HIV InfectionPhase 1NCT01044654
Phase 1 Dose Escalation Study of Autologous T-cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases in HIV-Infected Patients
A Phase 1 study testing SB-728-T in people with HIV Infection and HIV Infections, run by Sangamo Therapeutics at 9 sites in United States.
Trial summary
This research study is being carried out to study a new way to possibly treat HIV. This agent is called a "Zinc Finger Nuclease" or ZFN for short. ZFNs are proteins that can delete another protein named CCR5. This CCR5 protein is required for certain types of HIV (CCR5 tropic) to enter into and infect your T-cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection, HIV Infections
- What is being tested?
- SB-728-T
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 9 sitesUnited States
- Study dates
- Dec 2009to Dec 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented HIV infection prior to study entry
- Must be willing to comply with study-mandated evaluations; including not changing their antiretroviral regimen (unless medically indicated) during the study period.
- Cohort 1, 2 and 3 (Enrollment Completed)
- Cohort 5:
- Must have received HAART therapy, and had undetectable viral loads for at least 1 year.
- HIV-1 RNA < 50 copies/mL obtained within 60 days prior to study entry performed with an ultrasensitive HIV-1 PCR assay.
Show all 13Show fewer
- CD4+ T cell count >500 cells/mm3
- Heterozygous for the CCR5 delta-32 mutation
- On stable antiretroviral medication (no changes to treatment within 4 weeks of screening and willing to discontinue current antiretroviral therapy during the structured therapy interruption
- Cohort 4
- On stable antiretroviral medication (no changes to treatment within 4 weeks of screening and willing to continue on current antiretroviral therapy through week 8 after infusion
- CD4+ T cell count >350 cells/mm3.
- HIV-1 >1,000 copies/mL at screen and not responding to current antiviral therapy (i.e. HIV-RNA plasma levels > 1000 copies/ml after at least 12 weeks of stable, unchanged ARV therapy).
Who cannot join
- Acute or chronic hepatitis B or hepatitis C infection
- Active or recent (in prior 6 months) AIDS defining complication.
- Any cancer or malignancy within the past 5 years, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin or low grade (0 or 1) anal or cervical dysplasia.
- Current diagnosis of NYHA grade 3 or 4 CHF, uncontrolled angina or uncontrolled arrhythmias.
- History or any features on physical examination indicative of a bleeding diathesis.
- Previous treatment with any HIV experimental vaccine within 6 months prior to screening, or any previous gene therapy using an integrating vector.
Show all 17Show fewer
- Use of chronic corticosteroids, hydroxyurea, or immunomodulating agents (e.g., interleukin-2, interferon-alpha or gamma, granulocyte colony stimulating factors, etc.) within 30 days prior to enrollment
- Breast-feeding, pregnant or unwilling to use acceptable methods of birth control for 6 months following the last infusion of SB-728-T cells.
- warfarin or any other medication that is likely to affect platelet function or other aspects of blood coagulation during the 2 week period prior to leukapheresis.
- Active drug or alcohol use or dependence
- Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to study entry.
- Recent vaccination or intercurrent illness (within 5 weeks prior to infusion)
- Have an allergy or hypersensitivity to study product excipients (human serum albumin, DMSO and Dextran 40).
- Subjects who are currently taking maraviroc or have received maraviroc within 6 months prior to screening.
- Cohort 4 only:
- HIV-1 RNA >1,000 copies/mL at screen and not responding to current antiviral therapy
- CD4+ T cell count >350 cells/mm3
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Gordon Crofoot, MD, PA
Houston, Texas, 77098
UCLA Center for AIDS Research and Education
Los Angeles, California, 90035
Ricky K Hsu, MD, PC
New York, New York, 10011
Orange Coast Medical Group
Newport Beach, California, 92663
Circle CARE Center, LLC
Norwalk, Connecticut, 06851
Orlando Immunology Center
Orlando, Florida, 32803
Quest Clinical Research
San Francisco, California, 94115
Southwest CARE Center
Santa Fe, New Mexico, 87505
Central West Clinical Research, Inc.
St Louis, Missouri, 63108
About this study
Official title: A Phase 1 Dose Escalation, Single Dose Study of Autologous T-Cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases SB-278 in HIV-Infected Patients Who Have Exhibited Suboptimal CD4+ T-Cell Gains During Long-Term Antiretroviral Therapy
This research study is being carried out to study a new way to possibly treat HIV. This agent is called a "Zinc Finger Nuclease" or ZFN for short. ZFNs are proteins that can delete another protein named CCR5. This CCR5 protein is required for certain types of HIV (CCR5 tropic) to enter into and infect your T-cells. T cells are one of the white blood cells used by the body to fight HIV. The most important of these are called "CD4 T-cells."
