Gene-Edited Stem Cell Therapy for HIV/AIDS

Not currently recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must be taking: cART

Must not be taking: AZT, Maraviroc

Disqualifiers: Hematologic diseases, Opportunistic infections, HBV, HCV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new gene-edited stem cell treatment for individuals with HIV/AIDS. The main goal is to determine if this treatment, called SB-728mR-HSPC, is safe and can be successfully administered following a specific pre-treatment with the drug busulfan. The trial includes two groups, each receiving a different dose of busulfan. It suits HIV-positive individuals on stable medication with controlled virus levels and without serious heart issues. Participants should not have conditions like active hepatitis or recent drug or alcohol abuse. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use AZT or maraviroc in your cART regimen. You also cannot be on any investigational agents, biological, chemotherapy, or radiation therapy.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that gene-edited stem cell therapy, such as SB-728mR-HSPC, is generally safe. Animal studies found that this treatment is well-tolerated, with animals surviving after receiving it. In another study, patients received a similar gene-edited stem cell treatment and demonstrated promising safety results. These findings suggest the treatment could be safe, but further research is needed to confirm this in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for HIV/AIDS, which typically involve antiretroviral therapy to control the virus, SB-728mR-HSPC offers a groundbreaking approach by using gene-edited stem cells. This treatment targets a key protein called CCR5, which the virus uses to enter human cells. By editing the genes of stem cells to disrupt the CCR5 protein, the therapy aims to create HIV-resistant immune cells. Researchers are excited because this approach could potentially reduce the need for lifelong medication and transform how HIV/AIDS is managed.

What evidence suggests that this treatment might be an effective treatment for HIV/AIDS?

Research has shown that SB-728mR-HSPC is promising in fighting HIV/AIDS. This treatment involves altering certain genes in stem cells to block the CCR5 gene, which HIV uses to enter cells. Studies have demonstrated that this method can reduce HIV levels by 80-95%. Additionally, the gene-editing process has successfully modified up to 72.9% of the targeted cells. Participants in this trial will receive SB-728mR-HSPC in different cohorts, with Cohort 1 targeting busulfan AUC levels of 8,000 µM*min (+/- 1,000) and Cohort 2 targeting 12,000 µM*min (+/- 1,000). These findings suggest that SB-728mR-HSPC could help control HIV more effectively by preventing it from entering cells. ^{1 2 6 7 8}

Who Is on the Research Team?

Amrita Y. Krishnan, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for HIV-1 infected patients under 75 years old, with controlled virus levels due to consistent antiretroviral therapy (cART) for at least a year, and specific CD4+ T-cell counts. They must not have significant heart issues or psychosocial conditions affecting study participation. Excluded are those with active hepatitis, pregnant or nursing women, recent investigational drug use, substance abuse history, certain hematologic diseases, recent opportunistic infections or malignancies.

Inclusion Criteria

I am 75 or younger for cohort 1, and 65 or younger for cohort 2.

I am HIV positive with only the R5 virus strain.

I have been on HIV treatment with undetectable levels for at least a year.

Exclusion Criteria

I have had an AIDS-related infection in the last year that hasn't improved with treatment.

You have a condition related to AIDS or other infections that could increase the risk of complications after the treatment, as decided by the main doctor in charge.

Any history of HIV-associated encephalopathy; dementia of any kind; seizures in the past 12 months; any perceived inability to directly provide informed consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants receive a two- or three-day course of busulfan to prepare for infusion of genetically modified cells

1 week

Treatment

Participants are infused with SB-728mR-HSPC, genetically modified hematopoietic stem/progenitor cells

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 9-12 months post-infusion

12 months

What Are the Treatments Tested in This Trial?

Interventions

• SB-728mR-HSPC

Trial Overview The trial tests the safety of SB-728mR-HSPC infusion in HIV/AIDS patients after busulfan conditioning. SB-728mR-HSPC is a genetically modified stem/progenitor cell product aimed at altering the immune system to resist HIV more effectively.

How Is the Trial Designed?

Group I: Cohort 2: Experimental Treatment 1 Intervention

busulfan AUC levels: 12,000 µM\*min (+/- 1,000)

Group II: Cohort 1: Experimental Treatment 1 Intervention

target busulfan AUC levels: 8,000 µM\*min (+/- 1,000)

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

Sangamo Therapeutics

Industry Sponsor

Trials

29

Recruited

950+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

Citations

1. withpower.com withpower.com/trial/phase-1-2-2016-b36a0

Gene-Edited Stem Cell Therapy for HIV/AIDS SB-728mR-HSPC is unique because it involves gene-editing of hematopoietic stem cells to disrupt the CCR5 gene, which is crucial for HIV to enter cells. This ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9275675/

Promising Stem Cell therapy in the Management of HIV and ... The outcome was an 80-to-95 percentage reduction in HIV levels, suggesting that stem-cell-based genetic engineering with a CAR might be a ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02500849

NCT02500849 | Safety Study of Zinc Finger Nuclease ... The objective of the study is to evaluate the safety and feasibility of giving autologous SB-728mR-HSPC to HIV-1 (R5) infected patients who are being treated ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2329050116301942

Preclinical development and qualification of ZFN-mediated ... Our results demonstrate effective biallelic CCR5 disruption in up to 72.9% of modified colony forming units from adult mobilized HSPC with maintenance of ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10862071/

In vivo selection of anti-HIV-1 gene-modified human ... Hematopoietic stem/progenitor cell (HSPC)–based anti-HIV-1 gene therapy holds great promise to eradicate HIV-1 or to provide long-term remission through a ...

6. cirm.ca.gov cirm.ca.gov/our-progress/awards/phase-i-open-label-study-assess-safety-feasibility-and-engraftment-zinc-finger-nucleases-zfn-ccr5-modified-autologous-cd34-hematopoietic-stem-progenitor-cells-sb-728mr-hspc-esc/

A Phase I, Open-Label Study To Assess The Safety, Feasibility ... Success of this therapy would establish the safety of a possible future cure for HIV-1/AIDS.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5102145/

Preclinical development and qualification of ZFN-mediated ... Our results demonstrate effective biallelic CCR5 disruption in up to 72.9% of modified colony forming units from adult mobilized HSPC with ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa1817426

CRISPR-Edited Stem Cells in a Patient with HIV and Acute ... We transplanted CRISPR-edited CCR5-ablated hematopoietic stem and progenitor cells (HSPCs) into a patient with HIV-1 infection and acute lymphoblastic leukemia.