Drug information

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Pronounce:
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 2b/3 development for HIV treatment.

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

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.2

Research may prove that leronlimab is a safe and effective option for treating people with R5-tropic virus (a strain of HIV), including those for whom other entry and fusion inhibitors, such as maraviroc (brand name: Selzentry), are not working.5

To learn about how investigational drugs are tested during clinical trials, read the HIVinfo 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?

Which clinical trials are studying leronlimab?

Study Name: NCT00642707
Phase: 2a
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.6,7

Study Names: (1) PRO 140_CD 01; NCT02175680 and (2) PRO 140_CD 01-Extension; NCT02355184
Phase: 2b
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.8-10

Study Names: (1) PRO 140_CD 02; NCT02483078 and (2) PRO 140_CD 02 Extension; NCT02990858and (3) PRO 140_CD02_OpenLabel; NCT03902522
Phase: 2b/3
Status: (1) PRO 140_CD 02 has been completed, (2) PRO 140_CD 02 Extension is enrolling participants by invitation and (3) PRO 140_CD02_OpenLabel is currently recruiting participants.
Location: United States and Puerto Rico
Purpose: The purpose of thePRO 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.11-13

Study Names: PRO 140_CD03; NCT02859961
Phase: 2b/3
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.4

For more details on the studies listed above, see the Health Professional versionof 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 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.7

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 treatment with leronlimab or study discontinuations due to a side effect. In both studies, mild and transient local injection site reactions accounted for all of the side effects that were related to the study drug.8-10

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

In the CD_02 study, 52 participants were randomly assigned to either the PRO 140 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 self-resolving. Forty participants have enrolled into the CD_02 Extension study.11,12,14

PRO 140_CD03 (NCT02859961):
In the ongoing 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 resolved on their own.4,15

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?

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

More information about leronlimab-related research studies is available from ClinicalTrials.gov.

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.

ReferencesReferences

References

  1. United States National Library of Medicine. ChemIDplus Advanced: leronlimab. https://chem.nlm.nih.gov/chemidplus/rn/674782-26-4. Accessed December 3, 2019
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed December 3, 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=/unstructured/binary/usan/leronlimab.pdf. Accessed December 3, 2019
  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. https://clinicaltrials.gov/ct2/show/NCT02859961. Accessed December 3, 2019
  5. 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
  6. 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 December 3, 2019
  7. 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
  8. 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 December 3, 2019
  9. 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 December 3, 2019
  10. 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
  11. 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 December 3, 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 December 3, 2019
  13. 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. https://clinicaltrials.gov/ct2/show/NCT03902522. Accessed December 3, 2019
  14. 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. https://content.equisolve.net/_0fabb8b784fee97a4a4b390ab5453a6b/cytodyn/db/193/2464/pdf/CytoDyn - ASM 2019 Poster Presentation re CD02_Final.pdf. Accessed December 3, 2019
  15. 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 December 3, 2019

Last Reviewed: December 3, 2019