Drugs

CYT-107

CYT-107

Other Names: IL-7, glycol-r-hIL-7, glycosylated recombinant human interleukin-7, interleukin-7, r-hIL-7, recombinant human interleukin-7, rhIL-7 Drug Class: Immune Modulators Registry Number: 858376-81-5 (CAS) Chemical Class: Recombinant interleukin Organization: Cytheris SA; Revimmune Phase of Development: CYT-107 has been studied in Phase II trials for HIV treatment.

(Compound details obtained from ChemIDplus Advanced,1 Cytheris SA news release,2 Annals of Oncology article,3 and Clin Infect Dis article4)

What is CYT-107?

What is CYT-107?

CYT-107 is an investigational drug that is categorized as an immune modulator.2 Immune modulators (also called immunomodulators) are substances that help to activate, boost, or restore normal immune function.

CYT-107 is a manufactured version of interleukin-7, a protein produced by the body to stimulate the immune system to produce more immune cells.2,5 Researchers have studied how CYT-107 can help modify the functioning of the immune system as part of a strategy to treat or cure HIV infection.6–8

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.

Which clinical trials are studying CYT-107?

Which clinical trials are studying CYT-107?

Study Names: INSPIRE; NCT00477321
Phase: I/IIa
Status: This study has been completed.
Location: United States, Canada, France, Italy
Purpose: The purpose of this study was to determine the safety of CYT-107 at three different dose levels in participants on stable ART with reduced CD4 counts.9

Study Names: 1) INSPIRE 2; NCT01190111 and 2) INSPIRE 3; NCT01241643
Phase: II
Status: INSPIRE 2 has been completed. INSPIRE 3 was terminated early because the company developing CYT-107 filed for bankruptcy in June 2013.
Location: INSPIRE 2: United States and Canada; INSPIRE 3: Italy, South Africa, and Switzerland
Purpose: The purpose of these studies was to evaluate the safety and effect on the immune system of repeated treatments with CYT-107 in participants on stable ART with reduced CD4 counts.4,10,11

Study Names: ERAMUNE-01; NCT01019551
Phase: II
Status: This study has been completed.
Location: France, Italy, Spain, United Kingdom
Purpose: The purpose of this study was to see if CYT-107 plus the addition of 2 FDA-approved HIV medicines to participants’ current HIV medicines could reduce the size of latent HIV reservoirs.12

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

What side effects might CYT-107 cause?

What side effects might CYT-107 cause?

One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in the studies of CYT-107 listed above.

INSPIRE (NCT00477321):

In this Phase I/IIa study, 2 participants in the group receiving the highest dose of CYT-107 had serious side effects. One participant had temporary severe liver damage, and the other participant had a moderately severe rash. In the 2 lower dosage groups, there were no serious side effects.6,9

INSPIRE 2 (NCT01190111) and INSPIRE 3 (NCT01241643):

In the Phase II INSPIRE 2 study, many participants had mild to moderate reactions at the location of the CYT-107 injections, and 16% of the participants had flu-like symptoms, fever, or fatigue. Some participants also had temporary increases in HIV viral load (blips) during and after treatment with CYT-107.10,11,13

A combined analysis of INSPIRE 2 and INSPIRE 3 results indicated that serious side effects occurred in 4 participants, including 3 participants with rashes and 1 participant with elevated liver enzymes (indicating possible liver damage or inflammation).4

ERAMUNE-01 (NCT01019551):

In this Phase II study, 1 participant receiving both HIV medicines and CYT-107 had an inflamed vein (phlebitis) in the lower leg.12

Information on possible side effects of CYT-107 is not complete. As testing of CYT-107 continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying CYT-107?

Where can I get more information about clinical trials studying CYT-107?

More information about CYT-107-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 more information, visit NIH Clinical Research Trials and You.

