Gene-Edited Stem Cell Therapy for HIV/AIDS

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

12 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to evaluate the safety and feasibility of administering SB-728mR-HSPC after conditioning with busulfan.

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.

What data supports the effectiveness of the treatment SB-728mR-HSPC for HIV/AIDS?

Research shows that gene-editing of hematopoietic stem cells (HSCs) to disrupt the CCR5 gene can create HIV-resistant immune cells. In animal studies, this approach delayed viral rebound and improved immune function, suggesting potential effectiveness for HIV treatment. ^{1 2 3 4 5}

Is gene-edited stem cell therapy for HIV/AIDS safe in humans?

Research on gene-edited stem cell therapy for HIV/AIDS, including studies on animals, shows that the treatment process is generally safe, with animals surviving transplantation and maintaining normal physiological functions. However, more research is needed to optimize the treatment and confirm its safety in humans. ^{1 2 4 6 7}

How is the treatment SB-728mR-HSPC different from other HIV/AIDS treatments?

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 approach aims to create HIV-resistant immune cells, potentially offering a long-term solution without the need for daily medication. ^{1 2 3 6 8}

Research Team

Amrita Y. Krishnan, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

1. United States pubmed.ncbi.nlm.nih.gov

Experimental Treatment of SIV-Infected Macaques via Autograft of CCR5-Disrupted Hematopoietic Stem and Progenitor Cells. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The CCR5 Gene Edited CD34+CD90+ Hematopoietic Stem Cell Population Serves as an Optimal Graft Source for HIV Gene Therapy. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Stem cell-based therapies for HIV/AIDS. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Development of hematopoietic stem cell based gene therapy for HIV-1 infection: considerations for proof of concept studies and translation to standard medical practice. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Hematopoietic-stem-cell-based gene therapy for HIV disease. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Generation of SIV-resistant T cells and macrophages from nonhuman primate induced pluripotent stem cells with edited CCR5 locus. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Engraftment and lineage potential of adult hematopoietic stem and progenitor cells is compromised following short-term culture in the presence of an aryl hydrocarbon receptor antagonist. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

CRISPR/Cas9-Mediated CCR5 Ablation in Human Hematopoietic Stem/Progenitor Cells Confers HIV-1 Resistance In Vivo. [2022]