HivPhase 1NCT03617198
CD4 CAR+ ZFN-modified T Cells in HIV Therapy
A Phase 1 study testing CD4 CAR+CCR5 ZFN T-cells in people with Hiv, run by University of Pennsylvania at 1 site in United States.
Trial summary
This research study is being carried out to study a new way to possibly treat HIV. As part of this study, doctors will take some of your own white blood cells, called T-cells, and modify them so that they can identify and target your HIV cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hiv
- What is being tested?
- CD4 CAR+CCR5 ZFN T-cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jul 2019to Dec 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infection
- Clinically stable on first or second HAART regimen
- Screening CD4+ T cell count of ≥450 cells/mm3 within 30 days of enrollment; and a documented CD4 nadir of not lower than 200 cells/mm3
- Screening HIV-1 RNA that is ≤50 copies/mL within 30 days prior to enrollment
- HIV-1 RNA ≤50 copies/mL for at least 24 weeks prior to enrollment
- Adequate venous access and no other contraindications for leukapheresis
Show all 14Show fewer
- Laboratory values within certain parameters, obtained within 30 days prior to enrollment
- Willing to comply with study-mandated evaluations
- Male or female, 18 years of age or older
- Ability and willingness to provide informed consent
- Karnofsky Performance Score of 70 or higher
- Negative HBsAg (hepatitis B) within 6 months prior to enrollment
- Negative HCV (hepatitis C) serology, or if positive, negative HCV RNA within 6 months prior to enrollment
- Have a recorded viral load set point prior to starting antiretroviral therapy
Who cannot join
- Acute or chronic hepatitis B or hepatitis C infection
- Current or prior AIDS diagnosis
- History of cancer or malignancy, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin
- History or any features on physical examination indicative of active or unstable cardiac disease or hemodynamic instability (subjects with a history of cardiac disease may participate with a physician's approval)
- History or any features of physical examination indicative of bleeding diathesis
- Have been previously treated with any HIV experimental vaccine within 6 months prior to screening, or any previous gene therapy using an integrating vector (subjects treated with placebo in an HIV vaccine study will not be excluded if documentation that they received placebo is provided)
Show all 14Show fewer
- Use of chronic systemic corticosteroids, hydroxyurea, or immunomodulating agents within 30 days prior to enrollment (recent or current use of inhaled steroids is not exclusionary)
- Breast-feeding, pregnant, or unwilling to use acceptable methods of birth control
- Anticipated use of aspirin, dipyridamole, 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 that, in the opinion of the investigator, would interfere with adherence to study requirements
- Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to the study screening visit
- Receipt of vaccination within 30 days prior to study screening visit
- Have an allergy to hypersensitivity to study product components (human serum albumin, DMSO and Dextran 40)
- Currently taking a non-nucleoside reverse transcriptase inhibitor (NNRTI)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Pilot Study of T Cells Genetically Modified by Zinc Finger Nucleases SB-728mR and CD4 Chimeric Antigen Receptor in HIV-infected Subjects
This research study is being carried out to study a new way to possibly treat HIV. As part of this study, doctors will take some of your own white blood cells, called T-cells, and modify them so that they can identify and target your HIV cells. The purpose of the study is to evaluate the safety of these modified T cells and determine whether they have any effect on HIV infection.
Read the detailed description
Step 1:
Subject is screened, undergoes leukaphereses, and optional rectal biopsy, and safety evaluations before dosing. The University of Pennsylvania manufactures the study product.
Step 2:
Subjects receive a single infusion of 0.5-1x10(10) CD4 CAR+CCR5 ZFN modified T cells. Cohort 2 participants undergo a mini-leukapheresis and optional rectal biopsy at the end of step 2.
The duration of Step 2 will be:
- Cohort 1: 1 day
- Cohort 2: 8 weeks
Step 3:
All subjects will participate in a 16 week analytical treatment interruption (ATI). ATI will be less than 16 weeks if patient's viral load is sustained >100,000 or CD4 count <350 or less than 50% of baseline. At the end of step 3 all participants will undergo mini-leukapheresis and optional rectal biopsy.
