Other Names: PA14
Drug Class: Entry Inhibitor
Registry Number: 674782-26-4 (CAS)
Organization: CytoDyn, Inc.
Phase of Development: IIb/III
(Compound details obtained from ChemIDplus Advanced1, NIAID Therapeutics Database2, and CytoDyn website3, and ClinicalTrials.gov4)
What Is PRO-140?
PRO-140 is an investigational drug that is being studied to treat HIV.
PRO-140 belongs to a class (group) of HIV drugs called CCR5 antagonists.4 CCR5 antagonists work 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 This prevents HIV from multiplying and can reduce the amount of HIV in the body.
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
Which Clinical Trials Are Studying PRO-140?
Study Name: NCT00642707
Status: This study has been completed.
Location: United States
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 subcutaneousinfusion. (A subcutaneous infusion is an injection placed under the skin to deliver a drug or other fluids over a period of time.)8,9
Study Names: (1) PRO 140_CD 01; NCT02175680 and (2) PRO 140_CD 01-Extension; NCT02355184
Status: (1) PRO 140_CD 01 has been completed and (2) PRO 140_CD 01-Extension is ongoing, but not recruiting participants.
Location: United States
Purpose: The purpose of the PRO 140_CD 01 study was to evaluate whether certain individuals who already had undetectable viral loads could take a planned temporary break from their daily ART by using PRO-140 to maintain viral suppression. The PRO 140_CD 01-Extension study is evaluating the long-term effectiveness and safety of taking only PRO-140 for HIV treatment.10-12
Study Names: (1) PRO 140_CD 02; NCT02483078 and (2) PRO 140_CD 02 Extension; NCT02990858
Status: (1) PRO 140_CD 02 is ongoing, but not recruiting participants and (2) PRO 140_CD 02 Extension is enrolling participants by invitation.
Location: United States and Puerto Rico
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.) PRO 140_CD 02 Extension is designed to provide eligible participants with continued access to PRO-140.4,13
Study Names: PRO 140_CD03; NCT02859961
Status: This study is currently recruiting participants.
Location: United States
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.7
For more details on the studies listed above, see the Health Professional version.
What Side Effects Might PRO-140 Cause?
One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in some of the studies of PRO-140 listed above.
In this Phase IIa study, 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.9
There were no drug-related serious side effects and no participants dropped out of the study 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.10-12
Researchers presented an update on the ongoing CD 01-Extension study in February 2017. At the time of the update, 10 participants were still receiving PRO-140, with 9 participants close to completing 2 years of treatment. PRO-140 continued to be generally well tolerated, with no drug-related side effects. No participants have dropped out of the study due to a treatment-related side effect.14
A June 2018 safety analysis looked at data from the CD 02 study. None of the participants dropped out of the study due to side effects and there were no drug-related serious side effects. Injection site reactions, which were described as infrequent and mild, occurred in less than 10% of study participants. These reactions were temporary and went away on their own. So far, the CD 02 Extension study has enrolled 35 participants.4,13,15
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 AIDS_info_ 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. Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a clinical trial is right for you. For information, visit NIH Clinical Research Trials and You.
- United States National Library of Medicine. ChemIDplus Advanced. Available at: https://chem.sis.nlm.nih.gov/chemidplus/rn/674782-26-4. Last accessed on June 19, 2018.
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on June 19, 2018.
- CytoDyn, Inc.: Press Release, dated July 30, 2012. CytoDyn announces entry into agreement with Progenics Pharmaceuticals, Inc. to acquire PRO 140. Available at: www.cytodyn.com/media/press-releases/detail/33/cytodyn-announces-entry-into-agreement-with-progenics. Last accessed on June 19, 2018. [Archived at WebCite]
- 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: www.clinicaltrials.gov/ct2/show/NCT02483078. Last accessed on June 19, 2018.
- 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: www.ncbi.nlm.nih.gov/pmc/articles/PMC113953/. Last accessed on June 19, 2018.
- 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: www.ncbi.nlm.nih.gov/pmc/articles/PMC1610098/. Last accessed on June 19, 2018.
- 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 June 19, 2018.
- 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: www.clinicaltrials.gov/ct2/show/NCT00642707. Last accessed on June 19, 2018.
- 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: www.ncbi.nlm.nih.gov/pmc/articles/PMC2856743/. Last accessed on June 19, 2018.
- 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: www.clinicaltrials.gov/ct2/show/NCT02175680. Last accessed on June 19, 2018.
- 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: www.clinicaltrials.gov/ct2/show/NCT02355184. Last accessed on June 19, 2018.
- 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: www.natap.org/2016/HIV/062216_03.htm. Last accessed on June 19, 2018. [Archived at WebCite]
- CytoDyn, Inc. An extension protocol for subjects who successfully completed PRO140_CD02 study. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 17, 2016. NLM Identifier: NCT02990858. Available at: www.clinicaltrials.gov/ct2/show/NCT02990858. Last accessed on June 19, 2018.
- Lalezari J, Dhody K, Kowalczyk U, Kazempour K, Pourhassan N, Maddon PJ. PRO140 single-agent maintenance therapy for HIV-1 infection: a 2-year update. Abstract presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 13-16, 2017; Seattle, WA. Abstract 437. Available at: www.croiconference.org/sessions/pro140-single-agent-maintenance-therapy-hiv-1-infection-2-year-update. Last accessed on June 19, 2018. [Archived at WebCite]
- Dhody K, Kazempour K, Pourhassan N, Maddon PJ. Primary efficacy results of PRO 140 SC in a pivotal Phase 2b/3 study in heavily treatment-experienced HIV-1 patients. American Society for Microbiology (ASM) Microbe; June 7-11, 2018; Atlanta, GA. Mascolini: ASM - Primary Efficacy Results of PRO 140 SC in a Pivotal Phase 2b/3 Study in Heavily Treatment-Experienced HIV-1 Patients; HIV Articles; 2018. Available at: www.natap.org/2018/HIV/061118_02.htm. Last accessed on June 19, 2018. [Archived at WebCite]
[Note from TheBody.com: This article was created by AIDSinfo, who last updated it on June 19, 2018. We have cross-posted it with their permission.]