bNAbs and Anti-PD-1 in HIV

NCT07820813 | Not Yet Recruiting Phase 2 DMC

• 3 other identifiers: IDUNN-0012025-523725-17-002025
• Study Type: interventional
• Target: 90
• Locations: 0 countries
• Sites: N/A

Brief Summary

Antiretroviral therapy (ART) has significantly extended the life expectancy of people living with HIV-1 (PLWH), but it does not cure the infection. Broadly neutralizing antibodies (bNAbs), such as 3BNC117 and 10-1074, not only neutralize circulating virus but also engage the immune system to enhance HIV-1-specific CD8+ T cell responses and stimulate autologous neutralizing antibody production. In some individuals who discontinue ART, bNAb treatment resulted in long-term post-treatment control. However, a major obstacle to immunotherapeutic strategies in PLWH is the immune dysfunction that persists despite long-term suppressive ART. One contributing factor is the immune checkpoint receptor programmed death-1 (PD-1), which is expressed on T cells and suppresses their function when engaged by its ligands. Blocking PD-1 with monoclonal antibodies (mAbs) can reverse T cell exhaustion, a strategy that has resulted in extraordinary increases in survival and cure in cancer treatment and in ex vivo and animal studies of HIV. These findings support the rationale for incorporating PD-1 inhibition in HIV cure strategies. Low-dose nivolumab, an anti-PD-1 mAb, has been shown to be safe in clinical trials. The hypothesis is that combining a single low-dose of nivolumab with long-acting bNAbs (3BNC117-LS and 10-1074-LS) during an analytical treatment interruption (ATI) will reduce T cell exhaustion and boost HIV-1-specific immune responses, as a novel strategy to induce sustained virological control without ART even after the bNAbs have been cleared from the body.

Conditions

HIV-1

Keywords

HIV-1; IDUNN; bNAbs; 3BNC117-LS; 10-1074-LS; anti-PD-1; nivolumab

Outcome Measures

Primary Outcomes (1)

• Time from the day of stopping ART to the day of meeting criteria for loss of immunological control of HIV-1 (defined below)

  Loss of immunological control of HIV-1 is defined as one or more of the following three criteria: * Six weeks of consecutive plasma HIV-1 RNA \>1,000 copies/mL or confirmed \>100,000 copies/mL * Confirmed (on two consecutive measurements) CD4+ T cell count \<350 cells/mm3 * Participant's request or if the ATI in the opinion of the Sponsor or Investigator poses an unacceptable risk to the participant

  60 weeks

Secondary Outcomes (7)

• The safety and tolerability of the Investigational Medicinal Products (IMPs)

  Adverse events will be recorded from signing of the informed consent form and until end of study week 60 or visit 50 following restart of ART, whichever comes first.

• The frequency of post-interventional immunological control of HIV-1

  At week 24, 36, 48 and 60

• The effect of the IMPs on HIV-1-specific T cells responses before, during and after the ATI

  From baseline to weeks 8, 12, 16, 24 and 60 or ART-restart, whichever comes first

• The effect of the IMPs on the intact HIV-1 reservoir before, during and after the ATI

  From baseline to weeks 24 and 60 or ART-restart, whichever comes first

• The effect of the IMPs on the immune cell phenotype, activation and exhaustion

  From baseline to weeks 8, 16, 24 and 60 or ART-restart, whichever comes first

Study Arms (2)

A: bNAbs/anti-PD-1a

EXPERIMENTAL

3BNC117-LS, 10-1074-LS and nivolumab

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

B: bNAbs/placebo

ACTIVE COMPARATOR

3BNC117-LS, 10-1074-LS and placebo

Drug: 3BNC117-LS; Drug: 10-1074-LS; Other: Placebo

Interventions

3BNC117-LS DRUG

bNAb; 30 mg/kg

A: bNAbs/anti-PD-1a; B: bNAbs/placebo

10-1074-LS DRUG

bNAb; 10 mg/kg

A: bNAbs/anti-PD-1a; B: bNAbs/placebo

Nivolumab DRUG

Anti-PD-1a; low dose 1.0 mg/kg

A: bNAbs/anti-PD-1a

Placebo OTHER

Saline

B: bNAbs/placebo

Eligibility Criteria

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

You may qualify if:

• Ability and willingness to provide informed consent
• HBV sAg or HBV DNA as well as HCV Ag or HCV RNA negative or anti-core antibody negative
• Current CD4 count \>500 cells/μL (at screening)
• Plasma HIV-1 RNA \<50 copies/mL by standard assays for at least 15 months (a single measurement \>50 but \<500 copies/mL during this time period is allowable)
• On integrase inhibitor (INSTI) or boosted protease inhibitor (PI) based regimen at time of randomization, if previously on non-nucleoside reverse transcriptase inhibitor (NNRTI) has switched at least 4 weeks prior to randomization
• Females of childbearing potential (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 or bilateral salpingectomy), negative serum or urine pregnancy test monthly
• Pregnancy prevention (heterosexual contact(s)):
• o Females must agree to use highly eWective contraceptive methods: Hormonal contraception, intrauterine device, or intrauterine hormone-releasing system from at least 2 weeks before the bNAb infusion and for entire trial period of 60 weeks and 15 months following the bNAb infusion
• Transmission prevention
• Participants must agree to use barrier prevention during ART interruption and until plasma HIV-1 RNA levels are resuppressed again following ART re-start
• Partners of study participants should be willing to receive counselling on the need for PrEP according to national recommendations

You may not qualify if:

• Current, or history of:
• Clinically significant cardiovascular disease (e.g., cardiac insuWiciency, coronary artery disease, cardiomyopathy, congestive heart failure, family history of congenital long QT syndrome, family history of sudden death)
• Malignancy, excluding non-melanoma skin cancers
• Solid organ transplant
• Autoimmune or antibody-mediated diseases (including not limited to type 1 diabetes mellitus, inflammatory bowel diseases, scleroderma, severe psoriasis, myocarditis, uveitis, pneumonitis, systemic lupus erythematosus, rheumatoid arthritis, optic neuritis, myasthenia gravis, adrenal insuWiciency, hypothyroidism and/or hyperthyroidism, autoimmune thyroiditis, sarcoidosis, and vitiligo)
• Known hypersensitivity to the components of 3BNC117-LS, 10-1074-LS or nivolumab or their analogues
• HIV-1 reservoir predicted resistant to neutralization by 10-1074 using genotypic analysis (as defined in section 11.3.2.9)
• Known HIV-1 subtype CRF01-AE due to resistance to 10-1074-LS
• Receipt of strong immunosuppressive or systemic chemotherapeutic agents within 28 days prior to screening
• Laboratory abnormalities in the parameters listed below:
• Estimated glomerular filtration rate (eGFR) \<60 mL/min
• AST or ALT \>x1.25 upper limit of normal (ULN)
• Positive Quantiferon test
• TPO antibodies \>35 IU/mL
• Partial thromboplastin time \>1.25 ULN

Sponsors & Collaborators

• Ole Schmeltz Søgaard: lead
• Monash University: collaborator
• Aalborg University Hospital: collaborator
• Gødstrup Hospital: collaborator
• Odense University Hospital: collaborator
• Hvidovre University Hospital: collaborator
• Rigshospitalet, Denmark: collaborator
• Oslo University Hospital: collaborator
• Karolinska University Hospital: collaborator
• Landspitali University Hospital: collaborator
• Royal Prince Alfred Hospital, Sydney, Australia: collaborator

MeSH Terms

Interventions

Nivolumab

Intervention Hierarchy (Ancestors)

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

Study Officials

• James McMahon, Professor

  Alfred Hospital; Monash University

  STUDY CHAIR

• Jesper D Gunst, Ass. professor

  Aarhus University; Aarhus University Hospital

  STUDY CHAIR

Central Study Contacts

Ole S Søgaard, Professor

CONTACT

olesoega@rm.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 31, 2026
• First Posted: September 15, 2026
• Study Start: September 15, 2026
• Primary Completion (Estimated): September 15, 2029
• Study Completion (Estimated): September 15, 2030
• Last Updated: September 15, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share