A Study to Evaluate the Safety and Effects of Repeated Doses of 3BNC117-LS and 10-1074-LS on Persistent Viral Reservoirs in People Living With HIV and on Suppressive Antiretroviral Therapy

NCT05612178 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10001037001037-I
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 2

Brief Summary

Background: Antiretroviral therapy (ART) can suppress HIV to undetectable levels in people, but the virus rebounds quickly if the drug treatment is stopped; this is because HIV can remain dormant in a pool of blood cells called the persistent viral reservoir (PVR). Yet lifelong ART is expensive and can lead to serious side effects over the long term. Some drugs may be more effective at reducing the PVR. Objective: To see if 2 study drugs (3BNC117-LS and 10-1074-LS) are safe and if they can lower the number of HIV-infected blood cells in people with HIV who are on ART. Eligibility: People aged 18 to 70 years with HIV who are on ART. Design: Participants will be screened. They will have a physical exam and blood and urine tests. They will undergo leukapheresis. Leukapheresis is a procedure where blood is drawn from a needle in one arm. The blood will pass through a machine that separates out the white blood cells. The remaining blood will be given back through a second needle in the other arm. The study drugs or placebo (normal saline) will be administered 3 times at 20-week intervals. The drugs will be given through a tube attached to a needle inserted into a vein in the arm. This will take 1 hour. Some participants will receive only a saline solution. They will not know if they are getting the drugs or the placebo. Participants will undergo leukapheresis up to 4 more times during the study. Participants will have follow-up visits every 10 weeks until the study ends.

Conditions

HIV-1

Keywords

bNAb; HIV Reservoir

Outcome Measures

Primary Outcomes (1)

• Solicited and unsolicited grade 3 or higher adverse events

  The occurrence of solicited and unsolicited grade 3 or higher adverse events (AE) (including confirmed laboratory abnormalities) that are possibly, probably, or definitely related to 3BNC117-LS and/or 10-1074-LS, or premature study treatment discontinuation due to an AE (regardless of grade).

  Week 0 to End of Study

Secondary Outcomes (4)

• Occurrence of Serious Adverse Events

  Week 0 to End of Study

• Change in the intact proviral reservoir size

  Baseline to Weeks 40 and 80

• Changes in HIV-1 specific T cell immune responses in peripheral blood

  Throughout

• Pharmacokinetic parameters

  Throughout

Study Arms (2)

3BNC117-LS and 10-1074-LS

EXPERIMENTAL

Participants will receive three intravenous infusions of 3BNC117-LS (dosed at 30 mg /kg) and 10-1074-LS (dosed at 10 mg/kg) at weeks 0, 20 and 40.

Biological: 3BNC117-LS; Biological: 10-1074-LS

Placebo

PLACEBO COMPARATOR

Participants will receive three intravenous infusions of placebo (Sterile Saline) at weeks 0, 20 and 40.

Other: Sterile Saline

Interventions

10-1074-LS BIOLOGICAL

Participants will receive three intravenous infusions of 3BNC117-LS (dosed at 30 mg /kg) and 10- 1074-LS (dosed at 10 mg/kg) or placebo at weeks 0, 20 and 40.

3BNC117-LS and 10-1074-LS

Sterile Saline OTHER

Participants will receive three intravenous infusions of 3BNC117-LS (dosed at 30 mg /kg) and 10-1074-LS (dosed at 10 mg/kg) or placebo at weeks, 20 and 40.

Placebo

3BNC117-LS BIOLOGICAL

Participants will receive three intravenous infusions of 3BNC117-LS (dosed at 30 mg /kg) and 10-1074-LS (dosed at 10 mg/kg) or placebo at weeks 0, 20 and 40.