References

References

  1. United States National Library of Medicine. ChemIDPlus Advanced: Interleukin-7. https://chem.nlm.nih.gov/chemidplus/rn/858376-81-5. Accessed August 27, 2018.
  2. Cytheris SA. Press release, dated October 19, 2010. Cytheris announces initiation of ORVACS-sponsored Phase II clinical study to attack viral reservoir of HIV patients. http://www.natap.org/2010/newsUpdates/102210_04.htm. Accessed August 27, 2018.
  3. Trédan O, Ménétrier-Caux C, Ray-Coquard I, et al. ELYPSE-7: a randomized placebo-controlled phase IIa trial with CYT107 exploring the restoration of CD4+ lymphocyte count in lymphopenic metastatic breast cancer patients. Ann Oncol. 2015;26(7):1353-1362. doi:10.1093/annonc/mdv173
  4. Thiébaut R, Jarne A, Routy JP, et al. Repeated cycles of recombinant human interleukin 7 in HIV-infected patients with low CD4 T-cell reconstitution on antiretroviral therapy: results of 2 Phase II multicenter studies. Clin Infect Dis. 2016;62(9):1178-1185. doi:10.1093/cid/ciw065
  5. National Cancer Institute (NCI). NCI Drug Dictionary: glycosylated recombinant human interleukin-7. https://www.cancer.gov/publications/dictionaries/cancer-drug?CdrID=597722. Accessed August 27, 2018.
  6. Lévy Y, Sereti I, Tambussi G, et al. Effects of recombinant human interleukin 7 on T-cell recovery and thymic output in HIV-infected patients receiving antiretroviral therapy: results of a Phase I/IIa randomized, placebo-controlled, multicenter study. Clin Infect Dis. 2012;55(2):291-300. doi:10.1093/cid/cis383
  7. Vandergeeten C, Fromentin R, DaFonseca S, et al. Interleukin-7 promotes HIV persistence during antiretroviral therapy. Blood. 2013;121(21):4321-4329. doi:10.1182/blood-2012-11-465625
  8. Katlama C, Lambert-Niclot S, Assoumou L, et al. Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: a randomized trial. AIDS. 2016;30(2):221-230. doi:10.1097/QAD.0000000000000894
  9. Cytheris SA. A Ph I/IIa rand placebo ctrl, s-blind multictr dose-esc study of SC intermittent interleukin-7 CYT107 in chronically HIV-infected pts with CD4 T lymphocyte counts 101-400 cells-/mm(3) and plasma HIV RNA less than 50 copies/mL after at least 12 m of HAART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 22, 2007. NLM Identifier: NCT00477321. https://clinicaltrials.gov/ct2/show/NCT00477321. Accessed August 27, 2018.
  10. Cytheris SA. An open-label, multicenter study of subcutaneous intermittent recombinant interleukin-7 (CYT107) in chronically HIV-infected patients with CD4 T-lymphocyte counts between 101-400 cells/mm3 and plasma HIV RNA< 50 copies/mL after at least 12 months of HAART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 23, 2010. NLM Identifier: NCT01190111. https://clinicaltrials.gov/ct2/show/NCT01190111. Accessed August 27, 2018.
  11. Cytheris SA. A multicenter, open-labeled, controlled, randomized study of recombinant interleukin-7 (CYT107) treatment to restore and maintain CD4 T-lymphocyte counts above 500 cells/µL in HIV-infected patients with CD4 counts remaining between 101-350 cells/µL after at least 2 years of HAART and plasma HIV RNA < 50 copies/mL for 18 months. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 15, 2010. NLM Identifier: NCT01241643. https://clinicaltrials.gov/show/NCT01241643. Accessed August 27, 2018.
  12. Objectif Recherche Vaccins SIDA. International, multicenter, randomized, non-comparative controlled study of therapeutic intensification plus immunomodulation in HIV-infected patients with long-term viral suppression. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 23, 2009. NLM Identifier: NCT01019551. https://clinicaltrials.gov/ct2/show/NCT01019551. Accessed August 27, 2018.
  13. Sereti I, Routy J-P, Fischl M, et al. Recombinant interleukin-7 (CYT107) expands CD4 T cells in peripheral blood and gut mucosa of chronically HIV-infected immunological non-responder patients. Conference on Retroviruses and Opportunistic Infections (CROI); February 27 - March 2, 2011; Boston, MA. Levin: Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2011. http://www.natap.org/2011/CROI/croi_84.htm. Accessed August 27, 2018.

Last Reviewed: August 27, 2018