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

NCT02191098 | Completed Phase 1 DMC

• 1 other identifier: 1508M77601-1
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

HIV; Stable ART

Keywords

HIV; ART

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Assess the impact of ALT-803 on the size of the inducible reservoir,

  4 weeks

Study Arms (1)

ALT-803

EXPERIMENTAL

ALT-803

Drug: ALT-803

Interventions

ALT-803 DRUG

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

ALT-803

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (1)

• 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.

  PMID: 35102335 DERIVED

MeSH Terms

Interventions

ALT-803

Study Officials

• Tim Schacker, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2014
• First Posted: July 16, 2014
• Study Start: June 1, 2015
• Primary Completion: September 9, 2019
• Study Completion: September 9, 2019
• Last Updated: January 27, 2020

Record last verified: 2020-01

Locations

US (1)