Step 4:
Participants who have HIV viral loads ≤1000 copies/ml will continue in an extension of the analytical treatment interruption until viral load is sustained >100,000 or CD4 count <350 or less than 50% of baseline.
Step 5:
Reinitiation of antiretroviral therapy with monthly visits until the HIV RNA is below the limit of quantification. All participants undergo a mini-leukapheresis and optional rectal biopsy at the end of the step 5.
Step 6 (Secondary Follow-up):
All subjects will be followed for safety for up to 5 years post-infusion.
- Conditions
- Hiv
- Being tested
- CD4 CAR+CCR5 ZFN T-cells
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD4 CAR+CCR5 ZFN T-cellsBiological
A dual cohort, open-label, randomized study of the safety and tolerability of a single infusion of autologous T cells genetically modified to express a CD4 chimeric antigen receptor while also having zinc finger nuclease-mediated disruption of the CCR5 gene
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Cohort 1 subjects will begin treatment interruption approximately 24 hours after they receive the modified T-cells. All other study procedures are the same as Cohort 2. Receives: Biological: CD4 CAR+CCR5 ZFN T-cells |
| Cohort 2 | Experimental | Cohort 2 subjects will begin treatment interruption approximately 8 weeks after they receive the modified T-cells. All other study procedures are the same as Cohort 1. Receives: Biological: CD4 CAR+CCR5 ZFN T-cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects with treatment related adverse events.
Measured: After subjects have received infusion and up to 5 years from Day 0 infusion.
Secondary outcomes (7)
Compare the percentage of enriched modified CD4 CAR+ CCR5 ZFN cells and their subsets.
Measured: 2 weeks post infusion, prior to prior to analytical treatment interruption (ATI), 6-9 months post infusion.
Compare the change in CD4 count.
Measured: Baseline, week 2 post infusion, prior to ATI, weeks 8, 12, 16 of ATI.
Compare viral set point log 10 HIV RNA level.
Measured: Baseline and 6-9 months post infusion
Percentage of cells producing cytokines in response to HIV antigen/peptide as assessed by flow cytometry
Measured: Baseline and 6-9 months post infusion
Size of latent HIV reservoir as assessed by quantification of integrated copies of replication competent HIV
Measured: Baseline, pre-treatment interruption, prior to ART reinitiation, 6-9 months post infusion, and end of primary follow up (8-12 months)
Sequence of HIV envelope genes and coreceptor usage in breakthrough HIV infections
Measured: Baseline through 1 year.
Number of participants who control HIV replication that have similar gene expression patterns as determined by RNA quantification
Measured: Baseline through 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2018
- Study start31 Jul 2019
- Primary completionDec 2026 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HivStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pablo Tebas, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03617198
- Sponsor's protocol ID
- 831464
- Status last verified
- Aug 2026
- First submitted
- 9 Jul 2018
- Last updated
- 27 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of T Cells Genetically Modified by Zinc Finger Nucleases SB-728mR and CD4 Chimeric Antigen Receptor in HIV-infected Subjects
- ClinicalTrials.gov ID
- NCT03617198
- Acronym / sponsor ID
- 831464
- Conditions
- Hiv
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 31 Jul 2019 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 6 Aug 2018 (actual)
- 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. As part of this study, doctors will take some of your own white blood cells, called T-cells, and modify them so that they can identify and target your HIV cells. The purpose of the study is to evaluate the safety of these modified T cells and determine whether they have any effect on HIV infection.
Detailed description
Step 1:
Subject is screened, undergoes leukaphereses, and optional rectal biopsy, and safety evaluations before dosing. The University of Pennsylvania manufactures the study product.
Step 2:
Subjects receive a single infusion of 0.5-1x10(10) CD4 CAR+CCR5 ZFN modified T cells. Cohort 2 participants undergo a mini-leukapheresis and optional rectal biopsy at the end of step 2.
