Drug information

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Pronounce:
Other Names:
CCR5-ZFN, CCR5-specific zinc finger protein nuclease, SB-728, SB-728mR modified T cells, SB-728mR-T
Drug Class:
Gene Therapy Products
Registry Number:
S900006290 (ChemID)
Organization:
Sangamo Therapeutics
Phase of Development:

SB-728-T is in Phase 1/2 development for HIV treatment.

(Compound details obtained from ChemIDplus Advanced,1 Treatment Action Group website,2 and Viruses article3)

What is SB-728-T?What is SB-728-T?

What is SB-728-T?

SB-728-T is an investigational gene therapy product that is being studied to treat or possibly cure HIV.2 Gene therapy is a technique that is used to modify genes in order to treat or prevent disease.3

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

How does SB-728-T work?

SB-728-T is an investigational gene therapy product created by changing a gene in immune cells, primarily CD4 T cells.2,4 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.4-8

One way that HIV enters and infects immune cells is by attaching to a specific protein—called a CCR5 receptor—on the immune cell’s surface. In some people, a natural genetic modification disables the CCR5 receptor. People with this modification are less likely to get infected with the most common strain of HIV. SB-728-T treatment changes the gene responsible for the CCR5 receptor and deactivates the CCR5 receptor. By modifying the CCR5 gene, SB-728-T potentially eliminates one way for the most common type of HIV to infect immune cells.3,4,9-11

Which clinical trials are studying SB-728-T?Which clinical trials are studying SB-728-T?

Which clinical trials are studying SB-728-T?

Study Names: SB-728-1101; NCT01543152
Phase: 1/2
Status: This study has been completed.
Location: United States and Puerto Rico
Purpose: The purpose of this study was to find out whether administering cyclophosphamide (an FDA-approved drug for treating cancer) before participants received an SB-728-T infusion was safe and could help the CCR5-modified T cells multiply in the body. Investigators also looked at whether SB-728-T could control viral load levels during a structured treatment interruption of ART.6,12,13

Study Names: TRAILBLAZER; NCT03666871
Phase: 1/2
Status: This study is currently recruiting participants.
Location: United States
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 than participants who receive CD4 cells that are not genetically modified at the CCR5 gene.14

Study Names: SB-728mR-1401; NCT02225665
Phase: 1/2 
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to evaluate the safety of repeated SB-728mR-T infusions that were given to participants who also received cyclophosphamide. (SB-728mR-T is also an SB-728-T gene therapy product.)8

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 planned. These include the following Phase 1 studies:

  • SB-728-0902 (NCT01044654): This is a completed study that evaluated the safety and effectiveness of SB-728-T in participants with HIV who had suboptimal CD4 counts while on ART.4
  • SB-728mR (NCT02388594): This completed study evaluated the safety and effectiveness of SB-728mR-T when it was given with and without cyclophosphamide to participants with HIV who were on ART.7
  • NCT03617198: This study is examining the safety and effectiveness of using a genetically modified T cell product to treat people with HIV. This study is currently recruiting participants.15
  • SB-728-1003 (NCT04201782): This is a long-term follow-up study of participants who have received SB-728-T or SB-728mR-T in a previous trial and completed 3 years of post-infusion follow-up. This study does not involve any treatment. This study has been enrolling by invitation.16
What side effects might SB-728-T cause?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. In the SB-728-1101 (NCT01543152) study described under the previous question, side effects included mild infusion reactions related to SB-728-T, such as low-grade fever and chills. In addition, infusions with SB-728-T were associated with a garlic-like odor.6,17

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?

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 ClinicalInfo 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 more information, visit NIH Clinical Research Trials and You.

ReferencesReferences

References

  1. United States National Library of Medicine. ChemIDplus Advanced: SB-728-T. https://chem.nlm.nih.gov/chemidplus/sid/s900006290. Accessed July 30, 2020
  2. Treatment Action Group website. Research toward a cure trials. http://www.treatmentactiongroup.org/cure/trials. Accessed July 30, 2020
  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. 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 July 30, 2020
  5. 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 July 30, 2020
  6.  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 July 30, 2020
  7.  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 July 30, 2020
  8.  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 July 30, 2020
  9. National Institute of Allergy and Infectious Diseases. Genetic Modification of Cells Proves Generally Safe as HIV Treatment Strategy. ClinicalInfo. Accessed July 19, 2019. https://aidsinfo.nih.gov/news/1433/genetic-modification-of-cells-proves-generally-safe-as-hiv-treatment-strategy. Accessed July 30, 2020
  10. 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 July 30, 2020
  11.  Stan R and Zaia JA. Practical considerations in gene therapy for HIV cure. Curr HIVAIDS Rep. 2014;11(1):11-19.
  12. Baxter Healthcare Corporation. Cyclophosphamide: full prescribing information, March 2017. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid = 6bae5c14-9e87-4fb6-ae9c-4d875c1ecffe. Accessed July 30, 2020
  13. Sangamo Therapeutics: Press Release, dated February 26, 2015. Sangamo BioSciences presents new clinical data at CROI 2015 from trial of ZFP Therapeutic® designed to provide functional control of HIV. https://investor.sangamo.com/news-releases/news-release-details/sangamo-biosciences-presents-new-clinical-data-croi-2015-trial. Accessed July 30, 2020
  14. 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 July 30, 2020
  15. 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 July 30, 2020
  16.  Sangamo Therapeutics. Long-term follow-up of HIV-infected subjects treated with autologous T-cells genetically modified at the CCR5 gene by zinc finger nucleases (SB-728-T or SB-728mR-T). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 13, 2019. NLM Identifier: NCT04201782. https://clinicaltrials.gov/ct2/show/record/NCT04201782. Accessed July 30, 2020
  17.  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 July 30, 2020  

Last Reviewed: July 30, 2020