.

Group Type: EXPERIMENTAL

PGDM1400LS

Intervention Type: DRUG

IV Antibody Infusion based on subject's weight

VRC07-523LS

Intervention Type: DRUG

IV Antibody Infusion based on subject's weight

PGT121.414.LS

Intervention Type: DRUG

IV Antibody Infusion based on subject's weight

ART Regimen prior to enrolling in Step 1a

Intervention Type: DRUG

Antiviral drugs are not study product. However, participants will continue to receive the ART regimen they were receiving prior to enrolling in the study during Step 1a.

Step 1b Entry

ATI Only. For anyone directly enrolling in the Step 3 ATI and not participating in Steps 1 or 2

In Step 1b participants receive three bNAbs administered on a rotating schedule while continuing to receive ART.

Group Type: EXPERIMENTAL

PGDM1400LS

Intervention Type: DRUG

IV Antibody Infusion based on subject's weight

VRC07-523LS

Intervention Type: DRUG

IV Antibody Infusion based on subject's weight

PGT121.414.LS

Intervention Type: DRUG

IV Antibody Infusion based on subject's weight

ART Regimen prior to enrolling in Step 1b

Intervention Type: DRUG

Antiviral drugs are not study product. However, participants will continue to receive the ART regimen they were receiving prior to enrolling in the study during Step 1b.

Step 2a

In Step 2a participants discontinue ART and receive three bNAbs administered on a rotating schedule.

Group Type: EXPERIMENTAL

PGDM1400LS

Intervention Type: DRUG

IV Antibody Infusion based on subject's weight

VRC07-523LS

Intervention Type: DRUG

IV Antibody Infusion based on subject's weight

PGT121.414.LS

Intervention Type: DRUG

IV Antibody Infusion based on subject's weight

Step 2b

In Step 2b participants remain off ART and continue to receive three bNAbs administered on a rotating schedule.

Group Type: EXPERIMENTAL

PGDM1400LS

Intervention Type: DRUG

IV Antibody Infusion based on subject's weight

VRC07-523LS

Intervention Type: DRUG

IV Antibody Infusion based on subject's weight

PGT121.414.LS

Intervention Type: DRUG

IV Antibody Infusion based on subject's weight

Step 3 progression

ATI Only. Participants discontinue ART and bNAbs. For participants progressing to Step 3 after participating in Steps 1 and 2

Group Type: EXPERIMENTAL

Analytic Treatment Interruption

Intervention Type: OTHER

(all anti-HIV agents are discontinued)

Group 3- Step 3 Direct Entry

ATI Only. Participants discontinue ART. For anyone directly enrolling in the Step 3 ATI and not participating in Steps 1 or 2

Group Type: EXPERIMENTAL

Analytic Treatment Interruption

Intervention Type: OTHER

(all anti-HIV agents are discontinued)

Interventions

PGDM1400LS

IV Antibody Infusion based on subject's weight

Intervention Type: DRUG

VRC07-523LS

IV Antibody Infusion based on subject's weight

Intervention Type: DRUG

PGT121.414.LS

IV Antibody Infusion based on subject's weight

Intervention Type: DRUG

ART Regimen prior to enrolling in Step 1a

Antiviral drugs are not study product. However, participants will continue to receive the ART regimen they were receiving prior to enrolling in the study during Step 1a.

Intervention Type: DRUG

ART Regimen prior to enrolling in Step 1b

Antiviral drugs are not study product. However, participants will continue to receive the ART regimen they were receiving prior to enrolling in the study during Step 1b.

Intervention Type: DRUG

Analytic Treatment Interruption

(all anti-HIV agents are discontinued)

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Previously enrolled in the EIT/Tatelo, or Moso Cohort Study
• Receiving prescribed ART for at least 24 weeks prior to study entry as determined by the site investigator based on participant/parent/guardian report and available medical records
• 24 weeks to 12 years of age at enrollment, inclusive
• If entering Step 1a: HIV-1 RNA <40 copies/mL for at least 24 weeks prior to entry, including documented suppression to <40 copies/mL within 30 days of Step 1 entry
• If entering Step 1b: HIV-1 RNA <200 copies/mL for at least 24 weeks prior to entry, including documented suppression to <40 copies/mL within 30 days of Step 1 entry.
• Normal temperature (<37.4°C axillary, or <38°C non-axillary) and no signs or symptoms of acute illness at entry as determined by the site investigator based on participant/parent/guardian report and available medical records
• Normal, grade 1 or grade 2 results for all of the following laboratory tests at screening, based on testing of specimens collected within 30 days prior to entry and grading per protocol:

• Hemoglobin
• Absolute neutrophil count
• Platelet count
• Alanine aminotransferase
• Aspartate aminotransferase
• Creatinine
• For female participants who are able to become pregnant (defined as having reached menarche and not having undergone surgical sterilization), not pregnant based on testing performed from a specimen collected within 5 days prior to enrollment). Note: Pregnancy is not expected in Step 1 given the age range of eligible participants.
• Expected to be available for the duration of participation and expected to comply with the visit schedule and other requirements as determined by the site investigator based on participant/parent/guardian report at entry
• Not currently participating in another study of an investigational agent and is not expected to participate in any such study for the duration of participation, as determined by the site investigator based on participant/parent/guardian report at entry. Prior or current participation in the EIT/Tatelo or Moso cohort studies is permitted.
• Parental/legal guardian is willing and able to provide written permission for child's participation and, child is willing and able to provide written assent for participation if 7- 17 years of age

• At or beyond the Week 24 visit in Step 1
• Susceptible to at least 2 of the 3 bNAbs under study at or prior to Step 1 entry OR Negative EIA and negative qualitative DNA result at last available evaluation in Step 1 in the absence of available susceptibility data
• No confirmed HIV-1 RNA ≥40 copies/mL throughout Step 1 and for at least 24 weeks prior to Step 1 entry

• If entering from Step 1:

1. At or beyond the Week 24 visit in Step 1, with no confirmed HIV-1 RNA ≥40 copies/mL throughout Step 1

2. Not eligible for Step 2

3. No confirmed HIV-1 RNA ≥40 copies/mL for at least 96 weeks prior to Step 3 entry (or since 24 weeks of age if 96-120 weeks of age)

4. Detection of >80% of intact proviruses in heterochromatin DNA regions (i.e. non-genic DNA, satellite DNA, ZNF genes) from any PBMC sample analyzed by MIP-seq, and no recorded viremia (>40 copies/mL) after this evaluation OR Negative EIA and negative Qualitative HIV DNA result within 12 weeks prior to Step 3 entry

5. Approved for entry by Clinical Management Committee (CMC)

6. Willingness and ability to provide independent written informed consent for participation or parental/legal guardian is willing and able to provide written permission for child's participation and, child is willing and able to provide written assent for participation if 7-17 years of age

• If entering from Step 2:

1. At or beyond the Week 24 visit of Step 2, with HIV-1 RNA <40 copies/mL throughout Steps 1 and 2

2. No confirmed HIV-1 RNA ≥40 copies/mL for at least 96 weeks prior to Step 3 entry (or since 24 weeks of age if 96-120 weeks of age)

3. Negative EIA and negative qualitative DNA result within 12 weeks prior to Step 3 entry OR Detection of >80% of intact proviruses in heterochromatin DNA regions (i.e. non-genic DNA, satellite DNA, ZNF genes) from any PBMC sample analyzed by MIP-seq, and no recorded viremia (>40 copies/mL) after this evaluation entry AND approved for entry by CMC

4. For Moso participants, not currently being breastfed

5. Willingness and ability to provide independent written informed consent for participation or parental/legal guardian is willing and able to provide written permission for child's participation and, child is willing and able to provide written assent for participation if 7-17 years of age

• If entering Step 3 directly upon enrollment:

1. Previously enrolled in the EIT/Tatelo, Moso, or BHP Adolescent Cohort Study

2. 96 weeks to 25 years of age at enrollment, inclusive

3. "Non-encoding" virus: Detection of >80% of intact proviruses in heterochromatin DNA regions (i.e. non-genic DNA, satellite DNA, ZNF genes) from any PBMC sample analyzed by MIP-seq, and no recorded viremia (>40 copies/mL) after this evaluation OR "No intact virus": adolescent (13-25 years) with no intact HIV detected in at least 20 million PBMCs sampled within the prior 4 years

