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 peginterferon alfa-2a?
Peginterferon alfa-2a (brand name: Pegasys) is a drug that has been approved by FDA for the treatment of chronic hepatitis B virus (HBV) infection and chronic hepatitis c virus (HCV) infection.4 It is also being studied as an investigational drug for HIV infection. As an HIV therapy, peginterferon alfa-2a is categorized as an immune modulator.2 Immune modulators (also 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
Peginterferon alfa-2a is being studied for its ability to help activate the immune systems of HIV-infected individuals. Interferon
alfa is a protein
that is made naturally in the body to help fight viral infections. Peginterferon alfa-2a is a manufactured version of interferon alfa.10,11
When used along with other drugs, peginterferon alfa-2a may help to clear the body of latent HIV that cannot be removed with ART alone.12
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.13
- 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.13
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.13 (Some clinical trials are categorized as “a” or “b,” such as “Phase Ia” or “Phase IIb.” These different subphases typically mean that a study is researching certain types of information or using a certain type of participant population.)
In what phase of testing is peginterferon alfa-2a?
The use of peginterferon alfa-2a to reduce latent HIV is being studied in a Phase II clinical trial.12
What are some studies on peginterferon alfa-2a?
Study Names: ACTG A5192; NCT00078442
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Location: United States
- Participants were HIV-infected adults who had either never taken HIV medicines before entering the study or who had taken HIV medicines but were off treatment for at least 12 weeks before entering the study.
- Participants were not infected with HBV or HCV.
- Participants had viral load levels (the amount of HIV in a blood sample) of 5,000 copies/mL or more and CD4 counts of at least 300 cells/mm3.
Purpose: The purpose of this study was to evaluate the safety and antiviral activity of peginterferon alfa-2a given alone, without any other HIV medicines (also called monotherapy).10
Study Names: NCT00594880
Sponsor: The Wistar Institute
Location: United States
- Participants were HIV-infected adults who were receiving ART at the start of the study.
- Participants were not infected with HBV or HCV.
- Participants had viral loads of less than 50 copies/mL and CD4 counts of at least 450 cells/mm3. A participant’s lowest ever CD4 count was above 200 cells/mm3.
: The purpose of this study was to evaluate the safety and antiviral activity of 2 different doses of peginterferon alfa-2a.14, 15
: ACTIVATE trial; NCT02471430
: Massachusetts General Hospital
: United States
- Participants are HIV-infected adults who have been receiving ART continuously for at least 24 months and have been receiving the same ART regimen for at least 12 weeks before the start of the study.
- Participants are not infected with HBV or HCV.
- Participants have had viral load levels of less than 50 copies/mL for at least 24 months before the start of the study and have CD4 counts of at least 400 cells/mm3.
: The purpose of this study is to evaluate whether a combination of the HDAC inhibitor panobinostat
(brand name: Farydak) and peginterferon alfa-2a can reduce latent HIV reservoirs. (HDAC inhibitors are drugs that are being studied to reactivate latent HIV.)12
* This study is currently recruiting participants.
For more details on the studies listed above, see the Health Professional version
What side effects might peginterferon alfa-2a cause?
In the ACTG A5192 trial (NCT00078442) discussed under the previous question, the most common side effects related or possibly related to peginterferon alfa-2a were fatigue and mild to moderate decreases in the number of neutrophils, a type of infection-fighting immune cell. One participant experienced moderately severe treatment-related depression.10,16
In the other Phase II study (NCT00594880) that evaluated peginterferon alfa-2a at 2 different doses, participants’ CD4 counts decreased during the first 5 weeks of peginterferon alfa-2a treatment, but then remained stable throughout the rest of the study. No participants stopped peginterferon alfa-2a treatment because of a drop in CD4 count.14,15
Because peginterferon alfa-2a is still being studied, information on possible side effects of the drug is not complete. As testing of peginterferon alfa-2a continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying peginterferon alfa-2a?
More information about peginterferon alfa-2a-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.13
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/198153-51-4. Last accessed on March 8, 2017.
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on March 8, 2017.
- Shorr RI, Hoth AB, Rawls N. Entry for peginterferon alfa-2a. In: Drugs for the Geriatric Patient. Elsevier Inc.; 2007. ISBN: 978-1-4160-0208-6. Available at: http://topics.sciencedirect.com/topics/page/Peginterferon_alfa-2a. Last accessed on March 8, 2017.
- Genentech, Inc. PEGASYS- peginterferon alfa-2a: Full Prescribing Information, July 27, 2015. DailyMed. Available at: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de61685e-2b8c-4e22-84bb-869e13600440. Last accessed on March 8, 2017.
- 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 March 8, 2017.
- 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 March 8, 2017.
- 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 March 8, 2017.
- 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 March 8, 2017.
- 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 March 8, 2017.
- National Institute of Allergy and Infectious Diseases (NIAID). A Phase II Open-Label Pilot Trial of the Antiretroviral Activity, Safety, and Tolerability of Pegylated Interferon Alfa-2A (40KD) [PegasysTM] in HIV-1 Infected Subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 25, 2004. NLM Identifier: NCT00078442. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00078442. Last accessed on March 8, 2017.
- Gibbert K, Schlaak JF, Yang D, and Dittmer U. IFN-α subtypes: distinct biological activities in anti-viral therapy. Br J Pharmacol. 2013 Mar; 168(5): 1048–1058. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594665/. Last accessed on March 8, 2017.
- Massachusetts General Hospital. A Phase I-II Pilot Study to Assess the Safety and Efficacy of Combined Administration With Pegylated Interferon-alpha2a and the Histone Deacetylase Inhibitor (HDACi) Panobinostat for Reducing the Residual Reservoir of HIV-1 Infected Cells in cART-Treated HIV-1 Positive Individuals. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 11, 2015. NLM Identifier: NCT02471430. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02471430. Last accessed on March 8, 2017.
- 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 March 8, 2017.
- The Wistar Institute. Antiviral Activity of Peg-IFN-Alpha-2A in Chronic HIV-1 Infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 4, 2008. NLM Identifier: NCT00594880. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00594880. Last accessed on March 8, 2017.
- Azzoni L, Foulkes AS, Papasavvas E, et al. Pegylated Interferon Alfa-2a Monotherapy Results in Suppression of HIV Type 1 Replication and Decreased Cell-Associated HIV DNA Integration. J Infect Dis. 2013 Jan 15; 207(2): 213–222. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532820/. Last accessed on March 8, 2017.
- Asmuth DM, Murphy RL, Rosenkranz SL, et al. Safety, Tolerability and Mechanisms of Antiretroviral Activity of Peginterferon alfa-2a in HIV-1-Mono-infected Subjects: A Phase II Clinical Trial. J Infect Dis. 2010 Jun 1; 201(11): 1686–1696. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946345/. Last accessed on March 8, 2017.
Last Reviewed: March 8, 2017