HIVPhase 1NCT02500849
Safety Study of Zinc Finger Nuclease CCR5-modified Hematopoietic Stem/Progenitor Cells in HIV-1 Infected Patients
A Phase 1 study testing SB-728mR-HSPC Infusion 3 days following busulfan conditioning in people with HIV, run by City of Hope Medical Center at 5 sites in United States.
Trial summary
The purpose of the study is to evaluate the safety and feasibility of administering SB-728mR-HSPC after conditioning with busulfan. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- HIV
- What is being tested?
- SB-728mR-HSPC Infusion 3 days following busulfan conditioning
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 5 sitesUnited States
- Study dates
- 10 Mar 2016to 23 Jul 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
City of Hope Medical Center
Duarte, California, 91010
UCLA CARE Center
Los Angeles, California, 90035
Mills Clinical Research
Los Angeles, California, 90069
Circle CARE Center, LLC
Norwalk, Connecticut, 06850
Quest Clinical Research
San Francisco, California, 94115
About this study
Official title: A Pilot Study to Evaluate the Feasibility, Safety and Engraftment of Zinc Finger Nuclease (ZFN) CCR5 Modified CD34+ Hematopoietic Stem/Progenitor Cells (SB-728mR-HSPC) in HIV-1 (R5) Infected Patients
The purpose of the study is to evaluate the safety and feasibility of administering SB-728mR-HSPC after conditioning with busulfan.
Read the 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
- Being tested
- SB-728mR-HSPC Infusion 3 days following busulfan conditioning
- Keywords
- Gene therapy, Acquired Immunodeficiency Syndrome, HIV Infections, Retroviridae Infections, RNA Virus Infections, Virus Diseases, Sexually Transmitted Diseases, Viral, Sexually Transmitted Diseases, Immunologic Deficiency Syndromes, Immune System Diseases, Busulfan, Pharmacologic Actions
- Medical subject headings
- Acquired Immunodeficiency Syndrome, HIV Infections, Retroviridae Infections, RNA Virus Infections, Virus Diseases, Sexually Transmitted Diseases, Viral, Sexually Transmitted Diseases, Immunologic Deficiency Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SB-728mR-HSPC Infusion 3 days following busulfan conditioningGenetic
Also called busulfan
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: | Experimental | target busulfan AUC levels: 8,000 µM*min (+/- 1,000) Receives: Genetic: SB-728mR-HSPC Infusion 3 days following busulfan conditioning |
| Cohort 2: | Experimental | busulfan AUC levels: 12,000 µM*min (+/- 1,000) Receives: Genetic: SB-728mR-HSPC Infusion 3 days following busulfan conditioning |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity in subjects who received SB-728mR-HSPC after each busulfan dose level
Measured: 18 months
Secondary outcomes (1)
Number of CD34+ HSPC collected, gene modified, and released throughout the manufacturing process
Measured: Approximately first 1-2 months on study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2015 (estimated)
- Study start10 Mar 2016
- Primary completion23 Jul 2027 (estimated)
- Study completion23 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Sangamo Therapeutics, California Institute for Regenerative Medicine (CIRM)
- Responsible party
- Sponsor
- Investigators
- Amrita Y. Krishnan, MD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02500849
- Sponsor's protocol ID
- 14017
- Status last verified
- Sep 2026
- First submitted
- 16 Mar 2015
- Last updated
- 2 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 27900346