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: I/II

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

What is an investigational drug?

What is an investigational drug?

An investigational drug is one that is under study and is not approved by the U.S. Food and Drug Administration (FDA) for sale in the United States. Medical research studies are conducted to evaluate the safety and effectiveness of an investigational drug. These research studies are also called clinical trials. Once an investigational drug has been proven safe and effective in clinical trials, FDA may approve the drug for sale in the United States.

To learn more about investigational drugs, read the AIDSinfo What is an Investigational HIV Drug? fact sheet.

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 genes (short sections of genetic material) to treat or prevent disease. SB-728-T is a gene therapy product created by changing a gene in immune cells, primarily CD4 cells. (CD4 cells are a type of immune cell that HIV attacks and destroys.)3,5

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.5,6

SB-728-T is being studied for its ability to restore immune function and as a possible strategy to cure HIV.3,5,7-10

How is SB-728-T made?

How is SB-728-T made?

SB-728-T is made by first collecting immune cells, such as CD4 cells, from a person with HIV. The cells are sent to a laboratory where they are genetically modified to make the CCR5 receptors nonfunctional. The cells are then stimulated to produce many more immune cells with nonfunctional CCR5 receptors. Finally, the immune cells are infused back into the person. This treatment may provide someone with a population of immune cells that are permanently resistant to HIV strains that use CCR5 as an entryway. The modified immune cells may also produce additional HIV-resistant immune cells in the body.3,5,6

How are clinical trials of investigational drugs conducted?

How are clinical trials of investigational drugs conducted?

Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.11

  • Phase I trials: Researchers test an investigational drug in a small group of people (20–80) for the first time. The purpose is to evaluate its safety and identify side effects.
  • Phase II trials: The investigational drug is administered to a larger group of people (100–300) to determine its effectiveness and to further evaluate its safety.
  • Phase III trials: The investigational drug is administered to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments, and collect information that will allow the investigational drug to be used safely.11

In most cases, an investigational drug must be proven effective and must show continued safety in a Phase III clinical trial to be considered for approval by FDA for sale in the United States. Some drugs go through FDA’s accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by FDA and made available to the public, researchers track its safety in Phase IV trials to seek more information about the drug’s risks, benefits, and optimal use.11

Some clinical trials are categorized as “a” or “b,” such as “Phase Ia” or “Phase IIb.” These different subphases typically mean that a study is researching certain types of information or using a certain type of participant population.

In what phase of testing is SB-728-T?

In what phase of testing is SB-728-T?

SB-728-T is being studied in Phase I/II clinical trials.2

What are some studies on SB-728-T?

What are some studies on SB-728-T?

Study Names: SB-728-0902; NCT01044654
Sponsor: Sangamo Therapeutics
Phase: I
Status: This study has been completed.
Location: United States
Participants: Several groups of participants with HIV on antiretroviral therapy (ART) were studied. (ART is the recommended treatment for HIV infection and involves using a combination of different antiretroviral [ARV] drugs to prevent HIV from multiplying.)

  • Three of the groups included participants with undetectable viral loads (the amount of HIV in the body) and CD4 counts between 200 to 500 cells/mm3. (A CD4 count is a laboratory test that measures the number of CD4 cells in a sample of blood and is an important indicator of immune function.)
  • One group included participants with undetectable viral load levels and CD4 counts above 500 cells/mm3. All participants in this group were CCR5-Δ32 heterozygous. This means that one copy of their CCR5 gene was already naturally mutated, while the other copy of their CCR5 gene was not mutated.
Purpose: The purpose of this study was to look at the safety and effects of intravenous (IV) infusions of SB-728-T in people with HIV. (An IV infusion is given directly into a vein, usually over a period of time.)5,7,12,13


Study Names: SB-728-1101; NCT01543152
Sponsor: Sangamo Therapeutics
Phase: I/II
Status: This study is ongoing, but not recruiting participants.
Location: United States and Puerto Rico
Participants:
  • Participants are adults with HIV who had been on ART for more than 6 months at the start of the study.
  • Participants had no changes to their ART regimen during the 4 weeks before the start of the study.
  • All participants had undetectable viral load levels for at least 3 months at the start of the study.
  • Participants have CD4 counts of at least 500 cells/mm3.
Purpose: The purpose of this study is to look at whether giving different doses of IV cyclophosphamide (an FDA-approved drug for treating cancer) before participants receive an SB-728-T infusion could help the CCR5-modified cells multiply and produce new cells in the body. Investigators are also looking at how cyclophosphamide given before SB-728-T affects viral load levels during a treatment interruption of ART. (A treatment interruption is a planned break from HIV medicines to evaluate how well an investigational drug can maintain control of a participant’s viral load during a clinical trial.)8


