Safety Study of Zinc Finger Nuclease CCR5-modified Hematopoietic Stem/Progenitor Cells in HIV-1 Infected Patients

NCT ID: NCT02500849

Last Updated: 2025-10-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-10
• Study Completion Date: 2026-08-24

Brief Summary

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

Detailed Description

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 with cART and have undetectable virus but suboptimal CD4+ cell levels. To strengthen the possibility that CCR5-disrupted HSPCs engraft, patients will receive either a two- or three-day (Cohort 1 or Cohort 2) course of busulfan (dose targeting AUC of 4000 µM/day) before being infused with the genetically modified cells. At 9-12 months after SB-728mR-HSPC infusion, subjects who are aviremic with CD4 cell counts ≥600 cells/µL and have ≥1% CCR5-modified CD4 cells within the peripheral blood detected by pentamer PCR will undergo an ATI.

Conditions

HIV

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1:

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

Group Type: EXPERIMENTAL

SB-728mR-HSPC Infusion 3 days following busulfan conditioning

Intervention Type: GENETIC

Cohort 2:

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

Group Type: EXPERIMENTAL

SB-728mR-HSPC Infusion 3 days following busulfan conditioning

Intervention Type: GENETIC

Interventions

SB-728mR-HSPC Infusion 3 days following busulfan conditioning

Intervention Type: GENETIC

Other Intervention Names

busulfan

Eligibility Criteria

Inclusion Criteria

• Maximum age 75 years for cohort 1 and 65 years for cohort 2.
• HIV-1 R5 seropositive with no evidence of CXCR4-tropic virus.
• On cART with undetectable HIV-1 (<20 gc/ml HIV-1 RNA) for at least 12 months prior to screening evaluations.
• CD4+ T-cell counts ≥200 cells/µL and ≤750 cells/µL.
• No psychosocial conditions that would hinder study compliance and follow-up.
• Absence of clinically significant cardiomyopathy, congestive heart failure.

Secondary Eligibility Criteria (for registration):

• Complete G-CSF/Plerixafor mobilization of HSPC.
• Collect ≥7.5 x 10^6 CD34+ cells/kg in two aphereses.
• The SB-728mR-HSPC product passed all release testing

Exclusion Criteria

• Use of AZT or maraviroc in the cART regimen.
• History of significant hematologic diseases such as leukemia, myelodysplasia, coagulopathy, and thromboembolism.
• Any AIDS-related opportunistic infection occurring within the past year such as tuberculosis, cryptococcosis and for which treatment has been unsuccessful as determined by the Principal Investigator.
• AIDS-related syndromes, infectious or otherwise, if perceived to cause excessive risk for morbidity post-HSPC infusion, as determined by the Principal Investigator.
• Patients with active HBV or HCV infection, i.e., HBV DNA and HCV RNA in blood, are excluded. Those with inactive, but past infection with HBV (positive HBV surface antigen or HBV surface antibody) or inactive HCV (positive HCV antibody), must have no cirrhosis, as determined by abdominal ultrasound with elastography.
• Active CMV retinitis or other active CMV-related organ dysfunction.
• CXCR4-tropic virus.
• Pregnant or nursing women.
• Any history of HIV-associated encephalopathy; dementia of any kind; seizures in the past 12 months; any perceived inability to directly provide informed consent.
• Participants may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy. Participation in prior investigational drug or medical device study within the previous 45 days.
• Current or history of immunomodulatory agent or steroid use.
• Prior therapy with HIV vaccine or gene therapy product.
• History of alcohol or substance abuse for the previous 12 months.
• Participants with active malignancies. However, participants with skin cancers, namely basal cell or squamous cell carcinoma, and malignancies treated with curative intent having no known active disease present for ≥2 years, may be eligible.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sangamo Therapeutics

INDUSTRY

Sponsor Role: collaborator

California Institute for Regenerative Medicine (CIRM)

OTHER

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amrita Y. Krishnan, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

City of Hope Medical Center

Duarte, California, United States

UCLA CARE Center

Los Angeles, California, United States

Mills Clinical Research

Los Angeles, California, United States

Quest Clinical Research

San Francisco, California, United States

Circle CARE Center, LLC

Norwalk, Connecticut, United States

Countries

United States

References

DiGiusto DL, Cannon PM, Holmes MC, Li L, Rao A, Wang J, Lee G, Gregory PD, Kim KA, Hayward SB, Meyer K, Exline C, Lopez E, Henley J, Gonzalez N, Bedell V, Stan R, Zaia JA. Preclinical development and qualification of ZFN-mediated CCR5 disruption in human hematopoietic stem/progenitor cells. Mol Ther Methods Clin Dev. 2016 Nov 9;3:16067. doi: 10.1038/mtm.2016.67. eCollection 2016.

Reference Type: DERIVED

PMID: 27900346 (View on PubMed)

Other Identifiers

14017

Identifier Type: -

Identifier Source: org_study_id