Drugs

Aldesleukin

Aldesleukin

Other Names: IL-2, Proleukin, interleukin-2, rIL-2, recombinant human interleukin-2, recombinant interleukin-2, rhIL-2 Drug Class: Immune Modulators Molecular Formula: C690 H1115 N177 O203 S Chemical Name: 2-133-Interleukin 2 (human reduced), 125-L-serine- Chemical Class: Recombinant interleukin Organization: Novartis Vaccines and Diagnostics, Inc. Phase of Development: Aldesleukin is in Phase III development as an immune modulator for HIV infection.

(Compound details obtained from ChemIDplus Advanced,1 Journal of Internal Medicine article,2 DailyMed Proleukin Full Prescribing Information,3 and ClinicalTrials.gov4,5)

What is aldesleukin?

What is aldesleukin?

Aldesleukin is being studied as an investigational drug to treat HIV infection. As an HIV medicine, aldesleukin is categorized as an immune modulator.2 Immune modulators (also called immunomodulators) are substances that help to activate, boost, or restore normal immune function.

To learn how investigational drugs are tested during clinical trials, read the AIDSinfo What is an Investigational HIV Drug? and HIV/AIDS Clinical Trials fact sheets.

Aldesleukin is a synthetic version of interleukin-2, which is a protein that is made naturally in the body. Interleukin-2 helps activate the immune system to make more immune cells and stimulates existing immune cells to fight infections, such as HIV infection.3,6

Aldesleukin is currently approved by the U.S. Food and Drug Administration (FDA) to treat two types of cancers: renal cell carcinoma and melanoma.3

Which clinical trials are studying aldesleukin?

Which clinical trials are studying aldesleukin?

Study Name: NCT03308786
Phase: II
Status: This study is not yet open for participant recruitment.
Location: Not available
Purpose: The purpose of this study is to see whether aldesleukin can decrease the number of resting CD4 cells within the latent HIV reservoir and reduce the size of the reservoir in individuals with viral suppression.7

Study Names: ANRS118; ILIADE; NCT00071890
Phase: II/III
Status: This study has been completed.
Location: United States and France
Purpose: The purpose of this study was to see whether aldesleukin given before a planned interruption of antiretroviral therapy (ART) could extend the time that participants are temporarily off treatment and also keep their CD4 counts above 350 cells/mm3.8

Study Names: ESPRIT; NCT00004978
Phase: III
Status: This study has been completed.
Location: Multiple countries, including the United States
Purpose: The purpose of this study was to evaluate whether aldesleukin plus ART could lower the risk of opportunistic infection and death in participants with HIV.4,9

Study Names: SILCAAT; NCT00013611
Phase: III
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to evaluate whether aldesleukin plus ART could lower the risk of opportunistic infection and death in participants with HIV.5,9

For more details on the studies listed above, see the Health Professional version of this drug summary.

A number of other HIV-related studies on aldesleukin have also been completed. These include:

  • The STALWART study (NCT00110812), which looked at the effects of aldesleukin with and without ART on CD4 counts in participants who were either off ART or who had never taken ART before.10,11
  • The ANRS 119 study (NCT00120185), which evaluated whether aldesleukin without ART could increase CD4 counts and delay the need to start ART in participants who were either off ART or who had never taken ART before.12,13
  • The COSMIC study, which looked at the effects of aldesleukin with and without ART on the latent HIV reservoir.14
The following studies evaluating the use of aldesleukin are ongoing:
  • NCT01013415 is a Phase I/II study that is currently evaluating a combination HIV cure approach using aldesleukin in combination with another investigational treatment.15
  • NCT03346499 is a Phase II study that is evaluating an infusion of natural killer cells and aldesleukin in people on ART with viral suppression.16

What side effects might aldesleukin cause?

What side effects might aldesleukin cause?

One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in some of the studies of aldesleukin listed above.

ANRS118; ILIADE (NCT00071890):
Many mild to moderate side effects associated with aldesleukin occurred in the first 24 weeks of the study. The most common side effects were weakness, fever, and nausea. Eleven participants receiving aldesleukin stopped the study early because of side effects related to aldesleukin. Overall, the few severe side effects that occurred during the study occurred more frequently in the aldesleukin group than in the ART-only group.17

ESPRIT (NCT00004978) and SILCAAT (NCT00013611):
In these studies, serious side effects were more common in participants who received aldesleukin plus ART than in participants who received ART alone. Serious side effects that occurred in either the ESPRIT study or the SILCAAT study included heart and blood vessel disorders, gastrointestinal disorders, and psychiatric disorders.9

Additional information on side effects known to be associated with aldesleukin can be found in the FDA-approved Full Prescribing Information for Proleukin.

Because aldesleukin is still being studied, information on possible side effects of the drug is not complete. As testing of aldesleukin continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying aldesleukin?

Where can I get more information about clinical trials studying aldesleukin?

More information about aldesleukin-related research studies is available from the AIDSinfo database of ClinicalTrials.gov study summaries. Click on the title of any trial in the list to see the ClinicalTrials.gov trial summary and more information about the study.

Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a clinical trial is right for you. For information, visit NIH Clinical Research Trials and You.

