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

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.

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