ALT-803: Proof of Principle Study of Pulse Dosing of IL-15 to Deplete the Reservoir in HIV Infected People
Study Details
Study Description
Brief Summary
To assess the safety and tolerability of ALT-803, as well as, the potential efficacy of ALT-803 in HIV
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ALT-803 ALT-803 |
Drug: ALT-803
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
|
Outcome Measures
Primary Outcome Measures
- Assess the safety and tolerability of ALT-803 in HIV-infected subjects [4 weeks]
Safety and tolerability is determined by the incidence of adverse events, size of the inducible reservoir as estimated using the TILDA assay
Secondary Outcome Measures
- Assess the impact of ALT-803 on the size of the inducible reservoir, [4 weeks]
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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
HIV-1 infected adults aged 18 years or over.
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Stable ART for at least 36 months
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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)
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Screening CD4 count ≥500 cells/mm3
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Laboratory tests performed within 14 days of study enrollment:
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WBC ≥ 3000/mm3
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Platelets ≥ 50,000/mm3 [Patients may be transfused to meet this requirement]
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Hemoglobin ≥ 8 g/dL (>80g/L) [Patients may be transfused to meet this requirement]
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Calculated glomerular filtration rate (GFR) >45 mL/min/1.73m2
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Total bilirubin ≤ 2.0 X upper limit of institutional normal (ULN)
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AST, ALT, ALP ≤ 2.0 X ULN
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Adequate pulmonary function without any clinical sign of severe pulmonary dysfunction. PFTs > 50% of predicted if symptomatic or prior known impairment.
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Ability to be off prednisone and other immunosuppressive drugs for at least 14 days before first dose of study drug
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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
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Voluntary written consent
Exclusion Criteria:
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Active infection other than HIV currently requiring systemic antimicrobial therapy
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Previously treated on this study or received previous ALT-803
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Latent TB infection or active TB disease prior to completing a standard regimen of anti-TB therapy
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Active fungal infection requiring systemic antifungal therapy
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Active or recurrent herpes or varicella-zoster virus infection requiring treatment (or chronic suppression)
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Chronic hepatitis B or C
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Planning or current pregnancy or breastfeeding
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Intended modification of antiretroviral therapy in the next 24 weeks
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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
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Symptomatic congestive heart failure, unstable angina pectoris, or Myocardial infarction within 6 months prior to screening
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Marked baseline prolongation of QT/QTc interval (e.g. demonstration of a QTc interval greater than 500 milliseconds)
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History or evidence of uncontrollable CNS disease
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Prior organ allograft or allogeneic transplantation
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On-going chronic systemic or regular inhaled corticosteroid use or other immunosuppressive therapy (a history of mild asthma not requiring therapy is eligible)
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Psychiatric illness/social situations that would limit compliance with study requirements
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Other illness that in the opinion of the investigator would exclude the patient from participating in this study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Minnesota | Minneapolis | Minnesota | United States | 55455 |
Sponsors and Collaborators
- University of Minnesota
Investigators
- Principal Investigator: Tim Schacker, MD, University of Minnesota
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1508M77601-1