3BNC117-LS and 10-1074-LS

Eligibility Criteria

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

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Ability to provide informed consent;
• Stated willingness to comply with all study procedures and availability for the duration of the study;
• Adult persons of any sex or gender, aged 18 years to 70;
• Confirmed HIV-1 infection and clinically stable;
• On antiretroviral therapy with plasma HIV-1 RNA levels of \< 50 copies/mL and no reported interruption of ART for 7 consecutive days or longer for at least 96 weeks. NOTE: At least two viral load (VL) measurements within 48 weeks prior to the screening visit must be available for review. A single plasma HIV-1 RNA \> 50 copies/mL but \< 200 copies/mL over 48 weeks that is followed by an HIV-1 RNA \< 50 copies/mL is permitted;
• Current CD4+ T cell counts \> 300 cells/mcL;
• For participants who can become pregnant (i.e., participants who have not been postmenopausal for at least 24 consecutive months, who have had menses within the preceding 24 months, or who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy), must have a negative pregnancy test at screening and within 48 hours prior to day 0; NOTE: Participant-reported history is acceptable as documentation of hysterectomy and bilateral oophorectomy, tubal ligation, tubal micro-inserts, and vasectomy.
• Participants who can become pregnant must agree to use adequate measures to prevent pregnancy. This includes the use an effective method of contraception for the study duration. Contraception must be used from 10 days prior to the first dose of the investigational products (IPs), while receiving the IPs and during study follow up. Acceptable methods of contraception include:
• Contraceptive subdermal implant
• Intrauterine device or intrauterine system
• Combined estrogen and progestogen oral contraceptive
• Injectable progestogen
• Contraceptive vaginal ring
• Percutaneous contraceptive patches

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• History of AIDS-defining illness within 3 years prior to enrollment;
• History of systemic corticosteroids (e.g., an equivalent dose of prednisone of \> 20 mg daily for \>14 days), immunosuppressive anti-cancer, interleukins, systemic interferons, systemic chemotherapy or other medications considered significant by the trial physician within the last 6 months;
• Any clinically significant acute or chronic medical condition (e.g. such as autoimmune diseases, cirrhosis, active malignancy that may require systemic chemotherapy or radiation therapy), other than HIV infection, that in the opinion of the investigator would preclude participation;
• Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood. NOTE: Participants with a positive test for HCV antibody and a negative test for HCV RNA are eligible;
• Participants with known hypersensitivity to any constituent of the investigational products;
• Pregnancy or lactation;
• ART initiated during acute infection (defined as p24, HIV nucleic acid amplification technique \[NAAT\], or HIV RNA PCR positive, and negative or indeterminate HIV antibody testing);
• Laboratory abnormalities in the parameters listed below:
• Absolute neutrophil count \< 1,000 cells/microliter
• Hemoglobin \< 10 gm/dL
• Platelet count \< 100,000 cells/microliter
• ALT \> 1.5 x ULN
• AST \> 1.5 x ULN
• Total bilirubin \> 1.5 x ULN

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

The Rockefeller University

New York, New York, 10065, United States

Location

Related Publications (3)

• Mendoza P, Gruell H, Nogueira L, Pai JA, Butler AL, Millard K, Lehmann C, Suarez I, Oliveira TY, Lorenzi JCC, Cohen YZ, Wyen C, Kummerle T, Karagounis T, Lu CL, Handl L, Unson-O'Brien C, Patel R, Ruping C, Schlotz M, Witmer-Pack M, Shimeliovich I, Kremer G, Thomas E, Seaton KE, Horowitz J, West AP Jr, Bjorkman PJ, Tomaras GD, Gulick RM, Pfeifer N, Fatkenheuer G, Seaman MS, Klein F, Caskey M, Nussenzweig MC. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature. 2018 Sep;561(7724):479-484. doi: 10.1038/s41586-018-0531-2. Epub 2018 Sep 26.

  PMID: 30258136 BACKGROUND

• Niessl J, Baxter AE, Mendoza P, Jankovic M, Cohen YZ, Butler AL, Lu CL, Dube M, Shimeliovich I, Gruell H, Klein F, Caskey M, Nussenzweig MC, Kaufmann DE. Combination anti-HIV-1 antibody therapy is associated with increased virus-specific T cell immunity. Nat Med. 2020 Feb;26(2):222-227. doi: 10.1038/s41591-019-0747-1. Epub 2020 Feb 3.

  PMID: 32015556 BACKGROUND

• Gaebler C, Nogueira L, Stoffel E, Oliveira TY, Breton G, Millard KG, Turroja M, Butler A, Ramos V, Seaman MS, Reeves JD, Petroupoulos CJ, Shimeliovich I, Gazumyan A, Jiang CS, Jilg N, Scheid JF, Gandhi R, Walker BD, Sneller MC, Fauci A, Chun TW, Caskey M, Nussenzweig MC. Prolonged viral suppression with anti-HIV-1 antibody therapy. Nature. 2022 Jun;606(7913):368-374. doi: 10.1038/s41586-022-04597-1. Epub 2022 Apr 13.

  PMID: 35418681 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

Study Officials

• Michael C Sneller, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 9, 2022
• First Posted: November 10, 2022
• Study Start: July 26, 2023
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: June 4, 2026

Record last verified: 2026-06-01

Locations

US (2)