What is an investigational drug?
An investigational drug is one that is under study and is not approved by the U.S. Food and Drug Administration (FDA) for sale in the United States. Medical research studies are conducted to evaluate the safety and effectiveness of an investigational drug. These research studies are also called clinical trials. Once an investigational drug has been proven safe and effective in clinical trials, FDA may approve the drug for sale in the United States.
To learn more about investigational drugs, read the AIDSinfo What is an Investigational HIV Drug? fact sheet.
What is CYT-107?
CYT-107 is an investigational drug that is categorized as an immune modulator.2 Immune modulators, which can also be called immunomodulators, are substances that modify (activate, enhance, or suppress) the functioning of the immune system.
HIV infection can make a person’s immune system not work properly over the course of the viral infection. When this happens:
- CD4 counts can drop and HIV infection can worsen.
(A CD4 count is a laboratory test that measures the number of CD4 cells—a type of immune cell—in a sample of blood and is an important indicator of immune function.)
- Other immune system cells or proteins may not be produced in normal amounts and may not work normally.
- A person may not respond well to antiretroviral therapy (ART).
(ART is the recommended treatment for HIV infection and involves using a combination of different antiretroviral [ARV] drugs to prevent HIV from multiplying.)
- Latent HIV reservoirs can form and persist in the body.
(Latent HIV reservoirs are “resting” CD4 cells or other cells that are infected with HIV but not actively producing HIV in the body. Because ART does not work against HIV that’s hidden in latent reservoirs, these reservoirs are one of the main obstacles to curing HIV infection.)5-9
CYT-107 is a synthetic version of interleukin-7, which is a protein that is made naturally in the body to help activate the immune system to make more immune cells.3,10 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.11-13
How are clinical trials of investigational drugs conducted?
Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.14
- Phase I trials: Researchers test an investigational drug in a small group of people (20–80) for the first time. The purpose is to evaluate its safety and identify side effects.
- Phase II trials: The investigational drug is administered to a larger group of people (100–300) to determine its effectiveness and to further evaluate its safety.
- Phase III trials: The investigational drug is administered to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments, and collect information that will allow the investigational drug to be used safely.14
In most cases, an investigational drug must be proven effective and must show continued safety in a Phase III clinical trial to be considered for approval by FDA for sale in the United States. Some drugs go through FDA’s accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by FDA and made available to the public, researchers track its safety in Phase IV trials to seek more information about the drug’s risks, benefits, and optimal use.14
In what phase of testing is CYT-107?
CYT-107 has been studied in Phase 2 clinical trials.3
What are some studies on CYT-107?
Study Name: INSPIRE; NCT00477321
Sponsor: Cytheris SA
Location: United States, Canada, France, Italy
- Participants were HIV-infected adults who had taken HIV medicines before (called treatment-experienced) and who had been on HIV medicines for at least 12 months before entering the study.
- Participants had viral load levels (the amount of HIV in a blood sample) of less than 50 copies/mL for at least 6 months while on HIV medicines. Participants had CD4 counts between 101 and 400 cells/mm3. (A CD4 count is a laboratory test that measures the number of CD4 cells in a sample of blood and is an important indicator of immune function. The CD4 count of a healthy person ranges from 500 to 1,600 cells/mm3.)
The purpose of this study was to determine the best dose
of CTY-107 in terms of safety and effectiveness in improving CD4 counts.15
For more details on this study, see the Health Professional version
1) INSPIRE 2; NCT01190111
and 2) INSPIRE 3; NCT01241643
INSPIRE 2: United States and Canada; INSPIRE 3: Italy, South Africa, and Switzerland
- INSPIRE 2: HIV-infected, treatment-experienced adults who had been taking HIV medicines for at least 12 months before entering the study. Participants had viral load levels of less than 50 copies/mL for at least 6 months and CD4 counts between 101 and 400 cells/mm3.
- INSPIRE 3: HIV-infected, treatment-experienced adults who had been taking HIV medicines for at least 24 months before entering the study. Participants had viral load levels of less than 50 copies/mL for at least 18 months and CD4 counts between 101 and 350 cells/mm3.
The purpose of the two studies was to evaluate the safety and effect on the immune system of repeated cycles of CYT-107.16,17
For more details on this study, see the Health Professional version
Objectif Recherche Vaccins SIDA
France, Italy, Spain, United Kingdom
- Participants were HIV-infected, treatment-experienced adults whose HIV had been controlled with HIV medicines for at least 3 years.
- Participants had undetectable viral load levels, which is when the amount of HIV in the blood is too low to be detected with a viral load (HIV RNA) test.
- Participants had CD4 counts of at least 350 cells/mm3 and HIV DNA levels between 10 to 1,000 copies/106 in peripheral blood mononuclear cells (PBMCs). (Levels of HIV DNA in PBMCs is a measure of low levels of residual HIV in the body that cannot be detected by standard viral load tests.)
The purpose of this study was to see if CYT-107 plus the addition of two FDA-approved HIV medicines to participants’ current ART regimens could reduce latent HIV.18
For more details on this study, see the Health Professional version
What side effects might CYT-107 cause?
