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 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 (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 PRO-140?
PRO-140 is currently being studied in Phase IIb/III clinical trials.4,8
What are some studies on PRO-140?
Study Names: NCT00642707
Sponsor: CytoDyn, Inc.
Location: United States
- Participants were HIV-infected adults with R5-tropic HIV (virus that uses CCR5 as a co-receptor). If participants had been on antiretroviral therapy (ART) before, they were required to be off ART for at least 12 weeks before starting the study. (ART is the recommended treatment for HIV infection and involves using a combination of different antiretroviral [ARV] drugs to prevent HIV from replicating.)
- Participants had viral load levels (the amount of HIV in a blood sample) of at least 5,000 copies/mL.
- Participants had CD4 counts of at least 300 cells/mm3, and their lowest ever CD4 count was above 250 cells/mm3. (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.)
Purpose: The purpose of this study was to look at the effectiveness, safety, and drug properties of different doses 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.) 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.)9,10
Study Names: (1) PRO 140_CD 01; NCT02175680 and (2) PRO 140_CD 01-Extension; NCT02355184
Sponsor: CytoDyn, Inc.
Location: United States
- Participants were HIV-infected adults with R5-tropic HIV.
- During the 12 months before starting the main study (PRO 140_CD 01), participants had been on ART and had had undetectable viral loads. In the 4 weeks prior to the main study, participants did not change their ART regimens. Also, participants had at least 2 other possible ART regimens that they could consider taking.
- For the main study, participants had viral load levels that were less than 100 copies/mL. Their CD4 counts were greater than 350 cells/mm3, and their lowest ever CD4 count was above 200 cells/mm3.
- Participants who completed 12 weeks of treatment in the main study without having virologic failure were allowed to enroll in the PRO 140_CD 01-Extension study, which is now ongoing. (Virologic failure is when ART cannot suppress a person’s viral load to less than 200 cells/mL.)
Purpose: The purpose of this study and its extension study is 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.11-13
Study Names: PRO 140_CD 02; NCT02483078
Sponsor: CytoDyn, Inc.
Location: United States and Puerto Rico
- Participants are HIV-infected adults with R5-tropic HIV.
- Participants have been on their current ART regimens for at least 3 months. However, these ART regimens are failing, which means the participants’ HIV infections are not being controlled with their current ART regimens.
- Participants have drug resistance to at least 1 drug in 3 different ARV drug classes OR participants have drug resistance to at least 1 drug in 2 different ARV drug classes and have limited treatment options.
- Participants have viral load levels of at least 400 copies/mL at the start of the study and have had detectable viral load levels of more than 50 copies/mL during the 3 months before the study started.
Purpose: 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 ART regimen for 24 weeks. (An optimized ART regimen is a combination of drugs chosen on the basis of a person’s resistance test results and treatment history.)4
* PRO 140_CD 02 is currently recruiting participants.4
- An expanded access study (PRO140 CD02_EA; NCT02759042) will allow for 1 participant who completes the main study (PRO 140_CD 02) to continue to receive PRO-140.
- The company developing PRO-140 is also planning a “roll-over” study that will allow for all ongoing and future participants who successfully complete the main study to continue receiving PRO-140.14,15
Study Names: PRO 140_CD03; NCT02859961
Sponsor: CytoDyn, Inc.
Location: United States
- Participants are adults with CCR5-tropic HIV.
- Participants have been on ART for the past 24 weeks, have had no changes to their ART regimen in the 4 weeks before the study, and have at least 2 possible ART drugs to consider.
- Participants have viral load levels of less than 50 copies/mL at the start of the study. Participants have had CD4 counts greater than 350 cells/mm3 in the 24 weeks before the study and at the start of the study. A participant’s lowest ever CD4 count while on ART has been above 200 cells/mm3.
Purpose: The purpose of this study is to evaluate the safety and effectiveness of PRO-140 monotherapy for the maintenance of viral suppression over 48 weeks.8
* This study is currently recruiting participants.8
Another Phase IIb study (PRO 140 2102; NCT02438345 and NCT01272258) is looking at PRO-140 plus an optimized ART 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 ART. This study is currently recruiting participants.16,17
For more details on the studies listed above, see the Health Professional version.
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 the Phase IIb PRO140_CD 01 study (NCT02175680) and PRO 140_CD 01-Extension study (NCT02355184), there were no drug-related serious side effects and no study discontinuations because of a side effect. All of the reported side effects that were definitely or probably related to PRO-140 were local injection site reactions of mild or moderate severity.11-13
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 December 16, 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 December 16, 2016.
- 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 December 16, 2016.
- 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 December 16, 2016.
- 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 December 16, 2016.
- 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 December 16, 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 December 16, 2016.
- CytoDyn, Inc. A Phase 2b/3, Multicenter Study to Assess the Treatment Strategy of Using PRO 140 SC as Long-Acting Single-Agent Maintenance Therapy for 48 Weeks in Virologically Suppressed Subjects With CCR5-tropic HIV-1 Infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 13, 2016. NLM Identifier: NCT02859961. Available at: https://clinicaltrials.gov/ct2/show/NCT02859961. Last accessed on December 16, 2016.
- 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 December 16, 2016.
- 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 December 16, 2016.
- 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 December 16, 2016.
- 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 160 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 December 16, 2016.
- Lalezari J, Dhody K, Kowalczyk U, Kazempour K, Pourhassan N, Maddon PJ. PRO140 SC Monotherapy (MT) Provides Long-Term, Full Virologic Suppression in HIV Patients. American Society for Microbiology (ASM) Microbe; June 16-20, 2016; Boston, MA. Levin: National AIDS Treatment Advocacy Project (NATAP); HIV Articles; 2016. Available at: http://www.natap.org/2016/HIV/062216_03.htm. Last accessed on December 16, 2016.
- CytoDyn, Inc. An Expanded Compassionate Access Protocol for a Single Subject Who Has Completed 24-Weeks of Treatment in PRO140_CD02 Study. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 19, 2016. NLM Identifier: NCT02759042. Available at: https://clinicaltrials.gov/ct2/show/NCT02759042. Last accessed on December 16, 2016.
- CytoDyn Inc: News Release, dated October 24, 2016. CytoDyn Files Protocol for Extended Access to PRO 140 for Patients Who Reach the End of PRO 140 Pivotal Phase 3 Trial. Available at: http://content.equisolve.net/cytodyn/news/2016-10-24_CytoDyn_Files_Protocol_for_Extended_Access_to_PRO__245.pdf. Last accessed on December 16, 2016.
- 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 December 16, 2016.
- 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. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01272258. Last accessed on December 16, 2016.
Last Reviewed: December 16, 2016