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 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.6
In what phase of testing is PRO-140?
PRO-140 is currently being studied in Phase IIb clinical trials.2
What are some studies on PRO-140?
In a Phase IIa study, the antiviral activity and safety of PRO-140 was compared to that of a 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 without any other HIV medicines (also known as monotherapy) and by subcutaneous infusion. (A subcutaneous infusion is an injection placed under the skin to deliver a drug or other fluids over a period of time.)7,8
Some of the participants had never taken HIV medicines before entering the study (also called treatment-naive), and others had taken HIV medicines previously (also called treatment-experienced). The treatment-experienced participants were required to be off HIV medicines for at least 12 weeks before starting the study. Participants were assigned to one of the following four groups:
- 162 mg of PRO-140 given weekly on Days 1, 8, and 15.
- 324 mg of PRO-140 given every 2 weeks on Days 1 and 15 (placebo given on Day 8).
- 324 mg of PRO-140 given weekly on Days 1, 8, and 15.
- Placebo given weekly on Days 1, 8, and 15.7,8
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
The following two Phase IIb studies of long-acting subcutaneous PRO-140 are also being undertaken:
- One study is looking at how well PRO-140 monotherapy can maintain viral suppression in HIV-infected, treatment-experienced participants. (Viral suppression is when antiretroviral therapy [ART] reduces the amount of HIV in a person’s blood sample to an undetectable level.) Investigators are evaluating whether certain individuals who already have undetectable viral loads might be able to take a planned temporary break from their daily antiretroviral drug regimen by using PRO-140 as a treatment substitution.9,10
- The other study will look at PRO-140 plus an optimized antiretroviral regimen 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. (An optimized antiretroviral regimen is a combination of drugs chosen on the basis of a person’s resistance test results and treatment history.)11
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).12
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. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/674782-26-4. Last accessed on October 22, 2014.
- 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 October 22, 2014.
- CytoDyn, Inc.: Press Release, dated July 30, 2012. CytoDyn Announces Entry into Agreement with Progenics Pharmaceuticals, Inc. to Acquire PRO 140. Available at: http://www.cytodyn.com/media/press-releases/detail/33/cytodyn-announces-entry-into-agreement-with-progenics. Last accessed on October 22, 2014.
- 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. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC113953/. Last accessed on October 22, 2014.
- 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. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1610098/. Last accessed on October 22, 2014.
- National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: http://nih.gov/health/clinicaltrials/index.htm. Last accessed on October 22, 2014.
- Thompson M, Lalezari J, Saag M, et al. Weekly and Biweekly Subcutaneous PRO 140 Demonstrates Potent, Sustained Antiviral Activity. 16th Conference on Retroviruses and Opportunistic Infections (CROI); February 8-11, 2009; Montreal, Canada. Levin: Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2009. Available at: http://www.natap.org/2009/CROI/croi_99.htm. Last accessed on October 22, 2014.
- 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. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856743/. Last accessed on October 22, 2014.
- CytoDyn, Inc. A Phase 2b Study to Assess Suppression of HIV-1 Replication Following Substitution of Stable Combination Antiretroviral Therapy With a PRO 140 (Monoclonal CCR5 Antibody) Monotherapy in Adult Subjects With HIV-1 Infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 24, 2014. NLM Identifier: NCT02175680. Available at: http://www.clinicaltrials.gov/ct2/show/NCT02175680. Last accessed on October 22, 2014.
- CytoDyn, Inc.: Press Release, dated May 14, 2014. CytoDyn Inc. Announces First HIV Patient Dosing With PRO 140 in Phase 2b Clinical Trial for Treatment Substitution Protocol. Available at: http://www.cytodyn.com/media/press-releases/detail/114/cytodyn-inc-announces-first-hiv-patient-dosing-with-pro. Last accessed on October 22, 2014.
- CytoDyn, 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. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01272258. Last accessed on October 22, 2014.
- 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. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2944554/. Last accessed on October 22, 2014.
Last Reviewed: October 22, 2014