In the INSPIRE study (NCT00477321) discussed under the previous question, two participants in the highest dosing group had dose-limiting side effects. (A dose-limiting side effect is a side effect that is serious enough to prevent an increase in dose.) One participant had temporary severe liver toxicity, and the other participant had a moderate rash. In the two lower dosing groups, there were no reports of dose-limiting side effects. In the INSPIRE 2 and INSPIRE 3 studies (NCT0119011 and NCT01241643), there were four participants who had severe liver toxicity.11,19
A common side effect in INSPIRE and INSPIRE 2 was a mild to moderate reaction at the location of the CYT-107 injections. Symptoms showing up in other parts of the body (systemic reactions), such as flu-like symptoms, fever, or fatigue, occurred in 16% of participants who received one cycle of CYT-107 in INSPIRE 2.19,20
In the ERAMUNE-01 study (NCT01019551), one participant receiving ART plus CYT-107 had an inflamed vein (phlebitis) in the lower leg.21
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?
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.
How can I find more information about participating in a clinical trial?
Participating in a clinical trial can provide benefits. For example, a volunteer participant can benefit from new research treatments before they are widely available. Participants also receive regular and careful medical attention from a research team that includes doctors and other health professionals. However, clinical trials may also involve risks of varying degrees, such as unpleasant, serious, or even life-threatening side effects from the treatment being studied.14
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.
- United States National Library of Medicine. ChemIDPlus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/858376-81-5. Last accessed on July 17, 2016.
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HCV Drugs in Development. Available at: https://chemdb.niaid.nih.gov/DrugDevelopmentHCV.aspx. Last accessed on July 17, 2016.
- 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. Available at: http://www.natap.org/2010/newsUpdates/102210_04.htm. Last accessed on July 17, 2016.
- 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 Jul; 26(7): 1353-62. Available at: http://www.ncbi.nlm.nih.gov/pubmed/25851629. Last accessed on July 17, 2016.
- Barouch DH, Deeks SG. Immunologic Strategies for HIV-1 Remission and Eradication. Science. 2014 Jul 11; 345(6193): 169–174. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096716/. Last accessed on July 17, 2016.
- Lederman MM, Rodriguez B, Sieg S. Immunopathogenesis of HIV Infection. In: Coffey S and Volberding P, eds. HIV InSite Knowledge Base. University of California San Francisco; 2004. Available at: http://hivinsite.ucsf.edu/InSite?page=kb-00&doc=kb-02-01-04. Last accessed on July 17, 2016.
- Kedzierska K, Crowe SM. Cytokines and HIV-1: interactions and clinical implications. Antivir Chem Chemother. 2001 May; 12(3): 133-50. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12959322. Last accessed on July 17, 2016.
- Siliciano RF, Greene WC. HIV Latency. Cold Spring Harb Perspect Med. 2011 Sep; 1(1): a007096. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234450/. Last accessed on July 17, 2016.
- Savarino A, Shytaj IL. Chloroquine and beyond: exploring anti-rheumatic drugs to reduce immune hyperactivation in HIV/AIDS. Retrovirology. 2015; 12: 51. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472405/. Last accessed on July 17, 2016.
- National Cancer Institute (NCI). NCI Drug Dictionary: glycosylated recombinant human interleukin-7. Available at: http://www.cancer.gov/publications/dictionaries/cancer-drug?CdrID=597722. Last accessed on July 17, 2016.
- 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 Jul 15; 55(2): 291–300. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3381639/. Last accessed on July 17, 2016.
- Vandergeeten C, Fromentin R, DaFonseca S, et al. Interleukin-7 promotes HIV persistence during antiretroviral therapy. Blood. 2013 May 23; 121(21): 4321–4329. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663425/. Last accessed on July 17, 2016.
- 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 Jan; 30(2): 221-30. Available at: http://www.ncbi.nlm.nih.gov/pubmed/26684819. Last accessed on July 17, 2016.
- National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: http://www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on July 17, 2016.
- 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. Available at: https://clinicaltrials.gov/ct2/show/NCT00477321. Last accessed on July 17, 2016.
- 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. Available at: https://clinicaltrials.gov/ct2/show/NCT01190111. Last accessed on July 17, 2016.
- 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. Available at: https://clinicaltrials.gov/show/NCT01241643. Last accessed on July 17, 2016.
- 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. Available at: https://clinicaltrials.gov/ct2/show/NCT01019551. Last accessed on July 17, 2016.
- Levy Y, Sereti I, Tambussi G, et al. INSPIRE Study: Effects of r-hIL-7 on T Cell Recovery and Thymic Output in HIV-infected Patients Receiving c-ART - Interim Analysis of a Phase I/IIa Multicenter Study. 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 12-15, 2009; San Francisco, CA. Levin: Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2009. Available at: http://www.natap.org/2009/ICCAC/ICCAC_39.htm. Last accessed on July 17, 2016.
- 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. 18th 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. Available at: http://www.natap.org/2011/CROI/croi_84.htm. Last accessed on July 17, 2016.
- Katlama C, Lambert-Niclot S, Assoumou L, et al. Impact of Interleukin 7 and Raltegravir plus Maraviroc intensification on total HIV DNA reservoir: Results from ERAMUNE 01. 20th Conference on Retroviruses and Opportunistic Infections (CROI); March 3 - 6, 2013; Atlanta, GA. Levin: Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2013. Available at: http://www.natap.org/2013/CROI/croi_177.htm. Last accessed on July 17, 2016.
Last Reviewed: July 17, 2016