The duration of Step 2 will be:
- Cohort 1: 1 day
- Cohort 2: 8 weeks
Step 3:
All subjects will participate in a 16 week analytical treatment interruption (ATI). ATI will be less than 16 weeks if patient's viral load is sustained >100,000 or CD4 count <350 or less than 50% of baseline. At the end of step 3 all participants will undergo mini-leukapheresis and optional rectal biopsy.
Step 4:
Participants who have HIV viral loads ≤1000 copies/ml will continue in an extension of the analytical treatment interruption until viral load is sustained >100,000 or CD4 count <350 or less than 50% of baseline.
Step 5:
Reinitiation of antiretroviral therapy with monthly visits until the HIV RNA is below the limit of quantification. All participants undergo a mini-leukapheresis and optional rectal biopsy at the end of the step 5.
Step 6 (Secondary Follow-up):
All subjects will be followed for safety for up to 5 years post-infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: CD4 CAR+CCR5 ZFN T-cellsCohort 1 subjects will begin treatment interruption approximately 24 hours after they receive the modified T-cells. All other study procedures are the same as Cohort 2. |
| Cohort 2 | Experimental | Biological: CD4 CAR+CCR5 ZFN T-cellsCohort 2 subjects will begin treatment interruption approximately 8 weeks after they receive the modified T-cells. All other study procedures are the same as Cohort 1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- HIV-1 infection
- Clinically stable on first or second HAART regimen
- Screening CD4+ T cell count of ≥450 cells/mm3 within 30 days of enrollment; and a documented CD4 nadir of not lower than 200 cells/mm3
- Screening HIV-1 RNA that is ≤50 copies/mL within 30 days prior to enrollment
- HIV-1 RNA ≤50 copies/mL for at least 24 weeks prior to enrollment
Key exclusion criteria (14 listed)
- Acute or chronic hepatitis B or hepatitis C infection
- Current or prior AIDS diagnosis
- History of cancer or malignancy, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin
- History or any features on physical examination indicative of active or unstable cardiac disease or hemodynamic instability (subjects with a history of cardiac disease may participate with a physician's approval)
- History or any features of physical examination indicative of 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 |
|---|---|---|
| CD4 CAR+CCR5 ZFN T-cellsA dual cohort, open-label, randomized study of the safety and tolerability of a single infusion of autologous T cells genetically modified to express a CD4 chimeric antigen receptor while also having zinc finger nuclease-mediated disruption of the CCR5 gene | Biological | Cohort 1, Cohort 2 |
Primary outcome
Number of subjects with treatment related adverse events.
Time frame: After subjects have received infusion and up to 5 years from Day 0 infusion.
7 secondary outcomes
Compare the percentage of enriched modified CD4 CAR+ CCR5 ZFN cells and their subsets.
Time frame: 2 weeks post infusion, prior to prior to analytical treatment interruption (ATI), 6-9 months post infusion.
Compare the change in CD4 count.
Time frame: Baseline, week 2 post infusion, prior to ATI, weeks 8, 12, 16 of ATI.
Compare viral set point log 10 HIV RNA level.
Time frame: Baseline and 6-9 months post infusion
Percentage of cells producing cytokines in response to HIV antigen/peptide as assessed by flow cytometry
Time frame: Baseline and 6-9 months post infusion
Size of latent HIV reservoir as assessed by quantification of integrated copies of replication competent HIV
Time frame: Baseline, pre-treatment interruption, prior to ART reinitiation, 6-9 months post infusion, and end of primary follow up (8-12 months)
Sequence of HIV envelope genes and coreceptor usage in breakthrough HIV infections
Time frame: Baseline through 1 year.
Number of participants who control HIV replication that have similar gene expression patterns as determined by RNA quantification
Time frame: Baseline through 1 year.
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 27 Aug 2026.
Related trials for Hiv
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.
Pablo Tebas, MD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CD4 CAR+CCR5 ZFN T-cells in people with Hiv, run by University of Pennsylvania at 1 site 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 14 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 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Number of subjects with treatment related adverse events. (time frame: After subjects have received infusion and up to 5 years from Day 0 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 27 Aug 2026.