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. It is currently being studied to see if it can be effective as part of a strategy to cure HIV infection.4-8
Currently, there is no cure for HIV infection. One of the main obstacles to curing HIV infection is that the virus can remain hidden and inactive (latent) inside certain cells of the immune system (such as resting CD4 T cells) for many months or even years. While HIV is in this latent state, the immune system cannot recognize the virus, and antiretroviral therapy (ART) has no effect on it. (ART is the recommended treatment for HIV infection and involves using a combination of different antiretroviral [ARV] drugs to prevent HIV from replicating.)9,10
Peginterferon alfa-2a belongs to a class (group) of HIV drugs called immune modulators.2 Immune modulators (also called immunomodulators) are substances that help to activate, boost, or restore normal immune function. Interferon alfa is a protein that is made naturally in the body to help fight viral infections. Peginterferon alfa-2a is a synthetic version of interferon alfa.5,11
Peginterferon alfa-2a is being studied for its ability to help activate the immune systems of HIV-infected individuals. 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.7
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.12
- 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.12
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.12
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.2
What are some studies on peginterferon alfa-2a?
Study Names: ACTG A5192; NCT00078442
Location: United States
- HIV-infected adults who had either 1) never taken HIV medicines before entering the study (also called treatment-naive) or 2) taken HIV medicines before entering the study (also called treatment-experienced) 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 5000 copies/mL or more and CD4 counts of at least 300 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 evaluate the safety and antiviral
activity of peginterferon alfa-2a given alone, without any other HIV medicines (also called monotherapy
Participants received peginterferon alfa-2a once a week by subcutaneous
injection for 12 weeks. (A subcutaneous injection is placed under the skin.)
- Treatment with peginterferon alfa-2a monotherapy reduced the viral load in some of the participants. At Week 12, peginterferon alfa-2a’s effect on reducing viral load was similar to the antiviral effect seen with many ARV drugs.
- Participants’ CD4 counts did not change significantly during the study.
- In terms of safety, three participants experienced severe side effects related to peginterferon alfa-2a treatment. One participant had severe fatigue and two participants had severe drops in their absolute neutrophil counts. (An absolute neutrophil count is a measure of the number of neutrophils [a type of white blood cell] in the blood.)5,13
Study Names: NCT00594880
Location: United States
- HIV-infected, treatment-experienced adults who were receiving ART at the time of study entry.
- Participants were not infected with HBV or HCV.
- Participants had suppressed viral loads of less than 50 copies/mL and CD4 counts of at least 450 cells/mm3.
The purpose of this study was to evaluate the safety and antiviral activity of two different doses of peginterferon alfa-2a.
Participants received peginterferon alfa-2a once weekly by subcutaneous injection for 5 weeks, in combination with their current ART regimens. All participants then underwent a 12-week-long treatment interruption of ART during which they received peginterferon alfa-2a monotherapy. (A treatment interruption of ART is a planned break from ART to evaluate how well an investigational drug can maintain control of a participant’s viral load during a clinical trial.) Those participants who had a sustained viral load of less than 400 copies/mL at the end of the 12–week treatment interruption of ART had the option to continue treatment interruption for up to 24 weeks.
- Twenty partcipants were evaluated after the 12-week long ART treatment interruption. Nine of these participants were able to successfully matintain control of their viral loads at less than 400 copies/mL while on peginterferon alfa-2a monotherapy.
- Eight participants stayed on peginterferon alfa-2a monotherapy while completing an additional 12 weeks of ART treatment interruption (for a treatment interruption duration lasting a total of 24 weeks). Six participants were able to control their viral loads at less than 400 copies/mL through 24 weeks.
- Investigators noted that the level of viral load control seen during treatment interruption in this study was greater than that seen in previous studies evaluating ART treatment interruptions.
- The dose of peginterferon-alfa 2a did not appear to affect treatment success or failure.
- Participants who were able to control their viral loads during treatment interruption while on peginterferon-alfa 2a monotherapy also had a significant reduction in the amount of latent HIV in their bodies.
- In terms of safety, three participants stopped peginterferon alfa-2a treatment because of depression of moderate severity. One participant experienced severe neutropenia (a low level of neutrophils in the blood) while still receiving ART and dropped out of the study.6,14
Study Names: ACTIVATE trial; NCT02471430
Location: United States
Participants: HIV-infected, treatment-experienced adults who have been receiving ART for at least 2 years and have been receiving the same ART regimen for at least 12 weeks prior to screening. Participants have viral load levels less than 50 copies/mL.
Purpose: The purpose of this study is to evaluate whether a combination strategy consisting of the HDAC inhibitor panobinostat (brand name: Farydak) and the immunomodulator peginterferon alfa-2a can reduce latent HIV reservoirs. (HDAC inhibitors are drugs that are being studied to reactivate latent HIV.)
Study Design: Participants will be randomly assigned to one of the following two groups:
Participants will receive four consecutive treatment cycles, with each treatment cycle lasting 4 weeks. Each treatment cycle will involve 1 week of treatment with oral panobinostat taken 3 times, followed by 3 weeks off treatment.
Participants will receive four consecutive treatment cycles, with each treatment cycle lasting 4 weeks. Each treatment cycle will begin with a single injection of peginterferon alfa-2a plus 1 week of treatment with oral panobinostat taken 3 times. The first week of treatment will be followed by 3 weeks off of treatment.
All participants will continue receiving ART during the entire treatment period. After treatment is completed, a follow-up period is planned to last 6 months.7
* This study is not yet open for enrollment and results are not yet available.7
What side effects might peginterferon alfa-2a cause?
In the ACTG A5192 trial discussed under the previous question, the most common side effects related or possibly related to peginterferon alfa-2a treatment were mild to moderate decreases in absolute neutrophil counts and fatigue. One participant experienced treatment-related depression of moderate severity.13
In the other Phase II study (NCT00594880) that evaluated peginterferon alfa-2a at two 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 counts.14
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.
I am interested in participating in a clinical trial of peginterferon alfa-2a. 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.12
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 19, 2016.
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: http://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on March 19, 2016.
- 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 19, 2016.
- 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 19, 2016.
- 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 19, 2016.
- 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 19, 2016.
- 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 19, 2016.
- Treatment Action Group website. Research Toward a Cure Trials. Available at: http://www.treatmentactiongroup.org/cure/trials. Last accessed on March 19, 2016.
- National Institute of Allergy and Infectious Diseases (NIAID): News Release, dated June 16, 2009. NIAID Invites Applications to Conduct Basic Research on HIV Persistence. Available at: http://www.niaid.nih.gov/news/newsreleases/Archive/2009/Pages/HIV_persistence.aspx. Last accessed on March 19, 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 March 19, 2016.
- 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 19, 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 March 19, 2016.
- 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 19, 2016.
- 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 19, 2016.
Last Reviewed: March 19, 2016