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 a protein on the surface of the immune cells. The protein is called the CCR5 co-receptor. When PRO-140 attaches to the CCR5 co-receptor, certain strains of HIV—called R5-tropic virus—cannot attach to, enter, or infect the cell.5
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.6
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.7
- 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.7
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.7
In what phase of testing is PRO-140?
PRO-140 is currently being studied in a Phase IIb/III clinical trial.2,4
What are some studies on PRO-140?
Study Names: NCT00642707
Location: Not available
Participants: HIV-infected adults with R5-tropic HIV (virus that uses CCR5 as a co-receptor). Some 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.
Purpose: The purpose of this study was to look at the antiviral activity and safety of PRO-140 and compare PRO-140 to a placebo. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.)
Study Design: 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.) 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.
- PRO-140 at all of the doses studied was shown to have significant antiviral activity. Participants in the group receiving 324 mg of PRO-140 weekly had the greatest reduction in viral load (the amount of HIV in a blood sample). The same group had greater reductions in viral load in the least amount of time when compared to the other dose groups.
- In terms of safety, PRO-140 was generally well tolerated. No drug-related serious side effects occurred.8-10
: (1) PRO 140_CD 01; NCT02175680 and (2) PRO 140_CD 01-Extension; NCT02355184
: Not available
: HIV-infected, treatment-experienced adults with R5-tropic HIV. Participants were on antiretroviral therapy
(ART) for the last 12 months and had undetectable viral loads for the last 12 months.
: The purpose of this study was to evaluate whether certain individuals who already have undetectable viral loads might be able to take a planned temporary break from their daily ART by using PRO-140 as a treatment substitution to maintain viral suppression
- Participants received 350 mg of PRO-140 monotherapy, given weekly by subcutaneous injection for 12 weeks. (The total treatment duration with PRO-140 was 14 weeks. There were 1-week overlaps at the beginning of the study and at the end of the study during which participants received ART along with PRO-140.)
- Participants who completed 12 weeks of PRO-140 monotherapy while maintaining viral load control could enroll in an extension study (PRO 140_CD 01-Extension; NCT02355184). During the extension study, participants will receive PRO-140 monotherapy for an additional 24 weeks. (The total treatment duration with PRO-140 during the extension study will be up to 25 weeks, with a 1-week overlap of ART and PRO-140 at the end of the extension phase.)
- The company developing PRO-140 has reported results on the effectiveness of PRO-140 monotherapy during both the 14-week study and the extension study. Further details about the results beyond what was provided in the company’s press releases are not yet available.11-15
: PRO 140_CD 02; NCT02483078
: Not available
: HIV-infected, treatment-experienced adults who have R5-tropic HIV. Participants’ HIV infections are not being controlled with their current ART regimens (also called a failing ART regimen), and participants have limited treatment options.
: The purpose of this study is to look at the safety and effectiveness of using PRO-140 with a failing ART regimen for 1 week and then using PRO-140 with an optimized antiretroviral regimen for 24 weeks. (An optimized antiretroviral regimen is a combination of drugs chosen on the basis of a person’s resistance test results and treatment history.)
Part 1: For 1 week, participants continue their failing ART regimens and receive one dose of either PRO-140 or placebo via subcutaneous injection.
Part 2: For 24 weeks, participants receive an optimized antiretroviral regimen plus either PRO-140 or placebo weekly via subcutaneous injection.16
(This study does not have results yet.)
Another Phase IIb study will be looking at subcutaneous 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.17
What side effects might PRO-140 cause?
In the Phase IIa study (NCT00642707) discussed under the previous question, the most common side effects reported that were associated with either placebo or PRO-140 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.10
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).18
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.7
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 November 11, 2015.
- 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 November 11, 2015.
- 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 November 11, 2015.
- CytoDyn, Inc. A Multi-center, Randomized, Double-blind, Placebo-controlled Trial, Followed by Single-arm Treatment of PRO 140 in Combination With Optimized Background Therapy in Treatment-Experienced HIV-1 Subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 24, 2015. NLM Identifier: NCT02483078. Available at https://www.clinicaltrials.gov/ct2/show/NCT02483078. Last accessed on November 11, 2015.
- 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 November 11, 2015.
- 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 November 11, 2015.
- 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 November 11, 2015.
- CytoDyn, Inc. A Phase 2a, Randomized, Double-blind, Placebo Controlled Study of PRO 140 by Subcutaneous Administration in Adult Subjects With Human Immunodeficiency Virus Type 1 Infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 21, 2008. NLM Identifier: NCT00642707. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00642707. Last accessed on November 11, 2015.
- 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 November 11, 2015.
- 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 November 11, 2015.
- 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 November 11, 2015.
- CytoDyn, Inc. Extension of Protocol PRO140_CD01 to Evaluate Long-term Suppression of HIV-1 Replication Following Substitution of Stable Combination ART With PRO 140 (Monoclonal CCR5 Antibody) Monotherapy for Additional 24 Weeks in Adult Subjects w/ HIV-1. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 30, 2015. NLM Identifier: NCT02355184. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02355184. Last accessed on November 11, 2015.
- 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 November 11, 2015.
- CytoDyn, Inc.: News, dated February 3, 2015. CytoDyn Concludes Phase 2b Study With 98% Success With 4 Weeks of Monotherapy – Many HIV Patients in Extension Study With Some Approaching 6 Months. Available at: http://content.equisolve.net/cytodyn/news/2015-02-03_CytoDyn_Concludes_Phase_2b_Study_With_98_Success_204.pdf. Last accessed on November 11, 2015.
- CytoDyn, Inc.: News, dated September 21, 2015. HIV Patients Successfully Reach One Year of Virologic Suppression in PRO 140 Monotherapy Study. Available at: http://content.equisolve.net/cytodyn/news/2015-09-21_HIV_Patients_Successfully_Reach_One_Year_of_211.pdf. Last accessed on November 11, 2015.
- Drexel University. A Phase 2b, Randomized, Double-blind, Placebo-controlled Clinical Trial of Observed Systemic, Long-acting, Anti-HIV Treatment With a Monoclonal CCR5 Antibody (PRO 140) as an Adjunct to a New, Optimized, Oral Antiretroviral Regimen in HIV-infected Recreational Drug Users With Viral Rebound and Poor Adherence to the Previous Antiretroviral Regimen. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 6, 2015. NLM Identifier: NCT02438345. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02438345. Last accessed on November 11, 2015.
- 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 November 11, 2015.
Last Reviewed: November 19, 2015