Some People are born without CCR5 on their T-cells. These people remain healthy and are resistant to infection with HIV. Other people have a low number of CCR5 on their T-cells, and their HIV disease is less severe and is slower to cause disease (AIDS).
Read more
Even with no detectable levels of HIV in the blood, HIV remains in some tissues in the body, primarily the gut tissue. HIV infects the CD4+ T-cells including in the blood and gut. The new treatment to be studied will involve removing white blood cell from the blood that contains CD4+ T-cells. The extracted CD4+ T-cells are then genetically modified by the ZFNs to be resistant to infection by HIV by removing the CCR5 gene from the surface of the CD4+ T cell where HIV enters the cell. Additional genetically modified cells are manufactured and then re-infused back into you. Researchers hope that these genetically modified cells will be resistant to infection by HIV and will be able to reproduce additional resistant CD4+ T-cells in your body.
Laboratory studies have shown that when CD4+ T-cells are modified with ZFNs, HIV is prevented from killing the CD4+ T-cells. On the basis of these laboratory results, thre is the potential that ZFNs may work in humans infected with HIV and improve their immune system by allowing their CD4+ T-cells to survive longer.
The purpose of this research study is to find out whether "zinc finger" modified CD4+ T-cells are safe to give to humans and find how "zinc finger" modified T-cell affects HIV.
- Conditions
- HIV Infection, HIV Infections
- Being tested
- SB-728-T
- Keywords
- HIV, Treatment Experienced
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SB-728-TGenetic
Each infusion will be 5-30 billion ZFN modified CD4+ T-cells
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 3 Subjects will receive a single infusion of 0.5-1.0 x 1010 SB-728-T Receives: Genetic: SB-728-T |
| Cohort 2 | Experimental | 3 Subjects will receive a single infusion of 2.0 x 1010 SB-728-T Receives: Genetic: SB-728-T |
| Cohort 3 | Experimental | 3 Subjects will receive a single infusion of 3.0 x 1010 SB-728-T Receives: Genetic: SB-728-T |
| Cohort 4 | Experimental | Up to 4 HAART failure subjects will receive a single intravenous infusion of 0.5 to 3.0 x 1010 SB-728-T Receives: Genetic: SB-728-T |
| Cohort 5 | Experimental | Up to 20 subjects with heterozygote CCR5 delta-32 mutation will receive a single intravenous infusion of 0.5 to 3.0 x 1010 SB-728-T.
Cohort 5 subjects will undergo a structured treatment interruption 2 months following infusion in which their anti-retroviral therapy will be discontinued for 16 weeks. HAART will be reinstituted in subjects whose CD4+ cell counts drop to <350 cells/mm3 and/or whose HIV-RNA increases to >100,000 on three consecutive weekly measurements.
At the end of the STI, subjects with a sustained detectable viral load will be reinstituted on HAART. Subjects with HIV RNA levels below the limit of detection will remain off HAART. Subjects with an undetectable viral load will remain off HAART until HIV RNA levels are detectable or their CD4 count drops below 350 cell/mm3 on three consecutive weekly measurements. Receives: Genetic: SB-728-T |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety - Treatment related adverse events
Measured: 12 months after the first infusion
Secondary outcomes (1)
Evaluate the long-term persistence and activity of CCR5 ZFN-modified autologous T-Cells
Measured: 12 months after the first infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2010 (estimated)
- Study startDec 2009
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- 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
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sangamo Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Winson Tang, M.D., Study director, Sangamo Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01044654
- Sponsor's protocol ID
- SB-728-0902
- Status last verified
- Mar 2015
- First submitted
- 6 Jan 2010
- Last updated
- 13 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Dose Escalation, Single Dose Study of Autologous T-Cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases SB-278 in HIV-Infected Patients Who Have Exhibited Suboptimal CD4+ T-Cell Gains During Long-Term Antiretroviral Therapy
- ClinicalTrials.gov ID
- NCT01044654
- Acronym / sponsor ID
- SB-728-0902
- Conditions
- HIV Infection, HIV Infections
- Keywords
- HIV, Treatment Experienced
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Sangamo TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Dec 2009
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 8 Jan 2010 (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.
This research study is being carried out to study a new way to possibly treat HIV. This agent is called a "Zinc Finger Nuclease" or ZFN for short. ZFNs are proteins that can delete another protein named CCR5. This CCR5 protein is required for certain types of HIV (CCR5 tropic) to enter into and infect your T-cells. T cells are one of the white blood cells used by the body to fight HIV. The most important of these are called "CD4 T-cells."
