Drug Database: Leronlimab

What is leronlimab?What is leronlimab?

What is leronlimab?

Leronlimab is an investigational drug that is being studied to treat HIV infection.² 

Leronlimab belongs to a group of HIV drugs called CCR5 antagonists.² CCR5 antagonists 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.

Studies indicate that leronlimab may be effective against R5-tropic virus that is resistant to maraviroc (brand name: Selzentry).^7,8

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

Select clinical trials of leronlimabSelect clinical trials of leronlimab

Select clinical trials of leronlimab

Study Name: NCT00642707

Phase: 2a
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to evaluate the antiviral activity, safety, and pharmacokinetics of multiple subcutaneous doses of leronlimab monotherapy.^9,10
Selected Study Results: Results published in The Journal of Infectious Diseases (2010) showed that leronlimab had substantial and prolonged activity against HIV. The level of antiviral response increased as the total amount of leronlimab administered over the treatment period increased. The greatest antiviral effect was seen with leronlimab 324 mg weekly, producing an average maximum reduction in viral load of 1.65 log₁₀ copies/mL.¹⁰

Study Names: (1) PRO 140_CD 01; NCT02175680 and (2) PRO 140_CD 01-Extension; NCT02355184

Phase: 2b
Status: PRO 140_CD 01 has been completed. The status of PRO 140_CD 01-Extension is unknown.
Location: United States
Purpose: The purpose of the PRO 140_CD 01 study was to evaluate the safety and efficacy of leronlimab monotherapy for the maintenance of viral suppression in participants who had undetectable viral load levels on ART. The PRO 140_CD 01-Extension study is evaluating the long-term effectiveness and safety of leronlimab monotherapy for HIV treatment.^8,11,12
Selected Study Results: Results published in HIV Clinical Trials (2018) showed that in the CD01 study, 23 out of 41 participants (56.1%) maintained viral suppression throughout the 12 week monotherapy treatment phase. Eighteen participants did not maintain suppression during the treatment phase, with a mean time to viral rebound of 51.3 days since the initiation of leronlimab monotherapy.⁸ Results published in PLoS Pathogens (2022) showed that in the CD01 Extension study, five participants have maintained viral suppression on leronlimab monotherapy for over 7 years.¹³

Study Names: (1) PRO 140_CD 02; NCT02483078 and (2) PRO 140_CD 02 Extension; NCT02990858 and (3) PRO 140_CD02_OpenLabel; NCT03902522

Phase: 2b/3
Status: PRO 140_CD 02 has been completed. The status of the PRO 140_CD 02 Extension and PRO 140_CD02_OpenLabel trials are unknown.
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. PRO 140_CD02_OpenLabel is a single-arm open-label trial.^14–16
Selected Study Results: Results from the CD 02 trial presented at ASM Microbe 2019 showed that 64% of participants who received a single subcutaneous dose of leronlimab had a significant reduction in viral load levels from baseline after 1 week, as compared to 23% of participants who received placebo.¹⁷

Study Names: PRO 140_CD03; NCT02859961 and (2) PRO 140_CD03 Extension; NCT05271370

Phase: 2b/3
Status: The status of the PRO 140_CD03 and PRO 140_CD03 Extension trials are unknown.
Location: United States
Purpose: The purpose of the PRO 140_CD03 study is to evaluate the safety and effectiveness of leronlimab monotherapy for the maintenance of viral suppression in participants who had undetectable viral load levels on ART. The PRO 140_CD03 Extension study is evaluating the long-term safety and effectiveness of leronlimab monotherapy.^4,18
Selected Study Results: Preliminary results presented at CROI 2019 indicated that the majority of participants who received higher weekly subcutaneous doses of leronlimab (525 mg and 700 mg) were able to maintain viral suppression.¹⁹

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?

