Drugs

Leronlimab

Leronlimab

Other Names: PA14, PRO-140 Drug Class: CCR5 Antagonist Molecular Formula: C6534 H10036 N1720 O2040 S42 (non glycosylated) Registry Number: 674782-26-4 (CAS) Chemical Name: Immunoglobulin G4, anti-(human Chemokine receptor CCR5) (humanized monoclonal PRO 140 γ4-chain), disulfide with humanized monoclonal PRO 140 κ-chain, dimer Organization: CytoDyn, Inc. Phase of Development: Leronlimab is in Phase IIb/III development for HIV treatment.

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 American Medical Association website,3 and ClinicalTrials.gov4)

What is leronlimab?

What is leronlimab?

Leronlimab is an investigational drug that is being studied to treat HIV infection

Leronlimab belongs to a 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 leronlimab 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.6

Research may prove that leronlimab 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

To learn about how investigational drugs are tested during clinical trials, read the AIDSinfo What is an Investigational HIV Drug? and HIV/AIDS Clinical Trials fact sheets.

Which clinical trials are studying leronlimab?

Which clinical trials are studying leronlimab?

Study Name: NCT00642707
Phase: IIa
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 leronlimab and compare leronlimab to a placebo. Leronlimab was given without any other HIV medicines and by subcutaneous infusion.7,8

Study Names: (1) PRO 140_CD 01; NCT02175680 and (2) PRO 140_CD 01-Extension; NCT02355184
Phase: IIb
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 load levels could take a planned temporary break from their daily ART by using leronlimab to maintain viral suppression. The PRO 140_CD 01-Extension study is evaluating the long-term effectiveness and safety of taking only leronlimab for HIV treatment.9–11

Study Names: (1) PRO 140_CD 02; NCT02483078 and (2) PRO 140_CD 02 Extension; NCT02990858
Phase: IIb/III
Status: (1) PRO 140_CD 02 has been completed and (2) PRO 140_CD 02 Extension is enrolling participants by invitation.
Location: United States and Puerto Rico
Purpose: The purpose of the PRO 140_CD 02 study was to look at the safety and effectiveness of using leronlimab with a failing ART regimen for 1 week and then using leronlimab with an optimized ART regimen for 24 weeks. PRO 140_CD 02 Extension is designed to provide eligible participants with continued access to leronlimab.4,12

Study Names: PRO 140_CD03; NCT02859961
Phase: IIb/III
Status: This study is currently recruiting participants.
Location: United States
Purpose: The purpose of this study is to evaluate the safety and effectiveness of leronlimab monotherapy for the maintenance of viral suppression over 48 weeks.13

For more details on the studies listed above, see the Health Professional version of this drug summary.

What side effects might leronlimab cause?

What side effects might leronlimab 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 leronlimab listed above.

NCT00642707:

In this Phase IIa study, the most common side effects reported that were associated with either placebo or leronlimab 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

PRO140_CD 01 (NCT02175680) and PRO 140_CD 01-Extension (NCT02355184):

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 leronlimab were local injection site reactions of mild or moderate severity.9,10,14

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 leronlimab, with nine participants close to completing 2 years of treatment. Leronlimab 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.11

PRO 140_CD 02 (NCT02483078); PRO 140_CD 02 Extension (NCT02990858):

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.4,12,15

Because leronlimab is still being studied, information on possible side effects of the drug is not complete. As testing of leronlimab continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying leronlimab?

Where can I get more information about clinical trials studying leronlimab?

More information about leronlimab-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.

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.

References

References

  1. United States National Library of Medicine. ChemIDplus Advanced: leronlimab. https://chem.nlm.nih.gov/chemidplus/rn/674782-26-4. Accessed February 25, 2019.
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed February 25, 2019.
  3. American Medical Association website. Statement on a nonproprietary name adopted by the USAN Council: Leronlimab. https://searchusan.ama-assn.org/undefined/documentDownload?uri=%2Funstructured%2Fbinary%2Fusan%2Fleronlimab.pdf. Accessed February 25, 2019.
  4. 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. https://clinicaltrials.gov/ct2/show/NCT02483078. Accessed February 25, 2019.
  5. 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;75(2):579-588. doi:10.1128/JVI.75.2.579-588.2001. Accessed February 25, 2019.
  6. 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;50(10):3289-3296. doi:10.1128/AAC.00699-06
  7. 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. https://clinicaltrials.gov/ct2/show/NCT00642707. Accessed February 25, 2019.
  8. 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;201(10):1481-1487. doi:10.1086/652190
  9. 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. https://clinicaltrials.gov/ct2/show/NCT02175680. Accessed February 25, 2019.
  10. 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. https://clinicaltrials.gov/ct2/show/NCT02355184. Accessed February 25, 2019.
  11. 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. http://www.croiconference.org/sessions/pro140-single-agent-maintenance-therapy-hiv-1-infection-2-year-update. Accessed February 25, 2019.
  12. 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. https://clinicaltrials.gov/ct2/show/NCT02990858. Accessed February 25, 2019.
  13. 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. https://clinicaltrials.gov/ct2/show/NCT02859961. Accessed February 25, 2019.
  14. 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. http://www.natap.org/2016/HIV/062216_03.htm. Accessed February 25, 2019.
  15. 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. http://www.natap.org/2018/HIV/061118_02.htm. Accessed February 25, 2019.

Last Reviewed: February 25, 2019