Health TrialsbyHealthPanel

Low Dose Nivolumab in Adults Living With HIV on Antiretroviral Therapy

ConditionHIV I Infection
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-65
SponsorUniversity of Melbourne

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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;

Disqualifiers

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;

Trial design

Design model

Sequential

Treatments tested in this trial

  • 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.

  • Nivolumab 10 MG/ML [Opdivo]

    Drug

    Cohort B: Randomization phase: Nivolumab will be administered intravenously as a fixed single dose (1.0 mg/kg) in the randomization phase.

  • Saline

    Drug

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

Treatment groups

42 Participants
are divided into 3 treatment groups
Group A: Dose escalation phase (Cohort A)Experimental treatment 1 intervention
Group B: Randomization phase (Cohort B)Experimental treatment 1 intervention
Group C: Randomization phase comparator (Cohort B)Placebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

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

Time frame
23 weeks
2

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

Time frame
31 weeks

Secondary outcomes

1

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

Time course change in the percentage PD-1 receptor occupancy on T-cells in peripheral blood determined by flow cytometry. Nivolumab infusion occurs on Day 7 study visit. Day 168 timepoint only applicable to 1.0mg/kg cohort

Time frame
Day 7, Day 14, Day 21, Day 35, Day 63, Day 91, Day 126, Day 168
2

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

Time course change in the percentage PD-1 receptor occupancy on T-cells in inguinal lymph node T-cells determined by flow cytometry

Time frame
Day 0, Day 21
3

Cohort A: T-cell responses to Gag peptides

Number of cluster of differentiation 4 (CD4) and/or cluster of differentiation 8 (CD8) T-cells responses to Gag peptides by intracellular cytokine staining both in peripheral blood and lymph nodes

Time frame
Day 0, Day 126
4

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

Number of CD4 and/or CD8 T-cells responses to Pol/Env/Nef peptides by intracellular cytokine staining in both peripheral blood and lymph nodes

Time frame
Day 0, Day 126

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Melbourne

Lead sponsor

The Alfred

Collaborator

NCID

Collaborator

Source ClinicalTrials.gov
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