Some People are born without CCR5 on their T-cells. These people remain healthy and are resistant to infection with HIV. Other people have a low number of CCR5 on their T-cells, and their HIV disease is less severe and is slower to cause disease (AIDS).
Even with no detectable levels of HIV in the blood, HIV remains in some tissues in the body, primarily the gut tissue. HIV infects the CD4+ T-cells including in the blood and gut. The new treatment to be studied will involve removing white blood cell from the blood that contains CD4+ T-cells. The extracted CD4+ T-cells are then genetically modified by the ZFNs to be resistant to infection by HIV by removing the CCR5 gene from the surface of the CD4+ T cell where HIV enters the cell. Additional genetically modified cells are manufactured and then re-infused back into you. Researchers hope that these genetically modified cells will be resistant to infection by HIV and will be able to reproduce additional resistant CD4+ T-cells in your body.
Laboratory studies have shown that when CD4+ T-cells are modified with ZFNs, HIV is prevented from killing the CD4+ T-cells. On the basis of these laboratory results, thre is the potential that ZFNs may work in humans infected with HIV and improve their immune system by allowing their CD4+ T-cells to survive longer.
The purpose of this research study is to find out whether "zinc finger" modified CD4+ T-cells are safe to give to humans and find how "zinc finger" modified T-cell affects HIV.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Genetic: SB-728-T3 Subjects will receive a single infusion of 0.5-1.0 x 1010 SB-728-T |
| Cohort 2 | Experimental | Genetic: SB-728-T3 Subjects will receive a single infusion of 2.0 x 1010 SB-728-T |
| Cohort 3 | Experimental | Genetic: SB-728-T3 Subjects will receive a single infusion of 3.0 x 1010 SB-728-T |
| Cohort 4 | Experimental | Genetic: SB-728-TUp to 4 HAART failure subjects will receive a single intravenous infusion of 0.5 to 3.0 x 1010 SB-728-T |
| Cohort 5 | Experimental | Genetic: SB-728-TUp to 20 subjects with heterozygote CCR5 delta-32 mutation will receive a single intravenous infusion of 0.5 to 3.0 x 1010 SB-728-T. Cohort 5 subjects will undergo a structured treatment interruption 2 months following infusion in which their anti-retroviral therapy will be discontinued for 16 weeks. HAART will be reinstituted in subjects whose CD4+ cell counts drop to <350 cells/mm3 and/or whose HIV-RNA increases to >100,000 on three consecutive weekly measurements. At the end of the STI, subjects with a sustained detectable viral load will be reinstituted on HAART. Subjects with HIV RNA levels below the limit of detection will remain off HAART. Subjects with an undetectable viral load will remain off HAART until HIV RNA levels are detectable or their CD4 count drops below 350 cell/mm3 on three consecutive weekly measurements. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Documented HIV infection prior to study entry
- Must be willing to comply with study-mandated evaluations; including not changing their antiretroviral regimen (unless medically indicated) during the study period.
- Cohort 1, 2 and 3 (Enrollment Completed)
- Must have received HAART therapy, and had undetectable viral loads for at least 1 year.
- HIV-1 RNA < 50 copies/mL obtained within 60 days prior to study entry performed with an ultrasensitive HIV-1 PCR assay.
Key exclusion criteria (17 listed)
- Acute or chronic hepatitis B or hepatitis C infection
- Active or recent (in prior 6 months) AIDS defining complication.
- Any cancer or malignancy within the past 5 years, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin or low grade (0 or 1) anal or cervical dysplasia.
- Current diagnosis of NYHA grade 3 or 4 CHF, uncontrolled angina or uncontrolled arrhythmias.
- History or any features on physical examination indicative of a bleeding diathesis.
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-728-TEach infusion will be 5-30 billion ZFN modified CD4+ T-cells | Genetic | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5 |
Primary outcome
Safety - Treatment related adverse events
Time frame: 12 months after the first infusion
1 secondary outcome
Evaluate the long-term persistence and activity of CCR5 ZFN-modified autologous T-Cells
Time frame: 12 months after the first infusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2015.
Related trials for HIV Infection
Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
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.
Winson Tang, M.D. study director
Sangamo Therapeutics
9 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-728-T in people with HIV Infection and HIV Infections, run by Sangamo Therapeutics at 9 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 13 inclusion and 17 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: finished, as of the sponsor's last update on 13 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety - Treatment related adverse events (time frame: 12 months after the first infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Mar 2015.