Drugs

SB-728-T

SB-728-T

Other Names: CCR5-ZFN, CCR5-specific zinc finger protein nuclease, SB-728, SB-728mR, SB-728mR-T Drug Class: Gene Therapy Products Registry Number: S900006290 (ChemID) Organization: Sangamo Therapeutics Phase of Development: SB-728-T is in Phase I/II development for HIV treatment.

(Compound details obtained from ChemIDplus Advanced,1 Treatment Action Group 2017 Pipeline Report,2 Viruses article,3 and Sangamo Therapeutics website4)

What is SB-728-T?

What is SB-728-T?

SB-728-T is an investigational gene therapy product. Gene therapy is an experimental technique that uses short sections of genetic material to treat or prevent disease. SB-728-T is being studied for its ability to help CD4 cells survive during HIV infection and as a possible strategy to cure HIV 3,5–9

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

How does SB-728-T work?

How does SB-728-T work?

SB-728-T is a gene therapy product created by changing a gene in immune cells, primarily CD4 T cells.

One way that HIV enters and infects immune cells, such as CD4 T cells, is by attaching to a specific protein—called a CCR5 receptor—on the immune cell surface. In some people, the CCR5 receptor is naturally genetically modified. People with this gene modification are more resistant to infection with the most common strain of HIV. SB-728-T treatment changes the gene responsible for the CCR5 receptor and makes the CCR5 receptor non-functional. By modifying the CCR5 gene, SB-728-T potentially eliminates one way for the most common type of HIV to attach to and infect immune cells.3,5,10–12

SB-728-T is being studied for its ability to restore immune function and as a possible strategy to cure HIV.

Which clinical trials are studying SB-728-T?

Which clinical trials are studying SB-728-T?

Study Names: SB-728-0902; NCT01044654
Phase: I
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to look at the safety and effectiveness of intravenous (IV) infusions of SB-728-T in people with HIV.5,6,13,14

Study Names: SB-728-1101; NCT01543152
Phase: I/II
Status: This study has been completed.
Location: United States and Puerto Rico
Purpose: The purpose of this study was to look at whether giving different doses of IV cyclophosphamide (an FDA-approved drug for treating cancer) before participants received an SB-728-T infusion could help the CCR5-modified cells multiply and produce new cells in the body. Investigators also looked at how cyclophosphamide given before SB-728-T affected viral load levels during a treatment interruption of ART.7

Study Names: TRAILBLAZER; NCT03666871
Phase: I/II
Status: This study is not yet recruiting.
Purpose: The purpose of this study is to see whether participants who receive SB-728-T will have a greater reduction in the size of the latent HIV reservoir when compared to participants who receive unmodified CD4 cells.15

Study Names: SB-728mR-1401; NCT02225665
Phase: I/II
Status: This study is ongoing, but not recruiting participants.
Location: United States
Purpose: The purpose of this study is to evaluate the safety and effects of repeated infusions of SB-728mR-T that are given to people with HIV after they receive cyclophosphamide. (SB-728mR-T is also an SB-728-T gene therapy product.)9,16

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

Other studies on SB-728-T gene therapy have been completed or are currently recruiting participants. These include the following 2 ongoing Phase I studies: (1) NCT02388594, which is looking at SB-728mR-T given with and without cyclophosphamide beforehand in participants with HIV who are on ART, and (2) NCT03617198, which is a pilot study examining T-cells modified by a certain type of SB-728-T in adults with HIV.8,17

What side effects might SB-728-T cause?

What side effects might SB-728-T 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 SB-728-T listed above.

NCT01044654 and NCT01543152:
In these studies, SB-728-T was associated with some mild, reversible, infusion-related side effects. Mild infusion reactions related to SB-728-T, such as low-grade fever and chills, were reported in the SB-728-1101 study. In addition, a garlic-like odor has been associated with SB-728-T infusions.5,7,18–20

NCT00842634:
In this Phase I study, one serious side effect related to SB-728-T infusion was reported.20

Because SB-728-T is still being studied, information on possible side effects of the drug is not complete. As testing of SB-728-T continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying SB-728-T?

Where can I get more information about clinical trials studying SB-728-T?

