Pausing Antiretroviral Treatment Under Structured Evaluation

NCT06031272 | Active Not Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: ACTG A5416UM1AI068636HVTN 806HPTN 108
• Study Type: interventional
• Target: 32
• Locations: 3 countries
• Sites: 9

Brief Summary

The main purpose of this study is to see if it is safe to give the study antibodies (3BNC117-LS-J and 10-1074-LS-J) by intravenous infusion to people with HIV (PWH), and to see if they cause any side effects. In addition, to see how the study antibodies affect the level of HIV in the blood when participants are not taking regular HIV treatment for an extended period. This extended period of not taking regular HIV treatment is called an analytical treatment interruption (ATI).

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (2)

• Occurrence of a Grade ≥3 or higher systemic AE or any AE (regardless of grade) leading to premature study or treatment discontinuation

  The proportion of participants reporting a Grade ≥3 systemic (i.e., not a local reaction) adverse event (AE) or any AE (regardless of grade) leading to premature study or treatment discontinuation at least possibly related (as judged by the CMC, blinded to active/placebo treatment) to the combination of 3BNC117-LS-J and 10-1074-LS-J. An AE is any unfavorable and unintended sign, symptom, or diagnosis occurring in a study participant during the conduct of the study regardless of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=potentially life-threatening, 5=death.

  Step 1 Entry (Day 0) through to 48 weeks

• Viral suppression

  The difference in proportion of participants with viral suppression during analytical treatment interruption (ATI) between those receiving 3BNC117-LS-J and 10-1074-LS-J and those receiving placebo. Viral suppression is defined as no confirmed HIV-1 RNA \>200 copies/mL, at or prior to week 24 of ART discontinuation.

  Step 1 Entry (Day 0) through to Week 24

Secondary Outcomes (12)

• Viral rebound at or prior to week 24 of ART discontinuation

  Step 1 Entry (Day 0) through Week 24

• HIV-1 RNA levels <50 copies/mL through week 24 of ART discontinuation

  Step 1 Entry (Day 0) through Week 24

• Frequency of participants who do not meet the virologic or immunologic components of the ART resumption criteria while serum bNAb concentrations are ≥10 mcg/mL

  Step 1 Entry (Day 0) until ART restart (Step 3 Entry)

• Frequency of participants who do not meet the virologic or immunologic components of the ART resumption criteria for 24 weeks after serum bNAb concentrations fall below 10 mcg/mL.

  Step 1 Entry (Day 0) until ART restart (Step 3 Entry)

• Frequency of participants who remain off ART and do not meet ART resumption criteria by study week in Step 1 and 2.

  Step 1 Entry (Day 0) until ART restart (Step 3 Entry)

Study Arms (2)

Arm A: 30 mg/kg 3BNC117-LS-J + 10 mg/kg 10-1074-LS-J

EXPERIMENTAL

Participants will receive 30 mg/kg 3BNC117-LS-J and 10 mg/kg 10-1074-LS-J, administered as two intravenous (IV) infusions at Step 1 entry (Day 0). Participants will discontinue ART on Day 2.

Drug: 3BNC117-LS-J; Drug: 10-1074-LS-J

Arm B: Placebo

PLACEBO COMPARATOR

Participants will receive dose-volume equivalent placebo IV infusions for both 3BNC117-LS-J and 10-1074-LS-J at Step 1 entry (Day 0). Participants will discontinue ART on Day 2.