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 2a study, the most common side effects 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.¹⁰

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

Safety data from 41 participants in the CD_01 study and 16 participants in the CD_01-Extension study found no serious side effects related to leronlimab treatment or study discontinuations due to a side effect. In both studies, mild and temporary local injection site reactions accounted for all of the side effects that were related to the study drug.^8,11,12

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

In the CD_02 study, 52 participants were randomly assigned to either the leronlimab or placebo group. Final results from the study showed that 65.4% of participants experienced at least one side effect and 19.23% of participants had at least one treatment-related side effect. One participant discontinued treatment because of a side effect. No treatment-related serious side effects were reported. Injection site reactions that occurred during the study were mostly mild and went away on their own. Forty participants have enrolled into the CD_02 Extension study.^14,15,17

PRO 140_CD03 (NCT02859961)

In the CD03 trial of leronlimab monotherapy, preliminary data was presented on 226 participants in the 350-mg dose group, 115 participants in the 525-mg dose group, and 43 participants in the 700-mg dose group. Thus far, the incidence and severity of side effects have not increased with the dose. Most side effects were mild in intensity and no side effect pattern was observed. None of the serious side effects that occurred were related to leronlimab. The majority of injection site reactions were mild and went away on their own.^4,19

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?

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

More information about leronlimab-related research studies is available from ClinicalTrials.gov. (The ClinicalTrials.gov search can be modified so that you can get results that better match your interests.)

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 more information, visit NIH Clinical Research Trials and You.

ReferencesReferencesv

References

1. National Center for Biotechnology Information. PubChem Substance Record for SID 135308456, Leronlimab [USAN], Source: ChemIDplus. Accessed May 6, 2024
2. Jefferys R. The antiretroviral therapy pipeline 2023. Treatment Action Group Pipeline Report 2023. Accessed May 6, 2024
3. American Medical Association website. Statement on a nonproprietary name adopted by the USAN Council: Leronlimab. Accessed May 6, 2024
4. 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. Accessed May 6, 2024
5. CytoDyn Inc.: Press release, dated March 30, 2022. CytoDyn announces partial clinical hold of HIV program and full clinical hold of COVID-19 program. Accessed May 6, 2024
6. CytoDyn Inc.: Press release, dated February 29, 2024. CytoDyn announces FDA has lifted clinical hold. Accessed May 6, 2024
7. 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. Accessed May 6, 2024
8. Dhody K, Pourhassan N, Kazempour K, et al. PRO 140, a monoclonal antibody targeting CCR5, as a long-acting, single-agent maintenance therapy for HIV-1 infection. HIV Clin Trials. 2018;19(3):85-93. doi:10.1080/15284336.2018.1452842. Accessed May 6, 2024
9. 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. Accessed May 6, 2024
10. 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. Accessed May 6, 2024
11. 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. Accessed May 6, 2024
12. 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. Accessed May 6, 2024
13. Chang XL, Reed JS,  Webb GM, et al. Suppression of human and simian immunodeficiency virus replication with the CCR5-specific antibody leronlimab in two species. PLoS Pathog. 2022;18(3). Accessed May 6, 2024
14. 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. Accessed May 6, 2024
15. 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. Accessed May 6, 2024
16. CytoDyn, Inc. A multi-center, two-part, single-arm, open label, 25-week trial with PRO 140 in treatment-experienced HIV-1 subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 2, 2019. NLM Identifier: NCT03902522. Accessed May 6, 2024
17. Dhody K, Kazempour K, Pourhassan N, Maddon PJ. Final results of the pivotal study of PRO 140 SC in heavily treatment-experienced HIV patients. Poster presented at: American Society for Microbiology (ASM) Microbe; June 20-24, 2019; San Francisco, CA. Poster AAR-713. Accessed May 6, 2024
18. CytoDyn, Inc. An extension protocol for virologically suppressed subjects who successfully completed PRO140_CD03 study. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 13, 2022. NLM Identifier: NCT05271370. Accessed May 6, 2024
19. Dhody K, Kazempour K, Pourhassan N, Maddon PJ. PRO 140 (leronlimab) SC: long-acting single-agent maintenance therapy (SAMT) for HIV-1 infection. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 4-7, 2019; Seattle, WA. Poster 486. Accessed May 6, 2024