More information about SB-728-T-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: SB-728-T. https://chem.nlm.nih.gov/chemidplus/sid/s900006290. Accessed October 1, 2018.
  2. Frick M, Gaudino A, Harrington M, et al. Treatment Action Group. 2017 pipeline report. http://www.pipelinereport.org/sites/default/files/2017%20Pipeline%20Report%20Final.pdf. Published July 2017. Accessed October 1, 2018.
  3. Manjunath N, Yi G, Dang Y, Shankar P. Newer gene editing technologies toward HIV gene therapy. Viruses. 2013;5(11):2748-2766.
  4. Sangamo Therapeutics website. HIV. Sangamo Therapeutics, Inc. https://www.sangamo.com/product-pipeline/hiv. Accessed October 1, 2018.
  5. Sangamo Therapeutics. A Phase 1 dose escalation, single dose study of autologous T-cells genetically modified at the CCR5 gene by zinc finger nucleases SB-278 in HIV-infected patients who have exhibited suboptimal CD4+ T-cell gains during long-term antiretroviral therapy. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 6, 2010. NLM Identifier: NCT01044654. https://clinicaltrials.gov/ct2/show/NCT01044654. Accessed October 1, 2018.
  6. Ando D. Functional control of viremia in CCR5-Δ32 heterozygous (Δ32HZ) HIV+ subjects following adoptive transfer of zinc finger nuclease CCR5 modified autologous CD4 T-cells (SB-728-T). Annual Meeting of the European Society of Gene and Cell Therapy (ESGCT and SETGyC Collaborative Congress); October 25-28, 2013; Madrid, Spain. National AIDS Treatment Advocacy Project (NATAP): HIV Articles. http://www.natap.org/2013/HIV/103013_01.htm. Accessed October 1, 2018.
  7. Sangamo Therapeutics. A Phase I, open-label study to assess the effect of escalating doses of cyclophosphamide on the engraftment of SB-728-T in viremic HIV-infected subjects on HAART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 1, 2012. NLM Identifier: NCT01543152. https://clinicaltrials.gov/ct2/show/NCT01543152. Accessed October 1, 2018.
  8. University of Pennsylvania. A Phase I study of T-cells genetically modified at the CCR5 gene by zinc finger nucleases SB-728mR in HIV-infected patients, with or without the CCR5 delta-32 mutation, pre-treated with cyclophosphamide. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 24, 2015. NLM Identifier: NCT02388594. https://clinicaltrials.gov/ct2/show/NCT02388594. Accessed October 1, 2018.
  9. Sangamo Therapeutics. A Phase 1/2, open-label study to assess the safety and tolerability of repeat doses of autologous T-cells genetically modified at the CCR5 gene by zinc ginger nucleases in HIV-infected subjects following cyclophosphamide conditioning. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 22, 2014. NLM Identifier: NCT02225665. https://clinicaltrials.gov/ct2/show/NCT02225665. Accessed October 1, 2018.
  10. National Institute of Allergy and Infectious Diseases (NIAID). News release: genetic modification of cells proves generally safe as HIV treatment strategy.https://www.niaid.nih.gov/news-events/genetic-modification-cells-proves-generally-safe-hiv-treatment-strategy. Published March 5, 2014. Accessed October 1, 2018.
  11. Sheehy J, Zack J, Kiem HP, Handibode J. Cell/gene therapy—HIV cure research training curriculum. Located on the AVAC website (http://www.avac.org/cure-curriculum/module3), under PowerPoint. http://www.avac.org/sites/default/files/u16/Gene_Cell_Therapy_July.pptx. Accessed October 1, 2018.
  12. Stan R and Zaia JA. Practical considerations in gene therapy for HIV cure. Curr HIVAIDS Rep. 2014;11(1):11-19.
  13. Zeidan J, Lee G, Lalezari J, et al. Host immune environment significantly impact the level of CD4 reconstitution and the effects on latent reservoir in HIV subjects receiving ZFN CCR5 modified CD4 T-cells (SB-728-T). Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 10-13, 2013; Denver CO. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2013. http://www.natap.org/2013/ICAAC/ICAAC_57.htm. Accessed October 1, 2018.
  14. Zeidan J, Lee G, Lalezari J, et al. Host immune environment significantly impact the level of CD4 reconstitution and the effects on latent reservoir in HIV subjects receiving ZFN CCR5 modified CD4 T-cells (SB-728-T). Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 10-13, 2013; Denver CO. Abstract H-674. http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=1f74ce30-35e8-4251-b7b0-bb02b15f73df&cKey=457629d2-01e5-4baf-b4da-5544a73df974&mKey=%7b7DD36E88-52C3-4FF1-A5DF-1D00766558B8%7d. Accessed October 1, 2018.
  15. Case Western Reserve University. T-cell reinfusion after interfering with lymphocyte binding location of AIDS virus through zinc-finger-nuclease elimination of CCR5 receptors: The TRAILBLAZER Study. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 7, 2018. NLM Identifier: NCT03666871. https://clinicaltrials.gov/ct2/show/NCT03666871. Accessed October 1, 2018.
  16. Sangamo Therapeutics. Press Release: Sangamo BioSciences ZFP therapeutic program in HIV/AIDS featured at three major scientific conferences in October 2014.https://investor.sangamo.com/press-releases/detail/259/sangamo-biosciences-zfp-therapeutic-program-in-hivaids. Published October 16, 2014. Accessed October 1, 2018.
  17. University of Pennsylvania. A pilot study of T cells genetically modified by zinc finger nucleases SB-728mR, C34-peptide conjugated to the CXCR4 N-terminus, and CD4 chimeric antigen receptor in HIV-infected subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 9, 2018. NLM Identifier: NCT03617198. https://clinicaltrials.gov/ct2/show/ NCT03617198. Accessed October 1, 2018.
  18. Mitsuyasu R, Lalezari J, Deeks S, et al. Adoptive transfer of zinc finger nuclease (ZFN) modified autologous CD4 T-cells to aviremic HIV-infected subjects with suboptimal CD4 counts. Abstract presented at: Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 17-20, 2011; Chicago, IL. Abstract H1-375. http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=d4df5ac5-0855-47ac-9c87-f2c16aaeb7a9&cKey=72e47ff3-2053-458c-8d9c-3d32c27184a9&mKey=%7b0C918954-D607-46A7-8073-44F4B537A439%7d. Accessed October 1, 2018.
  19. Blick G, Lalezari J, Hsu R, et al. A dose escalation study of cyclophosphamide (CTX) to enhance SB-728-T engraftment. Conference on Retroviruses and Opportunistic Infections; February 23-26, 2015; Seattle, WA. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2015. http://www.natap.org/2015/CROI/croi_81.htm. Accessed October 1, 2018.
  20. Tebas P, Stein D, Tang WW, et al. Gene Editing of CCR5 in Autologous CD4 T Cells of Persons Infected with HIV. N Engl J Med. 2014;370(10):901-910.

Last Reviewed: October 1, 2018