Drug: Placebo for 3BNC117-LS-J; Drug: Placebo for 10-1074-LS-J

Interventions

3BNC117-LS-J DRUG

Administered by intravenous (IV) infusion

Arm A: 30 mg/kg 3BNC117-LS-J + 10 mg/kg 10-1074-LS-J

10-1074-LS-J DRUG

Administered by intravenous (IV) infusion

Arm A: 30 mg/kg 3BNC117-LS-J + 10 mg/kg 10-1074-LS-J

Placebo for 3BNC117-LS-J DRUG

Administered by intravenous (IV) infusion

Arm B: Placebo

Placebo for 10-1074-LS-J DRUG

Administered by intravenous (IV) infusion

Arm B: Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Step 1:
• Ability and willingness of participant to provide informed consent.
• HIV-1 infection, documented by:
• Any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry AND
• Confirmed by one of the following:
• A second antibody test from different manufacturers or based on different principles and epitopes (combination antigen-antibody-based rapid tests may be used)
• HIV-1 antigen, or
• Plasma HIV-1 RNA viral load, or
• A licensed Western blot \[NOTE: The term "licensed" refers to a U.S. FDA-approved kit.\]
• On stable suppressive ART for at least 96 weeks prior to study entry. \[NOTE: ART interruptions of up to 7 days occurring ≥90 days prior to study entry are acceptable. Within- and between-class changes in ART within the year prior to study entry are acceptable.\]
• Plasma HIV-1 RNA levels of \<50 copies/mL for at least 96 weeks prior to study entry at any licensed local laboratory or Network-approved non-US laboratory that is VQA certified.
• \[NOTE: Two "blips" (i.e., plasma HIV-1 RNA \>50 and \<400 copies/mL) are allowed if each blip is preceded and followed by values \<50 copies/mL. At least one viral load measurement in greater than 56 days and within 48 weeks prior to the entry visit and another viral load within 56 days prior to the entry visit must be available for review. \]
• CD4+ cell count \>450 cells/µL obtained within 56 days prior to study entry at any Network-approved non-US laboratory that is IQA certified.
• The following laboratory values obtained within 56 days prior to study entry by any Network-approved non-US laboratory that is EQA certified:
• Absolute neutrophil count (ANC) ≥750/mm3

You may not qualify if:

• Step 1:
• Known nadir CD4+ cell count \<200 cells/µL. \[NOTE: If laboratory reports or clinical notes are not available, then participant recall is acceptable for nadir CD4 T-cell count.\]
• Any clinically significant acute or chronic medical condition (such as autoimmune diseases or active tuberculosis), other than HIV infection, that in the opinion of the investigator would preclude participation.
• Any history of an HIV-associated malignancy, including Kaposi's sarcoma, or any type of lymphoma or virus-associated cancers.
• History of Progressive Multifocal Leukoencephalopathy (PML).
• Receipt of an NNRTI within 30 days prior to study entry.
• Receipt of cabotegravir-LA IM, rilpivirine-LA IM, or other long-acting ARVs within 24 months prior to study entry.
• Receipt of any standard-of-care (SOC) vaccines within 7 days prior to study entry.
• Known resistance to all drugs within two or more ARV drug classes. \[NOTE: M184V/I is an exception and should not be considered when assessing this criterion. Prior HIV resistance testing is not required.\]
• History of systemic corticosteroids (\>14 days concurrent use), immunosuppressive anti-cancer or other immunosuppressive agents, interleukins, systemic interferons, systemic chemotherapy, or other medications considered significant by the investigator within the 24 weeks prior to study entry.
• ART initiated during acute infection (defined as p24, HIV NAAT, or HIV RNA PCR positive, and negative or indeterminate HIV antibody testing).
• Any history of receipt of therapeutic HIV vaccine or HIV monoclonal antibody therapy.
• Participation in any clinical study of an investigational product within 12 weeks prior to study entry or expected participation in such a study while on A5416.
• Known allergy/sensitivity or any hypersensitivity to components of either study agent or their formulation.
• Breastfeeding.

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (9)

Gaborone CRS (12701)

Molepolole, Botswana

Location

Blantyre CRS (30301)

Blantyre, Malawi

Location

Lilongwe Malawi CRS (12001)

Lilongwe, Malawi

Location

Ward 21 CRS (31966)

Johannesburg, Gauteng, 2001, South Africa

Location

Soweto HVTN CRS (30351)

Soweto, Gauteng, 1862, South Africa

Location

CAPRISA eThekwini CRS (31422)

Durban, KwaZulu-Natal, 4011, South Africa

Location

Aurum Institute Klerksdorp CRS (30325)

Klerksdorp, North West, South Africa

Location

Rustenburg CRS (31684)

Rustenburg, North West, 0300, South Africa

Location

Groote Schuur HIV CRS (31708)

Cape Town, Western Cape, 7925, South Africa

Location

Related Links

• Related Info

Study Officials

• Mina Hosseinipour, MD, MPH

  University of North Carolina Global HIV Prevention and Treatment CTU

  STUDY CHAIR

• Rebone Maboa, MBChB, DOHM

  The Aurum Institute Pretoria CRS

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2023
• First Posted: September 11, 2023
• Study Start: May 28, 2024
• Primary Completion: April 5, 2026
• Study Completion: April 5, 2026
• Last Updated: August 15, 2025

Record last verified: 2025-01

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 AIDS Clinical Trials Group by NIH.
• Access Criteria: * With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. * For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group. * By what mechanism will data be made available? Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/about-actg/templates-and-forms. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.

Locations

MA (2); ZA (6); BO (1)