Low Dose Nivolumab in Adults Living With HIV on Antiretroviral Therapy

NCT05187429 | Recruiting Phase 1 DMC

• 1 other identifier: 358/20
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 2

Brief Summary

The purpose of this study is to evaluate whether a single dose of Nivolumab in people living with HIV can reduce the latent reservoir. The latent HIV reservoir is a group of immune system cells in the body that are infected with HIV but are not actively producing new virus. This is the reason why people living with HIV are unable to stop their antiretroviral treatment.

Conditions

HIV I Infection

Keywords

HIV; Antiretroviral interruption; ATI; Low dose Nivolumab; Clinical Trial

Outcome Measures

Primary Outcomes (2)

• Number of participants with treatment-emergent adverse events enrolled in Cohort A

  Incidence and severity of Adverse Events (defined as Common Terminology Criteria (CTC) grade 3 or higher according to the Division of AIDS (DAIDS) grading table) that are definitely, probably or possibly related to study treatment during the study period

  23 weeks

• Number of participants with treatment-emergent adverse events enrolled in Cohort B

  Incidence and severity of Adverse Events (defined as CTC grade 3 or higher according to the DAIDS grading table) that are definitely, probably or possibly related to study treatment during the study period

  31 weeks

Secondary Outcomes (9)

• Change in PD-1 receptor occupancy in peripheral blood following a single low dose of nivolumab in participants enrolled in Cohort A

  Day 7, Day 14, Day 21, Day 35, Day 63, Day 91, Day 126, Day 168

• Change in PD-1 receptor occupancy in lymph node T-cells following a single low dose of nivolumab in participants enrolled in Cohort A.

  Day 0, Day 21

• Cohort A: T-cell responses to Gag peptides

  Day 0, Day 126

• Cohort A: T-cell responses to Pol/Env/Nef peptides

  Day 0, Day 126

• Change in PD-1 receptor occupancy in peripheral blood following a single low dose of nivolumab in participants enrolled in Cohort B

  Day 0, Day 7, Day 28, Day 168

Study Arms (3)

Dose escalation phase (Cohort A)

EXPERIMENTAL

Drug: Nivolumab Dose form: infusion Dose route: intravenous Dosage: 0.1, 0.3 or 1.0 mg/kg Duration: Single dose administered on Study Day 7

Drug: Nivolumab 10 MG/ML [Opdivo]

Randomization phase (Cohort B)

EXPERIMENTAL

Drug: Nivolumab Dose form: infusion Dose route: intravenous Dosage: 1.0mg/kg (determined from Cohort A) Duration: single dose administered on Day 0 (baseline)

Drug: Nivolumab 10 MG/ML [Opdivo]

Randomization phase comparator (Cohort B)

PLACEBO COMPARATOR

Drug: Nivolumab Comparator: saline Dose form: infusion Dose route: intravenous Dosage: 1.0mg/kg of Nivolumab Duration: single dose administered on Day 0 (baseline)

Drug: Saline

Interventions

Nivolumab 10 MG/ML [Opdivo] DRUG

Cohort A: Dose escalation phase: Nivolumab will be administered intravenously as a single dose in the dose escalation phase.

Dose escalation phase (Cohort A)

Saline DRUG

Cohort B: Randomisation phase: Saline will be administered intravenously as a single dose in the randomisation arm.

Randomization phase comparator (Cohort B)

Eligibility Criteria

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

You may qualify if:

• Documented HIV-1 infection;
• Viral load \> 400 copies/mL prior to initiation of ART;
• Weight ≥ 50 kg;
• Ability and willingness to provide informed consent and to continue ART throughout the study;
• Receiving combination ART for at least 2 years and being on the same ART regimen for at least 4 weeks at the screening visit;
• HIV-1 plasma RNA \<50 copies/mL for \>2 years (documented on at least 2 occasions within the 2 years) and \<50 copies/mL at screening. Episodes of a single HIV plasma RNA 50-500 copies/mL will not exclude participation if the subsequent HIV plasma RNA was \<50 copies/mL;
• CD4+ T cell counts \>500 cells/μL at screening;
• Female participants if they meet one of the following criteria:
• Is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or,
• Is of child-bearing potential with a negative pregnancy test at both Screening and Day 0 and agrees to use one of the following methods of contraception to avoid pregnancy from 14 days prior to the first infusion until the end of the study:
• Complete abstinence from penile-vaginal intercourse;
• Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide);
• Any intrauterine device (IUD) with published data showing that the expected failure rate is \<1% per year;
• Male partner sterilization confirmed prior to the female participant's entry into the study, and this male is the sole partner for that participant;
• Approved hormonal contraception (Where other medications to be used in the study (e.g., efavirenz and darunavir) are known, or are likely, to significantly interact with systemic contraceptives, resulting in decreased efficacy of the contraceptive, then alternative methods of non-hormonal contraception are recommended);

You may not qualify if:

• Active, known and suspected autoimmune disease (including but not limited to including but not limited to inflammatory bowel diseases, scleroderma, severe psoriasis, myocarditis, uveitis, pneumonitis, systemic lupus erythematosus, rheumatoid arthritis, optic neuritis, myasthenia gravis, adrenal insufficiency, hypothyroidism and/or hyperthyroidism, autoimmune thyroiditis, sarcoidosis, and vitiligo);
• History of interstitial lung disease;
• History of chronic obstructive pulmonary disease (COPD);
• Type I diabetes mellitus;
• Active malignancy or history of malignancy requiring systemic chemotherapy or surgery in the preceding 24 months; exception -history of excised localized non-melanomatous skin cancers (squamous cell carcinoma, basal cell carcinoma);
• History of solid organ transplant. Note Individuals with prior corneal transplants may be allowed to enroll after discussion with and approval from the study principal investigator;
• Active or previously treated active TB;
• History of HIV-related opportunistic infection within the last years prior to study entry;
• Prior history of immune reconstitution syndrome (IRIS);
• Current, chronic, acute or recurrent bacterial, fungal or viral (other than HIV) infections that are serious, in the opinion of the investigator, and require systemic therapy within 30 days prior to study entry;
• Immune deficiency other than that caused by HIV infection;
• Received investigational drug or device within 6 months prior to study entry
• Treatment for hepatitis C virus (HCV) within 6 months prior to study entry;
• History of previous treatment with an immune checkpoint inhibitor;
• History of prior immunoglobulin (IgG) therapy;

Sponsors & Collaborators

• University of Melbourne: lead
• The Alfred: collaborator
• NCID: collaborator

Study Sites (2)

Alfred Hospital - Department of Infecious Diseases

Melbourne, Victoria, 3181, Australia

RECRUITING

Tan Tock Seng Hospital

Singapore, 308433, Singapore

RECRUITING

MeSH Terms

Interventions

Nivolumab; Sodium Chloride

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Sharon Lewin

  University of Melbourne

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Audsley, BAppSC(Hons), PhD

CONTACT

+61 (0)3 8344 3266; jennifer.audsley@unimelb.edu.au

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: In Part 1 (Cohort A) - there is no masking and the Nivolumab administered is open-labeled. There is no randomization in this group. In Part 2 (Cohort B) - the participant, care provider and investigator are all masked to the treatment allocation. Participants in this group will be assigned to intervention treatment by chance.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2021
• First Posted: January 11, 2022
• Study Start: January 24, 2023
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029
• Last Updated: December 22, 2025

Record last verified: 2025-12

Locations

AU (1); SG (1)