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
- Are there results?
- Not yet: the study is under way
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
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02500849
- Acronym / sponsor ID
- 14017
- Conditions
- HIV
- Keywords
- Gene therapy, Acquired Immunodeficiency Syndrome, HIV Infections, Retroviridae Infections, RNA Virus Infections, Virus Diseases, Sexually Transmitted Diseases, Viral, Sexually Transmitted Diseases
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- Sangamo Therapeutics, California Institute for Regenerative Medicine (CIRM)
- Study start
- 10 Mar 2016 (actual)
- Primary completion
- 23 Jul 2027 (estimated)
- Study completion
- 23 Jul 2027 (estimated)
- First posted
- 17 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: | Experimental | Genetic: SB-728mR-HSPC Infusion 3 days following busulfan conditioningtarget busulfan AUC levels: 8,000 µM*min (+/- 1,000) |
| Cohort 2: | Experimental | Genetic: SB-728mR-HSPC Infusion 3 days following busulfan conditioningbusulfan AUC levels: 12,000 µM*min (+/- 1,000) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SB-728mR-HSPC Infusion 3 days following busulfan conditioningAlso: busulfan | Genetic | Cohort 1:, Cohort 2: |
Primary outcome
Toxicity in subjects who received SB-728mR-HSPC after each busulfan dose level
Time frame: 18 months
1 secondary outcome
Number of CD34+ HSPC collected, gene modified, and released throughout the manufacturing process
Time frame: Approximately first 1-2 months on study
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- Derived from this study: PubMed 27900346DiGiusto 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amrita Y. Krishnan, MD principal investigator
City of Hope Medical Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity in subjects who received SB-728mR-HSPC after each busulfan dose level (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02500849, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.