Proof of Principle Study of Pulse Dosing of IL-15 to Deplete the Reservoir in HIV Infected People

Study Overview
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Brief Summary
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To assess the safety and tolerability of ALT-803, as well as, the potential efficacy of ALT-803 in HIV

Detailed Description
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This is an open-label, single-arm intra-patient dose escalating pilot study of ALT-803, a recombinant human super agonist interleukin-15 (IL-15) complex with an expansion cohort at the maximum tolerated dose (MTD). The primary aim is to investigate the safety and tolerability of ALT-803 in HIV-infected people receiving potent and optimized antiretroviral therapy. All infusions will occur on a Monday. Subjects will be monitored for 24 hours after the first infusion and then for 6 hours after each subsequent infusion, provided no unacceptable toxicity.

Official Title
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Proof of Principle Study of Pulse Dosing of IL-15 to Deplete the Reservoir in HIV Infected People on Optimized ART With Undetectable Plasma HIV RNA

Conditions
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HIV, Stable ART

Intervention / Treatment
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* Drug: ALT-803


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infected adults aged 18 years or over. Stable ART for at least 36 months Screening plasma HIV RNA levels below level of quantification (<40 to <50 copies RNA/mL depending on the assay) ≥ 2 years (a single measurement above the level of detection but < 100-200 copies/ml will be allowed) Screening CD4 count ≥500 cells/mm3 Laboratory tests performed within 14 days of study enrollment: WBC ≥ 3000/mm3 Platelets ≥ 50,000/mm3 [Patients may be transfused to meet this requirement] Hemoglobin ≥ 8 g/dL (>80g/L) [Patients may be transfused to meet this requirement] Calculated glomerular filtration rate (GFR) >45 mL/min/1.73m2 Total bilirubin ≤ 2.0 X upper limit of institutional normal (ULN) AST, ALT, ALP ≤ 2.0 X ULN Adequate pulmonary function without any clinical sign of severe pulmonary dysfunction. PFTs > 50% of predicted if symptomatic or prior known impairment. Ability to be off prednisone and other immunosuppressive drugs for at least 14 days before first dose of study drug Women of child bearing potential and men with partners of child bearing potential must agree to use effective contraception during therapy and for 4 months after completion of therapy Voluntary written consent Exclusion Criteria: Active infection other than HIV currently requiring systemic antimicrobial therapy Previously treated on this study or received previous ALT-803 Latent TB infection or active TB disease prior to completing a standard regimen of anti-TB therapy Active fungal infection requiring systemic antifungal therapy Active or recurrent herpes or varicella-zoster virus infection requiring treatment (or chronic suppression) Chronic hepatitis B or C Planning or current pregnancy or breastfeeding Intended modification of antiretroviral therapy in the next 24 weeks NYHA (New York Heart Association) Class III or IV heart failure, uncontrollable supraventricular arrhythmias, any history of a ventricular arrhythmia, or other clinical signs of severe cardiac dysfunction Symptomatic congestive heart failure, unstable angina pectoris, or Myocardial infarction within 6 months prior to screening Marked baseline prolongation of QT/QTc interval (e.g. demonstration of a QTc interval greater than 500 milliseconds) History or evidence of uncontrollable CNS disease Prior organ allograft or allogeneic transplantation On-going chronic systemic or regular inhaled corticosteroid use or other immunosuppressive therapy (a history of mild asthma not requiring therapy is eligible) Psychiatric illness/social situations that would limit compliance with study requirements Other illness that in the opinion of the investigator would exclude the patient from participating in this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALT-803<br>ALT-803 | Drug: ALT-803<br>* Interleukin 15 (IL-15) is a common γ-chain cytokine that is related to interleukin-2 (IL-2) and is a critical factor for the development, proliferation, and activation of effector natural killer (NK) and CD8+ memory T cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the safety and tolerability of ALT-803 in HIV-infected subjects | Safety and tolerability is determined by the incidence of adverse events, size of the inducible reservoir as estimated using the TILDA assay | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the impact of ALT-803 on the size of the inducible reservoir, | Assess the impact of ALT-803 on the size of the inducible reservoir, as estimated using the TILDA assay, in total CD4+ T cells and memory subsets | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ART, HIV