4. For "non-encoding" virus: Receiving prescribed ART prior to Step 3 entry, with HIV-1 RNA <40 copies/mL for at least 96 weeks prior to entry (or since 24 weeks of age if 96-120 weeks of age), including documented suppression to <40 copies/mL within 30 days of Step 3 entry

5. For "no intact virus": Receiving prescribed ART prior to Step 3 entry, with HIV-1 RNA <40 copies/mL for at least 10 years prior to entry, including documented suppression to <40 copies/mL within 30 days of Step 3 entry

6. Approved for entry by CMC

7. For Moso participants, not currently being breastfed

8. For female participants who are able to become pregnant (defined as having experienced menarche and not having undergone surgical sterilization), not pregnant based on testing performed from a specimen collected within 5 days prior to enrollment)

9. For female participants who are able to become pregnant (defined as having reached menarche and not having undergone surgical sterilization) and report sexual activity that could lead to pregnancy, willing to use two methods of contraception while on study. One of the two methods must be highly effective; highly effective methods include the following:

• Contraceptive intrauterine device or intrauterine system
• Subdermal contraceptive implant
• Progestogen injections
• Combined estrogen and progestogen oral contraceptive pills
• Percutaneous contraceptive patch
• Contraceptive vaginal ring The highly effective method must be initiated prior to enrollment. The second method must be a barrier method for dual protection against pregnancy and to avoid transmission of HIV during the ATI and other sexually transmitted infections.

10. For female participants who are able to become pregnant, not currently breastfeeding an infant, and not intending to breastfeed an infant for the duration of the study, based on participant/parent/guardian report at entry

11. For participants who report sexual activity, willing to receive counseling and to use condoms to avoid transmission of HIV

12. Expected to be available for the duration of participation and expected to comply with the visit schedule and other requirements as determined by the site investigator based on participant/parent/guardian report at entry

13. Not currently participating in another study of an investigational agent and is not expected to participate in any such study for the duration of participation, as determined by the site investigator based on participant/parent/guardian report at entry. Prior or current participation in the EIT/Tatelo, Moso, or BHP Adolescent cohort studies is permitted.

14. Willingness and ability to provide independent written informed consent for participation or parental/legal guardian is willing and able to provide written permission for child's participation and, child is willing and able to provide written assent for participation if 7-17 years of age

• Previously entered the study in Step 1 or Step 3. All participants will enter Step 4 upon completing a prior study step. Participants ending Step 1a or Step 1b who, for any reason, do not proceed to Step 2 or to Step 3 will be eligible to proceed to Step 4. Participants ending Step 2 who, for any reason, do not proceed to Step 3 will be eligible to proceed to Step 4. Participants ending Step 3 for any reason will be eligible to proceed to Step 4.

Exclusion Criteria

• Active tuberculosis (either suspected or proven) or malignancy.
• Hepatitis B surface antigen (HBsAg) positive
• Received within 30 days prior to study entry, or is identified as requiring, any of the following:

• Any immunoglobulin-based treatment
• Chronic (more than 14 days) systemic steroid treatment
• Has any other documented or suspected clinically significant medical condition or any other condition that, in the opinion of the site investigator, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
• For participants entering Step 1 and Step 2: <5 kg or >115kg.
• For participants entering Step 3 directly: Received NNRTI-based ART (including efavirenz, nevirapine, rilpivirine) within 14 days of Step 3 entry

• Minimum Eligible Age: 24 Weeks
• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Francistown CRS (CRS #31891)

Francistown, , Botswana

Site Status: RECRUITING

Botswana Harvard Health Partnership CRS (CRS #31833)

Gaborone, , Botswana

Site Status: RECRUITING

Countries

Botswana

Central Contacts

Molly Pretorius Holme, MSc

Role: CONTACT

mpretori@hsph.harvard.edu

617-432-4377

Facility Contacts

Gbolahan Ajibola

Role: primary

gajibola@bhp.org.bw

267-390-2671

Gbolahan Ajibola, MBBS, MPH

Role: primary

gajibola@bhp.org.bw

+267-390-2671

Other Identifiers

IMPAACT 2042

Identifier Type: -

Identifier Source: org_study_id