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.
What is PRO-140?
PRO-140 is an investigational drug that is being studied for the treatment of HIV infection.
PRO-140 belongs to a class (group) of HIV drugs called entry and fusion inhibitors.2
Entry and fusion inhibitors block HIV from getting into and infecting certain cells of the immune system. This prevents HIV from multiplying and can reduce the amount of HIV in the body.
PRO-140 works by attaching to one of two proteins on the surface of the immune cells. These proteins are called the CCR5 and CXCR4 coreceptors. PRO-140 attaches to the CCR5 coreceptor. When PRO-140 attaches to the CCR5 coreceptor, certain strains of HIV—called R5-tropic virus—cannot attach to, enter, or infect the cell.4
Research may prove that PRO-140 is a safe and effective option for treating people with R5-tropic virus, including those for whom other entry and fusion inhibitors, such as maraviroc (brand name: Selzentry), are not working.5
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.6
- 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.6
In most cases, an investigational drug must be proven safe and effective in a Phase III clinical trial to be considered for approval by the FDA for sale in the United States. Some drugs go through the FDA’s accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by the 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.6
In what phase of testing is PRO-140?
PRO-140 is currently being studied in Phase II clinical trials.2
What have recent studies shown about PRO-140?
In a Phase IIa study, PRO-140 was compared with placebo in HIV-infected participants who had R5-tropic virus. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.) In this study, PRO-140 was given by subcutaneous (SC) infusion and at different strengths and dosing frequencies (every week or every other week). (An SC infusion is an injection placed under the skin to deliver a drug or other fluids over a period of time.) Some of the participants had never taken HIV medicines before entering the study (treatment-naive), and others had taken HIV medicines previously (treatment-experienced). The treatment-experienced participants were required to be off HIV medicines for at least 12 weeks before starting the study.7,8
In this study, PRO-140 at all of the dosages studied was shown to have significant antiviral activity. In terms of safety, PRO-140 was generally well tolerated. No drug-related serious side effects occurred.7,8
An additional Phase II study of long-acting PRO-140 given by SC infusion is under way in HIV-infected injection drug users who have viral rebound (detectable levels of HIV after a period of undetectable levels) and who had poor adherence to prior HIV medicine treatment.9
What side effects might PRO-140 cause?
In the Phase IIa study discussed under the previous question, the most common side effects reported included the following: diarrhea, headache, swollen lymph nodes, and high blood pressure. Side effects occurring at or around the injection site were mild and temporary and included hardening of the tissue, pain, and irritation.8
In a separate Phase IIa study of PRO-140 given by intravenous (IV) infusion, headache and nasal congestion were reported. (An IV infusion is an injection placed directly into a vein to deliver a drug or other fluids over a period of time).10
Because PRO-140 is still being studied, information on possible side effects of the drug is not complete. As testing of PRO-140 continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying PRO-140?
More information about PRO-140-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 PRO-140. 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.6
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
. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development
. CytoDyn Inc.: Press Releases. CytoDyn Announces Acquisition of PRO 140
. Accessed April 22, 2013.
. Trkola A, Ketas TJ, Nagashima KA, et al. Potent, broad-spectrum inhibition of human immunodeficiency virus type 1 by the CCR5 monoclonal antibody PRO 140
. J Virol
. 2001 Jan;75(2):579-88.
. Murga JD, Franti M, Pevear DC, Maddon PJ, Olson WC. Potent antiviral synergy between monoclonal antibody and small-molecule CCR5 inhibitors of human immunodeficiency virus type 1
. Antimicrob Agents Chemother
. 2006 Oct;50(10):3289-96.
. National Institutes of Health (NIH). NIH Clinical Research Trials and You
. Thompson M, Lalezari J, Saag M, et al. Weekly and Biweekly Subcutaneous PRO 140 Demonstrates Potent, Sustained Antiviral Activity
. Abstract presented at: 16th
Conference on Retroviruses and Opportunistic Infections (CROI); February 8-11, 2009; Montreal, Canada. Abstract 571a.
. Jacobson JM, Thompson MA, Lalezari JP, et al. Anti-HIV-1 activity of weekly or biweekly treatment with subcutaneous PRO 140, a CCR5 monoclonal antibody
. J Infect Dis
. 2010 May 15;201(10):1481-7.
. Progenics Pharmaceuticals, Inc. A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Observed Systemic, Long-Acting, Anti-HIV Treatment With a Monoclonal Anti CCR5 Antibody (PRO 140) as an Adjunct to a New, Optimized, Oral Antiretroviral Regimen in HIV-Infected Injection Drug Users With Viral Rebound and Documented Poor Adherence to the Previous Antiretroviral Regimen
. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 5, 2011. NLM Identifier: NCT01272258. Last accessed April 22, 2013.
. Jacobson JM, Lalezari JP, Thompson MA, et al. Phase 2a study of the CCR5 monoclonal antibody PRO 140 administered intravenously to HIV-infected adults
. Antimicrob Agents Chemother
. 2010 Oct;54(10):4137-42.
Last Reviewed: May 29, 2013
Last Updated: May 29, 2013