Clinical trial NCT02191098: Proof of Principle Study of Pulse Dosing of IL-15 to Deplete the Reservoir in HIV Infected People
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV
Stable ART
Keywords: HIV
ART
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2014-07-16
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To assess the safety and tolerability of ALT-803, as well as, the potential efficacy of ALT-803 in HIV

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.

Eligibility criteria: Inclusion Criteria:

1. HIV-1 infected adults aged 18 years or over.
2. Stable ART for at least 36 months
3. 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)
4. Screening CD4 count ≥500 cells/mm3
5. Laboratory tests performed within 14 days of study enrollment:

   1. WBC ≥ 3000/mm3
   2. Platelets ≥ 50,000/mm3 \[Patients may be transfused to meet this requirement\]
   3. Hemoglobin ≥ 8 g/dL (\>80g/L) \[Patients may be transfused to meet this requirement\]
   4. Calculated glomerular filtration rate (GFR) \>45 mL/min/1.73m2
   5. Total bilirubin ≤ 2.0 X upper limit of institutional normal (ULN)
   6. AST, ALT, ALP ≤ 2.0 X ULN
6. Adequate pulmonary function without any clinical sign of severe pulmonary dysfunction. PFTs \> 50% of predicted if symptomatic or prior known impairment.
7. Ability to be off prednisone and other immunosuppressive drugs for at least 14 days before first dose of study drug
8. 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
9. Voluntary written consent

Exclusion Criteria:

1. Active infection other than HIV currently requiring systemic antimicrobial therapy
2. Previously treated on this study or received previous ALT-803
3. Latent TB infection or active TB disease prior to completing a standard regimen of anti-TB therapy
4. Active fungal infection requiring systemic antifungal therapy
5. Active or recurrent herpes or varicella-zoster virus infection requiring treatment (or chronic suppression)
6. Chronic hepatitis B or C
7. Planning or current pregnancy or breastfeeding
8. Intended modification of antiretroviral therapy in the next 24 weeks
9. 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
10. Symptomatic congestive heart failure, unstable angina pectoris, or Myocardial infarction within 6 months prior to screening
11. Marked baseline prolongation of QT/QTc interval (e.g. demonstration of a QTc interval greater than 500 milliseconds)
12. History or evidence of uncontrollable CNS disease
13. Prior organ allograft or allogeneic transplantation
14. On-going chronic systemic or regular inhaled corticosteroid use or other immunosuppressive therapy (a history of mild asthma not requiring therapy is eligible)
15. Psychiatric illness/social situations that would limit compliance with study requirements
16. Other illness that in the opinion of the investigator would exclude the patient from participating in this study

Primary outcomes:
measure: Assess the safety and tolerability of ALT-803 in HIV-infected subjects
timeFrame: 4 weeks
Secondary outcomes:
measure: Assess the impact of ALT-803 on the size of the inducible reservoir,
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Tim Schacker, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Miller JS, Davis ZB, Helgeson E, Reilly C, Thorkelson A, Anderson J, Lima NS, Jorstad S, Hart GT, Lee JH, Safrit JT, Wong H, Cooley S, Gharu L, Chung H, Soon-Shiong P, Dobrowolski C, Fletcher CV, Karn J, Douek DC, Schacker TW. Safety and virologic impact of the IL-15 superagonist N-803 in people living with HIV: a phase 1 trial. Nat Med. 2022 Feb;28(2):392-400. doi: 10.1038/s41591-021-01651-9. Epub 2022 Jan 31.