References

References

  1. United States National Library of Medicine. ChemIDplus Advanced: Aldesleukin. https://chem.nlm.nih.gov/chemidplus/rn/110942-02-4. Accessed January 11, 2019.
  2. Gougeon M, Chiodi F. Impact of γ-chain cytokines on T cell homeostasis in HIV-1 infection: therapeutic implications. J Intern Med. 2010;(267):502-514.
  3. Prometheus Laboratories Inc. Proleukin: full prescribing information. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4e2b687e-47f2-4f3c-80ab-e3224befffca. Published December 31, 2014. Accessed January 11, 2019.
  4. National Institute of Allergy and Infectious Diseases (NIAID). A randomized, open-label, Phase III, international study of subcutaneous recombinant IL-2 in patients with HIV-1 infection and CD4+ cell counts 300/mm^3 or greater: evaluation of subcutaneous proleukin in a randomized international trial. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 10, 2000. NLM Identifier: NCT00004978. https://clinicaltrials.gov/ct2/show/NCT00004978. Accessed January 11, 2019.
  5. University of Minnesota - Clinical and Translational Science Institute. A Phase III multicenter randomized study of the biological and clinical efficacy of subcutaneous recombinant, human interleukin-2 in HIV-infected patients with low CD4+ counts under active antiretroviral therapy (SILCAAT Amendment 4). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 24, 2001. NLM Identifier: NCT00013611. https://clinicaltrials.gov/ct2/show/NCT00013611. Accessed January 11, 2019.
  6. Paredes R, López Benaldo de Quirós J, Fernández-Cruz E, Clotet B, Lane H. The potential role of interleukin-2 in patients with HIV infection. AIDS Rev. 2002;4(1):36-40.
  7. Case Western Reserve University. HIV reservoir reduction with interleukin-2. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 29, 2017. NLM Identifier: NCT03308786. https://clinicaltrials.gov/ct2/show/NCT03308786. Accessed January 11, 2019.
  8. National Institute of Allergy and Infectious Diseases (NIAID). Phase II/III study evaluating the effect of IL-2 on preservation of the CD4 T-lymphocytes after interruption of anti-retroviral tx in HIV infected patients with CD4 T-lymphocyte count greater than 500 cells/mm(3) who have received anti-retroviral tx. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 3, 2003. NLM Identifier: NCT00071890. https://clinicaltrials.gov/ct2/show/NCT00071890. Accessed January 11, 2019.
  9. Abrams D, Lévy Y, Losso M, et al. Interleukin-2 therapy in patients with HIV infection. N Engl J Med. 2009;361(16):1548-1559.
  10. Tavel JA. Effects of intermittent IL-2 alone or with peri-cycle antiretroviral therapy in early HIV infection: The STALWART study. PLoS ONE. 2010;5(2):e9334.
  11. National Institute of Allergy and Infectious Diseases (NIAID). STALWART: a randomized, open-label, international study of subcutaneous recombinant interleukin-2 with and without concomitant antiretroviral therapy in patients with HIV-1 infection and CD4+ cell counts of 300 cells/mm3 or more. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 13, 2005. NLM Identifier: NCT00110812. https://clinicaltrials.gov/ct2/show/NCT00110812. Accessed January 11, 2019.
  12. Molina J-M, Levy Y, Fournier I, et al. Interleukin-2 before antiretroviral therapy in patients with HIV infection: a randomized trial (ANRS 119). J Infect Dis. 2009;200(2):206–215.
  13. French National Agency for Research on AIDS and Viral Hepatitis. Study of the immunological efficacy of using subcutaneous interleukin-2 (IL-2) in antiretroviral naive HIV-1-infected subjects with a CD4 cell count above 300/mm3. ANRS 119 Trial INTERSTART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 8, 2005. NLM Identifier: NCT00120185. https://clinicaltrials.gov/ct2/show/NCT00120185. Accessed January 11, 2019.
  14. Stellbrink H-J, van Lunzen J, Westby M, et al. Effects of interleukin-2 plus highly active antiretroviral therapy on HIV-1 replication and proviral DNA (COSMIC trial). AIDS. 2002;16(11):1479-1487.
  15. University of Pennsylvania. A Phase I/II study of the safety, survival, and trafficking of autologous CD4-ZETA gene-modified T cells with and without extension interleukin-2 in HIV infected patients. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 5, 2009. NLM Identifier: NCT01013415. https://clinicaltrials.gov/ct2/show/NCT01013415. Accessed January 11, 2019.
  16. University of Minnesota - Clinical and Translational Science Institute. Adoptive transfer of haploidentical natural killer cells and IL-2 in human immunodeficiency virus (HIV). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 24, 2017. NLM Identifier: NCT03346499. https://www.clinicaltrials.gov/ct2/show/record/NCT03346499. Accessed January 11, 2019
  17. Lévy Y, Thiébaut R, Gougeon M-L, et al. Effect of intermittent interleukin-2 therapy on CD4+ T-cell counts following antiretroviral cessation in patients with HIV. AIDS. 2012;26(6):711.

Last Reviewed: January 16, 2019