3BNC117-LS and 10-1074-LS Plus N-803 (bNAb+N-803)

NCT05245292 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: MCA-1031 (ES38918)1U01AI145921
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

Brief Summary

The proposed study is a phase 1, open label, single arm study to evaluate the safety and antiretroviral activity of the combination of two long-acting broadly neutralizing antibodies, 3BNC117-LS dosed once at 30 mg/kg and 10-1074-LS dosed once at 10 mg/kg, both intravenously (IV) at week 0, plus an IL-15 superagonist complex, N-803, dosed at 6 mcg/kg, subcutaneously (SC) at week 1 and then every 3 weeks for a total of 8 doses, in ART-treated adults living with HIV during analytical treatment interruption.

Conditions

Human Immunodeficiency Virus

Keywords

3BNC117-LS; 10-1074-LS; Broadly Neutralizing Antibody; N-803; IL-15 superagonist complex

Outcome Measures

Primary Outcomes (6)

• Treatment-related Grade 3 adverse events and serious adverse events

  The number of participants with treatment-related solicited and unsolicited grade 3 and serious adverse events (including confirmed laboratory abnormalities), or premature study treatment discontinuation due to an adverse event (regardless of grade).

  72 weeks

• Any serious adverse events

  The number of participants with serious adverse events, regardless of relationship to 3BNC117-LS, 10-1074-LS and N-803.

  72 weeks

• Dosing completion

  The proportion of participants who complete dosing with 3BNC117-LS, 10-1074-LS and N-803.

  24 weeks

• Viral rebound before or at week 24 post withdrawing ART

  The number of participants experiencing viral rebound, defined as confirmed HIV-1 RNA \>200 copies/mL at or prior to week 24 of ART discontinuation.

  24 weeks

• ART not restarted by weeks 60 and 72

  The proportion of participants who do not meet ART restart criteria by weeks 60 and 72.

  72 weeks

• ART not restarted when bNABs below threshold

  The proportion of participants who do not meet ART restart criteria for 12 or more weeks after bNAbs are below a threshold of 10 mcg/ml.

  72 weeks

Secondary Outcomes (8)

• Treatment-related Grade 2 adverse events

  72 weeks

• Viral rebound through Step 2

  72 weeks

• Time from ART withdrawal to re-initiating ART

  72 weeks

• Viral rebound determined by Monogram assay

  72 weeks

• Size of latent HIV-1 reservoir

  72 weeks

Other Outcomes (4)

• Plasma rebound virus sensitivity

  48 weeks

• HIV-1 specific T cell immune response changes

  72 weeks

• Latent HIV-1 reservoir composition

  72 weeks

Study Arms (1)

3BNC117-LS + 10-1074-LS + N-803

EXPERIMENTAL

3BNC117-LS dosed at 30 mg/kg IV, day 0 10-1074-LS dosed at 10 mg/kg IV, day 0 N-803 dosed at 6 mcg/kg, SC, 8 doses every 3 weeks (week 1 through week 22)

Drug: 3BNC117-LS; Drug: 10-1074-LS; Drug: N803

Interventions

3BNC117-LS DRUG

Intravenous infusion of 3BNC117-LS at 30 mg/kg

Also known as: broadly neutralizing antibody, monoclonal antibody

3BNC117-LS + 10-1074-LS + N-803

10-1074-LS DRUG

Intravenous infusion of 10-1074-LS at 10 mg/kg

Also known as: broadly neutralizing antibody, monoclonal antibody

3BNC117-LS + 10-1074-LS + N-803

N803 DRUG

Subcutaneous injections of N803 at 6 mcg/kg

Also known as: IL-15 superagonist complex

3BNC117-LS + 10-1074-LS + N-803

Eligibility Criteria

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

You may qualify if:

• Male and females, age 18 to 70.
• Confirmed HIV-1 infection.
• 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 48 weeks, and \< 20 copies/ml at screening.
• NOTE: At least two Viral Load (VL) measurements within 48 weeks prior to the Step 0 screening visit must be available for review. A single plasma HIV-1 RNA \> 50 copies/mL but \< 200 copies/mL that is followed by an HIV-1 RNA \<50 copies/mL is permitted.
• Current CD4+ T cell counts \> 450 cells/mcL, CD4+ T cell % ≥ 15%, and CD4+ T cell count nadir of ≥ 200 cells/mcL.
• If on an NNRTI-based regimen, willing to switch to an integrase inhibitor-based regimen for at least 4 weeks prior to discontinuing ART.
• For participants who can become pregnant (i.e., participants who have not been post-menopausal 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), negative pregnancy test at screening (Step 0) and within 48 hours prior to day 0 (Step 1 entry).
• Participants who can become pregnant must agree to use two methods of contraception, one of which must be from the highly effective methods for contraception listed below. Barrier methods of contraception are permitted for the second method of contraception. Contraception must be used from 10 days prior to the first of the investigational products (IP), while receiving the IPs, for 12 months after the last IP dose and until ART is reinitiated and viral suppression is achieved.
• Participants who can impregnate a partner and who are engaging in sexual activity that could lead to pregnancy must agree to use condoms from 10 days prior to the first dose of the investigational products (IP), while receiving the IPs, and for 12 months after the last IP dose to avoid impregnating a partner who can get pregnant.
• Willingness to use barrier protection (male or female) during sexual activity during analytical treatment interruption (ATI) and until viral re-suppression for those who re-start ART.

You may not qualify if:

• 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), other than HIV infection, that in the opinion of the investigator would preclude participation.
• History of or current clinical atherosclerotic cardiovascular disease (ASCVD), as defined by 2013 ACC/AHA guidelines.
• QTcF interval ≥ 440 ms at screening.
• 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).
• Active or recent non-HIV-associated malignancy requiring systemic chemotherapy or surgery in the preceding 36 months or for whom such therapies are expected in the subsequent 12 months;
• 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.
• Participants with known hypersensitivity to any constituent of the investigational products.
• Pregnancy or lactation.
• ART initiated during acute infection (defined as p24, HIV NAAT, or HIV RNA PCR positive, and negative or indeterminate HIV antibody testing).
• Receipt of cabotegravir-LA IM or rilpivirine-LA IM within 24 months prior to Step 1 study entry.
• Known resistance to all drugs within two or more ARV drug classes.
• Laboratory abnormalities in the parameters listed below:

Sponsors & Collaborators

• University of Pennsylvania: collaborator
• Rockefeller University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Weill Medical College of Cornell University: collaborator

Study Sites (3)

Weill Cornell Medicine, Cornell Clinical Trials Unit

New York, New York, 10021, United States

Location

The Rockefeller University

New York, New York, 10065, United States

Location

Perelman School of Medicine University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Broadly Neutralizing Antibodies; Antibodies, Monoclonal; ALT-803

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Neutralizing; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Marina Caskey, MD

  The Rockefeller University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2022
• First Posted: February 17, 2022
• Study Start: December 7, 2022
• Primary Completion: December 9, 2025
• Study Completion: December 31, 2025
• Last Updated: March 31, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)