Study Names: SB-728mR-1401; NCT02225665
Sponsor: Sangamo Therapeutics
Phase: I/II
Status: This study is ongoing, but not recruiting participants.
Location: United States
Participants:
  • Participants are adults with HIV who started ART within a year of their HIV diagnosis or suspected time of infection.
  • Participants had undetectable viral loads for at least 2 months before the study and CD4 counts of at least 500 cells/mm3.
Study 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.)14,15

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

Other studies on SB-728-T gene therapy have been completed or are currently recruiting participants. This includes an ongoing Phase I study (NCT02388594) that is looking at SB-728mR-T given with and without cyclophosphamide beforehand in participants with HIV who are on ART.2,15-18

What side effects might SB-728-T cause?

What side effects might SB-728-T cause?

In the SB-728-0902 study (NCT01044654) discussed under the previous question, 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 also reported in the SB-728-1101 study (NCT01543152). In addition, a garlic-like odor has been associated with SB-728-T infusions.5,8,19,20

In a Phase I study (NCT00842634), one serious side effect related to SB-728-T infusion was reported.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?

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.

How can I find more information about participating in a clinical trial?

How can I find more information about participating in a clinical trial?

Participating in a clinical trial can provide benefits. For example, a volunteer participant can benefit from new research treatments before they are widely available. Participants also receive regular and careful medical attention from a research team that includes doctors and other health professionals. However, clinical trials may also involve risks of varying degrees, such as unpleasant, serious, or even life-threatening side effects from the treatment being studied.11

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.

 

References

References

  1. United States National Library of Medicine. ChemIDplus Advanced. Available at: https://chem.sis.nlm.nih.gov/chemidplus/rn/S900006290. Last accessed on September 14, 2017.
  2. Frick M, Gaudino A, Harrington M, et al. Treatment Action Group. 2017 Pipeline Report. July 2017. Available at: http://www.pipelinereport.org/sites/default/files/2017%20Pipeline%20Report%20Final.pdf. Last accessed on September 14, 2017.
  3. Manjunath N, Yi G, Dang Y, Shankar P. Newer Gene editing Technologies Toward HIV Gene Therapy. Viruses. 2013 Nov 14;5(11):2748-66. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3856413/. Last accessed on September 14, 2017.
  4. Sangamo Therapeutics website. HIV. Available at: http://www.sangamo.com/product-pipeline/hiv. Last accessed on September 14, 2017.
  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. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01044654. Last accessed on September 14, 2017.
  6. National Institute of Allergy and Infectious Diseases (NIAID): News Release, dated March 5, 2014. Genetic Modification of Cells Proves Generally Safe as HIV Treatment Strategy. Available at: https://www.niaid.nih.gov/news-events/genetic-modification-cells-proves-generally-safe-hiv-treatment-strategy. Last accessed on September 14, 2017.
  7. 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. Available at: http://www.natap.org/2013/HIV/103013_01.htm. Last accessed on September 14, 2017.
  8. 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 Aviremic HIV-Infected Subjects on HAART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 1, 2012. NLM Identifier: NCT01543152. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01543152. Last accessed on September 14, 2017.
  9. 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. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02388594. Last accessed on September 14, 2017.
  10. 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 Finger 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. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02225665. Last accessed on September 14, 2017.
  11. National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: https://www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on September 14, 2017.
  12. 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. Available at: http://www.natap.org/2013/ICAAC/ICAAC_57.htm. Last accessed on September 14, 2017.
  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. Abstract H-674. Available at: 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. Last accessed on September 14, 2017.
  14. 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 Finger 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. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02225665. Last accessed on September 14, 2017.
  15. Sangamo Therapeutics: Press Release, dated October 16, 2014. Sangamo BioSciences ZFP therapeutic program in HIV/AIDS featured at three major scientific conferences in October 2014. Available at: http://investor.sangamo.com/press-releases/detail/259/sangamo-biosciences-zfp-therapeutic-program-in-hivaids. Last accessed on September 14, 2017.
  16. 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. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02388594. Last accessed on September 14, 2017.
  17. 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 Mar 6;370(10):901-10. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4084652/. Last accessed on September 14, 2017.
  18. Sangamo Therapeutics. A Phase 1/2, Open Label, Single Infusion Study of Autologous T-Cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases (SB-728-T) in HIV Infected Subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 29, 2010. NLM Identifier: NCT01252641. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01252641. Last accessed on September 14, 2017.
  19. 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. Available at: 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. Last accessed on September 14, 2017.
  20. 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, Washington. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2015. Available at: http://www.natap.org/2015/CROI/croi_81.htm. Last accessed on September 14, 2017.

Last Reviewed: September 14, 2017